What are the fundamental modes of energy transfer and partitioning in the coupled Magnetosphere-Ionosphere system?

The fundamental processes responsible for energy exchange between large-scale electromagnetic fields and plasma are well understood theoretically, but in practice these theories have not been tested. These processes are ubiquitous in all plasmas, especially at the interface between high and low beta plasmas in planetary magnetospheres and other magnetic environments. Although such boundaries pervade the plasma Universe, the processes responsible for the release of the stored magnetic and thermal plasma energy have not been fully identified and the importance of the relative impact of each process is unknown. Despite advances in understanding energy release through the conversion of magnetic to kinetic energy in magnetic reconnection, how the extreme pressures in the regions between stretched and more relaxed field lines in the transition region are balanced and released through adiabatic convection of plasma and fields is still a mystery. Recent theoretical advances and the predictions of large-scale instabilities must be tested. In essence, the processes responsible remain poorly understood and the problem unresolved. The aim of the White Paper submitted to ESA's Voyage 2050 call, and the contents of this paper, is to highlight three outstanding open science questions that are of clear international interest: (i) the interplay of local and global plasma physics processes: (ii) the partitioning during energy conversion between electromagnetic and plasma energy: and (iii) what processes drive the coupling between low and high beta plasmas. We present a discussion of the new measurements and technological advances required from current state-of-the-art, and several candidate mission profiles with which these international high-priority science goals could be significantly advanced.Peer reviewe

Can computerized clinical decision support systems improve practitioners' diagnostic test ordering behavior? A decision-maker-researcher partnership systematic review

<p>Abstract</p> <p>Background</p> <p>Underuse and overuse of diagnostic tests have important implications for health outcomes and costs. Decision support technology purports to optimize the use of diagnostic tests in clinical practice. The objective of this review was to assess whether computerized clinical decision support systems (CCDSSs) are effective at improving ordering of tests for diagnosis, monitoring of disease, or monitoring of treatment. The outcome of interest was effect on the diagnostic test-ordering behavior of practitioners.</p> <p>Methods</p> <p>We conducted a decision-maker-researcher partnership systematic review. We searched MEDLINE, EMBASE, Ovid's EBM Reviews database, Inspec, and reference lists for eligible articles published up to January 2010. We included randomized controlled trials comparing the use of CCDSSs to usual practice or non-CCDSS controls in clinical care settings. Trials were eligible if at least one component of the CCDSS gave suggestions for ordering or performing a diagnostic procedure. We considered studies 'positive' if they showed a statistically significant improvement in at least 50% of test ordering outcomes.</p> <p>Results</p> <p>Thirty-five studies were identified, with significantly higher methodological quality in those published after the year 2000 (<it>p </it>= 0.002). Thirty-three trials reported evaluable data on diagnostic test ordering, and 55% (18/33) of CCDSSs improved testing behavior overall, including 83% (5/6) for diagnosis, 63% (5/8) for treatment monitoring, 35% (6/17) for disease monitoring, and 100% (3/3) for other purposes. Four of the systems explicitly attempted to reduce test ordering rates and all succeeded. Factors of particular interest to decision makers include costs, user satisfaction, and impact on workflow but were rarely investigated or reported.</p> <p>Conclusions</p> <p>Some CCDSSs can modify practitioner test-ordering behavior. To better inform development and implementation efforts, studies should describe in more detail potentially important factors such as system design, user interface, local context, implementation strategy, and evaluate impact on user satisfaction and workflow, costs, and unintended consequences.</p

DNA methylation and transcriptomic features are preserved throughout disease recurrence and chemoresistance in high grade serous ovarian cancers

BackgroundLittle is known about the role of global DNA methylation in recurrence and chemoresistance of high grade serous ovarian cancer (HGSOC).MethodsWe performed whole genome bisulfite sequencing and transcriptome sequencing in 62 primary and recurrent tumors from 28 patients with stage III/IV HGSOC, of which 11 patients carried germline, pathogenic BRCA1 and/or BRCA2 mutations.ResultsLandscapes of genome-wide methylation (on average 24.2 million CpGs per tumor) and transcriptomes in primary and recurrent tumors showed extensive heterogeneity between patients but were highly preserved in tumors from the same patient. We identified significant differences in the burden of differentially methylated regions (DMRs) in tumors from BRCA1/2 compared to non-BRCA1/2 carriers (mean 659 DMRs and 388 DMRs in paired comparisons respectively). We identified overexpression of immune pathways in BRCA1/2 carriers compared to non-carriers, implicating an increased immune response in improved survival (P = 0.006) in these BRCA1/2 carriers.ConclusionThese findings indicate methylome and gene expression programs established in the primary tumor are conserved throughout disease progression, even after extensive chemotherapy treatment, and that changes in methylation and gene expression are unlikely to serve as drivers for chemoresistance in HGSOC

What are the fundamental modes of energy transfer and partitioning in the coupled Magnetosphere-Ionosphere system?

The fundamental processes responsible for energy exchange between large-scale electromagnetic fields and plasma are well understood theoretically, but in practice these theories have not been tested. These processes are ubiquitous in all plasmas, especially at the interface between high and low beta plasmas in planetary magnetospheres and other magnetic environments. Although such boundaries pervade the plasma Universe, the processes responsible for the release of the stored magnetic and thermal plasma energy have not been fully identified and the importance of the relative impact of each process is unknown. Despite advances in understanding energy release through the conversion of magnetic to kinetic energy in magnetic reconnection, how the extreme pressures in the regions between stretched and more relaxed field lines in the transition region are balanced and released through adiabatic convection of plasma and fields is still a mystery. Recent theoretical advances and the predictions of large-scale instabilities must be tested. In essence, the processes responsible remain poorly understood and the problem unresolved. The aim of the White Paper submitted to ESA's Voyage 2050 call, and the contents of this paper, is to highlight three outstanding open science questions that are of clear international interest: (i) the interplay of local and global plasma physics processes: (ii) the partitioning during energy conversion between electromagnetic and plasma energy: and (iii) what processes drive the coupling between low and high beta plasmas. We present a discussion of the new measurements and technological advances required from current state-of-the-art, and several candidate mission profiles with which these international high-priority science goals could be significantly advanced.Peer reviewe

What are the fundamental modes of energy transfer and partitioning in the coupled Magnetosphere-Ionosphere system?

The fundamental processes responsible for energy exchange between large-scale electromagnetic fields and plasma are well understood theoretically, but in practice these theories have not been tested. These processes are ubiquitous in all plasmas, especially at the interface between high and low beta plasmas in planetary magnetospheres and other magnetic environments. Although such boundaries pervade the plasma Universe, the processes responsible for the release of the stored magnetic and thermal plasma energy have not been fully identified and the importance of the relative impact of each process is unknown. Despite advances in understanding energy release through the conversion of magnetic to kinetic energy in magnetic reconnection, how the extreme pressures in the regions between stretched and more relaxed field lines in the transition region are balanced and released through adiabatic convection of plasma and fields is still a mystery. Recent theoretical advances and the predictions of large-scale instabilities must be tested. In essence, the processes responsible remain poorly understood and the problem unresolved. The aim of the White Paper submitted to ESA’s Voyage 2050 call, and the contents of this paper, is to highlight three outstanding open science questions that are of clear international interest: (i) the interplay of local and global plasma physics processes: (ii) the partitioning during energy conversion between electromagnetic and plasma energy: and (iii) what processes drive the coupling between low and high beta plasmas. We present a discussion of the new measurements and technological advances required from current state-of-the-art, and several candidate mission profiles with which these international high-priority science goals could be significantly advanced