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BackgroundWe sought to describe trends in extracorporeal membrane oxygenation (ECMO) use, and define the impact on PGD incidence and early mortality in lung transplantation.MethodsPatients were enrolled from August 2011 to June 2018 at 10 transplant centers in the multi-center Lung Transplant Outcomes Group prospective cohort study. PGD was defined as Grade 3 at 48 or 72 hours, based on the 2016 PGD ISHLT guidelines. Logistic regression and survival models were used to contrast between group effects for event (i.e., PGD and Death) and time-to-event (i.e., death, extubation, discharge) outcomes respectively. Both modeling frameworks accommodate the inclusion of potential confounders.ResultsA total of 1,528 subjects were enrolled with a 25.7% incidence of PGD. Annual PGD incidence (14.3%-38.2%, p=.0002), median LAS (38.0-47.7 p=.009) and the use of ECMO salvage for PGD (5.7%-20.9%, p=.007) increased over the course of the study. PGD was associated with increased 1 year mortality (OR 1.7 [95% C.I. 1.2, 2.3], p=.0001). Bridging strategies were not associated with increased mortality compared to non-bridged patients (p=.66); however, salvage ECMO for PGD was significantly associated with increased mortality (OR 1.9 [1.3, 2.7], p=.0007). Restricted mean survival time comparison at 1-year demonstrated 84.1 days lost in venoarterial salvaged recipients with PGD when compared to those without PGD (ratio 1.3 [1.1, 1.5]) and 27.2 days for venovenous with PGD (ratio 1.1 [1.0, 1.4]).ConclusionsPGD incidence continues to rise in modern transplant practice paralleled by significant increases in recipient severity of illness. Bridging strategies have increased but did not affect PGD incidence or mortality. PGD remains highly associated with mortality and is increasingly treated with salvage ECMO.

OBJECTIVE To examine whether proximal sesamoid bone (PSB) articular cartilage and bone osteoarthritic changes or palmar osteochondral disease (POD) scores were associated with exercise history and catastrophic PSB fracture in Thoroughbred racehorses. SAMPLE PSBs from 16 Thoroughbred racehorses (8 with and 8 without PSB fracture). PROCEDURES Exercise history was collected, and total career high-speed furlongs was used as the measure of total exercise per horse. At necropsy, medial and lateral condyles of the third metacarpus from each forelimb were assigned a POD score, followed by imaging with micro-CT for evaluation of osteophyte size. Three investigators that were blinded to the type of PSB (fracture or no fracture) used the Osteoarthritis Research Society International (OARSI) scoring system to evaluate acellularity, chondrocyte necrosis, cartilage fibrillation, chondrone formation, safranin O stain uptake, and tidemark advancement of 1 central sagittal tissue section/PSB (4 PSBs/horse). Cartilage thickness and bone necrosis were scored on the basis of histologic examination. RESULTS POD score, osteophyte size score, percentage of bone necrosis, tidemark advancement, chondrone formation, and total OARSI score were greater in horses with more accrued total career high-speed furlongs. Scores for POD, osteophyte size, fibrillation, acellularity, chondrone formation, and total OARSI were greater for horses with PSB fracture. CONCLUSIONS AND CLINICAL RELEVANCE OARSI scoring revealed that more advanced osteoarthritic changes strongly correlated with total career high-speed furlongs and PSB fracture. However, the effect of exercise was dominant, suggesting that exercise history will be important to include in future models that aim to assess risk factors for catastrophic PSB fracture.

BACKGROUND Proximal sesamoid bone (PSB) fractures are the most common fatal musculoskeletal injury in North American racehorses. Computed tomography has the potential to detect morphological changes in bone structure but can be challenging to analyse reliably and quantitatively. OBJECTIVES To develop a radiomics platform that allows the comparison of features from micro-CTs (µCT) of PSBs in horses that sustained catastrophic fractures with horses that did not. To compare features calculated with a radiomics approach with features calculated from a previously published study that used quantitative µCT in the same specimens. STUDY DESIGN Retrospective study of cadaver specimens of µCT images of PSBs using prospectively applied radiomics. METHODS Radiomics features were computed on standardised CT datasets to benchmark the software. Features from µCT images of PSBs from eight horses that sustained PSB fracture and eight controls were computed using the contralateral, intact forelimb from horses sustaining PSB fracture (cases, n = 19) and all available forelimbs for controls (n = 30). Two-hundred and fifteen radiomic features were calculated, and similar or comparable features were compared with those reported in a previous study that used the same specimens. RESULTS Morphologic features computed with the radiomics approach, such as volume, minor axis dimensions and anisotropy were highly correlated with previously published data. A high number of imperceptible radiomic features, such as entropy, coarseness and histogram features were also found to be significantly different (P

Neurofilaments are structural proteins that are concentrated in the body and axons of neurons. Damage to the neurons or axons as a result of trauma or infectious diseases leads to the release of neurofilaments into blood and cerebrospinal fluid (CSF). This case-control study was carried out to compare serum levels of phosphorylated neurofilament heavy chain (pNF-H) between clinically healthy Thoroughbred (TB) horses and TB horses that suffered catastrophic musculoskeletal injuries (cMSI), and to investigate the correlation between putative risk factors and serum concentrations of pNF-H in injured horses. Blood samples were collected from clinically healthy horses and from horses that suffered cMSI. The concentration of pNF-H in serum samples was determined using the Phosphorylated Neurofilament H Sandwich enzyme-linked immunosorbent assay kit. A total of 343 horses were enrolled in the study (148 cases and 195 controls). The median serum concentration of pNF-H for controls was 0.0 ng/ml and for cases was 0.07 ng/ml. No significant difference was observed between the 2 groups in racing. The number of lifetime starts was correlated with serum pNF-H concentration in case horses. The serum concentration of pNF-H was higher in case horses that experienced cMSI while training than while racing. The number of lifetime starts is a proxy measure for several risk factors related to cumulative exercise load during the career of racehorses. Measurement of serum concentrations of pNF-H in TB racehorses does not support the hypothesis that subclinical neurologic injury or conditions are associated with catastrophic injury of TB racehorses.

Neurofilaments heavy chain proteins (pNF-H) have been identified as useful serum biomarkers for humans and animals with neurologic conditions, some of which can lead to poor performance, and athletic injuries. However, there are no published reports that describe a reference range for serum pNF-H levels in healthy racehorses. This cross-sectional study was carried out to determine the serum concentration of pNF-H in 1,349 samples collected from 1,291 clinically healthy standardbred (SB) racehorses. Data on age, time of sampling (pre-race or post-race), and finishing position during a race were collected. The concentration of pNF-H in serum samples was determined using an enzyme-linked immunosorbent assay (ELISA). The appropriate statistical techniques were used to determine the median serum concentration of pNF-H in these horses, if the serum concentration of pNF-H changed with age, if there were changes in the serum concentration of pNF-H during a race, and if there was an association between serum concentration of pNF-H, and the finishing position for the horse. The median serum concentration of pNF-H in this group of clinically healthy SB horses was 0.0 ng/mL. The concentration of pNF-H in serum was not associated with the age of the horses in this study as was determined by regression analysis. There was no significant change in the serum concentration of pNF-H before and after a race in paired samples. There was no association of serum concentration of pNF-H and the finishing position of the horses after the race. The data from this study supports use of0.412 ng/mL as a reference interval for measurement of serum levels of pNF-H in SB racehorses as 95% of the collected samples fell into the range 0.0-0.412 ng/mL.

Introduction: Histone Deacetylase 3 (HDAC3) is a Class I member of the histone deacetylase family that is recruited to nuclear enhancers. HDAC3 is located within the cell nucleus, where it constitutes the sole endogenous HDAC interacting with the nuclear-receptor corepressor complex containing NCOR and SMRT (NCOR2). As such, HDAC3 has a unique role in modulating the transcriptional activity of nuclear receptors. We have previously demonstrated its involvement in the inflammatory response in Lipopolysaccharide A (LPS)-stimulated human MH-S alveolar macrophages in vitro, and its interaction with pro-inflammatory IL-12 and anti-inflammatory IL-10. Similarly, our previous work using the broad spectrum HDAC inhibitor trichostatin A has demonstrated therapeutic efficacy reducing the pathogenesis of acute gram negative pneumonia in-vivo. With the current project, we aim to identify the HDAC3 interactome in LPS-stimulated human pulmonary epithelial cells type II (A549), the first immune defense in pathogens invading the lungs. Methods: Human A549 cells were transfected with a BioID2-tagged HDAC3 plasmid, and were divided in three groups: a. Untreated, b. stimulated with LPS, and c. stimulated with LPS and treated with Entinostat (MS275, a HDAC1/3 inhibitor). Cells were lysed, and total and biotinylated protein were submitted for quantitative Liquid Chromatography/Mass Spectrometry analysis to identify the peptides that directly bind with HDAC3. Data were searched against the Swiss Protein Human database, and False Discovery Rate (FDR) was set at 1%. Results: The dataset yielded 395,776 peptide matches. After peptide sequencing by database searching and validation, and FDR exclusion, we identified 2,666 proteins. Of these, 33 have been annotated to function in the NF-kB signaling pathway and/or NF-kB-regulated transcriptional activity.Conclusion: Protein acetylation is a reversible post-translational modification that is known to stabilize protein structure and modify function and localization. With the current project we have identified several potential proteins in the HDAC3 interactome that may be targeted early in the NF-κB activation process to disrupt HDAC3-substrate interaction and potentially downstream signaling. Nuclear activation of NF-κB is known to be involved in the early stages of Acute Respiratory Distress Syndrome and is a target of intense study for the development of novel therapeutics.

A longitudinal retrospective study was carried out to investigate the attrition of Thoroughbred (TB) and Standardbred (SB) horses racing at New York racetracks during the 2016 to 2019 seasons. The data were collected from the New York State Gaming Commission (NYSGC) Equine Breakdown, Death, Injury and Incident (EBDII), The Jockey Club InCompass Solutions, and The United States Trotting Association Pathway databases. Survival analysis was used to compare the predisposing factors by breed of the horse. The study included 431 horses (360 TB and 71 SB). There was a significant difference between the average incidence of attrition events per start for TB (0.304) and SB (0.035) horses. There was a significant difference in the median age to attrition between TB (4.2 years) and SB (7.5 years) horses. There was also a significant difference between the average number of starts to attrition for TB (13.6) and SB (125.5) horses. Among the causes of attrition events in the two breeds musculoskeletal injuries and medical conditions were significantly higher among TB horses, while sudden death was significantly higher among SB horses. The multivariate analysis showed that the hazard of attrition was affected by the age of the horse, age at first start, whether the horse was intact male, type of activity (racing training or other) and the breed of the horse. SB horses were less likely to experience attrition events in comparison to TB horses.

Conventional track circuit condition monitoring systems are fixed at the wayside, with each installation reporting on a single track circuit. In this work, we present a custom-built, sensitive, magnetic field detection system, which can be fitted to the underside of a rail vehicle. With this system installed, some characteristics of an operating track circuit can be monitored from the vehicle whilst it is in motion. By using appropriate analysis techniques, it is possible to identify the signatures of equipment relating to audio frequency track circuits, the topic of this work. Analysing the signatures of track circuit equipment demonstrated that there were clear differences between track circuit assets. By building on other research into the behaviours of failing track circuits, and continuing to conduct this research, the authors believe that it is possible, and beneficial, to perform condition monitoring of track circuits from low-cost equipment mounted on the train. Coupling this with advanced analysis techniques will allow predictive maintenance of track circuits with very little capital outlay.

BACKGROUND Fracture of the proximal sesamoid bones continues to be the most common fatal musculoskeletal injury in US racehorses. Identifying factors that influence fracture risk could lead to screening techniques to reduce catastrophic injury rates and improve animal welfare. OBJECTIVES To identify morphological differences between proximal sesamoid bones of the contralateral limb of fracture and control horses and assess the feasibility of computed tomography (CT) to detect traits associated with proximal sesamoid bone fracture. We hypothesised that horses with proximal sesamoid bone fracture would have greater bone density. STUDY DESIGN Cross-sectional cadaver morphological study. METHODS Proximal sesamoid bone morphology was measured using high-resolution micro-CT images from 16 Thoroughbred racehorses (eight fracture, eight control) euthanised on New York racetracks. Nominal logistic regression models and receiver operating characteristic curves were created to assess the ability of CT-derived morphological traits to accurately classify fracture horses vs. controls. RESULTS Bone volume fraction was greater in the fracture group (90.39 ± 1.76%) as compared to controls (87.20 ± 2.79%, P

Though it is well understood that all internal upheaval within a polity is a consequence of agency interacting with structure, the importance of the former has perhaps become too pushed to the rear...

The insurgent movement that calls itself the Communist Party of Peru Partido Comunista del Peru (PCP) and is called by others Shining Path is both a paradox and an anachronism. Shining Path had its origins in 1962 and 1963, in the provincial Ayacucho organization of Peru's then single-line Communist Party. The PCP, Shining Path, Guzman holds, is following the correct communist line almost alone and will eventually be vindicated by revolutionary triumph in Peru. Shining Path, in effect, pursues ideology at the expense of reality, convinced that its own "scientific interpretation of history" represents the real interests of the proletariat and will inevitably triumph. The United States government played a significant role in this process out of concern for Peru's domestic crises, including the insurgency, and committed some $90 million in economic and military assistance as well. Expenses may include some arms brought in by the mostly Colombian drug smuggling planes.

Neurofilaments (NFs) are structural proteins of neurons that are released in significant quantities in the cerebrospinal fluid and blood as a result of neuronal degeneration or axonal damage. Therefore, NFs have potential as biomarkers for neurologic disorders. Neural degeneration increases with age and has the potential to confound the utility of NFs as biomarkers in the diagnosis of neurologic disorders. We investigated this relationship in horses with and without neurological diagnosis. While controlling for horse type (draft, pleasure, and racing), we evaluated the relationship between serum heavy-chain phosphorylated neurofilaments (pNF-H) and age, sex, and serum vitamin E concentrations. Serum pNF-H concentrations increased by 0.002 ng/ml for each year increase in age. There were significant differences in the serum pNF-H concentration among the type of activity performed by the horse. The highest serum pNF-H concentration was found in horses performing heavy work activity (racehorse) and with lower serum pNF-H concentration found among light (pleasure riding) and moderate (draft) activity. There was no significant association between the pNF-H concentration and sex or vitamin E concentration. Serum pNF-H concentration was elevated among horses afflicted with EMND and EPM when compared with control horses without evidence of neurologic disorders. Accordingly, serum pNF-H concentration can serve as a useful biomarker to complement the existing diagnostic work-up of horses suspected of having EPM or EMND.

Postmortem evaluation of racehorses has focused primarily on musculoskeletal injuries; however, horses also die suddenly on the track (sudden death [SD]). Although cardiac conditions are frequently suspected as a cause of death, SD racehorses are often autopsy negative; however, previous studies have been limited due to inconsistent or insufficient cardiac sampling and lack of controls. SD in New York (NY) and Maryland (MD) racehorses was evaluated in an observational case vs control study comparing clinical information, postmortem evaluation including cardiac dissection, and cardiac conduction system histopathology. In the study period, there were 40 cases of SD. In NY, SD occurred in 12% (37/316) of submissions, and 36 (11%) cases of SD were exercise associated (EASD); 3 EASD cases occurred in MD. In NY/MD EASD cases with histologic examination of the heart, 11 of 36 (31%) had significant lesions, including mesenteric artery rupture (1), axial trauma (2), systemic inflammation (2), pulmonary hemorrhage (1), and cardiac disease (5). Mild myocardial fibrosis, mild inflammation, coronary arteriosclerosis, and variation in cardiac nodal connective tissue were present in both SD cases and controls and thus were not considered to be causes of SD. While not excluding a genetic basis for SD, analysis of the genotypes (GGP Equine 70 K Array) of cases and controls did not reveal significant differences in allele frequencies at any locus. Most SD racehorses were autopsy negative; further research using standardized protocols and controls is needed to understand the underlying causes of SD, which is crucial to protecting the viability of racing.