Evolution of drug-tolerant nematode populations in response to density reduction

Resistance to xenobiotics remains a pressing issue in parasite treatment and global agriculture. Multiple factors may affect the evolution of resistance, including interactions between life-history traits and the strength of selection imposed by different drug doses. We experimentally created replicate selection lines of free-living Caenorhabditis remanei exposed to Ivermectin at high and low doses to assess whether survivorship of lines selected in drug-treated environments increased, and if this varied with dose. Additionally, we maintained lines where mortality was imposed randomly to control for differences in density between drug treatments and to distinguish between the evolutionary consequences of drug-treatment versus ecological processes due to changes in density-dependent feedback. After 10 generations, we exposed all of the selected lines to high-dose, low-dose and drug-free environments to evaluate evolutionary changes in survivorship as well as any costs to adaptation. Both adult and juvenile survival were measured to explore relationships between life-history stage, selection regime and survival. Intriguingly, both drug-selected and random-mortality lines showed an increase in survivorship when challenged with Ivermectin; the magnitude of this increase varied with the intensity of selection and life-history stage. Our results suggest that interactions between density-dependent processes and life history may mediate evolved changes in susceptibility to control measures

Beyond Blobs in Percolation Cluster Structure: The Distribution of 3-Blocks at the Percolation Threshold

The incipient infinite cluster appearing at the bond percolation threshold can be decomposed into singly-connected ``links'' and multiply-connected ``blobs.'' Here we decompose blobs into objects known in graph theory as 3-blocks. A 3-block is a graph that cannot be separated into disconnected subgraphs by cutting the graph at 2 or fewer vertices. Clusters, blobs, and 3-blocks are special cases of $k$-blocks with $k=1$, 2, and 3, respectively. We study bond percolation clusters at the percolation threshold on 2-dimensional square lattices and 3-dimensional cubic lattices and, using Monte-Carlo simulations, determine the distribution of the sizes of the 3-blocks into which the blobs are decomposed. We find that the 3-blocks have fractal dimension $d_3=1.2\pm 0.1$ in 2D and $1.15\pm 0.1$ in 3D. These fractal dimensions are significantly smaller than the fractal dimensions of the blobs, making possible more efficient calculation of percolation properties. Additionally, the closeness of the estimated values for $d_3$ in 2D and 3D is consistent with the possibility that $d_3$ is dimension independent. Generalizing the concept of the backbone, we introduce the concept of a ``$k$-bone'', which is the set of all points in a percolation system connected to $k$ disjoint terminal points (or sets of disjoint terminal points) by $k$ disjoint paths. We argue that the fractal dimension of a $k$-bone is equal to the fractal dimension of $k$-blocks, allowing us to discuss the relation between the fractal dimension of $k$-blocks and recent work on path crossing probabilities.Comment: All but first 2 figs. are low resolution and are best viewed when printe

Properties of low-lying states in some high-nuclearity Mn, Fe and V clusters: Exact studies of Heisenberg models

Using an efficient numerical scheme that exploits spatial symmetries and spin parity, we have obtained the exact low-lying eigenstates of exchange Hamiltonians for the high nuclearity spin clusters, Mn_{12}, Fe_8 and V_{15}. The largest calculation involves the Mn_{12} cluster which spans a Fock space of a hundred million. Our results show that the earlier estimates of the exchange constants need to be revised for the Mn_{12} cluster to explain the level ordering of low-lying eigenstates. In the case of the Fe_8 cluster, correct level ordering can be obtained which is consistent with the exchange constants for the already known clusters with butterfly structure. In the V_{15} cluster, we obtain an effective Hamiltonian that reproduces exactly, the eight low-lying eigenvalues of the full Hamiltonian.Comment: Revtex, 12 pages, 16 eps figures; this is the final published versio

Playing the game: service users' management of risk status in a UK medium secure forensic mental health service

In this article we examine how forensic mental health service users actively attempt to manage their risk status through playing the game of containing frustration and demonstrating compliance. The article draws on an observational study (2006 to 2009) which explored the practices of risk assessment and management within one inner city forensic mental health medium secure service in the UK. We used a grounded theory approach to explore service users and providers experiences of risk assessment and management. We interviewed forensic mental health service users and providers. We also collected data using participant and non-participant observation. Since access to forensic mental health services is tightly controlled, there are participant observation studies undertaken in these settings. We found that service users attempted to understand the system of assessment and sought to affect and reduce their risk status by engaging in overt, compliant behaviours. We argue that in doing so service users are active agents in the process of risk management. However, we indicate that there are adverse effects of this approach to risk management as the risk assessment process is subverted by the restriction of the flow of information, and service users are left with frustrations that they must contain and manage

Pre-hospital body surface potential mapping improves early diagnosis of acute coronary artery occlusion in patients with ventricular fibrillation and cardiac arrest

Aims: To determine whether 80-lead body surface potential mapping (BSPM) improves detection of acute coronary artery occlusion in patients presenting with out-of-hospital cardiac arrest (OHCA) due to ventricular fibrillation (VF) and who survived to reach hospital. Methods and results: Of 645 consecutive patients with OHCA who were attended by the mobile coronary care unit, VF was the initial rhythm in 168 patients. Eighty patients survived initial resuscitation, 59 of these having had BSPM and 12-lead ECG post-return of spontaneous circulation (ROSC) and in 35 patients (age 69±13 yrs; 60% male) coronary angiography performed within 24. h post-ROSC. Of these, 26 (74%) patients had an acutely occluded coronary artery (TIMI flow grade [TFG] 0/1) at angiography. Twelve-lead ECG criteria showed ST-segment elevation (STE) myocardial infarction (STEMI) using Minnesota 9-2 criteria - sensitivity 19%, specificity 100%; ST-segment depression (STD) =0.05. mV in =2 contiguous leads - sensitivity 23%, specificity 89%; and, combination of STEMI or STD criteria - sensitivity 46%, specificity 100%. BSPM STE occurred in 23 (66%) patients. For the diagnosis of TFG 0/1 in a main coronary artery, BSPM STE had sensitivity 88% and specificity 100% (c-statistic 0.94), with STE occurring most commonly in either the posterior, right ventricular or high right anterior territories. Conclusion: Among OHCA patients presenting with VF and who survived resuscitation to reach hospital, post-resuscitation BSPM STE identifies acute coronary occlusion with sensitivity 88% and specificity 100% (c-statistic 0.94). © 2012 Elsevier Ireland Ltd

Magnetic Field Generation in Stars

Enormous progress has been made on observing stellar magnetism in stars from the main sequence through to compact objects. Recent data have thrown into sharper relief the vexed question of the origin of stellar magnetic fields, which remains one of the main unanswered questions in astrophysics. In this chapter we review recent work in this area of research. In particular, we look at the fossil field hypothesis which links magnetism in compact stars to magnetism in main sequence and pre-main sequence stars and we consider why its feasibility has now been questioned particularly in the context of highly magnetic white dwarfs. We also review the fossil versus dynamo debate in the context of neutron stars and the roles played by key physical processes such as buoyancy, helicity, and superfluid turbulence,in the generation and stability of neutron star fields. Independent information on the internal magnetic field of neutron stars will come from future gravitational wave detections. Thus we maybe at the dawn of a new era of exciting discoveries in compact star magnetism driven by the opening of a new, non-electromagnetic observational window. We also review recent advances in the theory and computation of magnetohydrodynamic turbulence as it applies to stellar magnetism and dynamo theory. These advances offer insight into the action of stellar dynamos as well as processes whichcontrol the diffusive magnetic flux transport in stars.Comment: 41 pages, 7 figures. Invited review chapter on on magnetic field generation in stars to appear in Space Science Reviews, Springe

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types