While the accuracy of 3D human pose estimation from images has steadily improved on benchmark datasets, the best methods still fail in many real-world scenarios. This suggests that there is a domain ...gap between current datasets and common scenes containing people. To obtain ground-truth 3D pose, current datasets limit the complexity of clothing, environmental conditions, number of subjects, and occlusion. Moreover, current datasets evaluate sparse 3D joint locations corresponding to the major joints of the body, ignoring the hand pose and the face shape. To evaluate the current state-of-the-art methods on more challenging images, and to drive the field to address new problems, we introduce AGORA, a synthetic dataset with high realism and highly accurate ground truth. Here we use 4240 commercially-available, high-quality, textured human scans in diverse poses and natural clothing; this includes 257 scans of children. We create reference 3D poses and body shapes by fitting the SMPL-X body model (with face and hands) to the 3D scans, taking into account clothing. We create around 14K training and 3K test images by rendering between 5 and 15 people per image using either image-based lighting or rendered 3D environments, taking care to make the images physically plausible and photoreal. In total, AGORA consists of 173K individual person crops. We evaluate existing state-of-the-art methods for 3D human pose estimation on this dataset. and find that most methods perform poorly on images of children. Hence, we extend the SMPL-X model to better capture the shape of children. Additionally, we fine-tune methods on AGORA and show improved performance on both AGORA and 3DPW, confirming the realism of the dataset. We provide all the registered 3D reference training data, rendered images, and a web-based evaluation site at https://agora.is.tue.mpg.de/.
Abstract
Multiple randomized multicentre clinical trials have established the role of the implantable cardioverter-defibrillator (ICD) as the mainstay in the treatment of ventricular tachyarrhythmias ...and sudden cardiac death (SCD) prevention. These trials have focused mainly on heart failure patients with advanced left ventricular dysfunction and were mostly conducted two decades ago, whereas a more recent trial has provided conflicting results. Therefore, much remains to be determined on how best to balance the identification of patients at high risk of SCD together with who would benefit most from ICD implantation in a contemporary setting. Implantable cardioverter-defibrillators have also evolved from the simple, defibrillation-only devices implanted surgically to more advanced technologies of multi-chamber devices, with physiologic bradycardic pacing, including cardiac resynchronization therapy, atrial and ventricular therapeutic pacing algorithms, and subcutaneous ICDs. These multiple options necessitate individualized approach to device selection and programming. This review will focus on the current knowledge on selection of patients for ICD treatment, device selection and programming, and future directions of implantable device therapy for SCD prevention.
This trial revisited research conducted about a decade ago that showed a survival benefit with early neuromuscular blockade in patients with acute respiratory distress syndrome. The new trial did not ...show a benefit with neuromuscular blockade with respect to overall survival or other clinical outcomes.
The initial presentation of sepsis in the emergency department (ED) is difficult to distinguish from other acute illnesses based upon similar clinical presentations. A new blood parameter, a ...measurement of increased monocyte volume distribution width (MDW), may be used in combination with other clinical parameters to improve early sepsis detection. We sought to determine if MDW, when combined with other available clinical parameters at the time of ED presentation, improves the early detection of sepsis.
A retrospective analysis of prospectively collected clinical data available during the initial ED encounter of 2158 adult patients who were enrolled from emergency departments of three major academic centers, of which 385 fulfilled Sepsis-2 criteria, and 243 fulfilled Sepsis-3 criteria within 12 h of admission. Sepsis probabilities were determined based on MDW values, alone or in combination with components of systemic inflammatory response syndrome (SIRS) or quick sepsis-related organ failure assessment (qSOFA) score obtained during the initial patient presentation (i.e., within 2 h of ED admission).
Abnormal MDW (> 20.0) consistently increased sepsis probability, and normal MDW consistently reduced sepsis probability when used in combination with SIRS criteria (tachycardia, tachypnea, abnormal white blood count, or body temperature) or qSOFA criteria (tachypnea, altered mental status, but not hypotension). Overall, and regardless of other SIRS or qSOFA variables, MDW > 20.0 (vs. MDW ≤ 20.0) at the time of the initial ED encounter was associated with an approximately 6-fold increase in the odds of Sepsis-2, and an approximately 4-fold increase in the odds of Sepsis-3.
MDW improves the early detection of sepsis during the initial ED encounter and is complementary to SIRS and qSOFA parameters that are currently used for this purpose. This study supports the incorporation of MDW with other readily available clinical parameters during the initial ED encounter for the early detection of sepsis.
ClinicalTrials.gov, NCT03145428. First posted May 9, 2017. The first subjects were enrolled June 19, 2017, and the study completion date was January 26, 2018.
Rechargeability and operational safety of commercial lithium (Li)-ion batteries demand further improvement. Plating of metallic Li on graphite anodes is a critical reason for Li-ion battery capacity ...decay and short circuit. It is generally believed that Li plating is caused by the slow kinetics of graphite intercalation, but in this paper, we demonstrate that thermodynamics also serves a crucial role. We show that a nonuniform temperature distribution within the battery can make local plating of Li above 0 V vs. Li⁰/Li⁺ (room temperature) thermodynamically favorable. This phenomenon is caused by temperature-dependent shifts of the equilibrium potential of Li⁰/Li⁺. Supported by simulation results, we confirm the likelihood of this failure mechanism during commercial Li-ion battery operation, including both slow and fast charging conditions. This work furthers the understanding of nonuniform Li plating and will inspire future studies to prolong the cycling lifetime of Li-ion batteries.
IMPORTANCE: The combination of ascorbic acid, corticosteroids, and thiamine has been identified as a potential therapy for septic shock. OBJECTIVE: To determine whether the combination of ascorbic ...acid, corticosteroids, and thiamine attenuates organ injury in patients with septic shock. DESIGN, SETTING, AND PARTICIPANTS: Randomized, blinded, multicenter clinical trial of ascorbic acid, corticosteroids, and thiamine vs placebo for adult patients with septic shock. Two hundred five patients were enrolled between February 9, 2018, and October 27, 2019, at 14 centers in the United States. Follow-up continued until November 26, 2019. INTERVENTIONS: Patients were randomly assigned to receive parenteral ascorbic acid (1500 mg), hydrocortisone (50 mg), and thiamine (100 mg) every 6 hours for 4 days (n = 103) or placebo in matching volumes at the same time points (n = 102). MAIN OUTCOMES AND MEASURES: The primary outcome was change in the Sequential Organ Failure Assessment (SOFA) score (range, 0-24; 0 = best) between enrollment and 72 hours. Key secondary outcomes included kidney failure and 30-day mortality. Patients who received at least 1 dose of study drug were included in analyses. RESULTS: Among 205 randomized patients (mean age, 68 SD, 15 years; 90 44% women), 200 (98%) received at least 1 dose of study drug, completed the trial, and were included in the analyses (101 with intervention and 99 with placebo group). Overall, there was no statistically significant interaction between time and treatment group with regard to SOFA score over the 72 hours after enrollment (mean SOFA score change from 9.1 to 4.4 −4.7 points with intervention vs 9.2 to 5.1 −4.1 points with placebo; adjusted mean difference, −0.8; 95% CI, −1.7 to 0.2; P = .12 for interaction). There was no statistically significant difference in the incidence of kidney failure (31.7% with intervention vs 27.3% with placebo; adjusted risk difference, 0.03; 95% CI, −0.1 to 0.2; P = .58) or in 30-day mortality (34.7% vs 29.3%, respectively; hazard ratio, 1.3; 95% CI, 0.8-2.2; P = .26). The most common serious adverse events were hyperglycemia (12 patients with intervention and 7 patients with placebo), hypernatremia (11 and 7 patients, respectively), and new hospital-acquired infection (13 and 12 patients, respectively). CONCLUSIONS AND RELEVANCE: In patients with septic shock, the combination of ascorbic acid, corticosteroids, and thiamine, compared with placebo, did not result in a statistically significant reduction in SOFA score during the first 72 hours after enrollment. These data do not support routine use of this combination therapy for patients with septic shock. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03389555
An imbalance between normal adipogenesis and osteogenesis by mesenchymal stem cells (MSCs) has been shown to be related to various human metabolic diseases, such as obesity and osteoporosis; however, ...the underlying mechanisms remain elusive. We found that the interaction between osteopontin (OPN), an arginine‐glycine‐aspartate‐containing glycoprotein, and integrin αv/β1 plays a critical role in the lineage determination of MSCs. Although OPN is a well‐established marker during osteogenesis, its role in MSC differentiation is still unknown. Our study reveals that blockade of OPN function promoted robust adipogenic differentiation, while inhibiting osteogenic differentiation. Re‐expression of OPN restored a normal balance between adipogenesis and osteogenesis in OPN−/− MSCs. Retarded bone formation by OPN−/− MSCs was also verified by in vivo implantation with hydroxyapatite‐tricalcium phosphate, a bone‐forming matrix. The role of extracellular OPN in MSC differentiation was further demonstrated by supplementation and neutralization of OPN. Blocking well‐known OPN receptors integrin αv/β1 but not CD44 also affected MSC differentiation. Further studies revealed that OPN inhibits the C/EBPs signaling pathway through integrin αv/β1. Consistent with these in vitro results, OPN−/− mice had a higher fat to total body weight ratio than did wild‐type mice. Therefore, our study demonstrates a novel role for OPN‐integrin αv/β1 in regulating MSC differentiation. Stem Cells 2014;32:327–337
The application of in situ electrochemical generation of ferrous (Fe(II)) ions for phosphorus (P) removal in wastewater treatment was investigated with attention to the efficacy, kinetics and ...mechanism. At concentrations typical of municipal wastewater, P could be removed by in situ Fe(II) with removal efficiency higher than achieved on addition of FeSO4 and close to that of FeCl3 under both anoxic and oxic conditions. The generation of alkalinity due to water electrolysis at the cathode created much higher pH conditions compared to FeSO4 dosing thereby resulting in very different pathways of Fe solid phase formation and associated P removal mechanisms. The remarkably similar dependence of P removal on accumulated Fe for all investigated currents, initial P concentrations and DO conditions indicated that kinetic aspects did not play a role in P removal during in situ Fe(II) dosing. Thermodynamic modelling was undertaken to investigate possible solid phase formation pathways under anoxic conditions and these insights were extended to oxic conditions. The exclusive formation of ferrous hydroxide during anoxic in situ Fe(II) dosing implied that P removal occurred via coprecipitation and adsorption. Under oxic conditions, the high pH conditions would have resulted in rapid Fe(II) oxidation and formation of ferric oxyhydroxides with associated coprecipitation and adsorption effecting P removal in a similar pattern to that observed under anoxic conditions. In situ Fe(II) dosing represents a versatile option for chemical P removal with the precise control of Fe dosage to optimize FeP forms for possible P recovery.
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•In situ Fe(II) had higher phosphorus removal efficiency than FeSO4 with rising pH.•Kinetics was not a crucial aspect for phosphorus removal by in situ Fe(II).•Ferrous hydroxide was the major in situ Fe(II) precipitate under anoxic condition.•Amorphous ferric oxyhydroxide was the major iron precipitate under oxic condition.•Phosphorus was predominantly removed through coprecipiation and adsorption.
Atypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in infants. Although the prognosis of ATRT patients is poor, some patients respond favorably to current treatments, ...suggesting molecular inter-tumor heterogeneity. To investigate this further, we genetically and epigenetically analyzed 192 ATRTs. Three distinct molecular subgroups of ATRTs, associated with differences in demographics, tumor location, and type of SMARCB1 alterations, were identified. Whole-genome DNA and RNA sequencing found no recurrent mutations in addition to SMARCB1 that would explain the differences between subgroups. Whole-genome bisulfite sequencing and H3K27Ac chromatin-immunoprecipitation sequencing of primary tumors, however, revealed clear differences, leading to the identification of subgroup-specific regulatory networks and potential therapeutic targets.
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•ATRTs are comprised of three epigenetically distinct subgroups: TYR, SHH, and MYC•H3K27Ac enhancer landscapes reveal ATRT subgroup-specific regulatory networks•Regulatory networks lead to identification of potential therapeutic targets•Epigenetic profiles point at distinct cellular origins of ATRT subgroups
SMARCB1 is the sole highly recurrently mutated gene in atypical teratoid/rhabdoid tumors (ATRTs). Johann et al. show that ATRTs are composed of three epigenetic subgroups that have different clinical characteristics, and identify subgroup-specific regulatory networks that suggest potential therapeutic targets.
A central issue in the control of apoptosis is whether its essential mediators Bax and Bak must be restrained by Bcl-2-like prosurvival relatives to prevent their damaging mitochondria and unleashing ...apoptosis. The issue is particularly vexed for Bax, which is largely a cytosolic monomer in unstressed cells. To determine whether Bax regulation requires its binding by prosurvival relatives, we replaced a conserved aspartate in its BH3 interaction domain with arginine. Bax D68R functioned and behaved like wild-type Bax in localization and activation but had greatly impaired binding to the prosurvival family members. Nevertheless, Bcl-xL remained able to block apoptosis induced by Bax D68R. Whereas cells with sufficient Bcl-xL tolerated expression of Bax D68R, it provoked apoptosis when Bcl-xL was absent, downregulated, or inactivated. Moreover, Bax D68R rendered membrane bound by a C-terminal anchor mutation overwhelmed endogenous Bcl-xL and killed cells. These unexpected results suggest that engagement of Bax by its prosurvival relatives is a major barrier to its full activation. We propose that the Bcl-2-like proteins must capture the small proportion of Bax molecules with an exposed BH3 domain, probably on the mitochondrial membrane, to prevent Bax-imposed cell death, but that Bcl-xL also controls Bax by other mechanisms.
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