340 research outputs found

    Cognitive Principles of Schematisation for Wayfinding Assistance

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    People often need assistance to successfully perform wayfinding tasks in unfamiliar environments. Nowadays, a huge variety of wayfinding assistance systems exists. All these systems intend to present the needed information for a certain wayfinding situation in an adequate presentation. Some wayfinding assistance systems utilize findings for the field of cognitive sciences to develop and design cognitive ergonomic approaches. These approaches aim to be systems with which the users can effortless interact with and which present needed information in a way the user can acquire the information naturally. Therefore it is necessary to determinate the information needs of the user in a certain wayfinding task and to investigate how this information is processed and conceptualised by the wayfinder to be able to present it adequately. Cognitive motivated schematic maps are an example which employ this knowledge and emphasise relevant information and present it in an easily readable way. In my thesis I present a transfer approach to reuse the knowledge of well-grounded knowledge of schematisation techniques from one externalisation such as maps to another externalization such as virtual environments. A analysis of the informational need of the specific wayfinding task route following is done one the hand of a functional decomposition as well as a deep analysis of representation-theoretic consideration of the external representations maps and virtual environments. Concluding from these results, guidelines for transferring schematisation principles between different representation types are proposed. Specifically, this thesis chose the exemplary transfer of the schematisation technique wayfinding choremes from a map presentation into a virtual environment to present the theoretic requirements for a successful transfer. Wayfinding choremes are abstract mental concepts of turning action which are accessible as graphical externalisation integrated into route maps. These wayfinding choremes maps emphasis the turning action along the route by displaying the angular information as prototypes of 45° or 90°. This schematisation technique enhances wayfinding performance by supporting the matching processes between the map representation and the internal mental representation of the user. I embed the concept of wayfinding choremes into a virtual environment and present a study to test if the transferred schematisation technique also enhance the wayfinding performance. The empirical investigations present a successful transfer of the concept of the wayfinding choremes. Depending on the complexity of the route the embedded schematization enhance the wayfinding performance of participants who try to follow a route from memory. Participants who trained and recall the route in a schematised virtual environment make fewer errors than the participants of the unmodified virtual world. This thesis sets an example of the close research circle of cognitive behavioural studies to representation-theoretical considerations to applications of wayfinding assistance and their evaluations back to new conclusions in cognitive science. It contributes an interdisciplinary comprehensive inspection of the interplay of environmental factors and mental processes on the example of angular information and mental distortion of this information

    What have transgenic and knockout animals taught us about respiratory disease?

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    Over the past decade there has been a significant shift to the use of murine models for investigations into the molecular basis of respiratory diseases, including asthma and chronic obstructive pulmonary disease. These models offer the exciting prospect of dissecting the complex interaction between cytokines, chemokines and growth related peptides in disease pathogenesis. Furthermore, the receptors and the intracellular signalling pathways that are subsequently activated are amenable for study because of the availability of monoclonal antibodies and techniques for targeted gene disruption and gene incorporation for individual mediators, receptors and proteins. However, it is clear that extrapolation from these models to the human condition is not straightforward, as reflected by some recent clinical disappointments. This is not necessarily a problem with the use of mice itself, but results from our continued ignorance of the disease process and how to improve the modelling of complex interactions between different inflammatory mediators that underlie clinical pathology. This review highlights some of the strengths and weaknesses of murine models of respiratory disease

    Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

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    Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

    Screening of protein kinase inhibitors identifies PKC inhibitors as inhibitors of osteoclastic acid secretion and bone resorption

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    <p>Abstract</p> <p>Background</p> <p>Bone resorption is initiated by osteoclastic acidification of the resorption lacunae. This process is mediated by secretion of protons through the V-ATPase and chloride through the chloride antiporter ClC-7. To shed light on the intracellular signalling controlling extracellular acidification, we screened a protein kinase inhibitor library in human osteoclasts.</p> <p>Methods</p> <p>Human osteoclasts were generated from CD14+ monocytes. The effect of different kinase inhibitors on lysosomal acidification in human osteoclasts was investigated using acridine orange for different incubation times (45 minutes, 4 and 24 hours). The inhibitors were tested in an acid influx assay using microsomes isolated from human osteoclasts. Bone resorption by human osteoclasts on bone slices was measured by calcium release. Cell viability was measured using AlamarBlue.</p> <p>Results</p> <p>Of the 51 compounds investigated only few inhibitors were positive in both acidification and resorption assays. Rottlerin, GF109203X, Hypericin and Ro31-8220 inhibited acid influx in microsomes and bone resorption, while Sphingosine and Palmitoyl-DL-carnitine-Cl showed low levels of inhibition. Rottlerin inhibited lysosomal acidification in human osteoclasts potently.</p> <p>Conclusions</p> <p>In conclusion, a group of inhibitors all indicated to inhibit PKC reduced acidification in human osteoclasts, and thereby bone resorption, indicating that acid secretion by osteoclasts may be specifically regulated by PKC in osteoclasts.</p

    Fenoldopam use in a burn intensive care unit: a retrospective study

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    <p>Abstract</p> <p>Background</p> <p>Fenoldopam mesylate is a highly selective dopamine-1 receptor agonist approved for the treatment of hypertensive emergencies that may have a role at low doses in preserving renal function in those at high risk for or with acute kidney injury (AKI). There is no data on low-dose fenoldopam in the burn population. The purpose of our study was to describe our use of low-dose fenoldopam (0.03-0.09 μg/kg/min) infusion in critically ill burn patients with AKI.</p> <p>Methods</p> <p>We performed a retrospective analysis of consecutive patients admitted to our burn intensive care unit (BICU) with severe burns from November 2005 through September 2008 who received low-dose fenoldopam. Data obtained included systolic blood pressure, serum creatinine, vasoactive medication use, urine output, and intravenous fluid. Patients on concomitant continuous renal replacement therapy were excluded. Modified inotrope score and vasopressor dependency index were calculated. One-way analysis of variance with repeated measures, Wilcoxson signed rank, and chi-square tests were used. Differences were deemed significant at p < 0.05.</p> <p>Results</p> <p>Seventy-seven patients were treated with low-dose fenoldopam out of 758 BICU admissions (10%). Twenty (26%) were AKI network (AKIN) stage 1, 14 (18%) were AKIN stage 2, 42 (55%) were AKIN stage 3, and 1 (1%) was AKIN stage 0. Serum creatinine improved over the first 24 hours and continued to improve through 48 hours (<it>p </it>< 0.05). There was an increase in systolic blood pressure in the first 24 hours that was sustained through 48 hours after initiation of fenoldopam (<it>p </it>< 0.05). Urine output increased after initiation of fenoldopam without an increase in intravenous fluid requirement (<it>p </it>< 0.05; <it>p </it>= NS). Modified inotrope score and vasopressor dependency index both decreased over 48 hours (<it>p </it>< 0.0001; <it>p </it>= 0.0012).</p> <p>Conclusions</p> <p>These findings suggest that renal function was preserved and that urine output improved without a decrease in systolic blood pressure, increase in vasoactive medication use, or an increase in resuscitation requirement in patients treated with low-dose fenoldopam. A randomized controlled trial is required to establish the efficacy of low-dose fenoldopam in critically ill burn patients with AKI.</p

    Upper abdominal body shape is the risk factor for postoperative pancreatic fistula after splenectomy for advanced gastric cancer: A retrospective study

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    <p>Abstract</p> <p>Background</p> <p>Postoperative pancreas fistula (POPF) is a major complication after total gastrectomy with splenectomy. We retrospectively studied the effects of upper abdominal shape on the development of POPF after gastrectomy.</p> <p>Methods</p> <p>Fifty patients who underwent total gastrectomy with splenectomy were studied. The maximum vertical distance measured by computed tomography (CT) between the anterior abdominal skin and the back skin (U-APD) and the maximum horizontal distance of a plane at a right angle to U-APD (U-TD) were measured at the umbilicus. The distance between the anterior abdominal skin and the root of the celiac artery (CAD) and the distance of a horizontal plane at a right angle to CAD (CATD) were measured at the root of the celiac artery. The CA depth ratio (CAD/CATD) was calculated.</p> <p>Results</p> <p>POPF occurred in 7 patients (14.0%) and was associated with a higher BMI, longer CAD, and higher CA depth ratio. However, CATD, U-APD, and U-TD did not differ significantly between patients with and those without POPF. Logistic-regression analysis revealed that a high BMI (≥25) and a high CA depth ratio (≥0.370) independently predicted the occurrence of POPF (odds ratio = 19.007, p = 0.002; odds ratio = 13.656, p = 0.038, respectively).</p> <p>Conclusion</p> <p>Surgical procedures such as total gastrectomy with splenectomy should be very carefully executed in obese patients or patients with a deep abdominal cavity to decrease the risk of postoperative pancreatic fistula. BMI and body shape can predict the risk of POPF simply by CT.</p

    Clinical implications of insulin-like growth factor 1 system in early-stage cervical cancer

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    This study was aimed to identify the expression and the correlation of insulin-like growth factor-1 (IGF-1) system and their prognostic impacts in cervical cancer. Seventy-two patients with early-stage cervical cancer were eligible. We obtained the serum levels of total IGF-1 and IGF binding protein-3 (IGFBP-3) by enzyme-linked immunosorbent assay and the expression of IGF-1 receptor (IGF-1R) in cancerous tissue by immuno-fluorescent (IF) stains. The 5-year recurrence-free and overall survival rates were significantly lower (P=0.003 and P=0.01, respectively) among patients with high-grade expression of tissue IGF-1R, compared with those with low-grade expression. After adjustment for other factors, preoperative serum total IGF-1 or IGFBP-3 levels failed to predict cancer death and recurrence. High-grade expression of IGF-1R and elevated preoperative squamous cell carcinoma antigen level were independent predictors of both death and recurrence, and combination of both factors could further help identify the subgroup of patients at higher death risk. The IF staining indicates the colocalisation of IGF-1 and IGF-1R in the cancerous tissues, whereas the IGF-1R expression is not correlated with circulating levels of IGF-1 or IGFBP-3. In early-stage cervical cancer, IGF-1 system may have a paracrine or autocrine function and the adverse impacts on prognosis by IGF-1R overexpression are implicated

    Long-Term Effects of Autologous Bone Marrow Stem Cell Treatment in Acute Myocardial Infarction: Factors That May Influence Outcomes

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    AIMS: To investigate whether there are important sources of heterogeneity between the findings of different clinical trials which administer autologous stem cell treatment for acute myocardial infarction (AMI) and to evaluate what factors may influence the long-term effects of this treatment. METHODS AND RESULTS: MEDLINE (1950-January 2011), EMBASE (1974-January 2011), CENTRAL (The Cochrane Library 2011, Issue 1), CINAHL (1982-January 2011), and ongoing trials registers were searched for randomised trials of bone marrow stem cells as treatment for AMI. Hand-searching was used to screen recent, relevant conference proceedings (2005-2010/11). Meta-analyses were conducted using random-effects models and heterogeneity between subgroups was assessed using chi-squared tests. Planned analyses included length of follow-up, timing of cell infusion and dose, patient selection, small trial size effect, methodological quality, loss of follow-up and date of publication. Thirty-three trials with a total of 1,765 participants were included. There was no evidence of bias due to publication or time-lag, methodological quality of included studies, participant drop-out, duration of follow-up or date of the first disclosure of results. However, in long-term follow-ups the treatment seemed more effective when administered at doses greater than 10(8) cells and to patients with more severe heart dysfunction. CONCLUSIONS: Evaluation of heterogeneity between trials has not identified significant sources of bias in this study. However, clinical differences between trials are likely to exist which should be considered when undertaking future trials
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