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    Predicting intensive care outcome: comparing three outcome prediction models, APACHE II, SAPS II, and MPM II

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    Dementia and osteoporosis in a geriatric population: Is there a common link?

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    AIM To determine the existence of a common pathological link between dementia and osteoporosis through reviewing the current evidence base. METHODS This paper reviews the current literature on osteoporosis and dementia in order to ascertain evidence of a common predisposing aetiology. A literature search of Ovid MEDLINE (1950 to June 2016) was conducted. The keywords “osteoporosis”, “osteoporotic fracture”, “dementia” and “Alzheimer’s disease” (AD) were used to determine the theoretical links with the most significant evidence base behind them. The key links were found to be vitamins D and K, calcium, thyroid disease, statins, alcohol and sex steroids. These subjects were then searched in combination with the previous terms and the resulting papers manually examined. Theoretical, in vitro and in vivo research were all used to inform this review which focuses on the most well developed theoretical common causes for dementia (predominantly Alzheimer’s type) and osteoporosis. RESULTS Dementia and osteoporosis are multifaceted disease processes with similar epidemiology and a marked increase in prevalence in elderly populations. The existence of a common link between the two has been suggested despite a lack of clear pathological overlap in our current understanding. Research to date has tended to be fragmented and relatively weak in nature with multiple confounding factors reflecting the difficulties of in vivo experimentation in the population of interest. Despite exploration of various possible mechanisms in search for a link between the two pathologies, this paper found that it is possible that these associations are coincidental due to the nature of the evidence available. One finding in this review is that prior investigation into common aetiologies has found raised amyloid beta peptide levels in osteoporotic bone tissue, with a hypothesis that amyloid beta disorders are systemic disorders resulting in differing tissue manifestations. However, our findings were that the most compelling evidence of a common yet independent aetiology lies in the APOE4 allele, which is a well-established risk for AD but also carries an independent association with fracture risk. The mechanism behind this is thought to be the reduced plasma vitamin K levels in individuals exhibiting the APOE4 allele which may be amplified by the nutritional deficiencies associated with dementia, which are known to include vitamins K and D. The vitamin theory postulates that malnutrition and reduced exposure to sunlight in patients with AD leads to vitamin deficiencies. CONCLUSION Robust evidence remains to be produced regarding potential links and regarding the exact aetiology of these diseases and remains relevant given the burden of dementia and osteoporosis in our ageing population. Future research into amyloid beta, APOE4 and vitamins K and D as the most promising aetiological links should be welcomed

    Decision-Making for Rewilding: An Adaptive Governance Framework for Social-Ecological Complexity

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    Rewilding can be defined as the reorganisation or regeneration of wildness in an ecologically degraded landscape with minimal ongoing intervention. While proposals for rewilding are increasingly common, they are frequently controversial and divisive amongst stakeholders. If implemented, rewilding initiatives may alter the social-ecological systems within which they are situated and thus generate sudden and unforeseen outcomes. So far, however, much of the discourse on the planning and implementation of rewilding has focused on identifying and mitigating ecological risks. There has been little consideration of how rewilding could alter the human components of the social-ecological systems concerned, nor governance arrangements that can manage these dynamics. This paper addresses this gap by proposing a generic adaptive governance framework tailored to the characteristics of rewilding, based on principles of managing complex social-ecological systems. We integrate two complementary natural resource governance approaches that lend themselves to the contentious and unpredictable characteristics of rewilding. First, adaptive co-management builds stakeholder adaptive capacity through iterative knowledge generation, collaboration and power-sharing, and cross-scale learning networks. Second, social licence to operate establishes trust and transparency between project proponents and communities through new public-private partnerships. The proposed framework includes structural and process elements which incorporate a boundary organisation, a decision-into-practise social learning exercise for planning and design, and participatory evaluation. The latter assesses rewilding outcomes and pre-conditions for the continuation of adaptive governance and conservation conflict resolution

    Analysis of radiation-induced cell death in head and neck squamous cell carcinoma and rat liver maintained in microfluidic devices

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    Objective The aim of this study was to investigate how head and neck squamous cell carcinoma (HNSCC) tissue biopsies maintained in a pseudo in vivo environment within a bespoke microfluidic device respond to radiation treatment. Study Design Feasibility study. Setting Tertiary referral center. Subjects and Methods Thirty-five patients with HNSCC were recruited, and liver tissue from 5 Wistar rats was obtained. A microfluidic device was used to maintain the tissue biopsy samples in a viable state. Rat liver was used to optimize the methodology. HNSCC was obtained from patients with T1-T3 laryngeal or oropharyngeal SCC; N1-N2 metastatic cervical lymph nodes were also obtained. Irradiation consisted of single doses of between 2 Gy and 40 Gy and a fractionated course of 5Ă—2 Gy. Cell death was assessed in the tissue effluent using the soluble markers lactate dehydrogenase (LDH) and cytochrome c and in the tissue by immunohistochemical detection of cleaved cytokeratin18 (M30 antibody). Results A significant surge in LDH release was demonstrated in the rat liver after a single dose of 20 Gy; in HNSCC, it was seen after 40 Gy compared with the control. There was no significant difference in cytochrome c release after 5 Gy or 10 Gy. M30 demonstrated a dose-dependent increase in apoptotic index for a given increase in single-dose radiotherapy. There was a significant increase in apoptotic index between 1Ă—2 Gy and 5Ă—2 Gy. Conclusion M30 is a superior method compared with soluble markers in detecting low-dose radiation-induced cell death. This microfluidic technique can be used to assess radiation-induced cell death in HNSCC and therefore has the potential to be used to predict radiation response

    Enhanced flight performance by genetic manipulation of wing shape in Drosophila

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    Insect wing shapes are remarkably diverse and the combination of shape and kinematics determines both aerial capabilities and power requirements. However, the contribution of any specific morphological feature to performance is not known. Using targeted RNA interference to modify wing shape far beyond the natural variation found within the population of a single species, we show a direct effect on flight performance that can be explained by physical modelling of the novel wing geometry. Our data show that altering the expression of a single gene can significantly enhance aerial agility and that the Drosophila wing shape is not, therefore, optimized for certain flight performance characteristics that are known to be important. Our technique points in a new direction for experiments on the evolution of performance specialities in animals

    On the unification of dwarf and giant elliptical galaxies

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    The near orthogonal distributions of dwarf elliptical (dE) and giant elliptical (E) galaxies in the mu_e-Mag and mu_e-log(R_e) diagrams have been interpreted as evidence for two distinct galaxy formation processes. However, continuous, linear relationships across the alleged dE/E boundary at M_B = -18 mag - such as those between central surface brightness (mu_0) and (i) galaxy magnitude and (ii) light-profile shape (n) - suggest a similar, governing formation mechanism. Here we explain how these latter two linear trends necessitate a different behavior for dE and E galaxies, exactly as observed, in diagrams involving mu_e (and also _e). A natural consequence is that the distribution of dEs and Es in Fundamental Plane type analyses that use the associated intensity I_e, or _e, are expected to appear different. Together with other linear trends across the alleged dE/E boundary, such as those between luminosity and color, metallicity, and velocity dispersion, it appears that the dEs form a continuous extension to the E galaxies. The presence of partially depleted cores in luminous (M_B < -20.5 mag) Es does however signify the action of a different physical process at the centers (< ~300 pc) of these galaxies.Comment: 5 pages from the proceedings of the 2004 conference "Penetrating bars through masks of cosmic dust: the Hubble tuning fork strikes a new note". Edited by D. L. Block, I. Puerari, K. C. Freeman, R. Groess, and E. K. Bloc

    The rectal route of medicine administration for children: Let's get to the bottom of it!

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    Aims: Research around paediatric rectal drug delivery has previously been based on views of parents and healthcare workers. The aim of this exploratory study was to gauge whether children and young adults in the UK were comfortable with the idea of rectal drug delivery. / Methods: Eleven children from a pre-existing patient and public advisory group were involved in the session. Rectal drug delivery was explained and group participants were asked a series of questions. Responses were discussed in a group and recorded individually. /Results: Of the group, 27% would consider the rectal route, while 64% said it depended on other options available. The primary concern focused on potential for abusive misuse by others. Participants thought this would be overcome if the child could self-administer, although there was also concern about the process of self-administration. / Conclusions: Not all children in the UK are against rectal drug delivery, but education is needed to teach children to self-administer medication in this way
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