Genetic fuzzy system predicting contractile reactivity patterns of small arteries

Monitoring of physiological surrogate end points in drug development generates dynamic time-domain data reflecting the state of the biological system. Conventional data analysis often reduces the information in these data by extracting specific data points, thereby discarding potentially useful information. We developed a genetic fuzzy system (GFS) algorithm that is capable of learning all information in time-domain physiological data. Data on isometric force development of isolated small arteries were used as a framework for developing and optimizing a GFS. GFS performance was improved by several strategies. Results show that optimized fuzzy systems (OFSs) predict contractile reactivity of arteries accurately. In addition, OFSs identified significant differences that were undetectable using conventional analysis in the responses of arteries between groups. We concluded that OFSs may be used in clustering or classification tasks as aids in the objective identification or prediction of dynamic physiological behavior

Comparison of three different application routes of butyrate to improve colonic anastomotic strength in rats

Despite extensive research, anastomotic leakage (AL) remains one of the most dreaded complications after colorectal surgery. Since butyrate enemas are known to enhance anastomotic healing, several administration routes have been explored in this study. Three intraluminal approaches involving butyrate were investigated: (1) butyrin-elucidating patch, (2) a single injection of hyaluronan-butyrate (HA-But) prior to construction of the proximal anastomosis and (3) rectal hyaluronan-butyrate (HA-But) enemas designed for distal anastomoses. The main outcome was AL and secondary outcomes were bursting pressure, histological analysis of the anastomosis, zymography to detect MMP activity and qPCR for gene expression of MMP2, MMP9, MUC2 and TFF3. RESULTS: Neither the patches nor the injections led to a reduction of AL in experiments 1 and 2. In experiment 3, a significant reduction of AL was accomplished with the (HA-But) enema compared to the control group together with a higher bursting pressure. Histological analysis detected only an increased inflammation in experiment 2 in the hyaluronan injection group compared to the control group. No other differences were found regarding wound healing. Zymography identified a decreased proenzyme of MMP9 when HA-But was administered as a rectal enema. qPCR did not show any significant differences between groups in any experiment. CONCLUSION: Butyrate enemas are effective in the enhancement of colonic anastomosis. Enhanced butyrate-based approaches designed to reduce AL in animal models for both proximal and distal anastomoses were not more effective than were butyrate enemas alone. Further research should focus on how exogenous butyrate can improve anastomotic healing after gastrointestinal surgery

Consumer evaluation of complaint handling in the Dutch health insurance market

<p>Abstract</p> <p>Background</p> <p>How companies deal with complaints is a particularly challenging aspect in managing the quality of their service. In this study we test the direct and relative effects of service quality dimensions on consumer complaint satisfaction evaluations and trust in a company in the Dutch health insurance market.</p> <p>Methods</p> <p>A cross-sectional survey design was used. Survey data of 150 members of a Dutch insurance panel who lodged a complaint at their healthcare insurer within the past 12 months were surveyed. The data were collected using a questionnaire containing validated multi-item measures. These measures assess the service quality dimensions consisting of functional quality and technical quality and consumer complaint satisfaction evaluations consisting of complaint satisfaction and overall satisfaction with the company after complaint handling. Respondents' trust in a company after complaint handling was also measured. Using factor analysis, reliability and validity of the measures were assessed. Regression analysis was used to examine the relationships between these variables.</p> <p>Results</p> <p>Overall, results confirm the hypothesized direct and relative effects between the service quality dimensions and consumer complaint satisfaction evaluations and trust in the company. No support was found for the effect of technical quality on overall satisfaction with the company. This outcome might be driven by the context of our study; namely, consumers get in touch with a company to resolve a specific problem and therefore might focus more on complaint satisfaction and less on overall satisfaction with the company.</p> <p>Conclusions</p> <p>Overall, the model we present is valid in the context of the Dutch health insurance market. Management is able to increase consumers' complaint satisfaction, overall satisfaction with the company, and trust in the company by improving elements of functional and technical quality. Furthermore, we show that functional and technical quality do not influence consumer satisfaction evaluations and trust in the company to the same extent. Therefore, it is important for managers to be aware of the type of consumer satisfaction they are measuring when evaluating the handling of complaints within their company.</p

Whole body MR imaging in ankylosing spondylitis: a descriptive pilot study in patients with suspected early and active confirmed ankylosing spondylitis

BACKGROUND: Ankylosing spondylitis is a chronic inflammatory rheumatic disorder which usually begins in early adulthood. The diagnosis is often delayed by many years. MR imaging has become the preferred imaging method for detection of early inflammation of the axial skeleton in ankylosing spondylitis. The goal of this study was to assess the frequency and distribution of abnormalities on whole body MR imaging in patients with suspected early ankylosing spondylitis and with active confirmed ankylosing spondylitis. METHODS: Ten patients with suspected early ankylosing spondylitis and ten patients with confirmed ankylosing spondylitis were enrolled. On an 18-channel MR system, coronal and sagittal T1 weighted and STIR sequences were acquired covering the entire spine, sacrum, anterior chest wall, shoulder girdle, and pelvis. The total examination time was 30 minutes. RESULTS: In both groups inflammatory lesions of the lower thoracic spine were frequent (number of patients with suspected early/confirmed ankylosing spondylitis: 7/9). In confirmed ankylosing spondylitis the upper thoracic spine (3/6) and the lumbar spine (4/8) were more commonly involved. The inferior iliac quadrant of the sacroiliac joints was frequently altered in both groups (8/8). The superior iliac (2/5), inferior sacral (6/10) and superior sacral (3/6) quadrants were more frequently affected in confirmed ankylosing spondylitis. Abnormalities of the manubriosternal joint (2/4), the sternoclavicular joints (1/2) and hip joint effusion (4/3) were also seen. CONCLUSION: In both suspected early ankylosing spondylitis and confirmed ankylosing spondylitis, whole body MR examinations frequently demonstrate inflammatory lesions outside the sacroiliac joints. These lesions are similarly distributed but occur less frequently in suspected early compared to confirmed ankylosing spondylitis. Due to the small sample size in this pilot study these results need to be confirmed in larger studies with this emerging technique

Optimal Reinsurance with One Insurer and Multiple Reinsurers

In this paper, we consider a one-period optimal reinsurance design model with n reinsurers and an insurer. For very general preferences of the insurer, we obtain that there exists a very intuitive pricing formula for all reinsurers that use a distortion premium principle. The insurer determines its optimal risk that it wants to reinsure via this pricing formula. This risk it wants to reinsure is then shared by the reinsurers via tranching. The optimal ceded loss functions among multiple reinsurers are derived explicitly under the additional assumptions that the insurer’s preferences are given by an inverse-S shaped distortion risk measure and that the reinsurer’s premium principles are some functions of the Conditional Value-at-Risk. We also demonstrate that under some prescribed conditions, it is never optimal for the insurer to cede its risk to more than two reinsurers

Acute interaction between hydrocortisone and insulin alters the plasma metabolome in humans

With the aim of identifying biomarkers of glucocorticoid action and their relationship with biomarkers of insulin action, metabolomic profiling was carried out in plasma samples from twenty healthy men who were administered either a low or medium dose insulin infusion (n = 10 each group). In addition, all subjects were given metyrapone (to inhibit adrenal cortisol secretion) +/-hydrocortisone (HC) in a randomised crossover design to produce low, medium and high glucocorticoid levels. The clearest effects of insulin were to reduce plasma levels of the branched chain amino acids (BCAs) leucine/isoleucine and their deaminated metabolites, and lowered free fatty acids and acylcarnitines. The highest dose of hydrocortisone increased plasma BCAs in both insulin groups but increased free fatty acids only in the high insulin group, however hydrocortisone did not affect the levels of acyl carnitines in either group. The clearest interaction between HC and insulin was that hydrocortisone produced an elevation in levels of BCAs and their metabolites which were lowered by insulin. The direct modulation of BCAs by glucocorticoids and insulin may provide the basis for improved in vivo monitoring of glucocorticoid and insulin action

Scholars’ open debate paper on the World Health Organization ICD-11 gaming disorder proposal

Concerns about problematic gaming behaviors deserve our full attention. However, we claim that it is far from clear that these problems can or should be attributed to a new disorder. The empirical basis for a Gaming Disorder proposal, such as in the new ICD-11, suffers from fundamental issues. Our main concerns are the low quality of the research base, the fact that the current operationalization leans too heavily on substance use and gambling criteria, and the lack of consensus on symptomatology and assessment of problematic gaming. The act of formalizing this disorder, even as a proposal, has negative medical, scientific, public-health, societal, and human rights fallout that should be considered. Of particular concern are moral panics around the harm of video gaming. They might result in premature application of diagnosis in the medical community and the treatment of abundant false-positive cases, especially for children and adolescents. Second, research will be locked into a confirmatory approach, rather than an exploration of the boundaries of normal versus pathological. Third, the healthy majority of gamers will be affected negatively. We expect that the premature inclusion of Gaming Disorder as a diagnosis in ICD-11 will cause significant stigma to the millions of children who play video games as a part of a normal, healthy life. At this point, suggesting formal diagnoses and categories is premature: the ICD-11 proposal for Gaming Disorder should be removed to avoid a waste of public health resources as well as to avoid causing harm to healthy video gamers around the world