A context-aware adaptive feedback agent for activity monitoring and coaching

A focus in treatment of chronic diseases is optimizing levels of physical activity. At Roessingh Research and Development, a system was developed, consisting of a Smartphone and an activity sensor, that can measure a patient’s daily activity behavior and provide motivational feedback messages. We are currently looking into ways of increasing the effectiveness of motivational messages that aim to stimulate sustainable behavioral change, by adapting its timing and content to individual patients in their current context of use

BI 6727 and gemcitabine combination therapy in pancreatic cancer

Introduction: Though adjuvant chemotherapy improves survival following surgery, pancreatic cancer carries a poor prognosis. Alternatives are required to the current drug regimens consisting of S-phase dependent drugs such as gemcitabine. PLK1 is a passenger protein involved in G2/M phases which presents a novel target to inhibit in combination with current therapies, which may help overcome inate and acquired resistance. Aim: To evaluate the potential role of a novel PLK1 inhibitor, BI 6727 in pancreatic cancer – both as monotherapy and in combination with gemcitabine in vitro. Methods: The IC50 concentrations of both drugs were established in Suit-2, BxPC-3, Panc-1 and MiaPaCa-2 pancreatic cancer cell lines and isobolar analyses undertaken with a variety of combination therapies. Cell cycle analyses were performed with Flow Activated Cell Sorting, with apoptosis and necrosis quantified on the basis of phosphatidylserine cell surface exposure, propidium iodide staining and cleavage of caspase-3. Results: IC50 ranges for BI 6727 and gemcitabine were 53-77nM and 11-34nM respectively across four pancreatic cell lines. Flow cytometry of MiaPaCa-2 cells demonstrated G2 arrest with BI 6727 and S-phase accumulation with gemcitabine monotherapy. Isobolar analyses showed that when added together the combination of drugs was additive, but BI 6727 pretreatment followed by combination was synergistic. Western blotting for cleaved caspase-3 showed evidence of apoptosis with gemcitabine monotherapy but none with BI 6727 treatment. Although membrane inversion was seen with synergistic drug combinations there was no evidence of cleaved-caspase-3, suggesting a modified form of apoptosis. Conclusion: BI 6727 is effective against a variety of pancreatic cancer cells in vitro. Synergy is demonstrated in MiaPaCa-2 cells when BI 6727 is administered prior to combination therapy with gemcitabine, though mode of cell death does not appear to be caspase-dependent. This supports the concept that PLK1 inhibition can overcome gemcitabine resistance in some cells by allowing resistant cells to initiate gemcitabine induced apoptosis, although this is dependent on drug phasing and the full apoptotic pathway may not be achieved

A Context-Aware Adaptive Feedback System for Activity Monitoring

An active lifestyle is an important factor in the prevention of deconditioning and many negative secondary effects in chronic diseases (e.g. COPD). A number of studies have been conducted with the aim of gaining insight into the daily activity patterns of these patients. Current research is focussing on motivating patients to stay physically active and balancing their activity patterns by using an activity sensor combined with remote monitoring and smart, personalised feedback

Functionally distinct contributions of the anterior and posterior putamen during sublexical and lexical reading.

Previous studies have investigated orthographic-to-phonological mapping during reading by comparing brain activation for (1) reading words to object naming, or (2) reading pseudowords (e.g., "phume") to words (e.g., "plume"). Here we combined both approaches to provide new insights into the underlying neural mechanisms. In fMRI data from 25 healthy adult readers, we first identified activation that was greater for reading words and pseudowords relative to picture and color naming. The most significant effect was observed in the left putamen, extending to both anterior and posterior borders. Second, consistent with previous studies, we show that both the anterior and posterior putamen are involved in articulating speech with greater activation during our overt speech production tasks (reading, repetition, object naming, and color naming) than silent one-back-matching on the same stimuli. Third, we compared putamen activation for words versus pseudowords during overt reading and auditory repetition. This revealed that the anterior putamen was most activated by reading pseudowords, whereas the posterior putamen was most activated by words irrespective of whether the task was reading words or auditory word repetition. The pseudoword effect in the anterior putamen is consistent with prior studies that associated this region with the initiation of novel sequences of movements. In contrast, the heightened word response in the posterior putamen is consistent with other studies that associated this region with "memory guided movement." Our results illustrate how the functional dissociation between the anterior and posterior putamen supports sublexical and lexical processing during reading

Four Functionally Distinct Regions in the Left Supramarginal Gyrus Support Word Processing

We used fMRI in 85 healthy participants to investigate whether different parts of the left supramarginal gyrus (SMG) are involved in processing phonological inputs and outputs. The experiment involved 2 tasks (speech production (SP) and one-back (OB) matching) on 8 different types of stimuli that systematically varied the demands on sensory processing (visual vs. auditory), sublexical phonological input (words and pseudowords vs. nonverbal stimuli), and semantic content (words and objects vs. pseudowords and meaningless baseline stimuli). In ventral SMG, we found an anterior subregion associated with articulatory sequencing (for SP > OB matching) and a posterior subregion associated with auditory short-term memory (for all auditory > visual stimuli and written words and pseudowords > objects). In dorsal SMG, a posterior subregion was most highly activated by words, indicating a role in the integration of sublexical and lexical cues. In anterior dorsal SMG, activation was higher for both pseudoword reading and object naming compared with word reading, which is more consistent with executive demands than phonological processing. The dissociation of these four “functionally-distinct” regions, all within left SMG, has implications for differentiating between different types of phonological processing, understanding the functional anatomy of language and predicting the effect of brain damage

Avatars of Eurocentrism in the critique of the liberal peace

Recent scholarly critiques of the so-called liberal peace raise important political and ethical challenges to practices of postwar intervention in the global South. However, their conceptual and analytic approaches have tended to reproduce rather than challenge the intellectual Eurocentrism underpinning the liberal peace. Eurocentric features of the critiques include the methodological bypassing of target subjects in research, the analytic bypassing of subjects through frameworks of governmentality, the assumed ontological split between the ‘liberal’ and the ‘local’, and a nostalgia for the liberal subject and the liberal social contract as alternative bases for politics. These collectively produce a ‘paradox of liberalism’ that sees the liberal peace as oppressive but also the only true source of emancipation. However, the article suggests that a repoliticization of colonial difference offers an alternative ‘decolonizing’ approach to critical analysis through repositioning the analytic gaze. Three alternative research strategies for critical analysis are briefly developed

Hyaluronan derived nanoparticle for simvastatin delivery: evaluation of simvastatin induced myotoxicity in tissue engineered skeletal muscle

Statins are currently the most prescribed hypercholesterolemia-lowering drugs worldwide, with estimated usage approaching one-sixth of the population. However, statins are known to cause pleiotropic skeletal myopathies in 1.5% to 10% of patients and the mechanisms by which statins induce this response, are not fully understood. In this study, a 3D collagen-based tissue-engineered skeletal muscle construct is utilised as a screening platform to test the efficacy and toxicity of a new delivery system. A hyaluronic acid derived nanoparticle loaded with simvastatin (HA-SIM-NPs) is designed and the effect of free simvastatin and HA-SIM-NPs on cellular, molecular and tissue response is investigated. Morphological ablation of myotubes and lack of de novo myotube formation (regeneration) was evident at the highest concentrations (333.33 μM), independent of delivery vehicle (SIM or HA-SIM-NP). A dose-dependent disruption of the cytoskeleton, reductions in metabolic activity and tissue engineered (TE) construct tissue relaxation was evident in the free drug condition (SIM, 3.33 μM and 33.33 nM). However, most of these changes were ameliorated when SIM was delivered via HA-SIM-NPs. Significantly, homogeneous expressions of MMP2, MMP9, and myogenin in HA-SIM-NPs outlined enhanced regenerative responses compared to SIM. Together, these results outline statin delivery via HA-SIM-NP as an effective delivery mechanism to inhibit deleterious myotoxic side-effects

Predicting feedback compliance in a teletreatment application

Health care provision is facing resourcing challenges which will further increase in the 21st century. Health care mediated by technology is widely seen as one important element in the struggle to maintain existing standards of care. Personal health monitoring and treatment systems with a high degree of autonomic operation will be required to support self-care. Such systems must provide many services and in most cases must incorporate feedback to patients to advise them how to manage the daily details of their treatment and lifestyle changes. As in many other areas of healthcare, patient compliance is however an issue. In this experiment we apply machine learning techniques to three corpora containing data from trials of body worn systems for activity monitoring and feedback. The overall objective is to investigate how to improve feedback compliance in patients using personal monitoring and treatment systems, by taking into account various contextual features associated with the feedback instances. In this article we describe our first machine learning experiments. The goal of the experiments is twofold: to determine a suitable classification algorithm and to find an optimal set of contextual features to improve the performance of the classifier. The optimal feature set was constructed using genetic algorithms. We report initial results which demonstrate the viability of this approach

Multilevel Mentoring Using TBL

Produce an action plan for using TBL in existing classroom applications, training programs, training faculty and future faculty, research teams, capstone projects, faculty learning community, scholarship using TBL