By Shepherd, et all, posted on November 29th, 2013 in Articles, Climate

Earth is increasingly an “urbanized ” planet. The “World Population Clock ” registered a Population of 7,175,309,538 at 8:30 pm (LST) on Oct. 6, 2013. Current and future trends suggest that this population will increasingly reside in cities. Currently, 52 percent of the world population is urban, which means we are a majority “urbanized ” society. Figure 1 indicates this trend will continue, wit

A Canadian paediatric brain tumour consortium (CPBTC) phase II molecularly targeted study of imatinib in recurrent and refractory paediatric central nervous system tumours

PURPOSE: To evaluate the safety, efficacy and pharmacokinetics of imatinib in children with recurrent or refractory central nervous system (CNS) tumours expressing KIT and/or PDGFRA. METHODS: Nineteen patients aged 2-18 years, with recurrent or refractory CNS tumours expressing either of the target receptors KIT and/or PDGFRA (by immunohistochemistry) were eligible. Participants received imatinib orally at a dose of 440 mg/m(2)/day and toxicities and tumour responses were monitored. Serial blood and cerebrospinal fluid samples for pharmacokinetics were obtained in a subset of consenting patients. Frozen tumour samples were analysed retrospectively for KIT and PDGFRA gene amplification in a subset of patients for whom samples were available. RESULTS: Common toxicities were lymphopaenia, neutropaenia, leucopaenia, elevated serum transaminases and vomiting. No intratumoural haemorrhages were observed. Although there were no objective responses to imatinib, four patients had long-term stable disease (SD) (38-104 weeks). Our results suggest a possible relationship between KIT expression and maintenance of SD with imatinib treatment; KIT immunopositivity was seen in only 58% (11/19) of study participants overall, but in 100% of patients with SD at 38 weeks. All patient tumours showed PDGFRA expression. Pharmacokinetic data showed a high interpatient variability, but corresponded with previously reported values. CONCLUSIONS: Imatinib at 440 mg/m(2)/day is relatively safe in children with recurrent CNS tumours, but induced no objective responses. Demonstration of SD in previously progressing patients (KIT-expressing) suggests cytostatic activity of imatinib.info:eu-repo/semantics/publishedVersio

White and Gray Matter Abnormalities After Cranial Radiation in Children and Mice

PurposePediatric patients treated with cranial radiation are at high risk of developing lasting cognitive impairments. We sought to identify anatomical changes in both gray matter (GM) and white matter (WM) in radiation-treated patients and in mice, in which the effect of radiation can be isolated from other factors, the time course of anatomical change can be established, and the effect of treatment age can be more fully characterized. Anatomical results were compared between species.Methods and MaterialsPatients were imaged with T1-weighted magnetic resonance imaging (MRI) after radiation treatment. Nineteen radiation-treated patients were divided into groups of 7 years of age and younger (7−) and 8 years and older (8+) and were compared to 41 controls. C57BL6 mice were treated with radiation (n=52) or sham treated (n=52) between postnatal days 16 and 36 and then assessed with in vivo and/or ex vivo MRI. In both cases, measurements of WM and GM volume, cortical thickness, area and volume, and hippocampal volume were compared between groups.ResultsWM volume was significantly decreased following treatment in 7− and 8+ treatment groups. GM volume was unchanged overall, but cortical thickness was slightly increased in the 7− group. Results in mice mostly mirrored these changes and provided a time course of change, showing early volume loss and normal growth. Hippocampal volume showed a decreasing trend with age in patients, an effect not observed in the mouse hippocampus but present in the olfactory bulb.ConclusionsChanges in mice treated with cranial radiation are similar to those in humans, including significant WM and GM alterations. Because mice did not receive any other treatment, the similarity across species supports the expectation that radiation is causative and suggests mice provide a representative model for studying impaired brain development after cranial radiation and testing novel treatments

Visual Exploration and Object Recognition by Lattice Deformation

Mechanisms of explicit object recognition are often difficult to investigate and require stimuli with controlled features whose expression can be manipulated in a precise quantitative fashion. Here, we developed a novel method (called “Dots”), for generating visual stimuli, which is based on the progressive deformation of a regular lattice of dots, driven by local contour information from images of objects. By applying progressively larger deformation to the lattice, the latter conveys progressively more information about the target object. Stimuli generated with the presented method enable a precise control of object-related information content while preserving low-level image statistics, globally, and affecting them only little, locally. We show that such stimuli are useful for investigating object recognition under a naturalistic setting – free visual exploration – enabling a clear dissociation between object detection and explicit recognition. Using the introduced stimuli, we show that top-down modulation induced by previous exposure to target objects can greatly influence perceptual decisions, lowering perceptual thresholds not only for object recognition but also for object detection (visual hysteresis). Visual hysteresis is target-specific, its expression and magnitude depending on the identity of individual objects. Relying on the particular features of dot stimuli and on eye-tracking measurements, we further demonstrate that top-down processes guide visual exploration, controlling how visual information is integrated by successive fixations. Prior knowledge about objects can guide saccades/fixations to sample locations that are supposed to be highly informative, even when the actual information is missing from those locations in the stimulus. The duration of individual fixations is modulated by the novelty and difficulty of the stimulus, likely reflecting cognitive demand

Controlled Unclassified Information: Recommendations for Information Control Reform

Controlled Unclassified Information: Recommendations for Information Control Reform shines a light on how government withholds unclassified information from the American people and offers recommendations on how to balance the need to protect sensitive materials with the duty to disclose information to the public.The report walks the reader through some of the aspects of secrecy labeling and explains technical terms such as sensitive but unclassified (SBU) information and controlled unclassified information (CUI). The report also:Provides a brief history of secrecy labeling, including the origins of sensitive but unclassified informationExplores several critiques of information sharing in the secrecy labeling eraExplains efforts by the George W. Bush administration to streamline the secrecy labeling system through the implementation of a consolidated controlled unclassified information policyOffers recommendations to the Obama administration on how to minimize the use of controlled unclassified information labels while still safeguarding sensitive material

Influence of serum inflammatory cytokines on cytochrome P450 drug metabolising activity during breast cancer chemotherapy: a patient feasibility study.

Individual response to chemotherapy in patients with breast cancer is variable. Obesity and exercise are associated with better and worse outcomes, respectively, and it is known that both impact the systemic cytokine milieu. Cytochrome P450 (CYP) enzymes are responsible for the metabolism of many chemotherapy agents, and CYP enzyme activity has been shown to be modified by inflammatory cytokines in vitro and in vivo. Cytokine-associated changes in CYP metabolism may alter chemotherapy exposure, potentially affecting treatment response and patient survival. Therefore, better understanding of these biological relationships is required. This exploratory single arm open label trial investigated changes in in vivo CYP activity in twelve women treated for stage II or III breast cancer, and demonstrated for the first time the feasibility and safety of utilising the Inje phenotyping cocktail to measure CYP activity in cancer patients receiving chemotherapy. Relative CYP activity varied between participants, particularly for CYP2C9 and CYP2D6, and changes in serum concentrations of the inflammatory cytokine monocyte chemoattractant protein 1 inversely correlated to CYP3A4 activity during chemotherapy. Future use of phenotyping cocktails in a clinical oncology setting may help guide drug dosing and improve chemotherapy outcomes

Survival Following Tumor Recurrence in Children With Medulloblastoma

Medulloblastoma is the most common malignant brain tumor in children. Published survival rates for this tumor are ∼70%; however, there is limited published information on outcome after disease recurrence. This was an observational study which included all persons under the age of 18 years diagnosed with medulloblastoma from 1990 to 2009 inclusive in Canada. Data collected included date of diagnosis, age at diagnosis, sex, stage, pathology, treatment, recurrence, and current status. Survival rates were determined. In total, 550 cases were ascertained meeting the study criteria. The overall survival rate at 1 year was 83.6%±1.7%, at 3 years 77.2%±1.9%, and at 5 years 72.5%±20%. The progression-free survival rates were 78%±1.9%, 70%±2.1%, and 69±2.1% at 1, 3, and 5 years from initial diagnosis. In total, 173 (31.2%) were reported to have had tumor recurrence and 23 (11.4%) of them were alive at the time of survey with an overall survival rate at 1 year of 38.3%±4%, at 2 years of 16.9%±3.3%, and at 5 years of 12.4%±2.8%. Our data confirm that children with recurrent medulloblastoma have a poor prognosis, supporting the need for novel treatment approaches for this group

ROOD-MRI: Benchmarking the robustness of deep learning segmentation models to out-of-distribution and corrupted data in MRI

Deep artificial neural networks (DNNs) have moved to the forefront of medical image analysis due to their success in classification, segmentation, and detection challenges. A principal challenge in large-scale deployment of DNNs in neuroimage analysis is the potential for shifts in signal-to-noise ratio, contrast, resolution, and presence of artifacts from site to site due to variances in scanners and acquisition protocols. DNNs are famously susceptible to these distribution shifts in computer vision. Currently, there are no benchmarking platforms or frameworks to assess the robustness of new and existing models to specific distribution shifts in MRI, and accessible multi-site benchmarking datasets are still scarce or task-specific. To address these limitations, we propose ROOD-MRI: a novel platform for benchmarking the Robustness of DNNs to Out-Of-Distribution (OOD) data, corruptions, and artifacts in MRI. This flexible platform provides modules for generating benchmarking datasets using transforms that model distribution shifts in MRI, implementations of newly derived benchmarking metrics for image segmentation, and examples for using the methodology with new models and tasks. We apply our methodology to hippocampus, ventricle, and white matter hyperintensity segmentation in several large studies, providing the hippocampus dataset as a publicly available benchmark. By evaluating modern DNNs on these datasets, we demonstrate that they are highly susceptible to distribution shifts and corruptions in MRI. We show that while data augmentation strategies can substantially improve robustness to OOD data for anatomical segmentation tasks, modern DNNs using augmentation still lack robustness in more challenging lesion-based segmentation tasks. We finally benchmark U-Nets and vision transformers, finding robustness susceptibility to particular classes of transforms across architectures. The presented open-source platform enables generating new benchmarking datasets and comparing across models to study model design that results in improved robustness to OOD data and corruptions in MRI

Brain-CODE: A Secure Neuroinformatics Platform for Management, Federation, Sharing and Analysis of Multi-Dimensional Neuroscience Data

Historically, research databases have existed in isolation with no practical avenue for sharing or pooling medical data into high dimensional datasets that can be efficiently compared across databases. To address this challenge, the Ontario Brain Institute’s “Brain-CODE” is a large-scale neuroinformatics platform designed to support the collection, storage, federation, sharing and analysis of different data types across several brain disorders, as a means to understand common underlying causes of brain dysfunction and develop novel approaches to treatment. By providing researchers access to aggregated datasets that they otherwise could not obtain independently, Brain-CODE incentivizes data sharing and collaboration and facilitates analyses both within and across disorders and across a wide array of data types, including clinical, neuroimaging and molecular. The Brain-CODE system architecture provides the technical capabilities to support (1) consolidated data management to securely capture, monitor and curate data, (2) privacy and security best-practices, and (3) interoperable and extensible systems that support harmonization, integration, and query across diverse data modalities and linkages to external data sources. Brain-CODE currently supports collaborative research networks focused on various brain conditions, including neurodevelopmental disorders, cerebral palsy, neurodegenerative diseases, epilepsy and mood disorders. These programs are generating large volumes of data that are integrated within Brain-CODE to support scientific inquiry and analytics across multiple brain disorders and modalities. By providing access to very large datasets on patients with different brain disorders and enabling linkages to provincial, national and international databases, Brain-CODE will help to generate new hypotheses about the biological bases of brain disorders, and ultimately promote new discoveries to improve patient care