The cuttlefish Sepia officinalis (Sepiidae, Cephalopoda) constructs cuttlebone from a liquid-crystal precursor

Cuttlebone, the sophisticated buoyancy device of cuttlefish, is made of extensive superposed chambers that have a complex internal arrangement of calcified pillars and organic membranes. It has not been clear how this structure is assembled. We find that the membranes result from a myriad of minor membranes initially filling the whole chamber, made of nanofibres evenly oriented within each membrane and slightly rotated with respect to those of adjacent membranes, producing a helical arrangement. We propose that the organism secretes a chitin-protein complex, which self-organizes layer-by-layer as a cholesteric liquid crystal, whereas the pillars are made by viscous fingering. The liquid crystallization mechanism permits us to homologize the elements of the cuttlebone with those of other coleoids and with the nacreous septa and the shells of nautiloids. These results challenge our view of this ultra-light natural material possessing desirable mechanical, structural and biological properties, suggesting that two self-organizing physical principles suffice to understand its formation.Spanish Ministerio de Ciencia e Innovacion [CGL2010-20748-CO2-01, CGL2013-48247-P, FIS2013-48444-C2-2-P]; Andalusian Consejeria de Innovacion Ciencia y Tecnologia [RNM6433]; (Sepiatech, PROMAR program) of the Portuguese Ministerio da Agricultura e do Mar, Portugal [31.03.05.FEP.002]; Junta de Andalucia [RNM363]; FP7 COST Action of the European Community. [TD0903]info:eu-repo/semantics/publishedVersio

From Macroscopic to Microscopic: Experimental and Computational Methods to Investigate Bio-tribology

Tribology is an important factor (among other factors) during biological interactions of devices and tissues. The paper discusses how new computational and experimental methods can be used to understand and improve the design and development of medical devices at macro and micro scales to sustain life beyond 50 years. We have used pre-clinical experiments and computational methods to understand interactions between orthopaedic implants at the macro scale. The computational model has been validated with experiments. Now this computational model can predict damage in implants for different patients. One such application was successfully tried and tested in collaboration with University National Autonomous Mexico. This methodology can be used in future to design patient specific, affordable (using 3D printing) and robust implants which will be useful for developing countries like Vietnam, India and Mexico. Improvement of catheter designs is important to reduce damage to the internal tissues while being used for cardiovascular problems. We are developing new experimental techniques (in micro scale) that can be used to understand the interaction of cells with the catheter material. These will help reduce the hospital costs incurred during longer stay of the patients admitted for cardiovascular related problems

Quantization of Midisuperspace Models

We give a comprehensive review of the quantization of midisuperspace models. Though the main focus of the paper is on quantum aspects, we also provide an introduction to several classical points related to the definition of these models. We cover some important issues, in particular, the use of the principle of symmetric criticality as a very useful tool to obtain the required Hamiltonian formulations. Two main types of reductions are discussed: those involving metrics with two Killing vector fields and spherically symmetric models. We also review the more general models obtained by coupling matter fields to these systems. Throughout the paper we give separate discussions for standard quantizations using geometrodynamical variables and those relying on loop quantum gravity inspired methods.Comment: To appear in Living Review in Relativit

Do images of a personalised future body shape help with weight loss? A randomised controlled study

Background: This randomised controlled study evaluated a computer-generated future self-image as a personalised, visual motivational tool for weight loss in adults. Methods: One hundred and forty-five people (age 18–79 years) with a Body Mass Index (BMI) of at least 25 kg/m2 were randomised to receive a hard copy future self-image at recruitment (early image) or after 8 weeks (delayed image). Participants received general healthy lifestyle information at recruitment and were weighed at 4-weekly intervals for 24 weeks. The image was created using an iPad app called ‘Future Me’. A second randomisation at 16 weeks allocated either an additional future self-image or no additional image. Results: Seventy-four participants were allocated to receive their image at commencement, and 71 to the delayed-image group. Regarding to weight loss, the delayed-image group did consistently better in all analyses. Twenty-four recruits were deemed non-starters, comprising 15 (21%) in the delayed-image group and 9 (12%) in the early-image group (χ2(1) = 2.1, p = 0.15). At 24 weeks there was a significant change in weight overall (p \u3c 0.0001), and a difference in rate of change between groups (delayed-image group: −0.60 kg, early-image group: −0.42 kg, p = 0.01). Men lost weight faster than women. The group into which participants were allocated at week 16 (second image or not) appeared not to influence the outcome (p = 0.31). Analysis of all completers and withdrawals showed a strong trend over time (p \u3c 0.0001), and a difference in rate of change between groups (delayed-image: −0.50 kg, early-image: −0. 27 kg, p = 0.0008). Conclusion: One in five participants in the delayed-image group completing the 24-week intervention achieved a clinically significant weight loss, having received only future self-images and general lifestyle advice. Timing the provision of future self-images appears to be significant, and promising for future research to clarify their efficacy. Trial Registration: Australian Clinical Trials Registry, identifier: ACTRN12613000883718. Registered on 8 August 2013

The nature of fibrous dysplasia

Fibrous dysplasia has been regarded as a developmental skeletal disorder characterized by replacement of normal bone with benign cellular fibrous connective tissue. It has now become evident that fibrous dysplasia is a genetic disease caused by somatic activating mutation of the Gsα subunit of G protein-coupled receptor resulting in upregulation of cAMP. This leads to defects in differentiation of osteoblasts with subsequent production of abnormal bone in an abundant fibrous stroma. In addition there is an increased production of IL-6 by mutated stromal fibrous dysplastic cells that induce osteoclastic bone resorption

Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

Outcome related to impact on daily living: preliminary validation of the ORIDL instrument

<p>Abstract</p> <p>Background</p> <p>The challenge of finding practical, patient-rated outcome measures is a key issue in the evaluation of health care systems and interventions. The ORIDL (Outcome in Relation to Impact on Daily Living) instrument (formerly referred to as the Glasgow Homoeopathic Hospital Outcomes Scale or GHHOS) has been developed to measure patient's views of the outcome of their care by asking about change, and relating this to impact on daily life. The aim of the present paper is to describe the background and potential uses of the ORIDL, and to report on its preliminary validation in a series of three studies in secondary and primary care.</p> <p>Methods</p> <p>In the first study, 105 patients attending the Glasgow Homoeopathic Hospital (GHH) were followed-up at 12 months and changes in health status were measured by the EuroQol (EQOL) and the ORIDL. In the second study, 187 new patients at the GHH were followed-up at 3, 12, and 33 months, using the ORIDL, the Short Form 12 (SF-12), and the Measure Yourself Medical Outcome Profile (MYMOP). In study three, 323 patients in primary care were followed for 1 month post-consultation using the ORIDL and MYMOP. In all 3 studies the Patient Enablement Instrument (PEI) was also used as an outcome measure.</p> <p>Results</p> <p>Study 1 showed substantial improvements in main complaint and well-being over 12 months using the ORIDL, with two-thirds of patients reporting improvements in daily living. These improvements were not significantly correlated with changes in serial measures of the EQOL between baseline and 12 months, but were correlated with the EQOL transitions measure. Study 2 showed step-wise improvements in ORIDL scores between 3 and 33 months, which were only weakly associated with similar changes in SF-12 scores. However, MYMOP change scores correlated well with ORIDL scores at all time points. Study 3 showed similar high correlations between ORIDL scores and MYMOP scores. In all 3 studies, ORIDL scores were also significantly correlated with PEI-outcome scores.</p> <p>Conclusion</p> <p>There is significant agreement between patient outcomes assessed by the ORIDL and the EQOL transition scale, the MYMOP, and the PEI-outcome instrument, suggesting that the ORIDL may be a valid and sensitive tool for measuring change in relation to impact on life.</p