The orientation and current density of the magnetotail current sheet: A statistical study of the effect of geomagnetic conditions

We examine the orientation and current density of the current sheet during current sheet crossings from Cluster's 2001–2007 tail seasons. The curlometer technique is used to estimate the current density and is combined with Minimum Variance Analysis (MVA) to calculate the direction of the current sheet normal. The SYM-H and AE indices at the time of each crossing are employed to assess how the tilt angle (the angle the normal makes with the Z axis in the GSM YZ plane) and current density depend on geomagnetic conditions. Our results indicate a larger current sheet tilt in the YZ plane during intervals of stronger and/or more prolonged substorm activity, as indicated by the AE index. There is also evidence that when the ring current is enhanced during magnetic storms, the current sheet is less tilted even though the AE index is also disturbed. In addition larger current densities are seen during times of both magnetic storms and substorms, compared to crossings during only substorms and a quiet ring current. We conclude that increased substorm activity disrupts the current sheet structure resulting in greater motion of the current sheet (as found by Davey et al. (2012)) and a greater local tilt to the current sheet. We propose that the increased open flux in the tail during magnetic storms stabilizes the current sheet such that the tilt angle of the current sheet is reduced. The increased amount of open flux during magnetic storms also results in larger current densities within the current sheet

Altitude Distribution of the Auroral Acceleration Potential Determined from Cluster Satellite Data at Different Heights

Aurora, commonly seen in the polar sky, is a ubiquitous phenomenon occurring on Earth and other solar system planets. The colorful emissions are caused by electron beams hitting the upper atmosphere, after being accelerated by quasistatic electric fields at 1–2 RE altitudes, or by wave electric fields. Although aurora was studied by many past satellite missions, Cluster is the first to explore the auroral acceleration region with multiprobes. Here, Cluster data are used to determine the acceleration potential above the aurora and to address its stability in space and time. The derived potential comprises two upper, broad U-shaped potentials and a narrower S-shaped potential below, and is stable on a 5 min time scale. The scale size of the electric field relative to that of the current is shown to depend strongly on altitude within the acceleration region. To reveal these features was possible only by combining data from the two satellites

Toward optimal implementation of cancer prevention and control programs in public health: A study protocol on mis-implementation

Abstract Background Much of the cancer burden in the USA is preventable, through application of existing knowledge. State-level funders and public health practitioners are in ideal positions to affect programs and policies related to cancer control. Mis-implementation refers to ending effective programs and policies prematurely or continuing ineffective ones. Greater attention to mis-implementation should lead to use of effective interventions and more efficient expenditure of resources, which in the long term, will lead to more positive cancer outcomes. Methods This is a three-phase study that takes a comprehensive approach, leading to the elucidation of tactics for addressing mis-implementation. Phase 1: We assess the extent to which mis-implementation is occurring among state cancer control programs in public health. This initial phase will involve a survey of 800 practitioners representing all states. The programs represented will span the full continuum of cancer control, from primary prevention to survivorship. Phase 2: Using data from phase 1 to identify organizations in which mis-implementation is particularly high or low, the team will conduct eight comparative case studies to get a richer understanding of mis-implementation and to understand contextual differences. These case studies will highlight lessons learned about mis-implementation and identify hypothesized drivers. Phase 3: Agent-based modeling will be used to identify dynamic interactions between individual capacity, organizational capacity, use of evidence, funding, and external factors driving mis-implementation. The team will then translate and disseminate findings from phases 1 to 3 to practitioners and practice-related stakeholders to support the reduction of mis-implementation. Discussion This study is innovative and significant because it will (1) be the first to refine and further develop reliable and valid measures of mis-implementation of public health programs; (2) bring together a strong, transdisciplinary team with significant expertise in practice-based research; (3) use agent-based modeling to address cancer control implementation; and (4) use a participatory, evidence-based, stakeholder-driven approach that will identify key leverage points for addressing mis-implementation among state public health programs. This research is expected to provide replicable computational simulation models that can identify leverage points and public health system dynamics to reduce mis-implementation in cancer control and may be of interest to other health areas

Cellular mechanisms by which proinsulin C-peptide prevents insulin-induced neointima formation in human saphenous vein

AIMS/HYPOTHESIS: Endothelial cells (ECs) and smooth muscle cells (SMCs) play key roles in the development of intimal hyperplasia in saphenous vein (SV) bypass grafts. In diabetic patients, insulin administration controls hyperglycaemia but cardiovascular complications remain. Insulin is synthesised as a pro-peptide, from which C-peptide is cleaved and released into the circulation with insulin; exogenous insulin lacks C-peptide. Here we investigate modulation of human SV neointima formation and SV-EC and SV-SMC function by insulin and C-peptide. METHODS: Effects of insulin and C-peptide on neointima formation (organ cultures), EC and SMC proliferation (cell counting), EC migration (scratch wound), SMC migration (Boyden chamber) and signalling (immunoblotting) were examined. A real-time RT-PCR array identified insulin-responsive genes, and results were confirmed by real-time RT-PCR. Targeted gene silencing (siRNA) was used to assess functional relevance. RESULTS: Insulin (100 nmol/l) augmented SV neointimal thickening (70% increase, 14 days), SMC proliferation (55% increase, 7 days) and migration (150% increase, 6 h); effects were abrogated by 10 nmol/l C-peptide. C-peptide did not affect insulin-induced Akt or extracellular signal-regulated kinase signalling (15 min), but array data and gene silencing implicated sterol regulatory element binding transcription factor 1 (SREBF1). Insulin (1-100 nmol/l) did not modify EC proliferation or migration, whereas 10 nmol/l C-peptide stimulated EC proliferation by 40% (5 days). CONCLUSIONS/INTERPRETATION: Our data support a causative role for insulin in human SV neointima formation with a novel counter-regulatory effect of proinsulin C-peptide. Thus, C-peptide can limit the detrimental effects of insulin on SMC function. Co-supplementing insulin therapy with C-peptide could improve therapy in insulin-treated patients

Synergistic effects of oncolytic reovirus and docetaxel chemotherapy in prostate cancer

Reovirus type 3 Dearing (T3D) has demonstrated oncolytic activity in vitro, in in vivo murine models and in early clinical trials. However the true potential of oncolytic viruses may only be realized fully in combination with other modalities such as chemotherapy, targeted therapy and radiotherapy. In this study, we examine the oncolytic activity of reovirus T3D and chemotherapeutic agents against human prostate cancer cell lines, with particular focus on the highly metastatic cell line PC3 and the chemotherapeutic agent docetaxel. Docetaxel is the standard of care for metastatic prostate cancer and acts by disrupting the normal process of microtubule assembly and disassembly. Reoviruses have been shown to associate with microtubules and may require this association for efficient viral replication

Regulation of the IGFBP-5 and MMP-13 genes by the microRNAs miR-140 and miR-27a in human osteoarthritic chondrocytes

<p>Abstract</p> <p>Background</p> <p>MMP-13 and IGFBP-5 are important factors involved in osteoarthritis (OA). We investigated whether two highly predicted microRNAs (miRNAs), miR-140 and miR-27a, regulate these two genes in human OA chondrocytes.</p> <p>Methods</p> <p>Gene expression was determined by real-time PCR. The effect of each miRNA on IGFBP-5 and MMP-13 expression/production was evaluated by transiently transfecting their precursors (pre-miRNAs) and inhibitors (anti-miRNAs) into human OA chondrocytes. Modulation of IGFBP-5, miR-140 and miR-27a expression was determined upon treatment of OA chondrocytes with cytokines and growth factors.</p> <p>Results</p> <p>IGFBP-5 was expressed in human chondrocytes with its level significantly lower (p < 0.04) in OA. Five computational algorithms identified miR-140 and miR-27a as possible regulators of MMP-13 and IGFBP-5 expression. Data showed that both miRNAs were expressed in chondrocytes. There was a significant reduction (77%, p < 0.01) in miR-140 expression in OA compared to the normal chondrocytes, whereas miR-27a expression was only slightly decreased (23%). Transfection with pre-miR-140 significantly decreased (p = 0.0002) and with anti-miR-140 significantly increased (p = 0.05) IGFBP-5 expression at 24 hours, while pre-miR-27a did not affect either MMP-13 or IGFBP-5. Treatment with anti-miR-27a, but not with anti-miR-140, significantly increased the expression of both MMP-13 (p < 0.05) and IGFBP-5 (p < 0.01) after 72 hours of incubation. MMP-13 and IGFBP-5 protein production followed the same pattern as their expression profile. These data suggest that IGFBP-5 is a direct target of miR-140, whereas miR-27a down-regulates, likely indirectly, both MMP-13 and IGFBP-5.</p> <p>Conclusion</p> <p>This study is the first to show the regulation of these miRNAs in human OA chondrocytes. Their effect on two genes involved in OA pathophysiology adds another level of complexity to gene regulation, which could open up novel avenues in OA therapeutic strategies.</p

Effective healthcare teams require effective team members: defining teamwork competencies

BACKGROUND: Although effective teamwork has been consistently identified as a requirement for enhanced clinical outcomes in the provision of healthcare, there is limited knowledge of what makes health professionals effective team members, and even less information on how to develop skills for teamwork. This study identified critical teamwork competencies for health service managers. METHODS: Members of a state branch of the professional association of Australian health service managers participated in a teamwork survey. RESULTS: The 37% response rate enabled identification of a management teamwork competency set comprising leadership, knowledge of organizational goals and strategies and organizational commitment, respect for others, commitment to working collaboratively and to achieving a quality outcome. CONCLUSION: Although not part of the research question the data suggested that the competencies for effective teamwork are perceived to be different for management and clinical teams, and there are differences in the perceptions of effective teamwork competencies between male and female health service managers. This study adds to the growing evidence that the focus on individual skill development and individual accountability and achievement that results from existing models of health professional training, and which is continually reinforced by human resource management practices within healthcare systems, is not consistent with the competencies required for effective teamwork