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Obstructive sleep apnea (OSA) is highly prevalent, conservatively estimated to affect 2%–4% of the middle-aged adult population in the United States.1 OSA is widely believed to contribute to impaired cognition,2 hypertension,3 cardiovascular disease,4 cerebrovascular disease,5 and increased risk for accidents.6 The most effective therapy is continuous positive airway pressure (CPAP), which improved select signs and symptoms of OSA in several randomized, placebo-controlled trials.7,8 However, the efficacy of CPAP may be limited by poor compliance. It has been estimated that as many as 50% of OSA patients for whom CPAP is initially recommended are not using this therapy one year later.9 Common reasons for discontinuation include mask discomfort, nasal drying or irritation, and intolerance of the pressure.10 Numerous studies have evaluated the benefits of various interventions at initial CPAP set-up to improve acceptance and compliance. Such interventions include intensified education and follow-up programs,11 the addition of humidification to CPAP,12 and alternative pressure delivery systems.13 Gay and colleagues have recently reviewed in detail factors that can affect initial CPAP tolerance and adherence, and interventions that might improve initial CPAP efficacy.14 However, few studies have evaluated interventions to improve CPAP compliance in OSA patients previously unable to comply with CPAP therapy. We evaluated a two phase intervention program intended to improve CPAP compliance in previously noncompliant OSA patients. The first phase assessed several standard interventions to improve CPAP comfort, while the second phase compared the efficacy of flexible bilevel positive airway pressure (BiFlex, Respironics Inc., Murrysville, PA) to standard CPAP. BiFlex differs from standard bilevel positive airway pressure (PAP) devices in that it allows reductions of the late inspiratory and early expiratory pressures.15

A significant number of patients with obstructive sleep apnea neither tolerate positive airway pressure (PAP) therapy nor achieve successful outcomes from either upper airway surgeries or use of an oral appliance. The purpose of this paper, therefore, was to systematically evaluate available peer-reviewed data on the effectiveness of adjunctive medical therapies and summarize findings from these studies. A review from 1985 to 2005 of the English literature reveals several practical findings. Weight loss has additional health benefits and should be routinely recommended to most overweight patients. Presently, there are no widely effective pharmacotherapies for individuals with sleep apnea, with the important exceptions of individuals with hypothyroidism or with acromegaly. Treating the underlying medical condition can have pronounced effects on the apnea/hypopnea index. Stimulant therapy leads to a small but statistically significant improvement in objective sleepiness. Nonetheless, residual sleepiness remains a significant health concern. Supplemental oxygen and positional therapy may benefit subsets of patients, but whether these therapies reduce morbidities as PAP therapy does will require rigorous randomized trials. PAP therapy has set the bar high for successful treatment of sleep apnea and its associated morbidities. Nonetheless, we should strive towards the development of universally effective pharmacotherapies for sleep apnea. To accomplish this, we require a greater knowledge of the neurochemical mechanisms underlying sleep apnea, and we must use this infrastructure of knowledge to design well-controlled, adequately powered studies that examine, not only effects on the apnea/hypopnea index, but also the effects of pharmacotherapies on all health related outcomes shown beneficial with PAP therapy.

Extensive evidence links cardiovascular disease and sleep disordered breathing. OSA has adverse effects on blood pressure, cardiovascular status,and mortality. Effective CPAP therapy can improve blood pressure and cardiac function in patients who have OSA. Patients who have congestive heart failure have a high prevalence of sleep-disordered breathing, with OSA occurring in 30% of such patients and Cheyne-Stokes respiration in 40%.CPAP is the preferred mode of therapy for both types of sleep-disordered breathing in patients who have coexistent congestive heart failure. Nocturnal worsening of asthma is a common manifestation of this disease that indicates increased disease severity. Therapy focuses on judicious use of long-acting bronchodilators, and the presence of OSA should also be considered. COPD is frequently associated with impaired sleep, likely because of chronic dyspnea and sleep-associated hypoxemia. Appropriate therapy again includes long-acting bronchodilators and possibly nocturnal supplemental oxygen. Gastroesophageal reflux during sleep may lead to prolonged episodes of esophageal acid exposure and may be a common sequela of OSA, perhaps triggering nocturnal worsening of asthma. Endstage renal disease and chronic dialysis are commonly associated with a host of troublesome sleep problems,including OSA, RLS, PLMD, and daytime sleepiness.

Aquariums and "blue water" oceanographic institutions in America have traditionally had completely separate missions, with the former concentrating on public outreach and education and the latter undertaking basic research. Recently, two new institutions, the Monterey Bay Aquarium Research Institute (MBARI) and the Mystic Aquarium/Institute for Exploration (MA/IFE), were founded for the expressed purpose of bridging the gap between basic ocean discovery and public education. In both cases, the ability to bring the excitement of undersea exploration to the public has been enabled by sophisticated undersea vehicles that permit the aquarium audience to participate in the research enterprise via telepresence. The fact that the research is constantly in the public eye provides researchers with frequent opportunities to explain the importance and the relevancy of their work for the benefit of society. Despite the efforts over the past 50 years, over 95 percent of the oceans remain unknown and unexplored. This fact combined with the realization that all citizens of the twenty-first century must be well informed on the consequences of their actions on the health of this ocean planet makes it likely that such partnerships between research and educational institutions will proliferate.

The nocturnal worsening of asthma is a common feature of this disease that recently has received extensive investigation. Most recent efforts have focused on the role of circadian biorhythms that could promote a nocturnal increase in airway inflammation, leading to a subsequent increase in airflow obstruction and asthma symptoms. However, definitive studies remain lacking. As discussed in this review, there is also substantial evidence that sleep itself may play a direct role in the nocturnal worsening of asthma. Potential mechanisms for such a sleep-related effect could include the supine posture, alterations in sympathetic and parasympathetic "balance," sleep-associated reductions in lung volume, intrapulmonary pooling of blood, and sleep-associated upper airway narrowing, both with and without snoring and obstructive sleep apnea (OSA). These potential contributors to this troublesome phenomenon deserve further consideration when investigating mechanisms of nocturnal asthma.

Mid-Cayman Rise objectives were built on exciting results from a flurry of recent expeditions that investigated hydrothermal sites in the region (German et al., 2010, 2012). The 2013 E/V Nautilus cruise explored oceanic core complexes (OCCs), tall, smooth-sided hills that rise from the seafloor on the flanks of some mid-ocean ridges. Dives (Figure 1) explored the full extent and nature of life around the Von Damm hydrothermal field, previously discovered there, as well as the geology to further understanding of the vents’ origins, and to survey the OCC summits that had never before been investigated by a deep diving vehicle. This 2013 study was the first Nautilus cruise to have more scientists participating in the expedition from locations on shore than from the ship, tripling the size of the science party.

The remotely operated vehicle (ROV) system MEDEA/JASON has been under development for the last decade. Adter a number of engineering test cruises, including the discovery of the R.M.S. Titanic and the German Battleship Bismarck, this ROV system is now being implemented in oceanographic investigations. This paper explains its development history and its unique ability to carry out a broad range of scientific research.

The nocturnal worsening of asthma is a common problem, and the contribution of inflammation to its pathogenesis remains unclear. We investigated the responses of 11 asthmatic subjects to overnight intravenous infusion of hydrocortisone. Prior to the study, all the subjects demonstrated clinically stable daytime asthma but persistent nocturnal worsening of spirometry. As a group, their overnight decrement in FEV1 improved from 46 +/- 4% at baseline to 12 +/- 3% (p less than 0.001) after steroid infusion. Nine of the 11 subjects demonstrated individual improvement in their overnight decrements in FEV1 of greater than 40%. The mean improvement between baseline and steroid infusion nights was 67 +/- 11%. A spectrum of response was evident, and only four of the subjects reached the normal circadian variability in overnight FEV1 measurements of less than 8%. We conclude that the nocturnal worsening of asthma often has a significant corticosteroid-sensitive component that may be both dose- and time-dependent.

Nocturnal asthma is a frequent problem, but the mechanism is unclear. We investigated the possibility that airways inflammation occurred during the night. Bronchoalveolar lavage fluid was analyzed in asthmatic patients with (n = 7) and without nocturnal asthma (n = 7) at 1600 and 0400 h. The nocturnal asthma group had an increase in the total leukocyte count (24.0 +/- 7.0 to 41.1 +/- 9.9 x 10(4) cells/ml, p less than 0.05), neutrophils (1.1 +/- 0.6 to 3.7 +/- 1.5 x 10(4) cells/ml, p less than 0.05), and eosinophils (0.5 +/- 0.1 to 1.7 +/- 0.7 x 10(4) cells/ml, p less than 0.05) from 1600 to 0400 h. Cellular components for the non-nocturnal asthma group did not change. Between groups, the 1600-h cells were similar. At 0400 h the nocturnal asthma group had significantly higher total leukocyte, neutrophil, eosinophil, lymphocyte, and epithelial cell counts. For all subjects, the overnight fall in peak expiratory flow rates was correlated to the change in neutrophils (r = 0.54, p less than 0.05) and eosinophils (r = 0.77, p less than 0.05). We conclude that the nocturnal worsening of asthma has an associated cellular inflammatory response that is not seen in patients without overnight decrements in lung function. This inflammatory response together with epithelial damage may be important factors in the etiology of nocturnal asthma.

The nocturnal worsening of asthma is a very common problem, yet little is known about the relationships between the nocturnal worsening and daytime lung function, methacholine bronchial responsiveness, the degree of the circadian variability in bronchial responsivity, and the nocturnal sleep pattern. This study demonstrates in 20 asthmatic patients that the overnight fall in the peak expiratory flow rates (PEFR) is related to the severity of daytime airflow limitation (r = 0.73, p less than 0.001) and daytime bronchial responsiveness (r = 0.48, p less than 0.05). In individuals with larger overnight decrements in PEFR, bronchial responsivity at 0400 h is so great that normal saline inhalation alone can produce a greater than 20% fall in the FEV1. Sleep quality and sleep staging are not correlated to the change in the PEFR. Thus, the overnight decrement in asthmatic lung function is related to the daytime severity of asthma as determined by daytime measurements of airflow limitation and bronchial responsiveness as well as the circadian variation in bronchial responsivity.

The ARGO/JASON system is an integrated system that performs survey and sampling to depths of 6000 meters. This paper summarizes the capabilities of the system and includes descriptions of three vehicles: the deep-towed imaging sled ARGO, the ROV JASON, and the sidescan sonar DSL-120.

Obstructive sleep apnea is an increasingly well-recognized disease characterized by periodic collapse of the upper airway during sleep. This leads to either complete or partial obstruction of the airway, resulting in apneas, hypopneas, or both. This disorder causes daytime somnolence, neurocognitive defects, and depression. It affects almost every system in the body, resulting in an increased incidence of hypertension, cardiovascular disease, stroke, pulmonary hypertension, cardiac arrhythmias, and altered immune function. It also increases the risk of having an accident, presumably as a result of associated somnolence. The gold standard for the diagnosis of sleep apnea is an overnight polysomnogram. Split-night studies are becoming increasingly common and allow for quicker implementation of therapy at a reduced cost. Treatment options for sleep apnea include weight loss, positional therapy, oral devices, continuous positive airway pressure (CPAP), and upper airway surgery. CPAP is the most efficacious and widely used therapy. Its complications include nasal congestion or dryness, mask discomfort, and claustrophobia. Heated humidifiers, newer types of masks, and nasal steroids have improved tolerance of this therapy. Bilevel positive-pressure therapy can be considered for patients who find it difficult to exhale against the consistently increased pressure of CPAP. The disease requires aggressive treatment to improve quality of life and prevent its complications.

To determine the effect of sleep upon intrapulmonary blood volume (as reflected by measurements of pulmonary capillary volume (VC), 5 normal subjects and 15 asthmatic patients were monitored overnight in our sleep laboratory. VC was determined before and after sleep from four measurements of DLCO using a single-breath technique, with subjects inspiring different oxygen concentrations for each measurement. Spirometry was performed in the supine posture before presleep VC measurements and immediately upon awakening before postsleep VC measurements. As defined by a > or = 15% overnight reduction in FEV1, 10 asthmatic subjects demonstrated nocturnal worsening. FEV1 decreased from 61.2 +/- 15.1 to 40.9 +/- 16.2% of predicted (p = 0.0001) in the 10 asthmatic patients with nocturnal worsening. Asthmatic patients with nocturnal worsening also demonstrated a 15.7 +/- 16.6% increase in VC from presleep to awakening (p = 0.02). Normal subjects and asthmatic patients without nocturnal worsening exhibited no significant overnight change in FEV1 or VC. We conclude that in asthmatic patients with nocturnal worsening sleep is likely associated with an increase in intrapulmonary blood volume.

To determine the effect of non-REM (NREM) sleep on inspiratory muscle electromyographic (EMG) activity in asthmatic patients and the subsequent effect of such changes on FRC, 12 asthmatic patients with nocturnal worsening were monitored overnight in a horizontal volume-displacement body plethysmograph. During studies FRC was monitored using the single inspiratory occlusion technique, whereas EMG activities of the diaphragm (DI), intercostal (IC), and sternocleidomastoid (SCM) muscles were monitored using surface electrodes. FRC decreased progressively, from 3.63 +/- 0.27 L while awake prior to "lights out" to 3.15 +/- 0.27 L after 60 min of NREM sleep (p0.005). With awakening at the end of the study FRC increased to 4.69 +/- 0.48 L (p0.01). Onset of NREM sleep was also associated with significant (p0.05) reductions in EMG tonic activities of all three inspiratory muscles. These levels of tonic activity returned and were further augmented (p0.001) with awakening at the conclusion of the study. Linear relationships were demonstrated between sleep-state dependent changes in FRC and EMG tonic activity for each of the three inspiratory muscles (r = 0.98, 0.93, and 0.97 for DI, IC, and SCM, respectively, p0.01). NREM sleep did not significantly alter mean inspiratory phasic activities of these muscles, although there was considerable heterogeneity between individual subjects in the effects of NREM sleep.(ABSTRACT TRUNCATED AT 250 WORDS)

The JASON remotely operated vehicle (ROV) system has been under development for the last decade. After a number of engineering test cruises, including the discovery of the R.M.S. Titanic and the German Battleship Bismarck, this ROV system is now being implemented in oceanographic investigations. This paper explains its development history and its unique ability to carry out a broad range of scientific research. Deep submergence engineering, Robotics and control, Telepresence and telecommunications.

The treatment of nocturnal asthma remains a challenge. We investigated the use of a pulsed-released albuterol in ten patients with nocturnal symptoms of asthma. In a randomized, double-blind, placebo-controlled, crossover designed study, we tested the use of 8 mg of pulsed-release albuterol sulfate (Proventil Repetabs) vs placebo. The pulsed-release albuterol significantly blunted the overnight drop in FEV1, improved peak flow readings in the morning, and decreased subjective awakenings from sleep. We conclude that pulsed-released albuterol is an effective therapeutic option in patients with nocturnal asthma.

Nocturnal worsening occurs commonly in the asthmatic patient population and contributes substantially to the morbidity and even mortality of asthma. However, no physiologic process has yet been identified as the major contributor to this pattern. Sleep is typically associated with both the supine posture and substantial decrements in lung volume, and both have been proposed to have a role in the pattern of nocturnal worsening. To assess the effects of posture and sleep-associated reductions in functional residual capacity on pulmonary function, eight asthmatic patients were first monitored overnight in a horizontal volume-displacement body plethysmograph to determine mean FRC during sleep for each subject. We then compared, during wakefulness, the effects on FEV1 and methacholine responsiveness from chest wall and abdomen strapping (to maintain FRC at mean sleep levels) for 6 h in the supine and upright postures. FEV1 was significantly decreased after strapping in the supine posture (2.54 +/- 0.36 versus 3.38 +/- 0.29 L on control day, p = 0.0001) but was not affected by strapping in the upright posture (3.07 +/- 0.30 versus 3.34 +/- 0.31 L on control day, not significant, NS). Bronchial responsiveness to methacholine was not altered after strapping in either posture. These observations suggest that the supine posture, in conjunction with the reduction in lung volume associated with sleep, may contribute to the nocturnal worsening of asthma.

We assessed the bronchodilator response to a recently available ultrasonic nebulizer (USN) in a population of 17 stable asthmatic patients. These patients were also evaluated for bronchodilator response to two other aerosol delivery systems routinely used in standard clinical practice, the metered-dose inhaler (MDI) and the jet nebulizer (JN). Albuterol was administered from each of the delivery systems in the following manner: MDI, two actuations (180 micrograms); JN, 0.5 ml of 0.5 percent solution (2.5 mg) in 1.0 ml saline solution diluent; and USN, 0.5 ml of 0.5 percent solution (2.5 mg) in 2.5 ml saline solution diluent. Patients demonstrated significant bronchodilator responses to all three delivery systems (p less than 0.0001). The USN produced a greater percentage of increase in FEV1 15 minutes after treatment with albuterol (35.8 +/- 2.3 percent) than either the MDI (18.2 +/- 3.4 percent) or JN (20.8 +/- 3.1 percent) (p less than 0.005). The mean percentage of increase in FE1 observed over a 4-h period after treatment was also greater for the USN (26.5 +/- 2.5 percent) than either the MDI (18.8 +/- 1.8 percent) or JN (15.0 +/- 1.6 percent) (p less than 0.001). We conclude that the USN yields effective bronchodilation in a population of stable asthmatics.

To characterize ventilatory responses to bronchoconstriction during sleep and to assess the effect of prior sleep deprivation on ventilatory and arousal responses to bronchoconstriction, bronchoconstriction was induced in eight asthmatic subjects while they were awake, during normal sleep, and during sleep after a 36-h period of sleep deprivation. Each subject was bronchoconstricted with increasing concentrations of aerosolized methacholine while ventilatory patterns and lower airway resistance (Rla) were continually monitored. The asthmatic patients maintained their minute ventilation as Rla increased under all conditions, demonstrating a stable tidal volume with a mild increase in respiratory frequency. Inspiratory drive, as measured by occlusion pressure (P0.1), increased progressively and significantly as Rla increased under all conditions (slopes of P0.1 vs. Rla = 0.249, 0.112, and 0.154 for awake, normal sleep, and sleep after sleep deprivation, respectively, P less than 0.0006). Chemostimuli did not appear to contribute significantly to the observed increases in P0.1. Prior sleep deprivation had no effect on ventilatory and P0.1 responses to bronchoconstriction but did significantly raise the arousal threshold to induced bronchoconstriction. We conclude that ventilatory responses to bronchoconstriction, unlike extrinsic loading, are not imparied by the presence of sleep, nor are they chemically mediated. However, prior sleep deprivation does increase the subsequent arousal threshold.

We examined the effect of intraesophageal acid (either spontaneous gastroesophageal reflux or infused) on airflow resistance in 15 sleeping asthmatic subjects. We observed no significant acute or sustained changes in airflow resistance relative to periods of intraesophageal acid. Overnight changes in spirometry and lower airway resistance also demonstrated similar nocturnal worsening of bronchoconstriction despite the occurrence of spontaneous or simulated gastroesophageal reflux. The presence or absence of clinical evidence of esophagitis (Bernstein test response) did not alter the observed lack of response to intraesophageal acid. We conclude that gastroesophageal reflux contributes little to the nocturnal worsening of asthma.

To assess the effect of sleep on functional residual capacity (FRC) in normal subjects and asthmatic patients, 10 adult subjects (5 asthmatic patients with nocturnal worsening, 5 normal controls) were monitored overnight in a horizontal volume-displacement body plethysmograph. With the use of a single inspiratory occlusion technique, we determined that when supine and awake, asthmatic patients were hyperinflated relative to normal controls (FRC = 3.46 +/- 0.18 and 2.95 +/- 0.13 liters, respectively; P less than 0.05). During sleep FRC decreased in both groups, but the decrease was significantly greater in asthmatic patients such that during rapid-eye-movement (REM) sleep FRC was equivalent between the asthmatic and normal groups (FRC = 2.46 +/- 0.23 and 2.45 +/- 0.09 liters, respectively). Specific pulmonary conductance decreased progressively and significantly in the asthmatic patients during the night, falling from 0.047 +/- 0.007 to 0.018 +/- 0.002 cmH2O-1.s-1 (P less than 0.01). There was a significant linear relationship through the night between FRC and pulmonary conductance in only two of the five asthmatic patients (r = 0.55 and 0.65, respectively). We conclude that 1) FRC falls during sleep in both normal subjects and asthmatic patients, 2) the hyperinflation observed in awake asthmatic patients is diminished during non-REM sleep and eliminated during REM sleep, and 3) sleep-associated reductions in FRC may contribute to but do not account for all the nocturnal increase in airflow resistance observed in asthmatic patients with nocturnal worsening.

To assess the accuracy of the respiratory inductance plethysmograph (RIP) for monitoring ventilation during sleep-associated bronchoconstriction, five adult patients with nocturnal worsening of their asthma were monitored overnight in the sleep laboratory. Three of the five patients demonstrated episodic paradoxic respiratory motion of the lower rib cage undetected by the RIP. Such paradoxic motion was consistently associated with overestimation of volumetric data by RIP compared to pneumotachygraphic measurements. With onset of lower rib cage paradox, the mean error of RIP-derived VT measurements increased from 9.1 +/- 1.7 to 27.9 +/- 3.8 percent (p less than .001). Flow measurements derived from RIP were also inaccurate in the presence of lower rib cage paradox, with the mean error of the measurement increasing from 9.0 +/- 2.5 to 33.5 +/- 5.3 percent (p less than .001). We conclude that RIP is an unreliable technique for quantitatively monitoring ventilation in sleeping asthmatic patients.

The nocturnal worsening of asthma is a common problem that can be difficult to treat. Two different sustained-release theophylline preparations were used to determine (1) if the serum theophylline concentrations (STC) depend on the type and dosing schedule of the preparation, (2) the relationship between STC and the circadian variations in asthma, and (3) the effect of STC on sleep quality and respiratory patterns during the night. In 16 subjects with nocturnal asthma, the STC were significantly higher during the daytime on twice-daily versus once-daily theophylline preparations given at 7 P.M., but the FEV1 values were similar. During the night, the STC were significantly higher with the once-daily regimen, and the awakening FEV1 value was also improved (p less than 0.05). All polysomnographic variables were similar between the two preparations, except that with the once-daily preparation there was a decreased number of hypopneas (p less than 0.05) and fewer minutes below an oxygen saturation of 90% (p less than 0.05). We conclude that patients with nocturnal asthma need their treatment focused on the nocturnal portion of the circadian cycle and that higher STC during this critical time period are beneficial without interfering with sleep quality.

To assess the effect of sleep on airflow resistance and patterns of ventilation in asthmatic patients with nocturnal worsening, 10 adult subjects (6 asthmatic patients with nocturnal worsening, 4 normal controls) were monitored overnight in the sleep laboratory on two separate occasions. During 1 night, subjects were allowed to sleep normally, whereas during the other night all sleep was prevented. The six asthmatic patients demonstrated progressive increases in lower airway resistance (Rla) on both nights, but the rate of increase was twofold greater (P less than 0.0001) during the sleep night compared with the sleep prevention night. However, overnight decrements in forced expired volume in 1 s (FEV1) were similar over the 2 nights. The asthmatic patients maintained their minute ventilation as Rla increased during sleep, demonstrating a stable tidal volume with a mild increase in respiratory frequency. We conclude that in asthmatic patients with nocturnal worsening 1) Rla increases and FEV1 falls overnight regardless of sleep state, 2) sleep enhances the observed overnight increases in Rla, and 3) sleep does not abolish compensatory ventilatory responses to spontaneously occurring bronchoconstriction.

Prepared for the Office of Naval Research under Contract N00014-73-C-0097; NR 265-107, the Department of Defense Research Project Agency Contract N00014-71-C-02B4; NR 293-00B, and for the National Science Foundation Grants GA-32454 and GD-3255B.

A hydrothermal vent field, here called the Feather Duster site, occurs on the eastern marginal high near the edge of a narrow (95-m) and shallow (15-20-m) axial graben, within an area dominated by sheet flows and collapse features. The sheet flows are intermediate in relative age between younger fluid-flow lavas on the floor of the axial graben and older pillow (constructional) lavas on the marginal highs. Hydrothermal activity occurs in two zones within a 65 by 45 m area. The main zone is located where a fissure system and sulfide-sulfate chimneys vent warm (9-47/sup 0/C) and hot (347/sup 0/C) hydrothermal fluids. Here, two mounds of massive sulfide totaling about 200 t are forming. One occurs at the base of a 3-m-high scarp which is the wall of a drained lava lake; the other is perched on top of the scarp. 19 references, 4 figures.