Interaction design issues for car navigation systems

We describe a study on the interaction design of in-car navigation systems. It focused on a commercial product. Critical incident analysis was performed based on natural use of the system by a usability analyst. A cognitive walkthrough was then performed based on actual scenarios from the natural use. This is a non-classic application of cognitive walkthrough. It allowed anecdotal critical incidents to be theoretically grounded. We draw conclusions about the interaction design of car navigation systems

The development of compartmentation of cAMP signaling in cardiomyocytes: the role of T-Tubules and caveolae microdomains

3′-5′-cyclic adenosine monophosphate (cAMP) is a signaling messenger produced in response to the stimulation of cellular receptors, and has a myriad of functional applications depending on the cell type. In the heart, cAMP is responsible for regulating the contraction rate and force; however, cAMP is also involved in multiple other functions. Compartmentation of cAMP production may explain the specificity of signaling following a stimulus. In particular, transverse tubules (T-tubules) and caveolae have been found to be critical structural components for the spatial confinement of cAMP in cardiomyocytes, as exemplified by beta-adrenergic receptor (β-ARs) signaling. Pathological alterations in cardiomyocyte microdomain architecture led to a disruption in compartmentation of the cAMP signal. In this review, we discuss the difference between atrial and ventricular cardiomyocytes in respect to microdomain organization, and the pathological changes of atrial and ventricular cAMP signaling in response to myocyte dedifferentiation. In addition, we review the role of localized phosphodiesterase (PDE) activity in constraining the cAMP signal. Finally, we discuss microdomain biogenesis and maturation of cAMP signaling with the help of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Understanding these mechanisms may help to overcome the detrimental effects of pathological structural remodeling

Central Nervous System Disease in phase III studies for advanced HER2 Positive Breast Cancer: A Review

IMPORTANCE: The introduction of human epidermal growth factor receptor 2 (HER2) directed therapy has transformed the outcomes of patients with advanced breast cancer (BC). However, HER2 positive breast cancer has a predilection for the central nervous system (CNS) which is associated with significant morbidity and mortality. Understanding the intracranial activity of novel HER2 directed agents is key to developing treatments as well as possible preventative strategies for HER2-positive CNS disease. OBSERVATIONS: Using protocols and data from published phase III clinical trials for locally advanced/metastatic HER2-positive breast cancer since the licensing of single agent trastuzumab for advanced BC we review the central nervous system related aspects. This includes CNS related entry criteria, use of baseline and on study cross-sectional imaging of the CNS and protocol and non-protocol defined CNS end points and reported data. CONCLUSIONS: and Relevance: This review found heterogeneity between studies with regard to the entry criteria, use of CNS imaging and reported end points within the pivotal phase III studies. Based on these data, a standardisation of both entry criteria and end points with regard to the CNS should be developed and applied to future studies of HER2-positive advanced BC. Such an approach would enable the generation of comparable data and allow a meaningful analysis of different treatment approaches with regard to the CNS. This in turn would allow the development of the most optimal treatment approaches for HER2 positive CNS disease and ultimately the development of preventative strategies

Changes in Nutrient Turnover and Supply During the Reversion of Arable Land to Acid Grassland/\u3ci\u3eCalluna\u3c/i\u3e Heathland

Lowland heath is of high conservation value because of the specialised and rare assemblages of plants and animals that it supports. Combinations of agricultural and urban development, and lack of appropriate management have resulted in large-scale loss and fragmentation of this habitat throughout the UK. Current UK conservation policies seek to re-create 6,000 ha of this habitat on land previously in agricultural and forestry production. Previous research indicated that high soil pH and fertility, together with a lack of propagules of heathland species, made it difficult to achieve this objective. The aim was to evaluate techniques to establish grass-Calluna heathland on ex-arable land in the Brecklands Environmentally Sensitive Area (ESA) in Norfolk, in particular, to assess the need for soil acidification to reduce competition and aid the establishment of Calluna

Autophagy: A cyto-protective mechanism which prevents primary human hepatocyte apoptosis during oxidative stress

The role of autophagy in the response of human hepatocytes to oxidative stress remains unknown. Understanding this process may have important implications for the understanding of basic liver epithelial cell biology and the responses of hepatocytes during liver disease. To address this we isolated primary hepatocytes from human liver tissue and exposed them ex vivo to hypoxia and hypoxia-reoxygenation (H-R). We showed that oxidative stress increased hepatocyte autophagy in a reactive oxygen species (ROS) and class III PtdIns3K-dependent manner. Specifically, mitochondrial ROS and NADPH oxidase were found to be key regulators of autophagy. Autophagy involved the upregulation of BECN1, LC3A, Atg7, Atg5 and Atg 12 during hypoxia and H-R. Autophagy was seen to occur within the mitochondria of the hepatocyte and inhibition of autophagy resulted in the lowering a mitochondrial membrane potential and onset of cell death. Autophagic responses were primarily observed in the large peri-venular (PV) hepatocyte subpopulation. Inhibition of autophagy, using 3-methyladenine, increased apoptosis during H-R. Specifically, PV human hepatocytes were more susceptible to apoptosis after inhibition of autophagy. These findings show for the first time that during oxidative stress autophagy serves as a cell survival mechanism for primary human hepatocytes

A research note on the Influence of relationship length and sex on preferences for altruistic and cooperative mates

Previous literature suggests that altruism may have evolved as a sexually selectable trait. Recent research suggests that women seek altruistic traits for long-term, not short-term relationships, as altruism can serve as an honest signal of one’s character. We tested this hypothesis by asking 102 participants to complete a modified version of Buss’s Mate Preferences Questionnaire. We found that women placed higher importance on altruism in a mate compared to men, and this preference was greater when seeking a long-term mate, compared to a short-term mate. We also found that although women placed greater importance on cooperativeness in a mate compared to men, this preference was not influenced by whether they were seeking a short-term or a long-term mate. We successfully replicate previous literature exploring the role of altruism in mate choice

Utilising semantic technologies for intelligent indexing and retrieval of digital images

The proliferation of digital media has led to a huge interest in classifying and indexing media objects for generic search and usage. In particular, we are witnessing colossal growth in digital image repositories that are difficult to navigate using free-text search mechanisms, which often return inaccurate matches as they in principle rely on statistical analysis of query keyword recurrence in the image annotation or surrounding text. In this paper we present a semantically-enabled image annotation and retrieval engine that is designed to satisfy the requirements of the commercial image collections market in terms of both accuracy and efficiency of the retrieval process. Our search engine relies on methodically structured ontologies for image annotation, thus allowing for more intelligent reasoning about the image content and subsequently obtaining a more accurate set of results and a richer set of alternatives matchmaking the original query. We also show how our well-analysed and designed domain ontology contributes to the implicit expansion of user queries as well as the exploitation of lexical databases for explicit semantic-based query expansion

Application of oxygen saturation variability analysis for the detection of exacerbation in individuals with COPD: A proof-of-concept study

BACKGROUND: Individuals with chronic obstructive pulmonary disease (COPD) commonly experience exacerbations, which may require hospital admission. Early detection of exacerbations, and therefore early treatment, could be crucial in preventing admission and improving outcomes. Our previous research has demonstrated that the pattern analysis of peripheral oxygen saturation (Sp O2 ) fluctuations provides novel insights into the engagement of the respiratory control system in response to physiological stress (hypoxia). Therefore, this pilot study tested the hypothesis that the pattern of Sp O2 variations in overnight recordings of individuals with COPD would distinguish between stable and exacerbation phases of the disease. METHODS: Overnight pulse oximetry data from 11 individuals with COPD, who exhibited exacerbation after a period of stable disease, were examined. Stable phase recordings were conducted overnight and one night prior to exacerbation recordings were also analyzed. Pattern analysis of Sp O2 variations was carried examined using sample entropy (for assessment of irregularity), the multiscale entropy (complexity), and detrended fluctuation analysis (self-similarity). RESULTS: Sp O2 variations displayed a complex pattern in both stable and exacerbation phases of COPD. During an exacerbation, Sp O2 entropy increased (p = 0.029) and long-term fractal-like exponent (α2) decreased (p = 0.002) while the mean and standard deviation of Sp O2 time series remained unchanged. Through ROC analyses, Sp O2 entropy and α2 were both able to classify the COPD phases into either stable or exacerbation phase. With the best positive predictor value (PPV) for sample entropy (PPV = 70%) and a cut-off value of 0.454. While the best negative predictor value (NPV) was α2 (NPV = 78%) with a cut-off value of 1.00. CONCLUSION: Alterations in Sp O2 entropy and the fractal-like exponent have the potential to detect exacerbations in COPD. Further research is warranted to examine if Sp O2 variability analysis could be used as a novel objective method of detecting exacerbations

The Protective Effect of Ursodeoxycholic Acid in an in vitro model of the Human Fetal Heart occurs via Targeting Cardiac Fibroblasts

Bile acids are elevated in the blood of women with intrahepatic cholestasis of pregnancy (ICP) and this may lead to fetal arrhythmia, fetal hypoxia and potentially fetal death in utero. The bile acid taurocholic acid (TC) causes abnormal calcium dynamics and contraction in neonatal rat cardiomyocytes. Ursodeoxycholic acid (UDCA), a drug clinically used to treat ICP, prevents adverse effects of TC. During development, the fetus is in a state of relative hypoxia. Although this is essential for the development of the heart and vasculature, resident fibroblasts can transiently differentiate into myofibroblasts and form gap junctions with cardiomyocytes in vitro, resulting in cardiomyocyte depolarization. We expanded on previously published work using an in vitro hypoxia model to investigate the differentiation of human fetal fibroblasts into myofibroblasts.Recent evidence shows that potassium channels are involved in maintaining the membrane potential of ventricular fibroblasts and that ATP-dependent potassium (KATP) channel subunits are expressed in cultured fibroblasts. KATP channels are a valuable target as they are thought to have a cardioprotective role during ischaemic and hypoxic conditions. We investigated whether UDCA could modulate fibroblast membrane potential.We established the isolation and culture of human fetal cardiomyocytes and fibroblasts to investigate the effect of hypoxia, TC and UDCA on human fetal cardiac cells.UDCA hyperpolarized myofibroblasts and prevented TC-induced depolarisation, possibly through the activation of KATP channels that are expressed in cultured fibroblasts. Also, similar to the rat model, UDCA can counteract TC-induced calcium abnormalities in human fetal cultures of cardiomyocytes and myofibroblasts. Under normoxic conditions, we found a higher number of myofibroblasts in cultures derived from human fetal hearts compared to cells isolated from neonatal rat hearts, indicating a possible increased number of myofibroblasts in human fetal hearts. Hypoxia further increased the number of human fetal and rat neonatal myofibroblasts. However, chronically administered UDCA reduced the number of myofibroblasts and prevented hypoxia-induced depolarisation.In conclusion, our results show that the protective effect of UDCA involves both the reduction of fibroblast differentiation into myofibroblasts, and hyperpolarisation of myofibroblasts, most likely through the stimulation of potassium channels, i.e. KATP channels. This could be important in validating UDCA as an antifibrotic and antiarrhythmic drug for treatment of failing hearts and fetal arrhythmia