Anatomically-Informed Multiple Linear Assignment Problems for White Matter Bundle Segmentation

Segmenting white matter bundles from human tractograms is a task of interest for several applications. Current methods for bundle segmentation consider either only prior knowledge about the relative anatomical position of a bundle, or only its geometrical properties. Our aim is to improve the results of segmentation by proposing a method that takes into account information about both the underlying anatomy and the geometry of bundles at the same time. To achieve this goal, we extend a state-of-the-art example-based method based on the Linear Assignment Problem (LAP) by including prior anatomical information within the optimization process. The proposed method shows a significant improvement with respect to the original method, in particular on small bundles

Results of a planned interim toxicity analysis with trimodality therapy, including carboplatin AUC = 4, paclitaxel, 5-fluorouracil, amifostine, and radiation for locally advanced esophageal cancer: preliminary analyses and treatment recommendations from the North Central Cancer Treatment Group

PURPOSE: An aggressive trimodality approach from the Minnie Pearl Cancer Research Network [carboplatin AUC = 6, days 1 and 22; 5-fluorouracil 225 mg/m2 continuous infusion, days 1–42, paclitaxel 200 mg/m2, days 1 and 22; 45 Gy] has resulted in remarkable pathologic response rates but notable toxicity. This trial was designed to mitigate this toxicity by starting with a lower carboplatin dose, AUC = 4, and by adding subcutaneous amifostine. METHODS: This phase II trial included patients with locally advanced, potentially resectable esophageal cancer. All were to receive the above regimen with modifications of carboplatin AUC = 4 and amifostine 500 mg subcutaneously before radiation. All were then to undergo an esophagectomy. A planned interim toxicity analysis after the first 10 patients was to determine whether the carboplatin dose should escalate to AUC = 6. RESULTS: Ten patients were enrolled, and all required dose reductions/omissions during neoadjuvant therapy. One patient died from paclitaxel anaphylaxis. Six patients manifested a complete pathologic response. CONCLUSION: With this regimen, carboplatin AUC = 4 for patients with locally advanced esophageal cancer is appropriate

White matter alterations in glaucoma and monocular blindness differ outside the visual system

The degree to which glaucoma has effects in the brain beyond the eye and the visual pathways is unclear. To clarify this, we investigated white matter microstructure (WMM) in 37 tracts of patients with glaucoma, monocular blindness, and controls. We used brainlife.io for reproducibility. White matter tracts were subdivided into seven categories ranging from those primarily involved in vision (the visual white matter) to those primarily involved in cognition and motor control. In the vision tracts, WMM was decreased as measured by fractional anisotropy in both glaucoma and monocular blind subjects compared to controls, suggesting neurodegeneration due to reduced sensory inputs. A test-retest approach was used to validate these results. The pattern of results was different in monocular blind subjects, where WMM properties increased outside the visual white matter as compared to controls. This pattern of results suggests that whereas in the monocular blind loss of visual input might promote white matter reorganization outside of the early visual system, such reorganization might be reduced or absent in glaucoma. The results provide indirect evidence that in glaucoma unknown factors might limit the reorganization as seen in other patient groups following visual loss

Inter‐Group Social Behavior, Contact Patterns and Risk for Pathogen Transmission in Cape Buffalo Populations

In social species, the transmission and maintenance of infectious diseases depends on the contact patterns between individuals within groups and on the interactions between groups. In southern Africa, the Cape buffalo (Syncerus caffer caffer) is a vector for many pathogens that can infect sympatric livestock. Although intra-group contact patterns of Cape buffalo have been relatively well described, how groups interact with each other and risks for pathogen transmission remain poorly understood. We identified and compared spatial behavior and contact patterns between neighboring groups of Cape buffalo under contrasting environments: within the seasonally flooded environment of the Okavango Delta in Botswana and the semi-arid environment of northern Kruger National Park in South Africa. We used telemetry data collected between 2007 and 2015 from 10 distinct groups. We estimated seasonal overlap and proximity between home ranges of pairwise neighboring groups, and we quantified seasonal contact patterns between these groups. We defined contact patterns within variable spatiotemporal windows compatible with the transmission of diseases carried by the Cape buffalo: bovine tuberculosis, brucellosis, and Rift Valley fever (mosquito-borne transmission). We examined the effects of habitat and distance to water on contact location. In both study populations, neighboring buffalo groups were highly spatially segregated in the dry and rainy seasons. Inter-group contact patterns were characterized by very few direct and short-term indirect (within 0–2 days) contacts, lasting on average 1 hour and 2 hours, respectively. Contact patterns were generally consistent across populations and seasons, suggesting species-specific behavior. In the drier study site, the probability of indirect and vector-borne contacts generally decreased during the dry season with increasing distance to water. In the seasonally flooded area, only the probability of vector-borne contact decreased with increasing distance to water. Our results highlight the importance of dry season water availability in influencing the dynamics of indirectly transmitted Cape buffalo pathogens but only in areas with low water availability. The results from this study have important implications for future modeling of pathogen dynamics in a single host, and the ecology and management of Cape buffalo at the landscape level

Essential role of beta-adrenergic receptor kinase 1 in cardiac development and function

The beta-adrenergic receptor kinase 1 (beta ARK1) is a member of the G protein-coupled receptor kinase (GRK) family that mediates the agonist-dependent phosphorylation and desensitization of G protein-coupled receptors. We have cloned and disrupted the beta ARK1 gene in mice by homologous recombination. No homozygote beta ARK1-/- embryos survive beyond gestational day 15.5. Prior to gestational day 15.5, beta ARK1-/- embryos display pronounced hypoplasia of the ventricular myocardium essentially identical to the "thin myocardium syndrome" observed upon gene inactivation of several transcription factors (RXR alpha, N-myc, TEF-1, WT-1). Lethality in beta ARK1-/- embryos is likely due to heart failure as they exhibit a > 70% decrease in cardiac ejection fraction determined by direct in utero intravital microscopy. These results along with the virtual absence of endogenous GRK activity in beta ARK1-/- embryos demonstrate that beta ARK1 appears to be the predominant GRK in early embryogenesis and that it plays a fundamental role in cardiac development

Children's Oncology Group's 2013 blueprint for research: Nursing discipline

Integration of the nursing discipline within cooperative groups conducting pediatric oncology clinical trials provides unique opportunities to maximize nursing's contribution to clinical care, and to pursue research questions that extend beyond cure of disease to address important gaps in knowledge surrounding the illness experience. Key areas of importance to the advancement of the nursing discipline's scientific knowledge are understanding the effective delivery of patient/family education, and reducing illness‐related distress, both of which are integral to facilitating parental/child coping with the diagnosis and treatment of childhood cancer, and to promoting resilience and well‐being of pediatric oncology patients and their families. Pediatr Blood Cancer 2013; 60: 1031–1036. © 2012 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97507/1/24415_ftp.pd

Oxygen as a Driver of Early Arthropod Micro-Benthos Evolution

BACKGROUND: We examine the physiological and lifestyle adaptations which facilitated the emergence of ostracods as the numerically dominant Phanerozoic bivalve arthropod micro-benthos. METHODOLOGY/PRINCIPAL FINDINGS: The PO(2) of modern normoxic seawater is 21 kPa (air-equilibrated water), a level that would cause cellular damage if found in the tissues of ostracods and much other marine fauna. The PO(2) of most aquatic breathers at the cellular level is much lower, between 1 and 3 kPa. Ostracods avoid oxygen toxicity by migrating to waters which are hypoxic, or by developing metabolisms which generate high consumption of O(2). Interrogation of the Cambrian record of bivalve arthropod micro-benthos suggests a strong control on ecosystem evolution exerted by changing seawater O(2) levels. The PO(2) of air-equilibrated Cambrian-seawater is predicted to have varied between 10 and 30 kPa. Three groups of marine shelf-dwelling bivalve arthropods adopted different responses to Cambrian seawater O(2). Bradoriida evolved cardiovascular systems that favoured colonization of oxygenated marine waters. Their biodiversity declined during intervals associated with black shale deposition and marine shelf anoxia and their diversity may also have been curtailed by elevated late Cambrian (Furongian) oxygen-levels that increased the PO(2) gradient between seawater and bradoriid tissues. Phosphatocopida responded to Cambrian anoxia differently, reaching their peak during widespread seabed dysoxia of the SPICE event. They lacked a cardiovascular system and appear to have been adapted to seawater hypoxia. As latest Cambrian marine shelf waters became well oxygenated, phosphatocopids went extinct. Changing seawater oxygen-levels and the demise of much of the seabed bradoriid micro-benthos favoured a third group of arthropod micro-benthos, the ostracods. These animals adopted lifestyles that made them tolerant of changes in seawater O(2). Ostracods became the numerically dominant arthropod micro-benthos of the Phanerozoic. CONCLUSIONS/SIGNIFICANCE: Our work has implications from an evolutionary context for understanding how oxygen-level in marine ecosystems drives behaviour

Transcription forms and remodels supercoiling domains unfolding large-scale chromatin structures

DNA supercoiling is an inherent consequence of twisting DNA and is critical for regulating gene expression and DNA replication. However, DNA supercoiling at a genomic scale in human cells is uncharacterized. To map supercoiling we used biotinylated-trimethylpsoralen as a DNA structure probe to show the genome is organized into supercoiling domains. Domains are formed and remodeled by RNA polymerase and topoisomerase activities and are flanked by GC-AT boundaries and CTCF binding sites. Under-wound domains are transcriptionally active, enriched in topoisomerase I, “open” chromatin fibers and DNaseI sites, but are depleted of topoisomerase II. Furthermore DNA supercoiling impacts on additional levels of chromatin compaction as under-wound domains are cytologically decondensed, topologically constrained, and decompacted by transcription of short RNAs. We suggest that supercoiling domains create a topological environment that facilitates gene activation providing an evolutionary purpose for clustering genes along chromosomes

brainlife.io: A decentralized and open source cloud platform to support neuroscience research

Neuroscience research has expanded dramatically over the past 30 years by advancing standardization and tool development to support rigor and transparency. Consequently, the complexity of the data pipeline has also increased, hindering access to FAIR data analysis to portions of the worldwide research community. brainlife.io was developed to reduce these burdens and democratize modern neuroscience research across institutions and career levels. Using community software and hardware infrastructure, the platform provides open-source data standardization, management, visualization, and processing and simplifies the data pipeline. brainlife.io automatically tracks the provenance history of thousands of data objects, supporting simplicity, efficiency, and transparency in neuroscience research. Here brainlife.io's technology and data services are described and evaluated for validity, reliability, reproducibility, replicability, and scientific utility. Using data from 4 modalities and 3,200 participants, we demonstrate that brainlife.io's services produce outputs that adhere to best practices in modern neuroscience research