Assessment of low-dose cisplatin as a model of nausea and emesis in beagle dogs, potential for repeated administration

Cisplatin is a highly emetogenic cancer chemotherapy agent, which is often used to induce nausea and emesis in animal models. The cytotoxic properties of cisplatin also cause adverse events that negatively impact on animal welfare preventing repeated administration of cisplatin. In this study, we assessed whether a low (subclinical) dose of cisplatin could be utilized as a model of nausea and emesis in the dog while decreasing the severity of adverse events to allow repeated administration. The emetic, nausea-like behavior and potential biomarker response to both the clinical dose (70 mg/m2) and low dose (15 mg/m2) of cisplatin was assessed. Plasma creatinine concentrations and granulocyte counts were used to assess adverse effects on the kidneys and bone marrow, respectively. Nausea-like behavior and emesis was induced by both doses of cisplatin, but the latency to onset was greater in the low-dose group. No significant change in plasma creatinine was detected for either dose groups. Granulocytes were significantly reduced compared with baseline (P = 0.000) following the clinical, but not the low-dose cisplatin group. Tolerability of repeated administration was assessed with 4 administrations of an 18 mg/m2 dose cisplatin. Plasma creatinine did not change significantly. Cumulative effects on the granulocytes occurred, they were significantly decreased (P = 0.03) from baseline at 3 weeks following cisplatin for the 4th administration only. Our results suggest that subclinical doses (15 and 18 mg/m2) of cisplatin induce nausea-like behavior and emesis but have reduced adverse effects compared with the clinical dose allowing for repeated administration in crossover studies

Jacobi Polynomials as su(2, 2) Unitary Irreducible Representation

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Cerebral perfusion pressure and brain ischaemia: can one size fit all?

Current recommendations regarding the management of patients after traumatic brain injury include reduction in brain tissue pressure (i.e. intracranial pressure) and maintenance of an adequate arterial pressure; these measures combined should result in cerebral perfusion pressure sufficient to achieve adequate oxygen delivery. After almost 20 years of observational studies comparing cerebral perfusion pressure and indices of cerebral oxygenation, it is apparent that there is no single value for cerebral perfusion pressure that, if achieved, will provide adequate cerebral oxygen delivery in all patients. Traumatic brain injury remains a common problem, and this should encourage researchers and clinicians to design better and adequately powered trials of monitors and associated interventions

Polarized disk emission from Herbig AE/BE stars observed using Gemini planet imager: HD 144432, HD 150193, HD 163296, and HD 169142

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.In order to look for signs of on-going planet formation in young disks, we carried out the first J-band polarized emission imaging of the Herbig Ae/Be stars HD 150193, HD 163296, and HD 169142 using the Gemini Planet Imager (GPI), along with new H band observations of HD 144432. We confirm the complex “double ring” structure for the nearly face-on system HD 169142 first seen in H-band, finding the outer ring to be substantially redder than the inner one in polarized intensity. Using radiative transfer modeling, we developed a physical model that explains the full spectral energy distribution (SED) and J- and H-band surface brightness profiles, suggesting that the di↵erential color of the two rings could come from reddened starlight traversing the inner wall and may not require di↵erences in grain properties. In addition, we clearly detect an elongated, o↵-center ring in HD 163296 (MWC 275), locating the scattering surface to be 18 AU above the midplane at a radial distance of 77 AU, cospatial with a ring seen at 1.3mm by ALMA linked to the CO snow line. Lastly, we report a weak tentative detection of scattered light for HD 150193 (MWC 863) and a non-detection for HD 144432; the stellar companion known for each of these targets has likely disrupted the material in the outer disk of the primary star. For HD 163296 and HD 169142, the prominent outer rings we detect could be evidence for giant planet formation in the outer disk or a manifestation of large-scale dust growth processes possibly related to snow-line chemistry.Exeter’s STFC Consolidated Grant (ST/J001627/1). SK acknowledges support from an STFC Rutherford Fellowship (ST/J004030/1) and a European Research Council (ERC) Starting Grant (Grant agreement No 639889). This publication makes use of data products from the Two Micron All Sky Survey, which is a joint project of the University of Massachusetts and the Infrared Processing and Analysis Center/California Institute of Technology, funded by the National Aeronautics and Space Administration and the National Science Foundation. Based on observations obtained at the Gemini Observatory (programs GS-2014A-SV-412, GS-2015A-Q-49), which is operated by the Association of Universities for Research in Astronomy, Inc., under a cooperative agreement with the NSF on behalf of the Gemini partnership: the National Science Foundation (United States), the National Research Council (Canada), CONICYT (Chile), Ministerio de Ciencia, Tecnologa e Innovacin Productiva (Argentina), and Ministrio da Cincia, Tecnologia e Inovao (Brazil)

Ferritins: furnishing proteins with iron

Ferritins are a superfamily of iron oxidation, storage and mineralization proteins found throughout the animal, plant, and microbial kingdoms. The majority of ferritins consist of 24 subunits that individually fold into 4-α-helix bundles and assemble in a highly symmetric manner to form an approximately spherical protein coat around a central cavity into which an iron-containing mineral can be formed. Channels through the coat at inter-subunit contact points facilitate passage of iron ions to and from the central cavity, and intrasubunit catalytic sites, called ferroxidase centers, drive Fe2+ oxidation and O2 reduction. Though the different members of the superfamily share a common structure, there is often little amino acid sequence identity between them. Even where there is a high degree of sequence identity between two ferritins there can be major differences in how the proteins handle iron. In this review we describe some of the important structural features of ferritins and their mineralized iron cores and examine in detail how three selected ferritins oxidise Fe2+ in order to explore the mechanistic variations that exist amongst ferritins. We suggest that the mechanistic differences reflect differing evolutionary pressures on amino acid sequences, and that these differing pressures are a consequence of different primary functions for different ferritins

European society of intensive care medicine study of therapeutic hypothermia (32-35 °C) for intracranial pressure reduction after traumatic brain injury (the Eurotherm3235Trial).

BACKGROUND: Traumatic brain injury is a major cause of death and severe disability worldwide with 1,000,000 hospital admissions per annum throughout the European Union.Therapeutic hypothermia to reduce intracranial hypertension may improve patient outcome but key issues are length of hypothermia treatment and speed of re-warming. A recent meta-analysis showed improved outcome when hypothermia was continued for between 48 hours and 5 days and patients were re-warmed slowly (1 °C/4 hours). Previous experience with cooling also appears to be important if complications, which may outweigh the benefits of hypothermia, are to be avoided. METHODS/DESIGN: This is a pragmatic, multi-centre randomised controlled trial examining the effects of hypothermia 32-35 °C, titrated to reduce intracranial pressure 20 mmHg in accordance with the Brain Trauma Foundation Guidelines, 2007. DISCUSSION: The Eurotherm3235Trial is the most important clinical trial in critical care ever conceived by European intensive care medicine, because it was launched and funded by the European Society of Intensive Care Medicine and will be the largest non-commercial randomised controlled trial due to the substantial number of centres required to deliver the target number of patients. It represents a new and fundamental step for intensive care medicine in Europe. Recruitment will continue until January 2013 and interested clinicians from intensive care units worldwide can still join this important collaboration by contacting the Trial Coordinating Team via the trial website http://www.eurotherm3235trial.eu. TRIAL REGISTRATION: Current Controlled Trials ISRCTN34555414

'Surely the most natural scenario in the world’: Representations of ‘Family’ in BBC Pre-school Television

Historically, the majority of work on British children’s television has adopted either an institutional or an audience focus, with the texts themselves often overlooked. This neglect has meant that questions of representation in British children’s television – including issues such as family, gender, class or ethnicity - have been infrequently analysed in the UK context. In this article, we adopt a primarily qualitative methodology and analyse the various textual manifestations of ‘family’, group, or community as represented in a selected number of BBC pre-school programmes. In doing so, we question the (limited amount of) international work that has examined representations of the family in children’s television, and argue that nuclear family structures do not predominate in this sphere