The pathophysiologic causes of obstructive sleep apnea (OSA) likely vary among patients but have not been well characterized.
To define carefully the proportion of key anatomic and nonanatomic ...contributions in a relatively large cohort of patients with OSA and control subjects to identify pathophysiologic targets for future novel therapies for OSA.
Seventy-five men and women with and without OSA aged 20-65 years were studied on three separate nights. Initially, the apnea-hypopnea index was determined by polysomnography followed by determination of anatomic (passive critical closing pressure of the upper airway Pcrit) and nonanatomic (genioglossus muscle responsiveness, arousal threshold, and respiratory control stability; loop gain) contributions to OSA.
Pathophysiologic traits varied substantially among participants. A total of 36% of patients with OSA had minimal genioglossus muscle responsiveness during sleep, 37% had a low arousal threshold, and 36% had high loop gain. A total of 28% had multiple nonanatomic features. Although overall the upper airway was more collapsible in patients with OSA (Pcrit, 0.3 -1.5 to 1.9 vs. -6.2 -12.4 to -3.6 cm H2O; P <0.01), 19% had a relatively noncollapsible upper airway similar to many of the control subjects (Pcrit, -2 to -5 cm H2O). In these patients, loop gain was almost twice as high as patients with a Pcrit greater than -2 cm H2O (-5.9 -8.8 to -4.5 vs. -3.2 -4.8 to -2.4 dimensionless; P = 0.01). A three-point scale for weighting the relative contribution of the traits is proposed. It suggests that nonanatomic features play an important role in 56% of patients with OSA.
This study confirms that OSA is a heterogeneous disorder. Although Pcrit-anatomy is an important determinant, abnormalities in nonanatomic traits are also present in most patients with OSA.
Abstract
Obstructive sleep apnea (OSA) is thought to affect almost 1 billion people worldwide. OSA has well established cardiovascular and neurocognitive sequelae, although the optimal metric to ...assess its severity and/or potential response to therapy remains unclear. The apnea-hypopnea index (AHI) is well established; thus, we review its history and predictive value in various different clinical contexts. Although the AHI is often criticized for its limitations, it remains the best studied metric of OSA severity, albeit imperfect. We further review the potential value of alternative metrics including hypoxic burden, arousal intensity, odds ratio product, and cardiopulmonary coupling. We conclude with possible future directions to capture clinically meaningful OSA endophenotypes including the use of genetics, blood biomarkers, machine/deep learning and wearable technologies. Further research in OSA should be directed towards providing diagnostic and prognostic information to make the OSA diagnosis more accessible and to improving prognostic information regarding OSA consequences, in order to guide patient care and to help in the design of future clinical trials.
Abstract
Aims
Apnoea–hypopnoea index (AHI), the universal clinical metric of sleep apnoea severity, poorly predicts the adverse outcomes of sleep apnoea, potentially because the AHI, a frequency ...measure, does not adequately capture disease burden. Therefore, we sought to evaluate whether quantifying the severity of sleep apnoea by the ‘hypoxic burden’ would predict mortality among adults aged 40 and older.
Methods and results
The samples were derived from two cohort studies: The Outcomes of Sleep Disorders in Older Men (MrOS), which included 2743 men, age 76.3 ± 5.5 years; and the Sleep Heart Health Study (SHHS), which included 5111 middle-aged and older adults (52.8% women), age: 63.7 ± 10.9 years. The outcomes were all-cause and Cardiovascular disease (CVD)-related mortality. The hypoxic burden was determined by measuring the respiratory event-associated area under the desaturation curve from pre-event baseline. Cox models were used to calculate the adjusted hazard ratios for hypoxic burden. Unlike the AHI, the hypoxic burden strongly predicted CVD mortality and all-cause mortality (only in MrOS). Individuals in the MrOS study with hypoxic burden in the highest two quintiles had hazard ratios of 1.81 95% confidence interval (CI) 1.25–2.62 and 2.73 (95% CI 1.71–4.36), respectively. Similarly, the group in the SHHS with hypoxic burden in the highest quintile had a hazard ratio of 1.96 (95% CI 1.11–3.43).
Conclusion
The ‘hypoxic burden’, an easily derived signal from overnight sleep study, predicts CVD mortality across populations. The findings suggest that not only the frequency but the depth and duration of sleep related upper airway obstructions, are important disease characterizing features.
Monitoring reactive intermediates can provide vital information in the study of synthetic reaction mechanisms, enabling the design of new catalysts and methods. Many synthetic transformations are ...centred on the alteration of oxidation states, but these redox processes frequently pass through intermediates with short life-times, making their study challenging. A variety of electroanalytical tools can be utilised to investigate these redox-active intermediates: from voltammetry to
in situ
spectroelectrochemistry and scanning electrochemical microscopy. This perspective provides an overview of these tools, with examples of both electrochemically-initiated processes and monitoring redox-active intermediates formed chemically in solution. The article is designed to introduce synthetic organic and organometallic chemists to electroanalytical techniques and their use in probing key mechanistic questions.
A range of electroanalytical tools can be applied to studying redox reactions, probing key mechanistic questions in synthetic chemistry.
There is currently no effective pharmacological treatment for obstructive sleep apnea (OSA). Recent investigations indicate that drugs with noradrenergic and antimuscarinic effects improve ...genioglossus muscle activity and upper airway patency during sleep.
We aimed to determine the effects of the combination of a norepinephrine reuptake inhibitor (atomoxetine) and an antimuscarinic (oxybutynin) on OSA severity (apnea-hypopnea index AHI; primary outcome) and genioglossus responsiveness (secondary outcome) in people with OSA.
A total of 20 people completed a randomized, placebo-controlled, double-blind, crossover trial comparing 1 night of 80 mg atomoxetine plus 5 mg oxybutynin (ato-oxy) to placebo administered before sleep. The AHI and genioglossus muscle responsiveness to negative esophageal pressure swings were measured via in-laboratory polysomnography. In a subgroup of nine patients, the AHI was also measured when the drugs were administered separately.
The participants' median (interquartile range) age was 53 (46-58) years and body mass index was 34.8 (30.0-40.2) kg/m
. ato-oxy lowered AHI by 63% (34-86%), from 28.5 (10.9-51.6) events/h to 7.5 (2.4-18.6) events/h (
< 0.001). Of the 15/20 patients with OSA on placebo (AHI > 10 events/hr), AHI was lowered by 74% (62-88%) (
< 0.001) and all 15 patients exhibited a ≥50% reduction. Genioglossus responsiveness increased approximately threefold, from 2.2 (1.1-4.7)%/cm H
O on placebo to 6.3 (3.0 to 18.3)%/cm H
O on ato-oxy (
< 0.001). Neither atomoxetine nor oxybutynin reduced the AHI when administered separately.
A combination of noradrenergic and antimuscarinic agents administered orally before bedtime on 1 night greatly reduced OSA severity. These findings open new possibilities for the pharmacologic treatment of OSA. Clinical trial registered with www.clinicaltrials.gov (NCT02908529).
Considerable progress has been made over the last several decades in our understanding of the pathophysiology of both central and obstructive sleep apnea. Central sleep apnea, in its various forms, ...is generally the product of an unstable ventilatory control system (high loop gain) with increased controller gain (high hypercapnic responsiveness) generally being the cause. High plant gain can contribute under certain circumstances (hypercapnic patients). On the other hand, obstructive sleep apnea can develop as the result of a variety of physiologic characteristics. The combinations of these may vary considerably between patients. Most obstructive apnea patients have an anatomically small upper airway with augmented pharyngeal dilator muscle activation maintaining airway patency awake, but not asleep. However, individual variability in several phenotypic characteristics may ultimately determine who develops apnea and how severe the apnea will be. These include: (1) upper airway anatomy, (2) the ability of upper airway dilator muscles to respond to rising intrapharyngeal negative pressure and increasing Co(2) during sleep, (3) arousal threshold in response to respiratory stimulation, and (4) loop gain (ventilatory control instability). As a result, patients may respond to different therapeutic approaches based on the predominant abnormality leading to the sleep-disordered breathing.
New and previously unimaginable Landsat applications have been fostered by a policy change in 2008 that made analysis-ready Landsat data free and open access. Since 1972, Landsat has been collecting ...images of the Earth, with the early years of the program constrained by onboard satellite and ground systems, as well as limitations across the range of required computing, networking, and storage capabilities. Rather than robust on-satellite storage for transmission via high bandwidth downlink to a centralized storage and distribution facility as with Landsat-8, a network of receiving stations, one operated by the U.S. government, the other operated by a community of International Cooperators (ICs), were utilized. ICs paid a fee for the right to receive and distribute Landsat data and over time, more Landsat data was held outside the archive of the United State Geological Survey (USGS) than was held inside, much of it unique. Recognizing the critical value of these data, the USGS began a Landsat Global Archive Consolidation (LGAC) initiative in 2010 to bring these data into a single, universally accessible, centralized global archive, housed at the Earth Resources Observation and Science (EROS) Center in Sioux Falls, South Dakota. The primary LGAC goals are to inventory the data held by ICs, acquire the data, and ingest and apply standard ground station processing to generate an L1T analysis-ready product. As of January 1, 2015 there were 5,532,454 images in the USGS archive. LGAC has contributed approximately 3.2 million of those images, more than doubling the original USGS archive holdings. Moreover, an additional 2.3 million images have been identified to date through the LGAC initiative and are in the process of being added to the archive. The impact of LGAC is significant and, in terms of images in the collection, analogous to that of having had two additional Landsat-5 missions. As a result of LGAC, there are regions of the globe that now have markedly improved Landsat data coverage, resulting in an enhanced capacity for mapping, monitoring change, and capturing historic conditions. Although future missions can be planned and implemented, the past cannot be revisited, underscoring the value and enhanced significance of historical Landsat data and the LGAC initiative. The aim of this paper is to report the current status of the global USGS Landsat archive, document the existing and anticipated contributions of LGAC to the archive, and characterize the current acquisitions of Landsat-7 and Landsat-8. Landsat-8 is adding data to the archive at an unprecedented rate as nearly all terrestrial images are now collected. We also offer key lessons learned so far from the LGAC initiative, plus insights regarding other critical elements of the Landsat program looking forward, such as acquisition, continuity, temporal revisit, and the importance of continuing to operationalize the Landsat program.
•USGS Landsat archive contained 5.5 million images as of January 1, 2015.•To date 3.2 million images were added by the Landsat Global Archive Consolidation (LGAC).•LGAC will consolidate an additional of ~2.3 million images into the UGSG archive.•As of January 1, 2015, LGAC had contributed 57% of the images in the USGS archive.•Ground systems are an important element of operational land imaging activities.
The Medical Research Council published the second edition of its framework in 2006 on developing and evaluating complex interventions. Since then, there have been considerable developments in the ...field of complex intervention research. The objective of this project was to update the framework in the light of these developments. The framework aims to help research teams prioritise research questions and design, and conduct research with an appropriate choice of methods, rather than to provide detailed guidance on the use of specific methods.
There were four stages to the update: (1) gap analysis to identify developments in the methods and practice since the previous framework was published; (2) an expert workshop of 36 participants to discuss the topics identified in the gap analysis; (3) an open consultation process to seek comments on a first draft of the new framework; and (4) findings from the previous stages were used to redraft the framework, and final expert review was obtained. The process was overseen by a Scientific Advisory Group representing the range of relevant National Institute for Health Research and Medical Research Council research investments.
Key changes to the previous framework include (1) an updated definition of complex interventions, highlighting the dynamic relationship between the intervention and its context; (2) an emphasis on the use of diverse research perspectives: efficacy, effectiveness, theory-based and systems perspectives; (3) a focus on the usefulness of evidence as the basis for determining research perspective and questions; (4) an increased focus on interventions developed outside research teams, for example changes in policy or health services delivery; and (5) the identification of six 'core elements' that should guide all phases of complex intervention research: consider context; develop, refine and test programme theory; engage stakeholders; identify key uncertainties; refine the intervention; and economic considerations. We divide the research process into four phases: development, feasibility, evaluation and implementation. For each phase we provide a concise summary of recent developments, key points to address and signposts to further reading. We also present case studies to illustrate the points being made throughout.
The framework aims to help research teams prioritise research questions and design and conduct research with an appropriate choice of methods, rather than to provide detailed guidance on the use of specific methods. In many of the areas of innovation that we highlight, such as the use of systems approaches, there are still only a few practical examples. We refer to more specific and detailed guidance where available and note where promising approaches require further development.
This new framework incorporates developments in complex intervention research published since the previous edition was written in 2006. As well as taking account of established practice and recent refinements, we draw attention to new approaches and place greater emphasis on economic considerations in complex intervention research. We have introduced a new emphasis on the importance of context and the value of understanding interventions as 'events in systems' that produce effects through interactions with features of the contexts in which they are implemented. The framework adopts a pluralist approach, encouraging researchers and research funders to adopt diverse research perspectives and to select research questions and methods pragmatically, with the aim of providing evidence that is useful to decision-makers.
We call for further work to develop relevant methods and provide examples in practice. The use of this framework should be monitored and the move should be made to a more fluid resource in the future, for example a web-based format that can be frequently updated to incorporate new material and links to emerging resources.
This project was jointly funded by the Medical Research Council (MRC) and the National Institute for Health Research (Department of Health and Social Care 73514).
Land cover 2.0 Wulder, Michael A.; Coops, Nicholas C.; Roy, David P. ...
International journal of remote sensing,
06/2018, Volume:
39, Issue:
12
Journal Article
Peer reviewed
Open access
Interest in knowing more about the Earth's land cover and how it has changed over time motivated the mission and sensor design of early terrestrial remote sensing systems. Rapid developments in ...computer hardware and software in the last four decades have greatly increased the capacity for satellite data acquisition, downlink, dissemination, and end user science and applications. In 1992, Townshend reviewed the state of land cover mapping using Earth observation data at a pivotal point in time and in the context of years of research and practical experience with Landsat Thematic Mapper (TM), Satellite Pour l'Observation de la Terre (SPOT) High Resolution Visible (HRV) and Advanced Very-High-Resolution Radiometer (AVHRR) data, demonstrating the opportunities and information content possible with increased spatial, spectral, and temporal resolutions. Townshend characterized the state-of-the-art for land cover at that time, identified trends, and shared insights on research directions. Now, on the 25th anniversary of Townshend's important work, given numerous advances and emerging trends, we revisit the status of land cover mapping with Earth observation data. We posit that a new era of land cover analysis - Land Cover 2.0 - has emerged, enabled by free and open access data, analysis ready data, high performance computing, and rapidly developing data processing and analysis capabilities. Herein we characterize this new era in land cover information, highlighting institutional, computational, as well as theoretical developments that have occurred over the past 25 years, identifying the key issues and opportunities that have emerged. We conclude that Land Cover 2.0 offers efficiencies in information generation that will result in a proliferation of land cover products, reinforcing the need for transparency regarding the input data and algorithms used as well as adoption, implementation, and communication of rigorous accuracy assessment protocols. Further, land cover and land change assessments are no longer independent activities. Knowledge of land change is available to inform and enrich land cover generation.
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