Evaluation of POSSUM scoring system in patients with gastric cancer undergoing D2-gastrectomy

BACKGROUND: Risk adjustment and stratification play an important role in quality assurance and in clinical research. The Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) is a patient risk prediction model based on 12 patient characteristics and 6 characteristics of the surgery performed. However, because the POSSUM was developed for quality assessment in general surgical units, its performance within specific subgroups still requires evaluation. The aim of the present study was to assess the accuracy of POSSUM in predicting mortality and morbidity in patients with gastric cancer undergoing D2-gastrectomy. METHODS: 137 patients with gastric cancer undergoing gastrectomy were included in this study. Detailed, standardized risk assessments and thorough documentation of the post-operative courses were performed prospectively, and the POSSUM scores were then calculated. RESULTS: The 30- and 90- day mortality rates were 3.6% (n = 5) and 5.8% (n = 8), respectively. 65.7% (n = 90) of patients had normal postoperative courses without major complications, 14.6% (n = 20) had moderate and 13.9% (n = 19) had severe complications. The number of mortalities predicted by the POSSUM-Mortality Risk Score (R1) was double the actual number of mortalities occurring in the median and high-risk groups, and was more than eight times the actual number of mortalities occurring in the low-risk group (R1 < 20%). However, the calculated R1 predicted rather well in terms of severe morbidity or post-operative death in each risk group: in predicted low risk patients the actual occurrence rate (AR) of severe morbidity or post-operative death was 14%, for predicted medium risk patients the AR was 23%, and for predicted high risk patients the AR was 50% (p < 0.05). The POSSUM-Morbidity Risk Score (R2) overestimated the risk of morbidity. CONCLUSION: The POSSUM Score may be beneficial and can be used for assessment of the peri- and post-operative courses of patients with gastric carcinoma undergoing D2-gastrectomy. However, none of the scores examined here are useful for preoperative prediction of postoperative course

Dense-core senile plaques in the Flemish variant of Alzheimer's disease are vasocentric

Alzheimer's disease (AD) is characterized by deposition of beta-amyloid (Abeta) in diffuse and senile plaques, and variably in vessels. Mutations in the Abeta-encoding region of the amyloid precursor protein (APP) gene are frequently associated with very severe forms of vascular Abeta deposition, sometimes also accompanied by AD pathology. We earlier described a Flemish APP (A692G) mutation causing a form of early-onset AD with a prominent cerebral amyloid angiopathy and unusually large senile plaque cores. The pathogenic basis of Flemish AD is unknown. By image and mass spectrometric Abeta analyses, we demonstrated that in contrast to other familial AD cases with predominant brain Abeta42, Flemish AD patients predominantly deposit Abeta40. On serial histological section analysis we further showed that the neuritic senile plaques in APP692 brains were centered on vessels. Of a total of 2400 senile plaque cores studied from various brain regions from three patients, 68% enclosed a vessel, whereas the remainder were associated with vascular walls. These observations were confirmed by electron

Characterization of the Biosynthesis, Processing and Kinetic Mechanism of Action of the Enzyme Deficient in Mucopolysaccharidosis IIIC

Heparin acetyl-CoA:alpha-glucosaminide N-acetyltransferase (N-acetyltransferase, EC 2.3.1.78) is an integral lysosomal membrane protein containing 11 transmembrane domains, encoded by the HGSNAT gene. Deficiencies of N-acetyltransferase lead to mucopolysaccharidosis IIIC. We demonstrate that contrary to a previous report, the N-acetyltransferase signal peptide is co-translationally cleaved and that this event is required for its intracellular transport to the lysosome. While we confirm that the N-acetyltransferase precursor polypeptide is processed in the lysosome into a small amino-terminal alpha- and a larger ß- chain, we further characterize this event by identifying the mature amino-terminus of each chain. We also demonstrate this processing step(s) is not, as previously reported, needed to produce a functional transferase, i.e., the precursor is active. We next optimize the biochemical assay procedure so that it remains linear as N-acetyltransferase is purified or protein-extracts containing N-acetyltransferase are diluted, by the inclusion of negatively charged lipids. We then use this assay to demonstrate that the purified single N-acetyltransferase protein is both necessary and sufficient to express transferase activity, and that N-acetyltransferase functions as a monomer. Finally, the kinetic mechanism of action of purified N-acetyltransferase was evaluated and found to be a random sequential mechanism involving the formation of a ternary complex with its two substrates; i.e., N-acetyltransferase does not operate through a ping-pong mechanism as previously reported. We confirm this conclusion by demonstrating experimentally that no acetylated enzyme intermediate is formed during the reaction

Perceived Social Support Network and Achievement : Mediation by Motivational Beliefs and Moderation by Gender

Research has shown that perceived social support (PSS) (from parents and teachers) influences achievement. However, little is known about how this relationship operates. This study examines the multiple mediational effects of students’ motivational beliefs in relationship to the association between PSS and mathematics achievement. The sample included the African countries that participated in the TIMSS 2011 (Ghana, Botswana, South Africa, Morocco, and Tunisia). A bootstrap analysis indicated a unique pattern of the role of motivational beliefs in mediating the relationships between PSS and achievement. Moreover, gender was found to moderate the indirect effect in some countries. The findings indicate that total mediation effect of students’ motivational belief on the relationship between PSS and achievement is “culture-fair but not culture-free”Research has shown that perceived social support (PSS) (from parents and teachers) influences achievement. However, little is known about how this relationship operates. This study examines the multiple mediational effects of students’ motivational beliefs in relationship to the association between PSS and mathematics achievement. The sample included the African countries that participated in the TIMSS 2011 (Ghana, Botswana, South Africa, Morocco, and Tunisia). A bootstrap analysis indicated a unique pattern of the role of motivational beliefs in mediating the relationships between PSS and achievement. Moreover, gender was found to moderate the indirect effect in some countries. The findings indicate that total mediation effect of students’ motivational belief on the relationship between PSS and achievement is “culture-fair but not culture-free”.Peer reviewe

Dementia care initiative in primary practice – study protocol of a cluster randomized trial on dementia management in a general practice setting

<p>Abstract</p> <p>Background</p> <p>Current guidelines for dementia care recommend the combination of drug therapy with non-pharmaceutical measures like counselling and social support. However, the scientific evidence concerning non-pharmaceutical interventions for dementia patients and their informal caregivers remains inconclusive. Targets of modern comprehensive dementia care are to enable patients to live at home as long and as independent as possible and to reduce the burden of caregivers. The objective of the study is to compare a complex intervention including caregiver support groups and counselling against usual care in terms of time to nursing home placement. In this paper the study protocol is described.</p> <p>Methods/Design</p> <p>The IDA (Initiative Demenzversorgung in der Allgemeinmedizin) project is designed as a three armed cluster-randomized trial where dementia patients and their informal caregivers are recruited by general practitioners. Patients in the study region of Middle Franconia, Germany, are included if they have mild or moderate dementia, are at least 65 years old, and are members of the German AOK (Allgemeine Ortskrankenkasse) sickness fund. In the control group patients receive regular treatment, whereas in the two intervention groups general practitioners participate in a training course in evidence based dementia treatment, recommend support groups and offer counseling to the family caregivers either beginning at baseline or after the 1-year follow-up. The study recruitment and follow-up took place from July 2005 to January 2009. 303 general practitioners were randomized of which 129 recruited a total of 390 patients. Time to nursing home admission within the two year intervention and follow-up period is the primary endpoint. Secondary endpoints are cognitive status, activities of daily living, burden of care giving as well as healthcare costs. For an economic analysis from the societal perspective, data are collected from caregivers as well as by the use of routine data from statutory health insurance and long-term care insurance.</p> <p>Discussion</p> <p>From a public health perspective, the IDA trial is expected to lead to evidence based results on the community effectiveness of non-pharmaceutical support measures for dementia patients and their caregivers in the primary care sector. For health policy makers it is necessary to make their decisions about financing new services based on strong knowledge about the acceptance of measures in the population and their cost-effectiveness.</p> <p>Trial registration</p> <p>ISRCTN68329593</p

Towards a Mathematical Theory of Cortical Micro-circuits

The theoretical setting of hierarchical Bayesian inference is gaining acceptance as a framework for understanding cortical computation. In this paper, we describe how Bayesian belief propagation in a spatio-temporal hierarchical model, called Hierarchical Temporal Memory (HTM), can lead to a mathematical model for cortical circuits. An HTM node is abstracted using a coincidence detector and a mixture of Markov chains. Bayesian belief propagation equations for such an HTM node define a set of functional constraints for a neuronal implementation. Anatomical data provide a contrasting set of organizational constraints. The combination of these two constraints suggests a theoretically derived interpretation for many anatomical and physiological features and predicts several others. We describe the pattern recognition capabilities of HTM networks and demonstrate the application of the derived circuits for modeling the subjective contour effect. We also discuss how the theory and the circuit can be extended to explain cortical features that are not explained by the current model and describe testable predictions that can be derived from the model