Mitochondrial DNA haplotypes indicate two postglacial re-colonization routes of the spruce bark beetle Ips typographus through northern Europe to Scandinavia

Species in northern Europe re-colonized the region after the last glacial maximum via several routes, which could have lingering signatures in current intraspecific trait variation. The spruce bark beetle, Ips typographus, occurs across Europe, and biological differences have been found between southern and northern Scandinavian populations. However, the postglacial history of I. typographus in Scandinavia has not been previously studied at a fine geographical scale. Therefore, we collected specimens across northern Europe and analysed the genetic variation in a quite large mitochondrial fragment (698 bp). A high genetic diversity was found in some of the most northern populations, in the Baltic States, Gotland and central Europe. Detected genetic and phylogeographic structures suggest that I. typographus re-colonized Scandinavia via two pathways, one from the northeast and one from the south. These findings are consistent with the re-colonization history of its host plant, Picea abies. However, we observed low haplotype and nucleotide diversity in southern Scandinavian populations of I. typographus, indicating that (unlike P. abies) it did not disperse across the Baltic Sea in multiple events. Further, the divergence among Scandinavian populations was shallow, conflicting with a scenario where I. typographus expanded concurrently with its host plant from a 'cryptic refugium' in the northwest

Fragmentation of exotic oxygen isotopes

Abrasion-ablation models and the empirical EPAX parametrization of projectile fragmentation are described. Their cross section predictions are compared to recent data of the fragmentation of secondary beams of neutron-rich, unstable 19,20,21O isotopes at beam energies near 600 MeV/nucleon as well as data for stable 17,18O beams

Implementation and Outcomes of Commercial Disease Management Programs in the United States: The Disease Management Outcomes Consolidation Survey

Despite widespread adoption of disease management (DM) programs by US health plans, gaps remain in the evidence for their benefit. The Disease Management Outcomes Consolidation Survey was designed to gather data on DM programs for commercial health plans, to assess program success and DM effectiveness. The questionnaire was mailed to 292 appropriate health plan contacts; 26 plans covering more than 14 million commercial members completed and returned the survey. Respondents reported that DM plays a significant and increasing role in their organizations. Key reasons for adopting DM were improving clinical outcomes, reducing medical costs and utilization, and improving member satisfaction. More respondents were highly satisfied with clinical results than with utilization or cost outcomes of their programs (46%, 17%, and 13%, respectively). Detailed results were analyzed for 57 DM programs with over 230,000 enrollees. Most responding plans offered DM programs for diabetes and asthma, with return on investment (ROI) ranging from 0.16:1 to 4:1. Weighted by number of enrollees per DM program, average ROI was 2.56:1 for asthma (n = 1,136 enrollees) and 1.98:1 for diabetes (n = 25,364). Most (but not all) respondents reported reduced hospital admissions, increasing rates of preventive care, and improved clinical measures. Few respondents provided detailed information about DM programs for other medical conditions, but most that did reported positive outcomes. Lack of standardized methodology was identified as a major barrier to in-house program evaluation. Although low response rate precluded drawing many general conclusions, a clear need emerged for more rigorous evaluation methods and greater standardization of outcomes measurement. (Disease Management 2005;8:253–264)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63399/1/dis.2005.8.253.pd

Easy dual-mode ambient mass spectrometry with Venturi self-pumping, canned air, disposable parts and voltage-free sonic-spray ionization

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)An exceptionally easy to assemble source for ambient mass spectrometry is described. Based on Venturi easy ambient sonic-spray ionization (V-EASI), the source was further simplified by the use of a can of compressed air which simultaneously provides solution or solvent Venturi self-pumping and continuous, stable and abundant low-noise ion signal via voltage-free sonic-spraying. Further simplification was also attained by the use of inexpensive and readily commercially available parts: a surgical 2-way catheter, an aerosol can of compressed air, a 30 cm long fused-silica capillary and a hypodermic needle. This 'Spartan' V-EASI source seems to offer one of the easiest and cheapest ways to make ions for ambient desorption/ionization mass spectrometry analysis of both liquid and solid samples.1371125372540Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Brazilian Science Foundation's FINEPFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Dioxin Toxicity In Vivo Results from an Increase in the Dioxin-Independent Transcriptional Activity of the Aryl Hydrocarbon Receptor

The Aryl hydrocarbon receptor (Ahr) is the nuclear receptor mediating the toxicity of dioxins -widespread and persistent pollutants whose toxic effects include tumor promotion, teratogenesis, wasting syndrome and chloracne. Elimination of Ahr in mice eliminates dioxin toxicity but also produces adverse effects, some seemingly unrelated to dioxin. Thus the relationship between the toxic and dioxin-independent functions of Ahr is not clear, which hampers understanding and treatment of dioxin toxicity. Here we develop a Drosophila model to show that dioxin actually increases the in vivo dioxin-independent activity of Ahr. This hyperactivation resembles the effects caused by an increase in the amount of its dimerisation partner Ahr nuclear translocator (Arnt) and entails an increased transcriptional potency of Ahr, in addition to the previously described effect on nuclear translocation. Thus the two apparently different functions of Ahr, dioxin-mediated and dioxin-independent, are in fact two different levels (hyperactivated and basal, respectively) of a single function

Region of hadron-quark mixed phase in hybrid stars

Hadron--quark mixed phase is expected in a wide region of the inner structure of hybrid stars. However, we show that the hadron--quark mixed phase should be restricted to a narrower region to because of the charge screening effect. The narrow region of the mixed phase seems to explain physical phenomena of neutron stars such as the strong magnetic field and glitch phenomena, and it would give a new cooling curve for the neutron star.Comment: to be published in Physical Review

Development of an invasively monitored porcine model of acetaminophen-induced acute liver failure

Background: The development of effective therapies for acute liver failure (ALF) is limited by our knowledge of the pathophysiology of this condition, and the lack of suitable large animal models of acetaminophen toxicity. Our aim was to develop a reproducible invasively-monitored porcine model of acetaminophen-induced ALF. Method: 35kg pigs were maintained under general anaesthesia and invasively monitored. Control pigs received a saline infusion, whereas ALF pigs received acetaminophen intravenously for 12 hours to maintain blood concentrations between 200-300 mg/l. Animals surviving 28 hours were euthanased. Results: Cytochrome p450 levels in phenobarbital pre-treated animals were significantly higher than non pre-treated animals (300 vs 100 pmol/mg protein). Control pigs (n=4) survived 28-hour anaesthesia without incident. Of nine pigs that received acetaminophen, four survived 20 hours and two survived 28 hours. Injured animals developed hypotension (mean arterial pressure; 40.8+/-5.9 vs 59+/-2.0 mmHg), increased cardiac output (7.26+/-1.86 vs 3.30+/-0.40 l/min) and decreased systemic vascular resistance (8.48+/-2.75 vs 16.2+/-1.76 mPa/s/m3). Dyspnoea developed as liver injury progressed and the increased pulmonary vascular resistance (636+/-95 vs 301+/-26.9 mPa/s/m3) observed may reflect the development of respiratory distress syndrome. Liver damage was confirmed by deterioration in pH (7.23+/-0.05 vs 7.45+/-0.02) and prothrombin time (36+/-2 vs 8.9+/-0.3 seconds) compared with controls. Factor V and VII levels were reduced to 9.3 and 15.5% of starting values in injured animals. A marked increase in serum AST (471.5+/-210 vs 42+/-8.14) coincided with a marked reduction in serum albumin (11.5+/-1.71 vs 25+/-1 g/dL) in injured animals. Animals displayed evidence of renal impairment; mean creatinine levels 280.2+/-36.5 vs 131.6+/-9.33 mumol/l. Liver histology revealed evidence of severe centrilobular necrosis with coagulative necrosis. Marked renal tubular necrosis was also seen. Methaemoglobin levels did not rise >5%. Intracranial hypertension was not seen (ICP monitoring), but there was biochemical evidence of encephalopathy by the reduction of Fischer's ratio from 5.6 +/- 1.1 to 0.45 +/- 0.06. Conclusion: We have developed a reproducible large animal model of acetaminophen-induced liver failure, which allows in-depth investigation of the pathophysiological basis of this condition. Furthermore, this represents an important large animal model for testing artificial liver support systems

Towards quantum thermodynamics in electronic circuits

Electronic circuits operating at sub-kelvin temperatures are attractive candidates for studying classical and quantum thermodynamics: their temperature can be controlled and measured locally with exquisite precision, and they allow experiments with large statistical samples. The availability and rapid development of devices such as quantum dots, single-electron boxes and superconducting qubits only enhance their appeal. But although these systems provide fertile ground for studying heat transport, entropy production and work in the context of quantum mechanics, the field remains in its infancy experimentally. Here, we review some recent experiments on quantum heat transport, fluctuation relations and implementations of Maxwell’s demon, revealing the rich physics yet to be fully probed in these systems.Peer reviewe

Tissue Microenvironments Define and Get Reinforced by Macrophage Phenotypes in Homeostasis or during Inflammation, Repair and Fibrosis

Current macrophage phenotype classifications are based on distinct in vitro culture conditions that do not adequately mirror complex tissue environments. In vivo monocyte progenitors populate all tissues for immune surveillance which supports the maintenance of homeostasis as well as regaining homeostasis after injury. Here we propose to classify macrophage phenotypes according to prototypical tissue environments, e.g. as they occur during homeostasis as well as during the different phases of (dermal) wound healing. In tissue necrosis and/or infection, damage- and/or pathogen-associated molecular patterns induce proinflammatory macrophages by Toll-like receptors or inflammasomes. Such classically activated macrophages contribute to further tissue inflammation and damage. Apoptotic cells and antiinflammatory cytokines dominate in postinflammatory tissues which induce macrophages to produce more antiinflammatory mediators. Similarly, tumor-associated macrophages also confer immunosuppression in tumor stroma. Insufficient parenchymal healing despite abundant growth factors pushes macrophages to gain a profibrotic phenotype and promote fibrocyte recruitment which both enforce tissue scarring. Ischemic scars are largely devoid of cytokines and growth factors so that fibrolytic macrophages that predominantly secrete proteases digest the excess extracellular matrix. Together, macrophages stabilize their surrounding tissue microenvironments by adapting different phenotypes as feed-forward mechanisms to maintain tissue homeostasis or regain it following injury. Furthermore, macrophage heterogeneity in healthy or injured tissues mirrors spatial and temporal differences in microenvironments during the various stages of tissue injury and repair. Copyright (C) 2012 S. Karger AG, Base

The 10th Biennial Hatter Cardiovascular Institute workshop: cellular protection—evaluating new directions in the setting of myocardial infarction, ischaemic stroke, and cardio-oncology

Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes. The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes. A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke. Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy. Consequently, strategies designed to protect the heart from lethal cell injury have the potential to be applicable across all three pathologies. The investigators meeting at the 10th Hatter Cardiovascular Institute workshop examined the parallels between ST-segment elevation myocardial infarction (STEMI), ischaemic stroke, and other pathologies that cause the loss of cardiomyocytes including cancer therapeutic cardiotoxicity. They examined the prospects for protection by remote ischaemic conditioning (RIC) in each scenario, and evaluated impasses and novel opportunities for cellular protection, with the future landscape for RIC in the clinical setting to be determined by the outcome of the large ERIC-PPCI/CONDI2 study. It was agreed that the way forward must include measures to improve experimental methodologies, such that they better reflect the clinical scenario and to judiciously select combinations of therapies targeting specific pathways of cellular death and injury