The use of mixture density networks in the emulation of complex epidemiological individual-based models

Complex, highly-computational, individual-based models are abundant in epidemiology. For epidemics such as macro-parasitic diseases, detailed modelling of human behaviour and pathogen life-cycle are required in order to produce accurate results. This can often lead to models that are computationally-expensive to analyse and perform model fitting, and often require many simulation runs in order to build up sufficient statistics. Emulation can provide a more computationally-efficient output of the individual-based model, by approximating it using a statistical model. Previous work has used Gaussian processes (GPs) in order to achieve this, but these can not deal with multi-modal, heavy-tailed, or discrete distributions. Here, we introduce the concept of a mixture density network (MDN) in its application in the emulation of epidemiological models. MDNs incorporate both a mixture model and a neural network to provide a flexible tool for emulating a variety of models and outputs. We develop an MDN emulation methodology and demonstrate its use on a number of simple models incorporating both normal, gamma and beta distribution outputs. We then explore its use on the stochastic SIR model to predict the final size distribution and infection dynamics. MDNs have the potential to faithfully reproduce multiple outputs of an individual-based model and allow for rapid analysis from a range of users. As such, an open-access library of the method has been released alongside this manuscript

Comparison of Cardiorespiratory Responses during Body Weight-Supported Treadmill and Standard Treadmill Exercise

Treadmills that partially support body weight are increasingly being used in athletic rehabilitation settings. The cardiorespiratory response during this type of exercise has been reported in very few published studies. This study was designed to determine the cardiorespiratory response during three exercise intensities during standard treadmill exercise (ST) and body weight-supported treadmill exercise (BWST). In random order, a total of 10 healthy, 18-44 yr old adults (6 males, 4 females) performed BWST and ST trials. Identical exercise sessions were performed on each treadmill except 25% of body weight was supported during BWST exercise such that each participant carried 75% of true body weight. On each treadmill a two-minute warm up was performed at 2 mph and 0% grade, followed by 6 minutes of exercise at 3% grade at each of the following treadmill velocities: 3 mph, 4.5 mph, and 6 mph. Expired respiratory gases were analyzed each minute. Steady state heart rate, VO2, VCO2 and RER were calculated as the average value during the final three minutes of each 6 min exercise stage. Blood pressure and RPE were recorded during the final minute of each stage. A 2x3 repeated measures ANOVA was used to determine significant differences at the p2 between ST and BWST at 4.5 mph (2.14±.39 v 1.42±.27, p2 was significantly different at each exercise intensity and treadmill (ST v BWST: 16.0±1.1 v 13.6±1.2; 31.2±2.0 v 20.6±2.4; 39.8±1.9 v 25.8±2.9 ml∙kg-1∙min-1, p2 between the ST and BWST at 4.5 mph (2.10±.43 v 1.32±.26 L/min,

Designing a Heat Sink for Lithium-ion Battery Packs in Electric Vehicles

This report addresses the concepts and implementation of fluid cooled heat sink designs for an electric or hybrid vehicle battery. To determine the battery’s temperature and heat flux profile, testing was performed by measuring these values at multiple locations on a lithium-ion pouch battery using heat flux sensors and thermocouples during the charge and discharge cycles of the battery. Once the data was collected and analyzed, trendlines were fit to the heat flux data then used to create equations for the heat flux profile during the discharging stage. Each equation represented a specific region on the battery geometry. Four heat sink designs were modeled in COMSOL Multiphysics to optimize cooling. The third model concept (Model 3) was chosen as the best model because it cooled the battery to the lowest temperature with the lowest pressure drop

Designing a Heat Sink for Lithium-ion Battery Packs in Electric Vehicles

This report addresses the concepts and implementation of fluid cooled heat sink designs for an electric or hybrid vehicle battery. To determine the battery’s temperature and heat flux profile, testing was performed by measuring these values at multiple locations on a lithium-ion pouch battery using heat flux sensors and thermocouples during the charge and discharge cycles of the battery. Once the data was collected and analyzed, trendlines were fit to the heat flux data then used to create equations for the heat flux profile during the discharging stage. Each equation represented a specific region on the battery geometry. Four heat sink designs were modeled in COMSOL Multiphysics to optimize cooling. The third model concept (Model 3) was chosen as the best model because it cooled the battery to the lowest temperature with the lowest pressure drop

The Determination of Total Energy Expenditure During and Following Repeated High-Intensity Intermittent Sprint Work

International Journal of Exercise Science 10(3): 312-321, 2017. The purpose of this study was to examine the variation in oxidative, glycolytic, and post-exercise O2 kinetic contribution during two distinct high-intensity interval training (HIIT) protocols using a 1:1 work-to-rest ratio (30:30 sec) and a 2:1 work-to-rest ratio (30:15 sec). HIIT familiarized males (n =6) and females (n = 8) were recruited for this study. All subject underwent 3 testing session, an incremental maximal exertion treadmill test and 30:30 and 30:15 HIIT protocols in a counterbalanced order. Each HIIT protocol measured oxygen consumption (VO2), carbon dioxide production (VCO2), and respiratory exchange ratio (RER) to represent oxidative contribution. Capillary blood lactate was also analyzed to represent glycolytic contribution during both HIIT sessions. Repeated-measures ANOVA revealed a relative and absolute significant difference between the oxidative, glycolytic, and post-exercise oxygen kinetics between 30:30 and 30:15 HIIT session. 30:30 displayed a greater contribution from the oxidative system while the 30:15 displayed an increase contribution from the glycolytic system and displayed an increase in EE during the post-exercise oxygen kinetics phase. Results also revealed no significant findings between the two HIIT sessions in regards to absolute EE (30:30 = 258.2 + 43 kcals, 30:15 = 261 + 43.6 kcals). The addition of blood lactate following exercise did display a noteworthy contribution from the glycolytic system. In conclusion, utilizing pulmonary gas exchange in conjunction with blood lactate depicts an acceptable EE estimation during a bout of HIIT

Evolution of the electrochemical interface in high-temperature fuel cells and electrolysers

C.C. acknowledges financial support from ECoProbe (DFF – 4005-00129) funded by the Danish Independent Research Council. C.G. and M.B.M. acknowledge financial support from Energinet.dk through the ForskEL programme Solid Oxide Fuel Cells for the Renewable Energy Transition contract no. 2014-1-12231. J.T.S.I., M.C.V. and D.N. acknowledge support from EPSRC Platform Grant EP/K015540/1, EPSRC Tailoring of microstructural evolution in impregnated SOFC electrodes EP/M014304/1 and Royal Society Wolfson Merit Award WRMA 2012/R2.The critical region determining the performance and lifetime of solid oxide electrochemical systems is normally at the electrode side of the electrode/electrolyte interface. Typically this electrochemically active region only extends a few micrometres and for best performance involves intricate structures and nanocomposites. Much of the most exciting recent research involves understanding processes occurring at this interface and in developing new means of controlling the structure at this interface on the nanoscale. Here we consider in detail the diverse range of materials architectures that may be involved, describe the evolution of these interface structures and finally explore the new chemistries that allow control and manipulation of these architectures to optimize both performance and durability.PostprintPeer reviewe

Nitroxyl, the novel redox sibling of NO, suppresses cerebrovascular NADPH oxidase

Background: Nitroxyl (HNO), the reduced and protonated congener of nitric oxide (NO), is emerging as a novel entity with distinct pharmacology and therapeutic advantages over NO• [1]. Importantly, HNO has vasoprotective actions with the potential to serve as an antioxidant. Here we explored the ability of HNO to modulate cerebrovascular NADPH oxidase activity, a major source of superoxide (.O2-) in the vasculature. Materials and methods: Intracranial (pooled middle cerebral and basilar) and extracranial (carotid) cerebral arteries from male C57BL/6J mice were treated with angiotensin II (10 nM) acutely (30 min) and chronically (24 h), respectively, in the absence and presence of the HNO donor, Angeli's salt (AS). NADPH (100 μM)-stimulated .O2- production was then measured using lucigenin (5 μM)-enhanced chemiluminescence. Results: AS (1 μM) did not scavenge .O2- generated in a cell free xanthine (100 μM)/xanthine oxidase (0.05 U/ml) activity assay (control: 447.9 ± 90.8; AS 507.1 ± 113.3 counts, n = 4). In contrast, acute and chronic treatment with AS (0.01–1 μM) caused a concentration-dependent decrease in NADPH oxidase-derived .O2- production by intracranial and extracranial cerebral arteries, respectively (carotid 0.59 ± 0.05; AS 0.1 μM 0.33 ± 0.08; AS 1 μM 0.16 ± 0.03 103 counts/s/mg, P < 0.05, n = 8). The effects of AS were reversed by the HNO scavenger, L-cysteine (3 mM) but unchanged in the presence of the NO• scavenger carboxy-PTIO (200 μM) and sGC inhibitor, ODQ (10 μM). Conclusion: HNO suppresses vascular NADPH-oxidase activity both acutely and chronically, possibly via a cGMP-independent mechanism. Such antioxidant actions of HNO may confer therapeutic advantages in the treatment of cerebrovascular disorders

Temporal variations in supraglacial debris distribution on Baltoro Glacier, Karakoram between 2001 and 2012

Distribution of supraglacial debris in a glacier system varies spatially and temporally due to differing rates of debris input, transport and deposition. Supraglacial debris distribution governs the thickness of a supraglacial debris layer, an important control on the amount of ablation that occurs under such a debris layer. Characterising supraglacial debris layer thickness on a glacier is therefore key to calculating ablation across a glacier surface. The spatial pattern of debris thickness on Baltoro Glacier has previously been calculated for one discrete point in time (2004) using satellite thermal data and an empirically based relationship between supraglacial debris layer thickness and debris surface temperature identified in the field. Here, the same empirically based relationship was applied to two further datasets (2001, 2012) to calculate debris layer thickness across Baltoro Glacier for three discrete points over an 11-year period (2001, 2004, 2012). Surface velocity and sediment flux were also calculated, as well as debris thickness change between periods. Using these outputs, alongside geomorphological maps of Baltoro Glacier produced for 2001, 2004 and 2012, spatiotemporal changes in debris distribution for a sub-decadal timescale were investigated. Sediment flux remained constant throughout the 11-year period. The greatest changes in debris thickness occurred along medial moraines, the locations of mass movement deposition and areas of interaction between tributary glaciers and the main glacier tongue. The study confirms the occurrence of spatiotemporal changes in supraglacial debris layer thickness on sub-decadal timescales, independent of variation in surface velocity. Instead, variation in rates of debris distribution are primarily attributed to frequency and magnitude of mass movement events over decadal timescales, with climate, regional uplift and erosion rates expected to control debris inputs over centurial to millennial timescales. Inclusion of such spatiotemporal variations in debris thickness in distributed surface energy balance models would increase the accuracy of calculated ablation, leading to a more accurate simulation of glacier mass balance through time, and greater precision in quantification of the response of debris-covered glaciers to climatic change

Training Manipulations Based on Acute Heart Rate Variability Measures

Heart rate variability (HRV) is an accurate indicator of sympathetic and parasympathetic nervous system activity. The balance between these systems affects the time between heartbeats. A high variability between heartbeats is equated to a greater influence from the parasympathetic nervous system. In this state, an individual is well rested, and therefore possesses higher readiness to perform physical activity. Through the use of smartphone applications (apps), athletes and coaches can collect accurate short-term HRV readings to assess autonomic nervous system balance. These apps provide a readiness to train score that may prove beneficial in adjusting daily training loads to maximize performance. PURPOSE: The purpose of this study is to characterize the changes in lower-body strength and power before and after a 6-week strength training program while manipulating intensity based on daily HRV readiness measures in female collegiate softball athletes. METHODS: Nine female NCAA Division II Softball athletes completed the 6-week training protocol. Participants were split into an experimental group (E; n = 5; age = 20.5±0.7 yrs, height = 166.9±2.7 cm, weight = 59.9±7.6 kg), who completed the training with the intensity adjusted based off of daily HRV readiness scores, and a control group (C; n = 4; age = 20.6±0.8 yrs, height = 171.7±1.2 cm, weight = 70.7±30.3 kg), who completed the training with no changes in exercise intensity. Measures of HRV were taken prior to each training session and used to calculate readiness scores with the use of a smartphone app. Participants completed 3 strength-training sessions per week throughout the study. Lower-body strength and power measurements were assessed before and after the protocol. One-repetition maximums on the back squat (SQ) and clean (CL) exercises and maximum vertical jump (VJ) height were collected. RESULTS: Lower-body power measurements were increased in the E group (CL: 51.3 vs. 56.9 kg, p = 0.047; VJ: 40.1 vs. 44.7 cm, p = 0.037) and the C group (CL: 56.8 vs. 63.6 kg, p = 0.021; VJ: 41.6 vs. 46.2 cm, p = 0.034), following 6 weeks of strength training. No significant differences were observed in lower body strength measurements in the E group (SQ: 74 vs. 84.1kg, p = 0.21) or the C group (SQ: 75.5 vs. 86.6 kg, p = 0.2). Significant differences were found between the prescribed volume of training and the completed volume of training (25364 vs 21650 kg, p = 0.014) in the E group. No significant differences (p \u3e 0.05) were found with SQ, CL, and VJ measures between the E and C groups following 6 weeks of strength training. No significant differences (p \u3e 0.05) were found in daily HRV measures between the E and C groups. CONCLUSION: Both groups exhibited similar HRV scores throughout the 6-week training protocol. Using daily short-term HRV readings, training intensity can be reduced without leading to any differences in lower-body strength and power improvements in female collegiate softball athletes

Polyunsaturated fatty acid biosynthesis is involved in phenylephrine-mediated calcium release in vascular smooth muscle cells

Stimulation of vascular smooth muscle (VSM) ?1-adrenoceptors induces myosin phosphorylation and vasoconstriction via mobilisation of intracellular calcium and production of specific eicosanoids. Polyunsaturated fatty acid (PUFA) biosynthesis in VSM cells is involved, although the precise mechanism is not known. To address this, we characterised PUFA biosynthesis in VSM cells and determined its role in intracellular calcium release and eicosanoid production. Murine VSM cells converted 18:2n-6 to longer chain PUFA including 22:5n-6. ?6 (D6d) and ?5 (D5d) desaturase, and elongase (Elovl) 5 were expressed. Elovl2 was not detected in human, mouse or rat VSM cells, or in rat or mouse aortae, but tit was not associated with hypermethylation of its promoter. D6d or D5d inhibition reduced 18:3n-6 and 20:4n-6 synthesis, respectively, and induced concentration-related decrease in phenylephrine-mediated calcium release, and in PGE2 and PGF2? secretion. Together these findings suggest that PUFA biosynthesis in VSM cells is involved in calcium release associated with vasoconstriction