Designing games for older adults: an affordance based approach

The main purpose of this study is to determine the game principles that need to be adopted in order to create an enjoyable and engaging game experience for older adults, whilst ensuring that the purpose of the game, encouraging upper limb mobility, is respected. The study reported in this paper involved a group of older adults who played and gave feedback on an early game prototype which feed into the design modification process. Each player's action capabilities were measured and taken into account in the design process. This helped ensure that opportunities for action that the game afforded were adapted to players' need.

BAR domains as sensors of membrane curvature:the amphiphysin BAR structure

The BAR (Bin/amphiphysin/Rvs) domain is the most conserved feature in amphiphysins from yeast to human and is also found in endophilins and nadrins. We solved the structure of the Drosophila amphiphysin BAR domain. It is a crescent-shaped dimer that binds preferentially to highly curved negatively charged membranes. With its N-terminal amphipathic helix and BAR domain (N-BAR), amphiphysin can drive membrane curvature in vitro and in vivo. The structure is similar to that of arfaptin2, which we find also binds and tubulates membranes. From this, we predict that BAR domains are in many protein families, including sorting nexins, centaurins, and oligophrenins. The universal and minimal BAR domain is a dimerization, membrane-binding, and curvature-sensing module.

Physical activity assessment in cystic fibrosis: A position statement

Background

The aim of this position statement was to inform the choice of physical activity tools for use within CF research and clinical settings.

Methods

A systematic review of physical activity tools to explore evidence for reliability, validity, and responsiveness. Narrative answers to “four key questions” on motion sensors, questionnaires and diaries were drafted by the core writing team and then discussed at the Exercise Working Group in ECFS Lisbon 2013.

Results and summary

Our current position is that activity monitors such as SenseWear or ActiGraph offer informed choices to facilitate a comprehensive assessment of physical activity, and should as a minimum report on dimensions of physical activity including energy expenditure, step count and time spent in different intensities and sedentary time. The DigiWalker pedometer offers an informed choice of a comparatively inexpensive method of obtaining some measurement of physical activity. The HAES represents an informed choice of questionnaire to assess physical activity. There is insufficient data to recommend the use of one diary over another. Future research should focus on providing additional evidence of clinimetric properties of these and new physical activity assessment tools, as well as further exploring the added value of physical activity assessment in CF.

A Fast Algorithm for Sparse Support Vector Machines for Mobile Computing Applications

This research presents a fast algorithm for projected support vector machines (PSVM) by selecting a basis vector set (BVS) for the kernel-induced feature space, the training points are projected onto the subspace spanned by the selected BVS. A standard linear support vector machine (SVM) is then produced in the subspace with the projected training points. As the dimension of the subspace is determined by the size of the selected basis vector set, the size of the produced SVM expansion can be specified. A two-stage algorithm is derived which selects and refines the basis vector set achieving a locally optimal model. The model expansion coefficients and bias are updated recursively for increase and decrease in the basis set and support vector set. The condition for a point to be classed as outside the current basis vector and selected as a new basis vector is derived and embedded in the recursive procedure. This guarantees the linear independence of the produced basis set. The proposed algorithm is tested and compared with an existing sparse primal SVM (SpSVM) and a standard SVM (LibSVM) on seven public benchmark classification problems. Our new algorithm is designed for use in the application area of human activity recognition using smart devices and embedded sensors where their sometimes limited memory and processing resources must be exploited to the full and the more robust and accurate the classification the more satisfied the user. Experimental results demonstrate the effectiveness and efficiency of the proposed algorithm. This work builds upon a previously published algorithm specifically created for activity recognition within mobile applications for the EU Haptimap project [1]. The algorithms detailed in this paper are more memory and resource efficient making them suitable for use with bigger data sets and more easily trained SVMs.

Is the raised volume rapid thoracic compression technique ready for use in clinical trials in infants with cystic fibrosis?

The European Cystic Fibrosis Society Clinical Trial Network (ECFS-CTN) has established a Standardization Committee to undertake a rigorous evaluation of promising outcome measures with regard to use in multicentre clinical trials in cystic fibrosis (CF). The aim of this article is to present a review of literature on clinimetric properties of the infant raised-volume rapid thoracic compression (RVRTC) technique in the context of CF, to summarise the consensus amongst the group on feasibility and answer key questions regarding the promotion of this technique to surrogate endpoint status.

METHODS: A literature search (from 1985 onwards) identified 20 papers that met inclusion criteria of RVRTC use in infants with CF. Data were extracted and tabulated regarding repeatability, validity, correlation with other outcome measures, responsiveness and reference values. A working group discussed the tables and answered 4 key questions.

RESULTS: Overall, RVRTC in particular forced expiratory volume in 0.5s, showed good clinimetric properties despite presence of individual variability. Few studies showed a relationship between RVRTC and inflammation and infection, and to date, data remains limited regarding the responsiveness of RVRTC after an intervention. Concerns were raised regarding feasibility in multi-centre studies and availability of reference values.

CONCLUSION: The ECFS-CTN Working Group considers that RVRTC cannot be used as a primary outcome in clinical trials in infants with CF before universal standardization of this measurement is achieved and implementation of inter-institutional networking is in place. We advise its use currently in phase I/II trials and as a secondary endpoint in phase III studies. We emphasise the need for (1) more short-term variability and longitudinal 'natural history' studies, and (2) robust reference values for commercially available devices.

Endothelium-derived intermedin/adrenomedullin-2 protects human ventricular cardiomyocytes from ischaemia-reoxygenation injury predominantly via the AM1 receptor

Application of intermedin/adrenomedullin-2 (IMD/AM-2) protects cultured human cardiac vascular cells and fibroblasts from oxidative stress and simulated ischaemia-reoxygenation injury (I-R), predominantly via adrenomedullin AM1 receptor involvement; similar protection had not been investigated previously in human cardiomyocytes (HCM). Expression of IMD, AM and their receptor components was studied in HCM. Receptor subtype involvement in protection by exogenous IMD against injury by simulated I-R was investigated using receptor component-specific siRNAs. Direct protection by endogenous IMD against HCM injury, both as an autocrine factor produced in HCM themselves and as a paracrine factor released from HCMEC co-cultured with HCM, was investigated using peptide-specific siRNA for IMD. IMD, AM and their receptor components (CLR, RAMPs1-3) were expressed in HCM. IMD 1 nmol L−1, applied either throughout ischaemia (3 h) and re-oxygenation (1 h) or during re-oxygenation (1 h) alone, attenuated HCM injury (P < 0.05); cell viabilities were 59% and 61% respectively vs. 39% in absence of IMD. Cytoskeletal disruption, protein carbonyl formation and caspase activity followed similar patterns. Pre-treatment (4 days) of HCM with CLR and RAMP2 siRNAs attenuated (P < 0.05) protection by exogenous IMD. Pre-treatment of HCMEC with IMD (and AM) siRNA augmented (P < 0.05) I-R injury: cell viabilities were 22% (and 32%) vs. 39% untreated HCMEC. Pre-treatment of HCM with IMD (and AM) siRNA did not augment HCM injury: cell viabilities were 37% (and 39%) vs. 39% untreated HCM. Co-culture with HCMEC conferred protection from injury on HCM; such protection was attenuated when HCMEC were pre-treated with IMD (but not AM) siRNA before co-culture. Although IMD is present in HCM, IMD derived from HCMEC and acting in a paracrine manner, predominantly via AM1 receptors, makes a marked contribution to cardiomyocyte protection by the endogenous peptide against acute I-R injury.

Inhibition of protease-ENaC signaling improves mucociliary function in cystic fibrosis airways

Rationale: In cystic fibrosis (CF) a reduction in airway surface liquid (ASL) height
compromises mucociliary clearance, favoring mucus plugging and chronic bacterial infection. Inhibitors of ENaC have therapeutic potential in CF airways to reduce the hyperstimulated sodium and fluid absorption to levels which can restore airways hydration.

Objectives: To determine whether a novel compound (QUB-TL1) designed to inhibit protease/ENaC signaling in CF airways restores ASL volume and mucociliary function.

Methods: Protease activity was measured using fluorogenic activity assays. Differentiated primary airway epithelial cell cultures (F508del homozygotes) were used to determined ENaC activity (Ussing chamber recordings), ASL height (confocal microscopy) and mucociliary function (by tracking the surface flow of apically applied microbeads). Cell toxicity was measured by LDH assay.

Measurements and Results: QUB-TL1 inhibits extracellularly-located CAPs, including prostasin, matriptase and furin, the activities of which are observed at excessive levels at the apical surface of CF airway epithelial cells (AECs). QUB-TL1-mediated CAPs inhibition results in diminished ENaC-mediated Na+ absorption in CF AECs due to internalization of a prominent pool of cleaved (active) ENaCγ from the cell surface. Importantly, diminished ENaC activity correlates with improved airway hydration status and mucociliary clearance. We further demonstrate QUB-TL1-mediated furin inhibition, which is in contrast to other serine protease inhibitors (camostat mesylate and aprotinin), affords protection against neutrophil elastase-mediated ENaC activation and Pseudomonas aeruginosa exotoxin A induced cell death.

Conclusions: QUB-TL1 corrects aberrant CAP activities providing a mechanism to delay or prevent the development of CF lung disease in a manner independent of CFTR mutation.

Fluid strategies and outcomes in patients with acute respiratory distress syndrome, systemic inflammatory response syndrome and sepsis: a protocol for a systematic review and meta-analysis

Background
Fluid administration to critically ill patients remains the subject of considerable controversy. While intravenous fluid given for resuscitation may be life-saving, a positive fluid balance over time is associated with worse outcomes in critical illness. The aim of this systematic review is to summarise the existing evidence regarding the relationship between fluid administration or balance and clinically important patient outcomes in critical illness.

Methods
We will search Medline, EMBASE, the Cochrane Central Register of Controlled Trials from 1980 to the present and key conference proceedings from 2009 to the present. We will include studies of critically ill adults and children with acute respiratory distress syndrome (ARDS), sepsis and systemic inflammatory response syndrome (SIRS). We will include randomised controlled trials comparing two or more fluid regimens of different volumes of fluid and observational studies reporting the relationship between volume of fluid administered or fluid balance and outcomes including mortality, lengths of intensive care unit and hospital stay and organ dysfunction. Two independent reviewers will assess articles for eligibility, data extraction and quality appraisal. We will conduct a narrative and/or meta-analysis as appropriate.

Discussion
While fluid management has been extensively studied and discussed in the critical care literature, no systematic review has attempted to summarise the evidence for post-resuscitation fluid strategies in critical illness. Results of the proposed systematic review will inform practice and the design of future clinical trials.

Systematic review registration
PROSPERO CRD42013005608. (http://​www.​crd.​york.​ac.​uk/​PROSPERO/​)

NAA and STS effects on bract survival time, carbohydrate content, respiration rate and carbohydrate balance of potted Bougainvillea spectabilis Willd

The aims of this work were to deepen the knowledge on the physiology of bract abscission in Bougainvillea spectabilis ‘Killie Campbell’ plants, in what relates to respiration and carbon balance. Using the effects induced by Silver Thiosulphate (STS) and/or Naphtalene Acetic Acid (NAA, at high concentration: 500 mg.l-1) on bract abscission under interior conditions, the relationship between bract survival time (longevity) and, respiration rate or carbohydrate levels, was investigated. Treatments that included NAA were the ones that reduced significantly bract abscission. Unexpectedly, the higher the levels of bract soluble and total carbohydrates, measured at day 10 postproduction (PP), the higher the abscission of bracts. These results show, for the first time, that abscission can positively correlate with non structural carbohydrates levels in the organ that abscise. Bract respiration rate was significantly affected by treatment and postproduction day (PP). Treatments that had higher bract respiration rates (WATER and STS) also had higher levels of non structural carbohydrates in the bracts. Bract respiration rate decreased from day 10 to day 17 PP by approximately 50% (on average of all treatments) and was negatively correlated with bract survival time. In the carbon balance per gram of bract dry weight, the treatments WATER and STS, showed the largest decrease in the content of total carbohydrates and had the highest consumption of carbohydrates through respiration. So, these were the bracts that needed to import a higher amount of carbohydrates per gram of bract dry weight. In the carbon balance for the whole mass of bracts and adjacent stems in an average plant, the treatments WATER and STS continued to allow for the largest decreases in total carbohydrate during postproduction. However, and contradicting the results per gram of bract dry weight, the highest total consumption of carbohydrates by respiration was obtained for the NAA and STS+NAA treatments. It makes sense that bracts that last longer have lower individual carbon consumption while, at the plant level, the increased number of remaining bracts causes a higher overall expenditure. Respiration rate has been used as an indicator of flower longevity, this correlation is here extended for the flower+bract system. Plants that had higher bract respiration rates, most probably, had a higher flow of carbohydrates through the bracts (and flowers), which, in the end, was sensed as a higher carbohydrate level.

CarolFest 2008, December 2, 2008

Concert Program for CarolFest 2008, December 2, 2008

The Winter Jazz Concert, December 8, 1976

Concert program for The Winter Jazz Concert, December 8, 1976

Perceptual user interface framework for immersive information retrieval environments (An experimental framework for testing and rapid iteration)

The use of perceptual inputs is an emerging area within HCI that suggests a developing Perceptual User Interface (PUI) that may prove advantageous for those involved in mobile serious games and immersive social network environments. Since there are a large variety of input devices, software platforms, possible interactions, and myriad ways to combine all of the above elements in pursuit of a PUI, we propose in this paper a basic experimental framework that will be able to standardize study of the wide range of interactive applications for testing efficacy in learning or information retrieval and also suggest improvements to emerging PUIs by enabling quick iteration. This rapid iteration will start to define a targeted range of interactions that will be intuitive and comfortable as perceptual inputs, and enhance learning and information retention in comparison to traditional GUI systems. The work focuses on the planning of the technical development of two scenarios, and the first steps in developing a framework to evaluate these and other PUIs for efficacy and pedagogy.

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.