Shape optimization is an indispensable step in any aerodynamic design. However, the inherent complexity and non-linearity associated with fluid mechanics as well as the high-dimensional design space ...intrinsic to such problems make airfoil shape optimization a challenging task. Current approaches relying on gradient-based or gradient-free optimizers are data-inefficient in that they do not leverage accumulated knowledge, and are computationally expensive when integrating Computational Fluid Dynamics (CFD) simulation tools. Supervised learning approaches have addressed these limitations but are constrained by user-provided data. Reinforcement learning (RL) provides a data-driven approach bearing generative capabilities. We formulate the airfoil design as a Markov decision process (MDP) and investigate a Deep Reinforcement Learning (DRL) approach to airfoil shape optimization. A custom RL environment is developed allowing the agent to successively modify the shape of an initially provided 2D airfoil and to observe the associated changes in aerodynamic metrics such as lift-to-drag (L/D), lift coefficient (C
) and drag coefficient (C
). The learning abilities of the DRL agent are demonstrated through various experiments in which the agent's objective-maximizing L/D, maximizing C
or minimizing C
-as well as the initial airfoil shape are varied. Results show that the DRL agent is able to generate high performing airfoils within a limited number of learning iterations. The strong resemblance between the artificially produced shapes and those found in the literature highlights the rationality of the decision-making policy learned by the agent. Overall, the presented approach demonstrates the relevance of DRL to airfoil shape optimization and brings forward a successful application of DRL to a physics-based aerodynamics problem.
Introduction
Patients who become severely ill from coronavirus disease 2019 (COVID‐19) have a high likelihood of needing prolonged intubation, making tracheostomy a likely consideration. The ...infectious nature of COVID‐19 poses an additional risk of transmission to healthcare workers that should be taken into consideration.
Methods
We explore current literature and recommendations for tracheostomy in patients with COVID‐19 and look back at previous data from severe acute respiratory syndrome coronavirus 1 (SARS‐CoV‐1), the virus responsible for the SARS outbreak of 2003.
Results
Given the severity and clinical uncertainty of patients with COVID‐19 and the increased risk of transmission to clinicians, careful consideration should be taken prior to performing tracheostomy. If tracheostomy is performed, we recommend a bedside approach to limit exposure time and number of exposed personnel. Bronchoscopy use with a percutaneous approach should be limited in order to decrease viral exposure.
Conclusion
Thorough preprocedural planning, use of experienced personnel, enhanced personal protective equipment where available, and a thoughtful anesthesia approach are instrumental in maximizing positive patient outcomes while successfully protecting the safety of healthcare personnel. Laryngoscope, 130:2546–2549, 2020
Abstract
Background
Hypothalamic dysfunction occurs early in the clinical course of Alzheimer’s disease (AD), likely contributing to disturbances in feeding behavior and metabolic function that are ...often observed years prior to the onset of cognitive symptoms. Late-life weight loss and low BMI are associated with increased risk of dementia and faster progression of disease. However, high-fat diet and metabolic disease (e.g., obesity, type 2 diabetes), particularly in mid-life, are associated with increased risk of AD, as well as exacerbated AD pathology and behavioral deficits in animal models. In the current study, we explored possible relationships between hypothalamic function, diet/metabolic status, and AD. Considering the sex bias in AD, with women representing two-thirds of AD patients, we sought to determine whether these relationships vary by sex.
Methods
WT and 3xTg-AD male and female mice were fed a control (10% fat) or high-fat (HF 60% fat) diet from ~ 3–7 months of age, then tested for metabolic and hypothalamic disturbances.
Results
On control diet, male 3xTg-AD mice displayed decreased body weight, reduced fat mass, hypoleptinemia, and mild systemic inflammation, as well as increased expression of gliosis- and inflammation-related genes in the hypothalamus (Iba1, GFAP, TNF-α, IL-1β). In contrast, female 3xTg-AD mice on control diet displayed metabolic disturbances opposite that of 3xTg-AD males (increased body and fat mass, impaired glucose tolerance). HF diet resulted in expected metabolic alterations across groups (increased body and fat mass; glucose intolerance; increased plasma insulin and leptin, decreased ghrelin; nonalcoholic fatty liver disease-related pathology). HF diet resulted in the greatest weight gain, adiposity, and glucose intolerance in 3xTg-AD females, which were associated with markedly increased hypothalamic expression of GFAP and IL-1β, as well as GFAP labeling in several hypothalamic nuclei that regulate energy balance. In contrast, HF diet increased diabetes markers and systemic inflammation preferentially in AD males but did not exacerbate hypothalamic inflammation in this group.
Conclusions
These findings provide further evidence for the roles of hypothalamic and metabolic dysfunction in AD, which in the 3xTg-AD mouse model appears to be dependent on both sex and diet.
Abstract
Background
Tissue sodium (Na+) content in patients on maintenance hemodialysis (MHD) and peritoneal dialysis (PD) was previously explored using 23Na+ magnetic resonance imaging (23NaMRI). ...Larger studies would provide a better understanding of Na+ stores in patients on dialysis as well as the factors influencing this Na+ accumulation.
Methods
In this cross-sectional study, we quantified the calf muscle and skin Na+ content in 162 subjects (10 PD, 33 MHD patients and 119 controls) using 23NaMRI. Plasma levels of interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) were measured to assess systemic inflammation. Sixty-four subjects had repeat 23NaMRI scans that were analyzed to assess the repeatability of the 23NaMRI measurements.
Results
Patients on MHD and PD exhibited significantly higher muscle and skin Na+ accumulation compared with controls. African American patients on dialysis exhibited greater muscle and skin Na+ content compared with non–African Americans. Multivariable analysis showed that older age was associated with both higher muscle and skin Na+ and male sex was associated with increased skin Na+ deposition. Greater ultrafiltration was associated with lower skin Na+ in patients on PD (Spearman’s ρ = −0.68, P = 0.035). Higher plasma IL-6 and hsCRP levels correlated with increased muscle and skin Na+ content in the overall study population. Patients with higher baseline tissue Na+ content exhibited greater variability in tissue Na+ stores on repeat measurements.
Conclusions
Our findings highlight greater muscle and skin Na+ content in dialysis patients compared with controls without kidney disease. Tissue Na+ deposition and systemic inflammation seen in dialysis patients might influence one another bidirectionally.
The COVID-19 pandemic is having profound mental health consequences for many people. Concerns have been expressed that, at their most extreme, these consequences could manifest as increased suicide ...rates. We aimed to assess the early effect of the COVID-19 pandemic on suicide rates around the world.
We sourced real-time suicide data from countries or areas within countries through a systematic internet search and recourse to our networks and the published literature. Between Sept 1 and Nov 1, 2020, we searched the official websites of these countries' ministries of health, police agencies, and government-run statistics agencies or equivalents, using the translated search terms "suicide" and "cause of death", before broadening the search in an attempt to identify data through other public sources. Data were included from a given country or area if they came from an official government source and were available at a monthly level from at least Jan 1, 2019, to July 31, 2020. Our internet searches were restricted to countries with more than 3 million residents for pragmatic reasons, but we relaxed this rule for countries identified through the literature and our networks. Areas within countries could also be included with populations of less than 3 million. We used an interrupted time-series analysis to model the trend in monthly suicides before COVID-19 (from at least Jan 1, 2019, to March 31, 2020) in each country or area within a country, comparing the expected number of suicides derived from the model with the observed number of suicides in the early months of the pandemic (from April 1 to July 31, 2020, in the primary analysis).
We sourced data from 21 countries (16 high-income and five upper-middle-income countries), including whole-country data in ten countries and data for various areas in 11 countries). Rate ratios (RRs) and 95% CIs based on the observed versus expected numbers of suicides showed no evidence of a significant increase in risk of suicide since the pandemic began in any country or area. There was statistical evidence of a decrease in suicide compared with the expected number in 12 countries or areas: New South Wales, Australia (RR 0·81 95% CI 0·72-0·91); Alberta, Canada (0·80 0·68-0·93); British Columbia, Canada (0·76 0·66-0·87); Chile (0·85 0·78-0·94); Leipzig, Germany (0·49 0·32-0·74); Japan (0·94 0·91-0·96); New Zealand (0·79 0·68-0·91); South Korea (0·94 0·92-0·97); California, USA (0·90 0·85-0·95); Illinois (Cook County), USA (0·79 0·67-0·93); Texas (four counties), USA (0·82 0·68-0·98); and Ecuador (0·74 0·67-0·82).
This is the first study to examine suicides occurring in the context of the COVID-19 pandemic in multiple countries. In high-income and upper-middle-income countries, suicide numbers have remained largely unchanged or declined in the early months of the pandemic compared with the expected levels based on the pre-pandemic period. We need to remain vigilant and be poised to respond if the situation changes as the longer-term mental health and economic effects of the pandemic unfold.
None.
Serotonin plays a central role in cognition and is the target of most pharmaceuticals for psychiatric disorders. Existing drugs have limited efficacy; creation of improved versions will require ...better understanding of serotonergic circuitry, which has been hampered by our inability to monitor serotonin release and transport with high spatial and temporal resolution. We developed and applied a binding-pocket redesign strategy, guided by machine learning, to create a high-performance, soluble, fluorescent serotonin sensor (iSeroSnFR), enabling optical detection of millisecond-scale serotonin transients. We demonstrate that iSeroSnFR can be used to detect serotonin release in freely behaving mice during fear conditioning, social interaction, and sleep/wake transitions. We also developed a robust assay of serotonin transporter function and modulation by drugs. We expect that both machine-learning-guided binding-pocket redesign and iSeroSnFR will have broad utility for the development of other sensors and in vitro and in vivo serotonin detection, respectively.
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•Developed a machine learning approach for rapid binding-pocket redesign•Engineered a high dynamic range, sensitive, selective sensor for 5-HT: iSeroSnFR•Demonstrated the use of iSeroSnFR for fiber photometry in awake behaving mice•Developed a clinically relevant assay using iSeroSnFR for 5-HT transporter function
Machine-learning-guided binding-pocket redesign enables engineering of genetically encoded sensor for serotonin that detects serotonin release in freely behaving mice and is used for the development of an assay for serotonin transporter function and modulation by drugs.
Food palatability is one of many factors that drives food consumption, and the hedonic drive to feed is a key contributor to obesity and binge eating. In this study, we identified a population of ...prepronociceptin-expressing cells in the central amygdala (PnocCeA) that are activated by palatable food consumption. Ablation or chemogenetic inhibition of these cells reduces palatable food consumption. Additionally, ablation of PnocCeA cells reduces high-fat-diet-driven increases in bodyweight and adiposity. PnocCeA neurons project to the ventral bed nucleus of the stria terminalis (vBNST), parabrachial nucleus (PBN), and nucleus of the solitary tract (NTS), and activation of cell bodies in the central amygdala (CeA) or axons in the vBNST, PBN, and NTS produces reward behavior but did not promote feeding of palatable food. These data suggest that the PnocCeA network is necessary for promoting the reinforcing and rewarding properties of palatable food, but activation of this network itself is not sufficient to promote feeding.
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•PnocCeA neurons are activated following palatable food consumption•PnocCeA neurons promote palatable food consumption specifically•PnocCeA neuronal projections in the CeA, vBNST, PBN, and NTS promote reward
Eating calorically dense, palatable foods is a major contributor to obesity and binge eating. In this article, Hardaway et al. identify a central amygdala brain circuit expressing the neuropeptide prepronociceptin in mice that promotes palatable food consumption and reward.
Glacial-state greenhouse gas concentrations and Southern Hemisphere climate conditions persisted until ∼17.7 ka, when a nearly synchronous acceleration in deglaciation was recorded in paleoclimate ...proxies in large parts of the Southern Hemisphere, with many changes ascribed to a sudden poleward shift in the Southern Hemisphere westerlies and subsequent climate impacts. We used high-resolution chemical measurements in the West Antarctic Ice Sheet Divide, Byrd, and other ice cores to document a unique, ∼192-y series of halogen-rich volcanic eruptions exactly at the start of accelerated deglaciation, with tephra identifying the nearby Mount Takahe volcano as the source. Extensive fallout from these massive eruptions has been found >2,800 km from Mount Takahe. Sulfur isotope anomalies and marked decreases in ice core bromine consistent with increased surface UV radiation indicate that the eruptions led to stratospheric ozone depletion. Rather than a highly improbable coincidence, circulation and climate changes extending from the Antarctic Peninsula to the subtropics—similar to those associated with modern stratospheric ozone depletion over Antarctica—plausibly link the Mount Takahe eruptions to the onset of accelerated Southern Hemisphere deglaciation ∼17.7 ka.
The causal mechanisms responsible for the abrupt climate changes of the Last Glacial Period remain unclear. One major difficulty is dating ice-rafted debris deposits associated with Heinrich events: ...Extensive iceberg influxes into the North Atlantic Ocean linked to global impacts on climate and biogeochemistry. In a new ice core record of atmospheric methane with ultrahigh temporal resolution, we find abrupt methane increases within Heinrich stadials 1, 2,4, and 5 that, uniquely, have no counterparts in Greenland temperature proxies. Using a heuristic model of tropical rainfall distribution, we propose that Hudson Strait Heinrich events caused rainfall intensification over Southern Hemisphere land areas, thereby producing excess methane in tropical wetlands. Our findings suggest that the climatic impacts of Heinrich events persisted for 740 to 1520 years.
Patients with end-stage kidney disease on maintenance hemodialysis commonly develop protein-energy wasting, a syndrome characterized by nutritional and metabolic abnormalities. Nutritional ...supplementation and exercise are recommended to prevent protein-energy wasting. In a 6-mo prospective randomized, open-label, clinical trial, we reported that the combination of resistance exercise and nutritional supplementation does not have an additive effect on lean body mass measured by dual-energy X-ray absorptiometry. To provide more mechanistic data, we performed a secondary analysis where we hypothesized that the combination of nutritional supplementation and resistance exercise would have additive effects on muscle protein accretion by stable isotope protein kinetic experiments, muscle mass by MRI, and mitochondrial content markers in muscle. We found that 6 mo of nutritional supplementation during hemodialysis increased muscle protein net balance baseline: 2.5 (-17.8, 13.0) µg·100 mL
·min
vs. 6 mo: 43.7 (13.0, 98.5) µg·100 mL
·min
, median (interquartile range),
= 0.04 and mid-thigh fat area baseline: 162.3 (104.7, 226.6) cm
vs. 6 mo: 181.9 (126.3, 279.2) cm
, median (interquartile range),
= 0.04. Three months of nutritional supplementation also increased markers of mitochondrial content in muscle. Although the study is underpowered to detected differences, the combination of nutritional supplementation and exercise failed to show further benefit in protein accretion or muscle cross-sectional area. We conclude that long-term nutritional supplementation increases the skeletal muscle anabolic effect, the fat cross-sectional area of the thigh, and markers of mitochondrial content in skeletal muscle.
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