Cloud Computing for COVID-19: Lessons Learned From Massively Parallel Models of Ventilator Splitting.

A patient-specific airflow simulation was developed to help address the pressing need for an expansion of the ventilator capacity in response to the COVID-19 pandemic. The computational model provides guidance regarding how to split a ventilator between two or more patients with differing respiratory physiologies. To address the need for fast deployment and identification of optimal patient-specific tuning, there was a need to simulate hundreds of millions of different clinically relevant parameter combinations in a short time. This task, driven by the dire circumstances, presented unique computational and research challenges. We present here the guiding principles and lessons learned as to how a large-scale and robust cloud instance was designed and deployed within 24 hours and 800 000 compute hours were utilized in a 72-hour period. We discuss the design choices to enable a quick turnaround of the model, execute the simulation, and create an intuitive and interactive interface.

Dissipation of four forest-use herbicides at high latitudes.

BACKGROUND, AIM, AND SCOPE: Large-scale deforestation is occurring in subarctic North America following clearing by salvage logging or insect attack. Numerous shrubs, herbs, and deciduous tree species tend to dominate areas on which stands of white spruce have grown. In the absence of economically advantageous mechanical methods, several herbicides have value in efforts to reforest by planting white spruce. Glyphosate, imazapyr, triclopyr, and hexazinone are all capable of selectively removing many competing species, but there is concern about whether they would degrade naturally or persist owing to the frigid climate. MATERIALS AND METHODS: We established test plots with all four herbicides in upland and river bottom sites at 65 degrees N and 58 degrees N latitudes. The northern site has extremely cold winters, with soils that freeze to a depth of 1-2 m, and precipitation of 275 mm/year. The southern site has heavy rain and snowfall, amounting to 2,250 mm/year evenly distributed. Soil seldom freezes deeply. On each test plot, one of the four herbicides was applied at twice the normal operational use rate to facilitate detection. They were applied at the normal timing, with hexazinone, imazapyr, and triclopyr applied in June and glyphosate applied in fall. Soils were sampled immediately after treatment and those samples used as references for dissipation data gathered over the next 11-14 months from soil 0- to 15- and 15- to 45-cm depths. RESULTS: Dissipation rates did not follow first-order rates because freezing conditions slowed most microbial activity. All products dissipated to close to or below detection limits within the time of the study. Dissipation from vegetation was substantially more rapid and depended on the nature of the plants treated as well as the product used. While soil residues dissipated more slowly than in temperate regions, they did display consistent dissipation patterns during above-freezing conditions and also the influence of microbial activity. Mobility was very limited with all products but hexazinone. DISCUSSION: These products dissipate during summer in high latitudes much as they would in temperate climates. Winter changes are small, but are not unlike some changes reported elsewhere under freezing conditions. Unlike many other studies, soil water did not influence dissipation heavily, but the high latitude and semi-arid climate also did not create severely droughty soils. Residues in plants were much higher than those in soils, but denatured the vegetation quickly, leading to unsuitability for forage in any case. CONCLUSIONS: Low toxicity of these products and their metabolites combined with consistent dissipation and low mobility suggest that toxic hazard of their use at high latitudes need not be a matter of serious concern to humans, terrestrial wildlife, or aquatic systems. They are safe for use in management and rehabilitation of boreal forests when used properly. RECOMMENDATIONS AND PERSPECTIVES: Dissipation at rates approaching those in warmer climates offer a hypothesis that microflora native to high latitudes may be adapted to destruction of such molecules at lower temperatures than may be indicated by experiments with microflora adapted to warmer climates. Residues pose no observable risk to wildlife or humans in the area of use when products are applied properly.

Is isometric strength loss immediately after eccentric exercise related to changes in indirect markers of muscle damage?

This study tested the hypothesis that the magnitude of maximal isometric strength (MVC) loss immediately following eccentric exercise (MVC-post) would relate to changes in other indirect markers of muscle damage following exercise. Eighty-nine men were recruited from the same student population and performed 24 maximal eccentric actions of the elbow flexors. Commonly used markers of muscle damage such as relaxed and flexed elbow joint angles, range of motion (ROM), upper-arm circumference, muscle soreness, and plasma creatine kinase (CK) activity were measured before, immediately after, and 1-4 d after exercise. Pearson's product-moment correlation coefficients (r) between change in MVC-post and other markers of muscle damage, as well as MVC during recovery days, were calculated. Changes in MVC-post ranged from -72.8% to -17.6%, and correlated significantly (p < 0.01) with MVC at 1 (r = 0.59), 2 (0.63), 3 (0.61), and 4 (0.62) d after exercise. Reduction in MVC-post also correlated significantly (p < 0.05) with changes in relaxed (r = 0.50) and flexed elbow joint angles (-0.40), ROM (0.55), arm circumference (-0.45), peak palpation (-0.34) and extension muscle soreness (-0.48), and peak CK activity (-0.59). However, the r values were not necessarily high, and MVC-post poorly reflected the distribution of some measures, such as peak CK activity (124 - 50 440 IU x L(-1). These results suggest that MVC-post is not a strong correlate of the changes in markers of muscle damage following eccentric exercise of the elbow flexors.

Light concentric exercise has a temporarily analgesic effect on delayed-onset muscle soreness, but no effect on recovery from eccentric exercise.

This study investigated the hypothesis that a bout of light concentric exercise (LCE) would alleviate delayed-onset muscle soreness (DOMS) and enhance recovery from muscle damage. Fourteen subjects performed two bouts of 60 maximal eccentric actions of the elbow flexors (Max-ECC) separated by 2-4 weeks. One arm performed LCE (600 elbow flexion and extension actions with minimal force generation) 1, 2, 3, and 4 d after Max-ECC; the contralateral (control) arm performed only Max-ECC. Changes in maximal isometric and isokinetic strength, range of motion (ROM), upper arm circumference, and muscle soreness and tenderness were assessed before and immediately after LCE bouts. Changes in these measures and plasma creatine kinase (CK) activity for 7 d after Max-ECC were compared between the control and LCE arms using 2-way repeated measures analysis of variance (ANOVA). Significant (p < 0.05) decreases in muscle soreness (approximately 40%) and tenderness (approximately 40%) were evident immediately after LCE, which also resulted in small but significant decreases in strength (approximately 15%) and increases in ROM (approximately 5 degrees ). No significant differences in the changes in the measures following Max-ECC were observed between the arms. These results suggest that LCE has a temporary analgesic effect on DOMS, but no effect on recovery from muscle damage.

Effects of massage on delayed-onset muscle soreness, swelling, and recovery of muscle function.

CONTEXT: Delayed-onset muscle soreness (DOMS) describes muscle pain and tenderness that typically develop several hours postexercise and consist of predominantly eccentric muscle actions, especially if the exercise is unfamiliar. Although DOMS is likely a symptom of eccentric-exercise-induced muscle damage, it does not necessarily reflect muscle damage. Some prophylactic or therapeutic modalities may be effective only for alleviating DOMS, whereas others may enhance recovery of muscle function without affecting DOMS. OBJECTIVE: To test the hypothesis that massage applied after eccentric exercise would effectively alleviate DOMS without affecting muscle function. DESIGN: We used an arm-to-arm comparison model with 2 independent variables (control and massage) and 6 dependent variables (maximal isometric and isokinetic voluntary strength, range of motion, upper arm circumference, plasma creatine kinase activity, and muscle soreness). A 2-way repeated-measures analysis of variance and paired t tests were used to examine differences in changes of the dependent variable over time (before, immediately and 30 minutes after exercise, and 1, 2, 3, 4, 7, 10, and 14 days postexercise) between control and massage conditions. SETTING: University laboratory. PATIENTS OR OTHER PARTICIPANTS: Ten healthy subjects (5 men and 5 women) with no history of upper arm injury and no experience in resistance training. INTERVENTION(S): Subjects performed 10 sets of 6 maximal isokinetic (90 degrees x s(-1)) eccentric actions of the elbow flexors with each arm on a dynamometer, separated by 2 weeks. One arm received 10 minutes of massage 3 hours after eccentric exercise; the contralateral arm received no treatment. MAIN OUTCOME MEASURE(S): Maximal voluntary isometric and isokinetic elbow flexor strength, range of motion, upper arm circumference, plasma creatine kinase activity, and muscle soreness. RESULTS: Delayed-onset muscle soreness was significantly less for the massage condition for peak soreness in extending the elbow joint and palpating the brachioradialis muscle (P < .05). Soreness while flexing the elbow joint (P = .07) and palpating the brachialis muscle (P = .06) was also less with massage. Massage treatment had significant effects on plasma creatine kinase activity, with a significantly lower peak value at 4 days postexercise (P < .05), and upper arm circumference, with a significantly smaller increase than the control at 3 and 4 days postexercise (P < .05). However, no significant effects of massage on recovery of muscle strength and ROM were evident. CONCLUSIONS: Massage was effective in alleviating DOMS by approximately 30% and reducing swelling, but it had no effects on muscle function.

Effects of partial immobilization after eccentric exercise on recovery from muscle damage.

CONTEXT: Short-term strict immobilization of the arm using a cast enhances recovery of muscle function after eccentric exercise. OBJECTIVE: To determine if placing one arm in a sling ("light" immobilization) for 4 days after eccentric exercise of the elbow flexor muscles would reduce muscle soreness and enhance recovery compared with the exercised but not immobilized contralateral arm. DESIGN: Subjects performed 10 sets of 6 maximal isokinetic (90 degrees x s(-1)) eccentric actions of the elbow flexors of each arm on a Cybex dynamometer, separated by 2 weeks. SETTING: University laboratory. PATIENTS OR OTHER PARTICIPANTS: Ten healthy subjects (5 men and 5 women) with no history of upper arm injury or resistance training. INTERVENTION(S): One randomly assigned arm was placed in a sling for 4 days after the 30-minute postexercise measurement to secure the elbow joint at 90 degrees ; the contralateral arm received no treatment. The subject removed the sling when showering and sleeping and during postexercise measurements. MAIN OUTCOME MEASURE(S): We used an activity monitor to record upper arm activity before and after immobilization. We also compared changes in maximal isometric and isokinetic voluntary strength, range of motion, upper arm circumference, plasma creatine kinase activity, and muscle soreness during 7 days postexercise between arms with a 2-way, repeated-measures analysis of variance. RESULTS: Eccentric exercise resulted in large losses in both isometric and isokinetic maximal voluntary contraction forces (approximately 40%), reduced range of motion (approximately 20%), increased arm circumference (approximately 10 mm), elevated plasma creatine kinase activity (approximately 2000 IU x L(-1)), and development of delayed-onset muscle soreness. No significant differences were noted between conditions for any measure except upper arm circumference, which increased significantly less for the immobilization than the control arm at 7 days postexercise (P < .05). CONCLUSIONS: Light immobilization had no effect on enhancing recovery of muscle function and delayed-onset muscle soreness after eccentric-exercise-induced muscle damage.

Partial protection against muscle damage by eccentric actions at short muscle lengths.

PURPOSE: This study investigated the hypothesis that maximal eccentric actions at a short muscle length would fail to confer a protective effect against muscle damage induced by maximal eccentric exercise at a long muscle length. METHODS: Eleven males performed 24 maximal eccentric actions of the nondominant elbow flexors over a short extension range from an elbow joint angle of 0.87-1.74 rad (S-ECC) followed 4 wk later by eccentric actions at a long range of 2.27-3.14 rad (L-ECC). A second group of 11 males performed L-ECC on two occasions using the nondominant arm separated by 4 wk. Changes in maximal isometric strength, range of motion, upper arm circumference, muscle soreness, plasma creatine kinase and aspartate aminotransferase activities, and B-mode ultrasound images were compared between bouts and between groups by two-way repeated measures ANOVA. RESULTS: All measures changed significantly (P < 0.01) after the first bout; however, the effects were significantly (P < 0.01) smaller after S-ECC compared with L-ECC. The second bout resulted in significantly (P < 0.01) reduced changes in all measures compared with the first bout in the subjects who performed L-ECC on both occasions. The subjects who performed S-ECC in the first bout displayed significantly smaller changes after L-ECC than those seen after L-ECC alone, with the degree of attenuation being around 50-70%. CONCLUSION: Contrary to the hypothesis, S-ECC provided partial but effective protection against L-ECC. This result suggests adaptations associated with the repeated bout effect were also produced after S-ECC, but the degree of adaptations was not as strong as that by L-ECC. Eccentric exercise at a short extension range can be used as a strategy to present severe muscle damage.

Influence of Pre-Exercise Muscle Temperature on Responses to Eccentric Exercise.

OBJECTIVE: We tested the hypothesis that altering the pre-exercise muscle temperature would influence the magnitude of muscle damage induced by eccentric exercise. SUBJECTS: Female students who had no experience in resistance training were placed into either a microwave treatment group (n = 10) or an icing treatment group (n = 10). DESIGN AND SETTING: Subjects in each group performed 12 maximal eccentric actions of the forearm flexors of each arm on 2 separate occasions separated by 4 weeks. Before testing, the exercise arm was subjected to either passive warming (microwave) or control for the microwave treatment group or cooling (icing) or control for the icing treatment group. The control arm performed the same exercise protocol without treatment. Limbs were randomized for treatment or control and order of testing. Deep muscle temperature increased by approximately 3 degrees C after the microwave treatment and decreased approximately 5 degrees C after the icing treatment. MEASUREMENTS: We evaluated changes in maximal isometric force and indirect markers of muscle damage, including range of motion, upper arm circumference, muscle soreness, and plasma creatine kinase activity, in the microwave and control and icing and control groups using a 2-way, repeated-measures analysis of variance. RESULTS: All measures changed significantly (P <.01) after exercise, but neither of the treatments demonstrated significant effects on most of the variables compared with the control. CONCLUSIONS: These results suggest that pre-exercise cooling does not affect the magnitude of muscle damage in response to eccentric exercise. Similarly, pre-exercise passive muscle warming did not prove beneficial in attenuating indicators of muscle damage. Thus, any beneficial effects of warm-up exercise cannot be attributed to the effects of increased muscle temperature.

Active and intelligent inhaler device development.

The dry powder inhaler, which has traditionally relied on the patient's inspiratory force to deaggregate and deliver the active agent to the target region of the lung, has been a successful delivery device for the provision of locally active agents for the treatment of conditions such as asthma and chronic obstructive pulmonary disease (COPD). However, such devices can suffer from poor delivery characteristics and/or poor reproducibility. More recently, drugs for systemic delivery and more high value compounds have been put into DPI devices. Regulatory, dosing, manufacturing and economic concerns have demanded that a more efficient and reproducible performance is achieved by these devices. Recently strategies have been put in place to produce a more efficient DPI device/formulation combination. Using one novel device as an example the paper will examine which features are important in such a device and some of the strategies required to implement these features. All of these technological advances are invisible, and may be irrelevant, to the patient. However, their inability to use an inhaler device properly has significant implications for their therapy. Use of active device mechanisms, which reduce the dependence on patient inspiratory flow, and sensible industrial design, which give the patient the right clues to use, are important determinants of performance here.

Delayed-onset muscle soreness does not reflect the magnitude of eccentric exercise-induced muscle damage.

This study investigated the relationship between delayed-onset muscle soreness and other indicators of muscle damage following eccentric exercise. Male students (n = 110) performed 12 (12ECC), 24 (24ECC), or 60 maximal eccentric actions of the elbow flexors (60ECC). Maximal isometric force, relaxed and flexed elbow joint angles, upper arm circumference, and plasma creatine kinase activity were assessed immediately before and after, and for 4 days after exercise. Muscle soreness (SOR) was evaluated by a visual analog scale (a 50-mm line, 0: no pain, 50: extremely painful) when the elbow flexors were palpated (SOR-Pal), flexed (SOR-Flx) and stretched (SOR-Ext). Although 24ECC and 60ECC resulted in significantly (P <; 0.05) larger changes in all indicators and slower recovery compared to 12ECC, no significant differences were evident for SOR-Pal and SOR-Flx between 12ECC and 24ECC, or 12ECC and 60ECC. In contrast, SOR-Ext was significantly (P <; 0.05) lower for 12ECC compared to 24ECC and 60ECC. A Pearson product-moment correlation showed SOR-Pal did not correlate significantly with any indicators, however, SOR-Ext and SOR-Flx showed weak (r <; 0.32) but significant (P <; 0.05) correlations with other indicators. Because of generally poor correlations between DOMS and other indicators, we conclude that use of DOMS is a poor reflector of eccentric exercise-induced muscle damage and inflammation, and changes in indirect markers of muscle damage and inflammation are not necessarily accompanied with DOMS.

Muscle damage and soreness after endurance exercise of the elbow flexors.

PURPOSE: This study investigated changes in indirect markers of muscle damage after endurance exercise of the elbow flexors and compared the changes with those after maximal eccentric actions (Max-ECC) of the elbow flexors. METHODS: Eighteen male students rhythmically lifted (1 s) and lowered (1 s) a light dumbbell (1.1-1.8 kg: 9% of MIF) in 60-180 degrees of elbow joint angle for 2 h (2-h Ex). Maximal isometric force (MIF), relaxed (RANG) and flexed elbow joint angles (FANG), upper-arm circumference (CIR), muscle soreness (SOR), B-mode ultrasound (US), and plasma creatine kinase (CK) activity were assessed before and immediately after, and up to 96 h after exercise. RESULTS: All measures were altered significantly (P < 0.05) after 2-h Ex in a similar time course to Max-ECC; however, changes in RANG, FANG, CIR, US, and CK (peak: 356 +/- 121 IU.L-1) were significantly (P < 0.05) smaller compared with those after Max-ECC. SOR developed immediately after 2-h Ex and peaked 24-48 h after exercise. MIF dropped to 44.1% of the preexercise level, which was significantly (P < 0.05) lower than that after Max-ECC (58.1%), immediately postexercise. MIF recovered to 79.8% at 24 h, and 97.8% at 96 h postexercise, which was a significantly (P < 0.05) faster recovery compared with that of Max-ECC (73.1% at 96 h). CONCLUSION: These results showed low-intensity continuous muscle contractions (3600 times) resulted in muscle damage; however, the magnitude of the muscle damage was less severe, and the recovery was faster compared with 12 maximal eccentric muscle actions.

Difference in the magnitude of muscle damage between maximal and submaximal eccentric loading.

This study compared maximal (MAX-ECC) and submaximal (50%-ECC) eccentric exercise of the elbow flexors. Untrained male students (n = 8) performed 3 sets of 10 repetitions of MAX-ECC with one arm and 50%-ECC with the other arm, separated by 4 weeks. In MAX-ECC, the elbow joint was forcibly extended from a flexed (90 degrees ) to a full-extended position (180 degrees ) in 3 seconds while producing maximal force. For 50%-ECC, a dumbbell set at 50% of the maximal isometric strength at 90 degrees of the elbow joint was lowered from the flexed to the extended position in 3 seconds. Changes in indicators of muscle damage were compared between the bouts by a 2-way repeated-measures analysis of variance. Changes in isometric strength, range of motion, upper arm circumference, and plasma creatine kinase activity were significantly smaller and the recovery was significantly faster for 50%-ECC compared with MAX-ECC, although the differences in the changes immediately after exercise were small. It appeared that the magnitude of initial muscle damage was similar between the bouts; however, secondary damage was less after 50%-ECC.

Repeated eccentric exercise bouts do not exacerbate muscle damage and repair.

This study examined whether performing repeated bouts of eccentric exercise 2 and 4 days after an initial damaging bout would exacerbate muscle damage. One arm performed 3 sets of 10 eccentric actions of the elbow flexors (ECC1) using a dumbbell set at 50% of the maximal isometric force at 90 degrees (SINGLE). Two weeks later the same exercise was performed by the opposite arm with the exception that subsequent bouts were performed 2 (ECC2) and 4 (ECC3) days after ECC1 (REPEATED). In the REPEATED condition, maximal isometric force (MIF) decreased to the same level immediately after ECC1-3, and the decreases in range of motion (ROM) and increases in upper arm circumference immediately postexercise were similar among the bouts. However, no significant differences in changes in MIF, ROM, muscle soreness, and plasma creatine kinase activity were evident between the SINGLE and REPEATED conditions when excluding the changes immediately after ECC2 and ECC3. These results suggest that ECC2 and ECC3 did not exacerbate muscle damage or affect the recovery process.

Concentric or eccentric training effect on eccentric exercise-induced muscle damage.

PURPOSE: The purpose of this study was to compare changes in muscle damage indicators following 24 maximal eccentric actions of the elbow flexors (Max-ECC) between the arms that had been previously trained either eccentrically or concentrically for 8 wk. METHODS: Fifteen subjects performed three sets of 10 repetitions of eccentric training (ECC-T) with one arm and concentric training (CON-T) with the other arm once a week for 8 wk using a dumbbell representing 50% of maximal isometric force of the elbow flexors (MIF) determined at the elbow joint of 90 degrees (1.57 rad). The dumbbell was lowered from a flexed (50 degrees, 0.87 rad) to an extended elbow position (180 degrees, 3.14 rad) in 3 s for ECC-T, and lifted from the extended to the flexed position in 3 s for CON-T. Max-ECC was performed 4 wk after CON-T and 6 wk after ECC-T. Changes in MIF, range of motion (ROM), upper arm circumference (CIR), muscle soreness (SOR), and plasma creatine kinase (CK) activity were compared between the ECC-T and CON-T arms. RESULTS: The first ECC-T session produced larger decreases in MIF and ROM, and larger increases in CIR and SOR compared with CON-T. CK increased significantly (P < 0.01) and peaked 4 d after the first training session, but did not increase in the following sessions. All measures changed significantly (P < 0.01) following Max-ECC; however, the changes were not significantly different between ECC-T and CON-T arms. CONCLUSION: These results showed that ECC-T did not mitigate the magnitude of muscle damage more than CON-T, and CON-T did not exacerbate muscle damage.