Metabolically Inactive Insulin Analog Prevents Type I Diabetes in Prediabetic NOD Mice

The purpose of this study was to determine the relative importance of the metabolic effects of insulin for diabetes prevention by administering insulin or an inactive insulin analog by daily subcutaneous injections to prediabetic mice. A recombinant monomeric human insulin analog, which does not bind to the insulin receptor as a consequence of an alteration of a single amino acid at position 25 of the B chain, was shown to be equally effective at diabetes prevention as was intact insulin. In contrast to native insulin, the insulin analog did not cause hypoglycemia after subcutaneous injection. The insulin analog, however, protected young adult mice from diabetes, even when it was initiated after the onset of extensive lymphocytic infiltration of the islets. Thus, preventative therapy by daily subcutaneous injections of insulin does not require the hypoglycemic response, or binding to the insulin receptor to prevent the onset of type I diabetes

Representation to the accident and emergency department within 1-year of a fractured neck of femur

Background: The fractured neck of femur (NOF) is a leading cause of morbidity and mortality. The mortality attendant upon such fractures is 10% at 1 month and 30% at one year with a cost to the NHS of £1.4 billion annually. This retrospective study sought to examine rates and prevailing trends in representation to A&E in the year following a NOF fracture in an attempt to identify the leading causes behind the morbidity and mortality associated with this fracture. Methods: 1108 patients who suffered a fractured NOF between 1 January 2002 and 31 December 2007 were identified from a University Hospital A&E database. This database was then used to identify those patients who represented within 1-year following the initial fracture. The presenting complaint, provisional diagnosis and the outcome of this presentation were identified at this time. Results: 234 patients (21%) returned to A&E on 368 occasions in the year following a hip fracture. 77% (284/368) of these presentations necessitated admission. Falls, infection and fracture were the leading causes of representation. Falls accounted for 20% (57/284) of admissions; 20.7% of patients were admitted because of a fracture, while 56.6% of admissions were for medical ailments of which infection was the chief precipitant (28% (45/161)). Discussion: The causes for representation are varied and multifactorial. The results of this study suggest that some of those events or ailments necessitating readmission may be obviated and potentially reduced by interventions that can be instituted during the primary admission and continued following discharge

Discovery of a Transiting Planet Near the Snow-Line

In most theories of planet formation, the snow-line represents a boundary between the emergence of the interior rocky planets and the exterior ice giants. The wide separation of the snow-line makes the discovery of transiting worlds challenging, yet transits would allow for detailed subsequent characterization. We present the discovery of Kepler-421b, a Uranus-sized exoplanet transiting a G9/K0 dwarf once every 704.2 days in a near-circular orbit. Using public Kepler photometry, we demonstrate that the two observed transits can be uniquely attributed to the 704.2 day period. Detailed light curve analysis with BLENDER validates the planetary nature of Kepler-421b to >4 sigmas confidence. Kepler-421b receives the same insolation as a body at ~2AU in the Solar System and for a Uranian albedo would have an effective temperature of ~180K. Using a time-dependent model for the protoplanetary disk, we estimate that Kepler-421b's present semi-major axis was beyond the snow-line after ~3Myr, indicating that Kepler-421b may have formed at its observed location.Comment: 14 pages, 10 figures, 3 tables. Accepted in Ap

Neoliberal governing through social enterprise: Exploring the neglected roles of deviance and ignorance in public value creation

This article makes a case for paying greater attention to how informal relationships between government officials and civil society practitioners impact processes of public value creation. Drawing on data from a five‐year qualitative longitudinal study, we illuminate how civil society practitioners deviate from the formal objectives of social enterprise policies in order to create what they see as having public value. Through a process of theory elaboration, we demonstrate how government officials’ wilful ignorance of, or informal collaboration in, such deviance, precipitates forms of public value that are consistent with wider political objectives. Our analysis adds nuance and granularity to the debate on public value by drawing attention to the arcane ways it may be informally negotiated and created outside of the public sphere. This opens up new empirical and theoretical opportunities for understanding how deviance and ignorance might be symbiotically related in processes of public value creation.

Performance Assessment of Bi-Directional Knotless Tissue-Closure Device in Juvenile Chinook Salmon Surgically Implanted with Acoustic Transmitters, 2010 - Final Report

In 2010, researchers at Pacific Northwest National Laboratory (PNNL) and the University of Washington (UW) conducted a compliance monitoring study—the Lower Columbia River Acoustic Transmitter Investigations of Dam Passage Survival and Associated Metrics 2010 (Carlson et al. in preparation)—for the U.S. Army Corps of Engineers (USACE), Portland District. The purpose of the compliance study was to evaluate juvenile Chinook salmon (Oncorhynchus tshawytscha) and steelhead (O. mykiss) passage routes and survival through the lower three Columbia River hydroelectric facilities as stipulated by the 2008 Federal Columbia River Power System (FCRPS) Biological Opinion (BiOp; NOAA Fisheries 2008) and the Columbia Basin Fish Accords (Fish Accords; 3 Treaty Tribes and Action Agencies 2008)

Long-lived magnetism from solidification-driven convection on the pallasite parent body.

Palaeomagnetic measurements of meteorites suggest that, shortly after the birth of the Solar System, the molten metallic cores of many small planetary bodies convected vigorously and were capable of generating magnetic fields. Convection on these bodies is currently thought to have been thermally driven, implying that magnetic activity would have been short-lived. Here we report a time-series palaeomagnetic record derived from nanomagnetic imaging of the Imilac and Esquel pallasite meteorites, a group of meteorites consisting of centimetre-sized metallic and silicate phases. We find a history of long-lived magnetic activity on the pallasite parent body, capturing the decay and eventual shutdown of the magnetic field as core solidification completed. We demonstrate that magnetic activity driven by progressive solidification of an inner core is consistent with our measured magnetic field characteristics and cooling rates. Solidification-driven convection was probably common among small body cores, and, in contrast to thermally driven convection, will have led to a relatively late (hundreds of millions of years after accretion), long-lasting, intense and widespread epoch of magnetic activity among these bodies in the early Solar System.The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013) / ERC Grant Agreement No. 320750, the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 312284, the Natural Environment Research Council, Fundación ARAID and the Spanish MINECO MAT2011-23791.This is the accepted manuscript. The final version is available from Nature at http://www.nature.com/nature/journal/v517/n7535/full/nature14114.html

Healthcare staff's experience in providing end-of-life care to children: A mixed-method review.

BACKGROUND: Staff who provide end-of-life care to children not only have to deal with their own sense of loss but also that of bereaved families. There is a dearth of knowledge on how they cope with these challenges. AIM: The aim of this review is to explore the experiences of healthcare professionals who provide end-of-life care to children in order to inform the development of interventions to support them, thereby improving the quality of paediatric care for both children and their families. DATA SOURCES: Searches included CINAHL, MEDLINE, Web of Science, EMBASE, PsychINFO and The Cochrane Library in June 2015, with no date restrictions. Additional literature was uncovered from searching reference lists of relevant studies, along with contacting experts in the field of paediatric palliative care. DESIGN: This was a systematic mixed studies review. Study selection, appraisal and data extraction were conducted by two independent researchers. Integrative thematic analysis was used to synthesise the data. RESULTS: The 16 qualitative, 6 quantitative and 8 mixed-method studies identified included healthcare professionals in a range of settings. Key themes identified rewards and challenges of providing end-of-life care to children, the impact on staff's personal and professional lives, coping strategies and key approaches to help support staff in their role. CONCLUSION: Education focusing on the unique challenges of providing end-of-life care to children and the importance of self-care, along with timely multidisciplinary debriefing, are key strategies for improving healthcare staff's experiences, and as such the quality of care they provide

Branch-and-lift algorithm for deterministic global optimization in nonlinear optimal control

This paper presents a branch-and-lift algorithm for solving optimal control problems with smooth nonlinear dynamics and potentially nonconvex objective and constraint functionals to guaranteed global optimality. This algorithm features a direct sequential method and builds upon a generic, spatial branch-and-bound algorithm. A new operation, called lifting, is introduced, which refines the control parameterization via a Gram-Schmidt orthogonalization process, while simultaneously eliminating control subregions that are either infeasible or that provably cannot contain any global optima. Conditions are given under which the image of the control parameterization error in the state space contracts exponentially as the parameterization order is increased, thereby making the lifting operation efficient. A computational technique based on ellipsoidal calculus is also developed that satisfies these conditions. The practical applicability of branch-and-lift is illustrated in a numerical example. © 2013 Springer Science+Business Media New York

Extensive and intensive globalizations: explicating the low connectivity puzzle of U.S. cities using a city-dyad analysis

This article reports an experiment in world city network analysis focusing on city-dyads. Results are derived from an unusual principal components analysis of 27,966 city-dyads across 5 advanced producer service sectors. A 2-component solution is found that identifies different forms of globalization: extensive and intensive. The latter is characterized by very high component scores and describes the more important city-dyads focused upon London-New York (NYLON). The extensive globalization component heavily features London and New York but with each linked to less important cities. U.S. cities score relatively high on the intensive globalization component and we use this finding to explain the low connectivities of U.S. cities in previous studies of the world city network. The two components are tentatively interpreted in world-systems terms: intensive globalization is the process of core-making through city-dyads; extensive globalization is the process of linking core with non-core through city-dyads