Melatonin as a potential therapy for sepsis : a phase I dose escalation study and an ex vivo whole blood model under conditions of sepsis

This article is protected by copyright. All rights reserved. This study was funded by the Chief Scientist Office, NHS Scotland. We would like to thank all the volunteers who gave up their time and blood to take part in the study and the data monitoring committee and staff of the intensive care unit for their support. In addition, thanks to Dr Malachy Columb for performing Page's trend test for us and to Annette Fearnley at Nu-Pharm Ltd for her advice.Peer reviewedPublisher PD

Fragility curves for non-ductile reinforced concrete frames that exhibit different component response mechanisms

Around the world, a large percentage of buildings in regions of high seismicity are older, non-ductile reinforced concrete. To assess the risk posed by these buildings, fragility functions are required to define the likelihood that these buildings will sustain damage and collapse under earthquake loading. This paper presents the initial phase of a research effort to develop fragility functions for non-ductile concrete frames using numerical simulation; the research presented in this paper focuses on development of the numerical model and application of the model to develop fragility functions for a prototype non-ductile concrete frame. To enable numerical simulation of concrete frame buildings, response models for beam–column joints and columns are developed to provide (1) appropriate simulation of component response and, thereby, reliable assessment of risk and (2) computational efficiency and robustness. These new models are developed using existing experimental data, build on response models proposed by others, and employ component and material models available in the OpenSees analysis platform (http://opensees.berkeley.edu). A new beam–column joint model combines a new expression for joint strength and newly developed cyclic response parameters; a new column response model includes a new shear-strength model and newly developed cyclic response parameters. Numerical models of a prototype non-ductile concrete frame are developed that include simulation of one or more of the following characteristics: (1) rigid beam–column joint, (2) nonlinear joint shear response, (3) nonlinear joint shear and bond–slip response, and (4) column shear failure. Dynamic analyses are performed using these frame models and a suite of ground motions; analysis results are used to develop fragility curves. Fragility curves quantify the vulnerability of the frame and provide understanding of the impact of different component failure mechanisms on frame vulnerability.This research was supported by the National Science Foundation under NSF Grant # 1000700.This is the accepted manuscript of a paper published in Engineering Structures (J-S Jeon, LN Lowes, R DesRoches, I Brilakis, Engineering Structures 2015, 85, 127–143

Spherical harmonic representation of the main geomagnetic field for world charting and investigations of some fundamental problems of physics and geophysics

Quiet-day data from MAGSAT were examined for effects which might test the validity of Maxwell's equations. Both external and toroidal fields which might represent a violation of the equations appear to exist, well within the associated errors. The external field might be associated with the ring current, and varies of a time-scale of one day or less. Its orientation is parallel to the geomagnetic dipole. The toriodal field can be confused with an orientation in error (in yaw). It the toroidal field really exists, its can be related to either ionospheric currents, or to toroidal fields in the Earth's core in accordance with Einstein's unified field theory, or to both

Family preferences for home or hospital care at diagnosis for children with diabetes in the DECIDE study.

This is the final version of the article. Available from Wiley via the DOI in this record.AIMS: A diagnosis of Type 1 diabetes in childhood can be a difficult life event for children and families. For children who are not severely ill, initial home rather than hospital-based care at diagnosis is an option although there is little research on which is preferable. Practice varies widely, with long hospital stays in some countries and predominantly home-based care in others. This article reports on the comparative acceptability and experience of children with Type 1 diabetes and their parents taking part in the DECIDE study evaluating outcomes of home or hospital-based treatment from diagnosis in the UK. METHODS: Semi-structured interviews with 11 (pairs of) parents and seven children were conducted between 15 and 20 months post diagnosis. Interviewees were asked about adaptation to, management and impact of the diabetes diagnosis, and their experience of initial post-diagnosis treatment. RESULTS: There were no differences between trial arms in adaptation to, management of or impact of diabetes. Most interviewees wanted to be randomized to the 'home' arm initially but expressed a retrospective preference for whichever trial arm they had been in, and cited benefits relating to learning about diabetes management. CONCLUSIONS: The setting for early treatment did not appear to have a differential impact on families in the long term. However, the data presented here describe different experiences of early treatment settings from the perspective of children and their families, and factors that influenced how families felt initially about treatment setting. Further research could investigate the short-term benefits of both settings.National Institute for Social Care and Health Research Clinical Research Centr

Spherical harmonic representation of the main geomagnetic field for world charting and investigations of some fundamental problems of physics and geophysics

The data processing of MAGSAT investigator B test tapes and data tapes, and tapes of selected data on 15 magnetically quiet days is reported. The 1980 World Chart spherical model was compared with the MAGSAT (3/80) and MAGSAT vector data were used in the models. An article on modelling the geomagnetic field using satellite data is included

Robotic Exploration of Moon and Mars: Thematic Education Approach

Safe, sustained, affordable human and robotic exploration of the Moon, Mars, and beyond is a major NASA goal. Robotic exploration of the Moon and Mars will help pave the way for an expanded human presence in our solar system. To help share the robotic exploration role in the Vision for Space Exploration with classrooms, informal education groups, and the public, our team researched and consolidated the thematic story components and associated education activities into a useful education materials set for educators. We developed the set of materials for a workshop combining NASA Science Mission Directorate and Exploration Systems Mission Directorate engineering, science, and technology to train informal educators on education activities that support the robotic exploration themes. A major focus is on the use of robotic spacecraft and instruments to explore and prepare for the human exploration of the Moon and Mars

The Effects of Pregnenolone 16α-Carbonitrile Dosing on Digoxin Pharmacokinetics and Intestinal Absorption in the Rat

The effect of Pgp induction in rats by pregnenolone 16α-carbonitrile (PCN) (3 days, 35 mg/kg/d, p.o.) on digoxin pharmacokinetics and intestinal transport has been assessed. After intravenous or oral digoxin dosing the arterial and hepatic portal vein (oral) AUC(0-24h) were significantly reduced by PCN pre-treatment. Biliary digoxin clearance increased 2-fold following PCN treatment. PCN significantly increased net digoxin secretion (2.05- and 4.5-fold respectively) in ileum and colon but not in duodenum or jejunum. This increased secretion correlated with increased Pgp protein expression in ileum and colon. Both intestinal and biliary excretion therefore contribute to altered digoxin disposition following PCN

Spherical harmonic representation of the main geomagnetic field for world charting and investigations of some fundamental problems of physics and geophysics

Progress in the harmonic analysis of MAGSAT data is reported. Single-day data sets were subdivided into information on the sunrise side of the Earth and information on the sunset side of the Earth. Data for the main and external fields each demonstrate a clear and consistent systematic difference between the sets of data which was determined to be, due to ionospheric currents which differ from the sunset to the sunrise terminator. A toroidal field was analyzed for and determined to be an apparent toroidal field resulting from electric currents concentrated in the two terminators. Progressive elimination of auroral zone data demonstrates that the information presented does not arise from complications due to Birkeland currents

Elucidating glycosaminoglycan–protein–protein interactions using carbohydrate microarray and computational approaches

Glycosaminoglycan polysaccharides play critical roles in many cellular processes, ranging from viral invasion and angiogenesis to spinal cord injury. Their diverse biological activities are derived from an ability to regulate a remarkable number of proteins. However, few methods exist for the rapid identification of glycosaminoglycan–protein interactions and for studying the potential of glycosaminoglycans to assemble multimeric protein complexes. Here, we report a multidisciplinary approach that combines new carbohydrate microarray and computational modeling methodologies to elucidate glycosaminoglycan–protein interactions. The approach was validated through the study of known protein partners for heparan and chondroitin sulfate, including fibroblast growth factor 2 (FGF2) and its receptor FGFR1, the malarial protein VAR2CSA, and tumor necrosis factor-α (TNF-α). We also applied the approach to identify previously undescribed interactions between a specific sulfated epitope on chondroitin sulfate, CS-E, and the neurotrophins, a critical family of growth factors involved in the development, maintenance, and survival of the vertebrate nervous system. Our studies show for the first time that CS is capable of assembling multimeric signaling complexes and modulating neurotrophin signaling pathways. In addition, we identify a contiguous CS-E-binding site by computational modeling that suggests a potential mechanism to explain how CS may promote neurotrophin-tyrosine receptor kinase (Trk) complex formation and neurotrophin signaling. Together, our combined microarray and computational modeling methodologies provide a general, facile means to identify new glycosaminoglycan–protein–protein interactions, as well as a molecular-level understanding of those complexes

Milne Bay Province: Text summaries, maps, code lists and village identification

The major purpose of the Papua New Guinea Agricultural Systems Project is to produce information on small holder (subsistence) agriculture at provincial and national levels (Allen et al 1995). Information was collected by field observation, interviews with villagers and reference to published and unpublished documents. Methods are described by Bourke et al. (1993). This Working Paper contains a written summary of the information on the Agricultural Systems in this Province, maps of the location of agriculture systems, a complete listing of all information in the database in coded form, and lists of villages with National Population Census codes, indexed by agricultural systems. This information is available as a map-linked database (GIS) suitable for use on a personal computer in ESRI and MapInfo formats. An Agricultural System is identified when a set of similar agricultural crops and practices occur within a defined area. Six criteria are used to distinguish one system from another: 1. Fallow type (the vegetation which is cleared from a garden site before cultivation). 2. Fallow period (the length of time a garden site is left unused between cultivations). 3. Cultivation intensity (the number of consecutive crops planted before fallow). 4. The staple, or most important, crops. 5. Garden and crop segregation (the extent to which crops are planted in separate gardens; in separate areas within a garden; or are planted sequentially). 6. Soil fertility maintenance techniques (other than natural regrowth fallows). Where one or more of these factors differs significantly and the differences can be mapped, then a separate system is distinguished. Where variation occurs, but is not able to be mapped at 1:500 000 scale because the areas in which the variation occurs are too small or are widely dispersed within the larger system, a subsystem is identified. Subsystems within an Agricultural System are allocated a separate record in the database, identified by the Agricultural System number and a subsystem number. Sago is a widespread staple food in lowland Papua New Guinea. Sago is produced from palms which are not grown in gardens. Most of the criteria above cannot be applied. In this case, systems are differentiated on the basis of the staple crops only. The Papua New Guinea Resource Information System (PNGRIS) is a GIS which contains information on the natural resources of PNG (Bellamy 1986). PNGRIS contains no information on agricultural practices, other than an assessment of land use intensity based on air photograph interpretation by Saunders (1993. The Agricultural Systems Project is designed to provide detailed information on agricultural practices and cropping patterns as part of an upgraded PNGRIS geographical information system. For this reason the Agricultural Systems database contains almost no information on the environmental settings of the systems, except for altitude and slope. The layout of the text descriptions, the database code files and the village lists are similar to PNGRIS formats (Cuddy 1987). The mapping of Agricultural Systems has been carried out on the same map base and scale as PNGRIS (Tactical Pilotage Charts, 1:500 000). Agricultural Systems were mapped within the areas of agricultural land use established by Saunders (1993) from aerial photography. Except where specifically noted, Agricultural Systems boundaries have been mapped without reference to PNGRIS Resource Mapping Unit (RMU) boundaries. Agricultural Systems are defined at the level of the Province (following PNGRIS) but their wider distribution is recognised in the database by cross-referencing systems which cross provincial borders. A preliminary view of the relationships between PNGRIS RMUs and the Agricultural Systems in this Province can be obtained from the listing of villages by Agricultural System, where RMU numbers are appended. Allen, B. J., R. M. Bourke and R. L. Hide 1995. The sustainability of Papua New Guinea agricultural systems: the conceptual background. Global Environmental Change 5(4): 297-312. Bourke, R. M., R. L. Hide, B. J. Allen, R. Grau, G. S. Humphreys and H. C. Brookfield 1993. Mapping agricultural systems in Papua New Guinea. Population Family Health and Development. T. Taufa and C. Bass. University of Papua New Guinea Press, Port Moresby: 205-224. Bellamy, J. A. and J. R. McAlpine 1995. Papua New Guinea Inventory of Natural Resources, Population Distribution and Land Use Handbook. Commonwealth Scientific and Industrial Research Organisation for the Australian Agency for International Development. PNGRIS Publication No. 6, Canberra. Cuddy, S. M. 1987. Papua New Guinea Inventory of Natural Resources, Population Distribution and Land Use: Code Files Part 1 Natural Resources. Division of Water and Land Resources, Commonwealth Scientific and Industrial Research Organisation and Land Utilization Section, Department of Primary Industry, Papua New Guinea, Canberra