GLACIER NATIONAL PARK BAT INVENTORY AND MONITORING Project

Prior to 2011, no formal bat surveys had been conducted in Glacier National Park (GNP). Given concerns about high bat mortalities due to the continual spread of white-nose syndrome (WNS) and placement of wind energy facilities, it was critical to learn about GNP’s bat diversity, abundance, and distributions before these risks could potentially impact our populations. Of the 11 potential species in GNP, six are Montana (or potential) species of concern. Three years of surveys have now been completed. Survey techniques included mist-netting, acoustic surveys, bridge, building, and cave inspections. To date, we have mist-netted bats over 44 nights in 24 sample units (grid cells-each unit 10 km2) in GNP, processing a total of 700 individuals. Results indicated no sign of WNS. In addition, we conducted nighttime acoustic surveys at 97 different locations within 31 grid cells. Thus far, we have confirmed nine different bat species throughout the park and added three new bat species to the mammals list for GNP. Acoustic surveys have also confirmed the presence of hibernating bats in the winter. The two most commonly captured bats were the little brown myotis (Myotis lucifugus) and the hoary bat (Lasiurus cinereus). GNP may be one of the most substantial migratory routes for hoary bats across North America. Plans include continuing with the inventory phase by surveying additional grid cells using both acoustic and visual techniques, and focusing on long-term monitoring using acoustic sampling and systematic and repeatable counts of little brown bat maternity roosts

Data compression and regression based on local principal curves.

Frequently the predictor space of a multivariate regression problem of the type y = m(x_1, …, x_p ) + ε is intrinsically one-dimensional, or at least of far lower dimension than p. Usual modeling attempts such as the additive model y = m_1(x_1) + … + m_p (x_p ) + ε, which try to reduce the complexity of the regression problem by making additional structural assumptions, are then inefficient as they ignore the inherent structure of the predictor space and involve complicated model and variable selection stages. In a fundamentally different approach, one may consider first approximating the predictor space by a (usually nonlinear) curve passing through it, and then regressing the response only against the one-dimensional projections onto this curve. This entails the reduction from a p- to a one-dimensional regression problem. As a tool for the compression of the predictor space we apply local principal curves. Taking things on from the results presented in Einbeck et al. (Classification – The Ubiquitous Challenge. Springer, Heidelberg, 2005, pp. 256–263), we show how local principal curves can be parametrized and how the projections are obtained. The regression step can then be carried out using any nonparametric smoother. We illustrate the technique using data from the physical sciences

Runx1 deficiency permits granulocyte lineage commitment but impairs subsequent maturation

First-hits in the multi-hit process of leukemogenesis originate in germline or hematopoietic stem cells (HSCs), yet leukemia-initiating cells (LICs) usually have a lineage-committed phenotype. The molecular mechanisms underlying this compartment shift during leukemia evolution have not been a major focus of investigation and remain poorly understood. Here a mechanism underlying this shift was examined in the context of Runx1 deficiency, a frequent leukemia-initiating event. Lineage-negative cells isolated from the bone marrow of Runx1-haploinsufficient and wild-type control mice were cultured in granulocyte-colony-stimulating factor to force lineage commitment. Runx1-haploinsufficient cells demonstrated significantly greater and persistent exponential cell growth than wild-type controls. Not surprisingly, the Runx1-haploinsufficient cells were differentiation-impaired, by morphology and by flow-cytometric evaluation for granulocyte differentiation markers. Interestingly, however, this impaired differentiation was not because of decreased granulocyte lineage commitment, as RNA and protein upregulation of the master granulocyte lineage-commitment transcription factor Cebpa, and Hoxb4 repression, was similar in wild-type and Runx1-haploinsufficient cells. Instead, RNA and protein expression of Cebpe, a key driver of progressive maturation after lineage commitment, were significantly decreased in Runx1-haploinsufficient cells. Primary acute myeloid leukemia cells with normal cytogenetics and RUNX1 mutation also demonstrated this phenotype of very high CEBPA mRNA expression but paradoxically low expression of CEBPE, a CEBPA target gene. Chromatin-immunoprecipitation analyses suggested a molecular mechanism for this phenotype: in wild-type cells, Runx1 binding was substantially greater at the Cebpe than at the Cebpa enhancer. Furthermore, Runx1 deficiency substantially diminished high-level Runx1 binding at the Cebpe enhancer, but lower-level binding at the Cebpa enhancer was relatively preserved. Thus, Runx1-deficiency permits Cebpa upregulation and the exponential cell growth that accompanies lineage commitment, but by impairing activation of Cebpe, a key proliferation-terminating maturation gene, extends this exponential growth. These mechanisms facilitate germline cell or HSC of origin, yet evolution into LIC with lineage-committed phenotype.Fil: Ng, K. P.. Cleveland Clinic. Translational Hematology and Oncology Research; Estados UnidosFil: Hu, Z.. Cleveland Clinic. Translational Hematology and Oncology Research; Estados UnidosFil: Ebrahem, Q.. Cleveland Clinic. Translational Hematology and Oncology Research; Estados UnidosFil: Negrotto, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Cleveland Clinic. Translational Hematology and Oncology Research; Estados UnidosFil: Lausen, J.. Georg-Speyer-Haus, Institute for Biomedical Research; AlemaniaFil: Saunthararajah, Y.. Cleveland Clinic; Estados Unido

Data compression and regression based on local principal curves

Frequently the predictor space of a multivariate regression problem of the type y = m(x_1, …, x_p ) + ε is intrinsically one-dimensional, or at least of far lower dimension than p. Usual modeling attempts such as the additive model y = m_1(x_1) + … + m_p (x_p ) + ε, which try to reduce the complexity of the regression problem by making additional structural assumptions, are then inefficient as they ignore the inherent structure of the predictor space and involve complicated model and variable selection stages. In a fundamentally different approach, one may consider first approximating the predictor space by a (usually nonlinear) curve passing through it, and then regressing the response only against the one-dimensional projections onto this curve. This entails the reduction from a p- to a one-dimensional regression problem. As a tool for the compression of the predictor space we apply local principal curves. Taking things on from the results presented in Einbeck et al. (Classification – The Ubiquitous Challenge. Springer, Heidelberg, 2005, pp. 256–263), we show how local principal curves can be parametrized and how the projections are obtained. The regression step can then be carried out using any nonparametric smoother. We illustrate the technique using data from the physical sciences

The vascular bone marrow niche influences outcome in chronic myeloid leukemia via the E-selectin - SCL/TAL1-CD44 axis.

The endosteal bone marrow niche and vascular endothelial cells provide sanctuaries for leukemic cells. In murine chronic myeloid leukemia (CML) CD44 on leukemia cells and E-selectin on bone marrow endothelium are essential mediators for the engraftment of leukemic stem cells. We hypothesized that non-adhesion of CML-initiating cells to E-selectin on the bone marrow endothelium may lead to superior eradication of leukemic stem cells in CML after treatment with imatinib than imatinib alone. Indeed, here we show that treatment with the E-selectin inhibitor GMI-1271 in combination with imatinib prolongs survival of mice with CML via decreased contact time of leukemia cells with bone marrow endothelium. Non-adhesion of BCR-ABL1(+) cells leads to an increase of cell cycle progression and an increase of expression of the hematopoietic transcription factor and proto-oncogene Scl/Tal1 in leukemia-initiating cells. We implicate SCL/TAL1 as an indirect phosphorylation target of BCR-ABL1 and as a negative transcriptional regulator of CD44 expression. We show that increased SCL/TAL1 expression is associated with improved outcome in human CML. These data demonstrate the BCR-ABL1-specific, cell-intrinsic pathways leading to altered interactions with the vascular niche via the modulation of adhesion molecules - which could be exploited therapeutically in the future

Influence of Prior Imaging Information on Diagnostic Accuracy for Focal Skeletal Processes-A Retrospective Analysis of the Consistency between Biopsy-Verified Imaging Diagnoses

Introduction: Comparing imaging examinations with those previously obtained is considered mandatory in imaging guidelines. To our knowledge, no studies are available on neither the influence, nor the sequence, of prior imaging and reports on diagnostic accuracy using biopsy as the reference standard. Such data are important to minimize diagnostic errors and to improve the preparation of diagnostic imaging guidelines. The aim of our study was to provide such data. Materials and methods: A retrospective cohort of 216 consecutive skeletal biopsies from patients with at least 2 different imaging modalities (X-ray, CT and MRI) performed within 6 months of biopsy was identified. The diagnostic accuracy of the individual imaging modality was assessed. Finally, the possible influence of the sequence of imaging modalities was investigated. Results: No significant difference in the accuracy of the imaging modalities was shown, being preceded by another imaging modality or not. However, the sequence analyses indicate sequential biases, particularly if MRI was the first imaging modality. Conclusion: The sequence of the imaging modalities seems to influence the diagnostic accuracy against a pathology reference standard. Further studies are needed to establish evidence-based guidelines for the strategy of using previous imaging and reports to improve diagnostic accuracy

Bayesian analysis for mixtures of discrete distributions with a non-parametric component

Bayesian finite mixture modelling is a flexible parametric modelling approach for classification and density fitting. Many areas of application require distinguishing a signal from a noise component. In practice, it is often difficult to justify a specific distribution for the signal component; therefore, the signal distribution is usually further modelled via a mixture of distributions. However, modelling the signal as a mixture of distributions is computationally non-trivial due to the difficulties in justifying the exact number of components to be used and due to the label switching problem. This paper proposes the use of a non-parametric distribution to model the signal component. We consider the case of discrete data and show how this new methodology leads to more accurate parameter estimation and smaller false non-discovery rate. Moreover, it does not incur the label switching problem. We show an application of the method to data generated by ChIP-sequencing experiments

RUNX1/ETO blocks selectin-mediated adhesion via epigenetic silencing of PSGL-1

RUNX1/ETO (RE),the t(8;21)-derived leukemic transcription factor associated with acute myeloid leukemia (AML) development, deregulates genes involved in differentiation, self-renewal and proliferation. In addition, these cells show differences in cellular adhesion behavior whose molecular basis is not well understood. Here, we demonstrate that RE epigenetically silences the gene encoding P-Selectin Glycoprotein Ligand-1 (PSGL-1) and downregulates PSGL-1 expression in human CD34+ and murine lin-hematopoietic progenitor cells. Levels of PSGL-1 inversely and dose-dependently correlate with RE oncogene levels. However, a DNA-binding defective mutant fails to downregulate PSGL-1. We show by ChIP experiments that the PSGL-1 promoter is a direct target of RE and binding is accompanied by high levels of the repressive chromatin mark histone H3K27me3. In t(8;21)+ Kasumi-1 cells, PSGL-1 expression is completely restored at both the mRNA and cell surface protein levels following RE downregulation with short hairpin RNA (shRNA) or RE inhibition with tetramerization-blocking peptides, and at the promoter H3K27me3 is replaced by the activating chromatin mark H3K9ac as well as by RNA polymerase II. Upregulation of PSGL-1 restores the binding of cells to P- and E-selectin and re-establishes myeloid-specific cellular adhesion while it fails to bind to lymphocyte-specific L-selectin. Overall, our data suggest that the RE oncoprotein epigenetically represses PSGL-1 via binding to its promoter region and thus affects the adhesive behavior of t(8;21)+ AML cells

Working together to increase Australian children’s liking of vegetables: A position statement by the vegetable intake strategic alliance (VISA)

Children need to be repeatedly and consistently exposed to a variety of vegetables from an early age to achieve an increase in vegetable intake. A focus on enjoyment and learning to like eating vegetables at an early age is critical to forming favourable lifelong eating habits. Coordinated work is needed to ensure vegetables are available and promoted in a range of settings, using evidence-based initiatives, to create an environment that will support children’s acceptance of vegetables. This will help to facilitate increased intake, and ultimately realise the associated health benefits. The challenges and evidence base for a new approach are described

Modified Pilates as an adjunct to standardphysiotherapy care for urinaryincontinence: a mixed methods pilot for arandomised controlled trial

Background Urinary incontinence (UI) is a distressing condition affecting at least 5 million women in England and Wales. Traditionally, physiotherapy for UI comprises pelvic floor muscle training, but although evidence suggests this can be effective it is also recognised that benefits are often compromised by patient motivation and commitment. In addition, there is increasing recognition that physical symptoms alone are poor indicators of the impact of incontinence on individuals’ lives. Consequently, more holistic approaches to the treatment of UI, such as Modified Pilates (MP) have been recommended. This study aimed to provide preliminary findings about the effectiveness of a 6-week course of MP classes as an adjunct to standard physiotherapy care for UI, and to test the feasibility of a randomised controlled trial (RCT) design. Methods The study design was a single centre pilot RCT, plus qualitative interviews. 73 women referred to Women’s Health Physiotherapy Services for UI at Colchester Hospital University NHS Foundation Trust were randomly assigned to two groups: a 6-week course of MP classes in addition to standard physiotherapy care (intervention) or standard physiotherapy care only (control). Main outcome measures were self-reported UI, quality of life and self-esteem at baseline (T1), completion of treatment (T2), and 5 months after randomisation (T3). Qualitative interviews were conducted with a subgroup at T2 and T3. Due to the nature of the intervention blinding of participants, physiotherapists and researchers was not feasible. Results Post-intervention data revealed a range of benefits for women who attended MP classes and who had lower symptom severity at baseline: improved self-esteem (p = 0.032), decreased social embarrassment (p = 0.026) and lower impact on normal daily activities (p = 0.025). In contrast, women with higher symptom severity showed improvement in their personal relationships (p = 0.017). Qualitative analysis supported these findings and also indicated that MP classes could positively influence attitudes to exercise, diet and wellbeing. Conclusions A definitive RCT is feasible but will require a large sample size to inform clinical practice. Trial registration ISRCTN74075972 Registered 12/12/12 (Retrospectively registered)