Irreversible Electroporation (IRE): Preclinical Assessment

Cancer Systems Imaginghttps://openworks.mdanderson.org/sumexp22/1079/thumbnail.jp

Management of Elbow Dislocations in the National Football League.

Background: Although much literature exists regarding the treatment and management of elbow dislocations in the general population, little information is available regarding management in the athletic population. Furthermore, no literature is available regarding the postinjury treatment and timing of return to play in the contact or professional athlete. Purpose: To review the clinical course of elbow dislocations in professional football players and determine the timing of return to full participation. Study Design: Case series; Level of evidence, 4. Methods: All National Football League (NFL) athletes with elbow dislocations from 2000 through 2011 who returned to play during the season were identified from the NFL Injury Surveillance System (NFL ISS). Roster position, player activity, use of external bracing, and clinical course were reviewed. Mean number of days lost until full return to play was determined for players with elbow dislocations who returned in the same season. Results: From 2000 to 2011, a total of 62 elbow dislocations out of 35,324 injuries were recorded (0.17%); 40 (64.5%) dislocations occurred in defensive players, 12 (19.4%) were in offensive players; and 10 (16.1%) were during special teams play. Over half of the injuries (33/62, 53.2%) were sustained while tackling, and 4 (6.5%) patients required surgery. A total of 47 (75.8%) players who sustained this injury were able to return in the same season. For this group, the mean number of days lost in players treated conservatively (45/47) was 25.1 days (median, 23.0 days; range, 0.0-118 days), while that for players treated operatively (2/47) was 46.5 days (median, 46.5 days; range, 29-64 days). Mean return to play based on player position was 25.8 days for defensive players (n = 28; median, 21.5 days; range, 3.0-118 days), 24.1 days for offensive players (n = 11; median, 19 days; range, 2.0-59 days), and 25.6 days for special teams players (n = 8; median, 25.5 days; range, 0-44 days). Conclusion: Elbow dislocations comprise less than a half of a percent of all injuries sustained in the NFL. Most injuries occur during the act of tackling, with the majority of injured athletes playing a defensive position. Players treated nonoperatively missed a mean of 25.1 days, whereas those managed operatively missed a mean of 46.5 days

Mitochondrial dysfunction and oxidative stress in patients with chronic kidney disease.

Mitochondria abnormalities in skeletal muscle may contribute to frailty and sarcopenia, commonly present in patients with chronic kidney disease (CKD). Dysfunctional mitochondria are also a major source of oxidative stress and may contribute to cardiovascular disease in CKD We tested the hypothesis that mitochondrial structure and function worsens with the severity of CKD Mitochondrial volume density, mitochondrial DNA (mtDNA) copy number, BNIP3, and PGC1α protein expression were evaluated in skeletal muscle biopsies obtained from 27 subjects (17 controls and 10 with CKD stage 5 on hemodialysis). We also measured mtDNA copy number in peripheral blood mononuclear cells (PBMCs), plasma isofurans, and plasma F2-isoprostanes in 208 subjects divided into three groups: non-CKD (eGFR>60 mL/min), CKD stage 3-4 (eGFR 60-15 mL/min), and CKD stage 5 (on hemodialysis). Muscle biopsies from patients with CKD stage 5 revealed lower mitochondrial volume density, lower mtDNA copy number, and higher BNIP3 content than controls. mtDNA copy number in PBMCs was decreased with increasing severity of CKD: non-CKD (6.48, 95% CI 4.49-8.46), CKD stage 3-4 (3.30, 95% CI 0.85-5.75, P = 0.048 vs. non-CKD), and CKD stage 5 (1.93, 95% CI 0.27-3.59, P = 0.001 vs. non-CKD). Isofurans were higher in patients with CKD stage 5 (median 59.21 pg/mL, IQR 41.76-95.36) compared to patients with non-CKD (median 49.95 pg/mL, IQR 27.88-83.46, P = 0.001), whereas F2-isoprostanes did not differ among groups. Severity of CKD is associated with mitochondrial dysfunction and markers of oxidative stress. Mitochondrial abnormalities, which are common in skeletal muscle from patients with CKD stage 5, may explain the muscle dysfunction associated with frailty and sarcopenia in CKD Further studies are required to evaluate mitochondrial function in vivo in patients with different CKD stages

Decentralized Reinforcement Learning: Global Decision-Making via Local Economic Transactions

This paper seeks to establish a framework for directing a society of simple, specialized, self-interested agents to solve what traditionally are posed as monolithic single-agent sequential decision problems. What makes it challenging to use a decentralized approach to collectively optimize a central objective is the difficulty in characterizing the equilibrium strategy profile of non-cooperative games. To overcome this challenge, we design a mechanism for defining the learning environment of each agent for which we know that the optimal solution for the global objective coincides with a Nash equilibrium strategy profile of the agents optimizing their own local objectives. The society functions as an economy of agents that learn the credit assignment process itself by buying and selling to each other the right to operate on the environment state. We derive a class of decentralized reinforcement learning algorithms that are broadly applicable not only to standard reinforcement learning but also for selecting options in semi-MDPs and dynamically composing computation graphs. Lastly, we demonstrate the potential advantages of a society's inherent modular structure for more efficient transfer learning.Comment: 18 pages, 13 figures, accepted to the International Conference on Machine Learning (ICML) 202

Multilocus Genetic Analysis of Brain Images

The quest to identify genes that influence disease is now being extended to find genes that affect biological markers of disease, or endophenotypes. Brain images, in particular, provide exquisitely detailed measures of anatomy, function, and connectivity in the living brain, and have identified characteristic features for many neurological and psychiatric disorders. The emerging field of imaging genomics is discovering important genetic variants associated with brain structure and function, which in turn influence disease risk and fundamental cognitive processes. Statistical approaches for testing genetic associations are not straightforward to apply to brain images because the data in brain images is spatially complex and generally high dimensional. Neuroimaging phenotypes typically include 3D maps across many points in the brain, fiber tracts, shape-based analyses, and connectivity matrices, or networks. These complex data types require new methods for data reduction and joint consideration of the image and the genome. Image-wide, genome-wide searches are now feasible, but they can be greatly empowered by sparse regression or hierarchical clustering methods that isolate promising features, boosting statistical power. Here we review the evolution of statistical approaches to assess genetic influences on the brain. We outline the current state of multivariate statistics in imaging genomics, and future directions, including meta-analysis. We emphasize the power of novel multivariate approaches to discover reliable genetic influences with small effect sizes

Glial βii spectrin contributes to paranode formation and maintenance

Action potential conduction along myelinated axons depends on high densities of voltage-gated Na channels at the nodes of Ranvier. Flanking each node, paranodal junctions (paranodes) are formed between axons and Schwann cells in the peripheral nervous system (PNS) or oligodendrocytes intheCNS. Paranodal junctions contribute to both no deassembly and maintenance. Despitetheir importance, the molecular mechanisms responsible for paranode assembly and maintenance remain poorly understood. βII spectrin is expressed in diverse cells and is an essential part of the submembranous cytoskeleton. Here, we show that Schwann cell βII spectrin is highly enriched at paranodes. To elucidate the roles of glial βII spectrin, we generated mutant mice lacking βII spectrin in myelinating glial cells by crossing mice with a floxed allele of Sptbn1 with Cnp-Cre mice, and analyzed both male and female mice. Juvenile (4 weeks) and middle-aged (60 weeks) mutant mice showed reduced grip strength and sciatic nerve conduction slowing, whereas no phenotype was observed between 8 and 24 weeks of age. Consistent with these findings, immunofluorescence microscopy revealed disorganized paranodes in the PNS and CNS of both postnatal day 13 and middle-aged mutant mice, but not in young adult mutant mice. Electron microscopy confirmed partial loss of transverse bands at the paranodal axoglial junction in the middle-aged mutant mice in both the PNS and CNS. These findings demonstrate that a spectrin-based cytoskeleton in myelinating glia contributes to formation and maintenance of paranodal junctions.Fil: Susuki, Keiichiro. Baylor College of Medicine; Estados UnidosFil: Zollinger, Daniel R.. Baylor College of Medicine; Estados UnidosFil: Chang, Kae Jiun. Baylor College of Medicine; Estados UnidosFil: Zhang, Chuansheng. Baylor College of Medicine; Estados UnidosFil: Huang, Claire Yu Mei. Baylor College of Medicine; Estados UnidosFil: Tsai, Chang Ru. Baylor College of Medicine; Estados UnidosFil: Galiano, Mauricio Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina. Baylor College of Medicine; Estados UnidosFil: Liu, Yanhong. Baylor College of Medicine; Estados UnidosFil: Benusa, Savannah D.. Virginia Commonwealth University; Estados UnidosFil: Yermakov, Leonid M.. Wright State University; Estados UnidosFil: Griggs, Ryan B.. Wright State University; Estados UnidosFil: Dupree, Jeffrey L.. Virginia Commonwealth University; Estados UnidosFil: Rasband, Matthew N.. Baylor College of Medicine; Estados Unido

Transport of Surface States in the Bulk Quantum Hall Effect

The two-dimensional surface of a coupled multilayer integer quantum Hall system consists of an anisotropic chiral metal. This unusual metal is characterized by ballistic motion transverse and diffusive motion parallel (\hat{z}) to the magnetic field. Employing a network model, we calculate numerically the phase coherent two-terminal z-axis conductance and its mesoscopic fluctuations. Quasi-1d localization effects are evident in the limit of many layers. We consider the role of inelastic de-phasing effects in modifying the transport of the chiral surface sheath, discussing their importance in the recent experiments of Druist et al.Comment: 9 pages LaTex, 9 postscript figures included using eps

A Conformal Field Theory for Eternal Inflation

We study a statistical model defined by a conformally invariant distribution of overlapping spheres in arbitrary dimension d. The model arises as the asymptotic distribution of cosmic bubbles in d+1 dimensional de Sitter space, and also as the asymptotic distribution of bubble collisions with the domain wall of a fiducial "observation bubble" in d+2 dimensional de Sitter space. In this note we calculate the 2-,3-, and 4-point correlation functions of exponentials of the "bubble number operator" analytically in d=2. We find that these correlators, when carefully defined, are free of infrared divergences, covariant under the global conformal group, charge conserving, and transform with positive conformal dimensions that are related in a novel way to the charge. Although by themselves these operators probably do not define a full-fledged conformal field theory, one can use the partition function on a sphere to compute an approximate central charge in the 2D case. The theory in any dimension has a noninteracting limit when the nucleation rate of the bubbles in the bulk is very large. The theory in two dimensions is related to some models of continuum percolation, but it is conformal for all values of the tunneling rate.Comment: 30 pages, 8 figure

Methods and apparatus for extraction and tracking of objects from multi-dimensional sequence data

An object tracking technique is provided which, given: (i) a potentially large data set; (ii) a set of dimensions along which the data has been ordered; and (iii) a set of functions for measuring the similarity between data elements, a set of objects are produced. Each of these objects is defined by a list of data elements. Each of the data elements on this list contains the probability that the data element is part of the object. The method produces these lists via an adaptive, knowledge-based search function which directs the search for high-probability data elements. This serves to reduce the number of data element combinations evaluated while preserving the most flexibility in defining the associations of data elements which comprise an object

Noninflammatory Changes of Microglia Are Sufficient to Cause Epilepsy.

Microglia are well known to play a critical role in maintaining brain homeostasis. However, their role in epileptogenesis has yet to be determined. Here, we demonstrate that elevated mTOR signaling in mouse microglia leads to phenotypic changes, including an amoeboid-like morphology, increased proliferation, and robust phagocytosis activity, but without a significant induction of pro-inflammatory cytokines. We further provide evidence that these noninflammatory changes in microglia disrupt homeostasis of the CNS, leading to reduced synapse density, marked microglial infiltration into hippocampal pyramidal layers, moderate neuronal degeneration, and massive proliferation of astrocytes. Moreover, the mice thus affected develop severe early-onset spontaneous recurrent seizures (SRSs). Therefore, we have revealed an epileptogenic mechanism that is independent of the microglial inflammatory response. Our data suggest that microglia could be an opportune target for epilepsy prevention