Experimental Spinal Cord Injury Models in Rodents: Anatomical Correlations and Assessment of Motor Recovery

Human traumatic spinal cord injury (SCI) causes disruption of descending motor and ascending sensory tracts, which leads to severe disturbances in motor functions. To date, no standard therapy for the regeneration of severed spinal cord axons in humans exists. Experimental SCI in rodents is essential for the development of new treatment strategies and for understanding the underlying mechanisms leading to motor recovery. Here, we provide an overview of the main rodent models and techniques available for the investigation of neuronal regeneration and motor recovery after experimental SCI

Cortical Gene Expression in Spinal Cord Injury and Repair: Insight into the Functional Complexity of the Neural Regeneration Program

Traumatic spinal cord injury (SCI) results in the formation of a fibrous scar acting as a growth barrier for regenerating axons at the lesion site. We have previously shown (Klapka et al., 2005) that transient suppression of the inhibitory lesion scar in rat spinal cord leads to long distance axon regeneration, retrograde rescue of axotomized cortical motoneurons, and improvement of locomotor function. Here we applied a systemic approach to investigate for the first time specific and dynamic alterations in the cortical gene expression profile following both thoracic SCI and regeneration-promoting anti-scarring treatment (AST). In order to monitor cortical gene expression we carried out microarray analyses using total RNA isolated from layer V/VI of rat sensorimotor cortex at 1–60 days post-operation (dpo). We demonstrate that cortical neurons respond to injury by massive changes in gene expression, starting as early as 1 dpo. AST, in turn, results in profound modifications of the lesion-induced expression profile. The treatment attenuates SCI-triggered transcriptional changes of genes related to inhibition of axon growth and impairment of cell survival, while upregulating the expression of genes associated with axon outgrowth, cell protection, and neural development. Thus, AST not only modifies the local environment impeding spinal cord regeneration by reduction of fibrous scarring in the injured spinal cord, but, in addition, strikingly changes the intrinsic capacity of cortical pyramidal neurons toward enhanced cell maintenance and axonal regeneration

Pre-Existing Superbubbles as the Sites of Gamma-Ray Bursts

According to recent models, gamma-ray bursts apparently explode in a wide variety of ambient densities ranging from ~ 10^{-3} to 30 cm^{-3}. The lowest density environments seem, at first sight, to be incompatible with bursts in or near molecular clouds or with dense stellar winds and hence with the association of gamma-ray bursts with massive stars. We argue that low ambient density regions naturally exist in areas of active star formation as the interiors of superbubbles. The evolution of the interior bubble density as a function of time for different assumptions about the evaporative or hydrodynamical mass loading of the bubble interior is discussed. We present a number of reasons why there should exist a large range of inferred afterglow ambient densities whether gamma-ray bursts arise in massive stars or some version of compact star coalescence. We predict that many gamma-ray bursts will be identified with X-ray bright regions of galaxies, corresponding to superbubbles, rather than with blue localized regions of star formation. Massive star progenitors are expected to have their own circumstellar winds. The lack of evidence for individual stellar winds associated with the progenitor stars for the cases with afterglows in especially low density environments may imply low wind densities and hence low mass loss rates combined with high velocities. If gamma-ray bursts are associated with massive stars, this combination might be expected for compact progenitors with atmospheres dominated by carbon, oxygen or heavier elements, that is, progenitors resembling Type Ic supernovae.Comment: 14 pages, no figures, submitted to The Astrophysical Journa

The Borexino Thermal Monitoring & Management System and simulations of the fluid-dynamics of the Borexino detector under asymmetrical, changing boundary conditions

A comprehensive monitoring system for the thermal environment inside the Borexino neutrino detector was developed and installed in order to reduce uncertainties in determining temperatures throughout the detector. A complementary thermal management system limits undesirable thermal couplings between the environment and Borexino's active sections. This strategy is bringing improved radioactive background conditions to the region of interest for the physics signal thanks to reduced fluid mixing induced in the liquid scintillator. Although fluid-dynamical equilibrium has not yet been fully reached, and thermal fine-tuning is possible, the system has proven extremely effective at stabilizing the detector's thermal conditions while offering precise insights into its mechanisms of internal thermal transport. Furthermore, a Computational Fluid-Dynamics analysis has been performed, based on the empirical measurements provided by the thermal monitoring system, and providing information into present and future thermal trends. A two-dimensional modeling approach was implemented in order to achieve a proper understanding of the thermal and fluid-dynamics in Borexino. It was optimized for different regions and periods of interest, focusing on the most critical effects that were identified as influencing background concentrations. Literature experimental case studies were reproduced to benchmark the method and settings, and a Borexino-specific benchmark was implemented in order to validate the modeling approach for thermal transport. Finally, fully-convective models were applied to understand general and specific fluid motions impacting the detector's Active Volume.Comment: arXiv admin note: substantial text overlap with arXiv:1705.09078, arXiv:1705.0965

Development and validation of colorectal cancer risk prediction tools:A comparison of models

Background: Identification of individuals at elevated risk can improve cancer screening programmes by permitting risk-adjusted screening intensities. Previous work introduced a prognostic model using sex, age and two preceding faecal haemoglobin concentrations to predict the risk of colorectal cancer (CRC) in the next screening round. Using data of 3 screening rounds, this model attained an area under the receiver-operating-characteristic curve (AUC) of 0.78 for predicting advanced neoplasia (AN). We validated this existing logistic regression (LR) model and attempted to improve it by applying a more flexible machine-learning approach. Methods: We trained an existing LR and a newly developed random forest (RF) model using updated data from 219,257 third-round participants of the Dutch CRC screening programme until 2018. For both models, we performed two separate out-of-sample validations using 1,137,599 third-round participants after 2018 and 192,793 fourth-round participants from 2020 onwards. We evaluated the AUC and relative risks of the predicted high-risk groups for the outcomes AN and CRC. Results: For third-round participants after 2018, the AUC for predicting AN was 0.77 (95% CI: 0.76–0.77) using LR and 0.77 (95% CI: 0.77–0.77) using RF. For fourth-round participants, the AUCs were 0.73 (95% CI: 0.72–0.74) and 0.73 (95% CI: 0.72–0.74) for the LR and RF models, respectively. For both models, the 5% with the highest predicted risk had a 7-fold risk of AN compared to average, whereas the lowest 80% had a risk below the population average for third-round participants. Conclusion: The LR is a valid risk prediction method in stool-based screening programmes. Although predictive performance declined marginally, the LR model still effectively predicted risk in subsequent screening rounds. An RF did not improve CRC risk prediction compared to an LR, probably due to the limited number of available explanatory variables. The LR remains the preferred prediction tool because of its interpretability.</p

Delayed Intrathoracic Gastric Perforation After Obesity Surgery: A Severe Complication

We describe a case of a patient with an intrathoracic gastric perforation, 6 months after she underwent a gastric banding procedure for the treatment of morbid obesity. After an urgent laparotomy during which the stomach was replaced and oversewn, she recovered uneventfully. The possible mechanism of this severe complication is discussed

Guideline versus non-guideline based management of rectal cancer in octogenarians

The number of octogenarians with rectal adenocarcinoma is growing. Current guidelines seem difficult to apply on octogenarians which may result in non-adherence. The aim of this retrospective cohort study is to give insight in occurrence of treatment-related complications, hospitalisations and survival among octogenarians treated according to guidelines versus octogenarians treated otherwise. 108 octogenarians with rectal adenocarcinoma were identified by screening of medical records. 22 patients were excluded for treatment process analysis because of stage IV disease or unknown stage. Baseline characteristics, diagnostic process, received treatment, motivation for deviation from guidelines, complications, hospitalisations and date of death were documented. Patients were divided in two groups depending on adherence to treatment guidelines. Differences in baseline characteristics, treatment-related complications and survival between both groups were evaluated. Diagnosis and treatment according to guidelines occurred in 95 and 54% of the patients, respectively. When documented, patient's preference and comorbidities were major reasons to deviate from guidelines. 66% of patients who were treated according to guidelines experienced complications versus 34% of those treated otherwise (p = 0.02). After adjustment for differences in age and polypharmacy, this association was not significant. Patients treated according to the guideline had better survival 18 months after diagnosis (80 versus 56%, p = 0.02). Treating octogenarians with rectal cancer according to guidelines seem to lead to better overall survival, but may lead to a high risk of complications. This may jeopardise quality of life. More and prospective studies in octogenarians with rectal cancer are needed to customize guidelines for these patients

Longitudinal associations of sociodemographic, lifestyle, and clinical factors with alcohol consumption in colorectal cancer survivors up to 2 years post-diagnosis

Purpose Alcohol consumption can lead to worse prognosis and mortality among colorectal cancer (CRC) patients. We investigated alcohol consumption of CRC survivors up to 2 years post-diagnosis, and how sociodemographic, lifestyle, and clinical factors were associated longitudinally with these habits. Methods We pooled longitudinal data of 910 CRC survivors from the ongoing PROCORE and EnCoRe studies with data collected at diagnosis (baseline) and 3, 6, 12, and 24 months post-diagnosis. Both studies assessed alcohol consumption, including beer, wine, and liquor. Generalized estimated equation models were used to examine changes over time in alcohol consumption and multivariable longitudinal associations of sociodemographic, lifestyle, and clinical factors with alcohol consumption. Results At baseline, participants were on average 67 years old, 332 (37%) were female, and alcohol was consumed by 79%. Most survivors (68-71%) drank less at all follow-ups. Beer, wine, and liquor were consumed by 51%, 58%, and 25% at baseline, respectively, and these declined over time. Males consumed more alcohol, and higher education, more physical activity, and not having a (permanent) stoma were associated with consuming more alcohol. Conclusion CRC survivors decreased their alcohol consumption in the 2 years post-diagnosis. Future studies should take the significant factors that were associated with alcohol post-diagnosis consumption into account, when they investigate CRC health outcomes or for identifying subgroups for interventions. Males with higher education, more physical activity, and no stoma should be reminded after diagnosis for reducing their alcohol consumption

On the use of fractional Brownian motion simulations to determine the 3D statistical properties of interstellar gas

Based on fractional Brownian motion (fBm) simulations of 3D gas density and velocity fields, we present a study of the statistical properties of spectro-imagery observations (channel maps, integrated emission, and line centroid velocity) in the case of an optically thin medium at various temperatures. The power spectral index gamma_W of the integrated emission is identified with that of the 3D density field (gamma_n) provided the medium's depth is at least of the order of the largest transverse scale in the image, and the power spectrum of the centroid velocity map is found to have the same index gamma_C as that of the velocity field (gamma_v). Further tests with non-fBm density and velocity fields show that this last result holds, and is not modified either by the effects of density-velocity correlations. A comparison is made with the theoretical predictions of Lazarian & Pogosyan (2000).Comment: 28 pages, 14 figures, accepted for publication in ApJ. For preprint with higher-resolution figures, see http://www.cita.utoronto.ca/~mamd/miville_fbm2003.pd