ObjectivesTo characterise the sketetal muscle metabolic phenotype during early critical illness.MethodsVastus lateralis muscle biopsies and serum samples (days 1 and 7) were obtained from 63 ...intensive care patients (59% male, 54.7±18.0 years, Acute Physiology and Chronic Health Evaluation II score 23.5±6.5).Measurements and main resultsFrom day 1 to 7, there was a reduction in mitochondrial beta-oxidation enzyme concentrations, mitochondrial biogenesis markers (PGC1α messenger mRNA expression (−27.4CN (95% CI −123.9 to 14.3); n=23; p=0.025) and mitochondrial DNA copy number (−1859CN (IQR −5557–1325); n=35; p=0.032). Intramuscular ATP content was reduced compared tocompared with controls on day 1 (17.7mmol/kg /dry weight (dw) (95% CI 15.3 to 20.0) vs. 21.7 mmol/kg /dw (95% CI 20.4 to 22.9); p<0.001) and decreased over 7 days (−4.8 mmol/kg dw (IQR −8.0–1.2); n=33; p=0.001). In addition, the ratio of phosphorylated:total AMP-K (the bioenergetic sensor) increased (0.52 (IQR −0.09–2.6); n=31; p<0.001). There was an increase in intramuscular phosphocholine (847.2AU (IQR 232.5–1672); n=15; p=0.022), intramuscular tumour necrosis factor receptor 1 (0.66 µg (IQR −0.44–3.33); n=29; p=0.041) and IL-10 (13.6 ng (IQR 3.4–39.0); n=29; p=0.004). Serum adiponectin (10.3 µg (95% CI 6.8 to 13.7); p<0.001) and ghrelin (16.0 ng/mL (IQR −7–100); p=0.028) increased. Network analysis revealed a close and direct relationship between bioenergetic impairment and reduction in muscle mass and between intramuscular inflammation and impaired anabolic signaling. ATP content and muscle mass were unrelated to lipids delivered.ConclusionsDecreased mitochondrial biogenesis and dysregulated lipid oxidation contribute to compromised skeletal muscle bioenergetic status. In addition, intramuscular inflammation was associated with impaired anabolic recovery with lipid delivery observed as bioenergetically inert. Future clinical work will focus on these key areas to ameliorate acute skeletal muscle wasting.Trial registration number NCT01106300.
The overturning circulation of the global ocean is critically shaped by deep-ocean mixing, which transforms cold waters sinking at high latitudes into warmer, shallower waters. The effectiveness of ...mixing in driving this transformation is jointly set by two factors: the intensity of turbulence near topography and the rate at which well-mixed boundary waters are exchanged with the stratified ocean interior. Here, we use innovative observations of a major branch of the overturning circulation—an abyssal boundary current in the Southern Ocean—to identify a previously undocumented mixing mechanism, by which deep-ocean waters are efficiently laundered through intensified near-boundary turbulence and boundary–interior exchange. The linchpin of the mechanism is the generation of submesoscale dynamical instabilities by the flow of deepocean waters along a steep topographic boundary. As the conditions conducive to this mode of mixing are common to many abyssal boundary currents, our findings highlight an imperative for its representation in models of oceanic overturning.
IMPORTANCE Survivors of critical illness demonstrate skeletal muscle wasting with associated functional
impairment. OBJECTIVE To perform a comprehensive prospective characterization of skeletal ...muscle wasting, defining the
pathogenic roles of altered protein synthesis and breakdown. DESIGN, SETTING, AND PARTICIPANTS Sixty-three critically ill patients (59% male; mean age: 54.7 years 95% CI, 50.0-59.6 years)
with an Acute Physiology and Chronic Health Evaluation II score of 23.5 (95% CI, 21.9-25.2) were
prospectively recruited within 24 hours following intensive care unit (ICU) admission from August
2009 to April 2011 at a university teaching and a community hospital in England. Patients were
recruited if older than 18 years and were anticipated to be intubated for longer than 48 hours, to
spend more than 7 days in critical care, and to survive ICU stay. MAIN OUTCOMES AND MEASURES Muscle loss was determined through serial ultrasound measurement of the rectus femoris
cross-sectional area (CSA) on days 1, 3, 7, and 10. In a subset of patients, the fiber CSA area was
quantified along with the ratio of protein to DNA on days 1 and 7. Histopathological analysis was
performed. In addition, muscle protein synthesis, breakdown rates, and respective signaling pathways
were characterized. RESULTS There were significant reductions in the rectus femoris CSA observed at day 10 (−17.7% 95%
CI, −25.9% to 8.1%; P < .001). In the 28 patients assessed by
all 3 measurement methods on days 1 and 7, the rectus femoris CSA decreased by 10.3% (95% CI, 6.1%
to 14.5%), the fiber CSA by 17.5% (95% CI, 5.8% to 29.3%), and the ratio of protein to DNA by 29.5%
(95% CI, 13.4% to 45.6%). Decrease in the rectus femoris CSA was greater in patients who experienced
multiorgan failure by day 7 (−15.7%; 95% CI, −27.7% to 11.4%) compared with single organ
failure (−3.0%; 95% CI, −5.3% to 2.1%) (P < .001), even
by day 3 (−8.7% 95% CI, −59.3% to 50.6% vs −1.8% 95% CI, −12.3% to
10.5%, respectively; P = .03). Myofiber necrosis occurred in 20 of 37
patients (54.1%). Protein synthesis measured by the muscle protein fractional synthetic rate was
depressed in patients on day 1 (0.035%/hour; 95% CI, 0.023% to 0.047%/hour) compared with rates
observed in fasted healthy controls (0.039%/hour; 95% CI, 0.029% to 0.048%/hour)
(P = .57) and increased by day 7 (0.076% 95% CI, 0.032%-0.120%/hour;
P = .03) to rates associated with fed controls (0.065%/hour 95% CI,
0.049% to 0.080%/hour; P = .30), independent of nutritional load. Leg
protein breakdown remained elevated throughout the study (8.5 95% CI, 4.7 to 12.3 to 10.6 95% CI,
6.8 to 14.4 μmol of phenylalanine/min/ideal body weight × 100;
P = .40). The pattern of intracellular signaling supported increased
breakdown (n = 9, r = −0.83,
P = .005) and decreased synthesis (n = 9,
r = −0.69, P = .04). CONCLUSIONS AND RELEVANCE Among these critically ill patients, muscle wasting occurred early and rapidly during the first
week of critical illness and was more severe among those with multiorgan failure compared with
single organ failure. These findings may provide insights into skeletal muscle wasting in critical
illness.
Terrain‐aided navigation (TAN) is a localisation method which uses bathymetric measurements for bounding the growth in inertial navigation error. The minimisation of navigation errors is of ...particular importance for long‐endurance autonomous underwater vehicles (AUVs). This type of AUV requires simple and effective on‐board navigation solutions to undertake long‐range missions, operating for months rather than hours or days, without reliance on external support systems. Consequently, a suitable navigation solution has to fulfil two main requirements: (a) bounding the navigation error, and (b) conforming to energy constraints and conserving on‐board power. This study proposes a low‐complexity particle filter‐based TAN algorithm for Autosub Long Range, a long‐endurance deep‐rated AUV. This is a light and tractable filter that can be implemented on‐board in real time. The potential of the algorithm is investigated by evaluating its performance using field data from three deep (up to 3,700 m) and long‐range (up to 195 km in 77 hr) missions performed in the Southern Ocean during April 2017. The results obtained using TAN are compared to on‐board estimates, computed via dead reckoning, and ultrashort baseline (USBL) measurements, treated as baseline locations, sporadically recorded by a support ship. Results obtained through postprocessing demonstrate that TAN has the potential to prolong underwater missions to a range of hundreds of kilometres without the need for intermittent surfacing to obtain global positioning system fixes. During each of the missions, the system performed 20 Monte Carlo runs. Throughout each run, the algorithm maintained convergence and bounded error, with high estimation repeatability achieved between all runs, despite the limited suite of localisation sensors.
Acute skeletal muscle wasting is a major contributor to post critical illness physical impairment. However, the bone response remains uncharacterized. We prospectively investigated the early changes ...in bone mineral density (BMD) and fracture risk in critical illness.
Patients were prospectively recruited ≤24 hours following intensive care unit (ICU) admission to a university teaching or a community hospital (August 2009 to April 2011). All were aged >18 years and expected to be intubated for >48 hours, spend >7 days in critical care and survive ICU admission. Forty-six patients were studied (55.3% male), with a mean age of 54.4 years (95% confidence interval (CI): 49.1 to 59.6) and an APACHE II score of 23.9 (95% CI: 22.4 to 25.5). Calcaneal dual X-ray absorptiometry (DXA) assessment of BMD was performed on day 1 and 10. Increase in fracture risk was calculated from the change in T-score.
BMD did not change between day 1 and 10 in the cohort overall (0.434 (95% CI: 0.405 to 0.463) versus 0.425 g/cm(2) (95% CI: 0.399 to 0.450), P = 0.58). Multivariable logistical regression revealed admission corrected calcium (odds ratio (OR): 1.980 (95% CI: 1.089 to 3.609), P = 0.026) and admission PaO2-to-FiO2 ratio (OR: 0.916 (95% CI: 0.833 to 0.998), P = 0.044) to be associated with >2% loss of BMD. Patients with acute respiratory distress syndrome had a greater loss in BMD than those without (-2.81% (95% CI: -5.73 to 0.118%), n = 34 versus 2.40% (95% CI: 0.204 to 4.586%), n = 12, P = 0.029). In the 34 patients with acute respiratory distress syndrome, fracture risk increased by 19.4% (95% CI: 13.9 to 25.0%).
Patients with acute respiratory distress syndrome demonstrated early and rapid bone demineralisation with associated increase in fracture risk.
Deploying long‐range autonomous underwater vehicles (AUVs) mid‐water column in the deep ocean is one of the most challenging applications for these submersibles. Without external support and speed ...over the ground measurements, dead‐reckoning (DR) navigation inevitably experiences an error proportional to the mission range and the speed of the water currents. In response to this problem, a computationally feasible and low‐power terrain‐aided navigation (TAN) system is developed. A Rao‐Blackwellized Particle Filter robust to estimation divergence is designed to estimate the vehicle's position and the speed of water currents. To evaluate performance, field data from multiday AUV deployments in the Southern Ocean are used. These form a unique test case for assessing the TAN performance under extremely challenging conditions. Despite the use of a small number of low‐power sensors and a Doppler velocity log to enable TAN, the algorithm limits the localisation error to within a few hundreds of metres, as opposed to a DR error of 40 km, given a 50 m resolution bathymetric map. To evaluate further the effectiveness of the system under a varying map quality, grids of 100, 200, and 400 m resolution are generated by subsampling the original 50 m resolution map. Despite the high complexity of the navigation problem, the filter exhibits robust and relatively accurate behaviour. Given the current aim of the oceanographic community to develop maps of similar resolution, the results of this study suggest that TAN can enable AUV operations of the order of months using global bathymetric models.
The desire to conduct research in the Arctic on an ever-larger spatiotemporal scale has led to the development of long-range autonomous underwater vehicles (AUVs), such as the Autosub Long-Range 1500 ...(ALR1500). While these platforms open up a world of new applications, their actual use is limited in GPS-denied environments since self-contained navigation remains yet unavailable. In response, this study evaluates whether terrain-aided navigation (TAN) can enable multimonth deployments using basic navigation sensors and sparse bathymetric maps. To evaluate the potential, ALR1500 undertakes a hypothetical science-driven mission from Svalbard (Norway) to Point Barrow (Alaska, USA) under the sea ice (a mission over 3200 km). Therefore, a simulated environment is developed, which integrates a state-of-the-art model of water circulation, error models for heading estimation at high latitudes, and an Arctic bathymetric map. Recognizing that this map is constructed based on sparse depth measurements and interpolation techniques, a bathymetric uncertainty model is developed. The performance of the TAN algorithm is examined with respect to the type of the heading sensor utilized and a range of vertical map distortions, calculated using the developed bathymetric uncertainty model. Simulations show that unaided navigation experiences an error of hundreds of kilometers, whereas TAN provides acceptable accuracy given a moderate map distortion. By degrading the quality of the map further, it appears that the navigation filter may diverge when traversing large regions subject to interpolation. Therefore, a rapidly-exploring random tree star algorithm is used to design a new path such that the AUV traverses reliable and rich in topographic information areas.
This paper describes a method for the precise postprocessed positioning of a deep-diving autonomous underwater vehicle (AUV) using only a set of acoustic ranges from a surface ship while the AUV ...executes a closed path under the ship. This approach avoids the use of either a precisely calibrated (and consequently expensive) ultrashort baseline (USBL), or a long baseline (LBL) system (which is expensive in ship time to deploy). Results of Monte Carlo simulation and field results from the first trials of the Autosub6000 AUV are presented to support the hypothesis that an AUV at 6000-m depth can be positioned to an accuracy commensurate with global positioning system (GPS) quality or better, within a period of 1 h.
PDF
