Identifying component modules

A computer-based system for modelling component dependencies and identifying component modules is presented. A variation of the Dependency Structure Matrix (DSM) representation was used to model component dependencies. The system utilises a two-stage approach towards facilitating the identification of a hierarchical modular structure. The first stage calculates a value for a clustering criterion that may be used to group component dependencies together. A Genetic Algorithm is described to optimise the order of the components within the DSM with the focus of minimising the value of the clustering criterion to identify the most significant component groupings (modules) within the product structure. The second stage utilises a 'Module Strength Indicator' (MSI) function to determine a value representative of the degree of modularity of the component groupings. The application of this function to the DSM produces a 'Module Structure Matrix' (MSM) depicting the relative modularity of available component groupings within it. The approach enabled the identification of hierarchical modularity in the product structure without the requirement for any additional domain specific knowledge within the system. The system supports design by providing mechanisms to explicitly represent and utilise component and dependency knowledge to facilitate the nontrivial task of determining near-optimal component modules and representing product modularity

A predictive score to identify hospitalized patients' risk of discharge to a post-acute care facility

<p>Abstract</p> <p>Background</p> <p>Early identification of patients who need post-acute care (PAC) may improve discharge planning. The purposes of the study were to develop and validate a score predicting discharge to a post-acute care (PAC) facility and to determine its best assessment time.</p> <p>Methods</p> <p>We conducted a prospective study including 349 (derivation cohort) and 161 (validation cohort) consecutive patients in a general internal medicine service of a teaching hospital. We developed logistic regression models predicting discharge to a PAC facility, based on patient variables measured on admission (day 1) and on day 3. The value of each model was assessed by its area under the receiver operating characteristics curve (AUC). A simple numerical score was derived from the best model, and was validated in a separate cohort.</p> <p>Results</p> <p>Prediction of discharge to a PAC facility was as accurate on day 1 (AUC: 0.81) as on day 3 (AUC: 0.82). The day-3 model was more parsimonious, with 5 variables: patient's partner inability to provide home help (4 pts); inability to self-manage drug regimen (4 pts); number of active medical problems on admission (1 pt per problem); dependency in bathing (4 pts) and in transfers from bed to chair (4 pts) on day 3. A score ≥ 8 points predicted discharge to a PAC facility with a sensitivity of 87% and a specificity of 63%, and was significantly associated with inappropriate hospital days due to discharge delays. Internal and external validations confirmed these results.</p> <p>Conclusion</p> <p>A simple score computed on the 3rd hospital day predicted discharge to a PAC facility with good accuracy. A score > 8 points should prompt early discharge planning.</p

Hospital-based, prospective, multicentre surveillance to determine the incidence of intussusception in children aged below 15 years in Germany

<p>Abstract</p> <p>Background</p> <p>A new vaccine against Rotavirus (RV) gastroenteritis was introduced in Germany in 2006. In 1997 the first RV vaccine was withdrawn due to an increased incidence in intussusception (IS). Thus, an accurate estimation of the incidence of IS is important for post-licensure surveillance.</p> <p>Methods</p> <p>IS-Data were obtained from the 'Erhebungseinheit für seltene pädiatrische Erkrankungen Deutschland' (ESPED, German surveillance unit for rare pediatric diseases) collaborations' central register where all cases of intussusception in Germany for the years 2006 and 2007 are collected (n = 1200). In order to obtain an unbiased estimate of the incidence, it is necessary to determine the population under risk out of which these cases originated, and the proportion of real cases not reported to the registry (underreporting). In order to assess underreporting, a random sample of 31 hospitals was re-assessed by an outside reviewer. The estimation of incidence was done using a single Maximum-Likelihood (ML) estimator based on data from both the registry and the sample.</p> <p>Results</p> <p>The uncorrected observed incidence was calculated to be 26.6/100,000 child-years for children below 1 year old, 23.8 for those below 2 years old, and 5.2 for those below 15 years old. The review revealed a mean reporting quota of about 41% and the ML approach yielded an incidence of 51.5/100,000 child-years (95%CI [41.7;61.1]) for children below 2 years of age.</p> <p>Conclusions</p> <p>While substantial under-reporting led to very conservative estimates of the IS incidence, the approach described here allows an accurate estimation of IS incidence including corresponding confidence bands. Therefore, ML estimation is a straightforward instrument to derive stable, unbiased estimates in epidemiological studies with incomplete data.</p

Genome-wide association study identifies 30 loci associated with bipolar disorder.

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P &lt; 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P &lt; 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder

Extramedullary plasmacytoma (EMP): Report of a case manifested as a mediastinal mass and multiple pulmonary nodules and review of literature

<p>Abstract</p> <p>Background</p> <p>Extramedullary plasmacytoma (EMP) is a rare plasma cell neoplasm of soft tissue without bone marrow involvement or other systemic characteristics of multiple myeloma</p> <p>Case presentation</p> <p>A 42 year-old woman presented with intermittent dry cough of 10 months duration. Her breathing sound was slightly coarse without rales or rhonchi on auscultation. CT scan revealed a right anterior mediastinal shadow with multiple pulmonary nodular lesions. A video-assisted thoracoscopic surgery (VATS) was performed. Histopathology showed it to be a myeloma.</p> <p>Conclusion</p> <p>This is the first presentation of EMP with a mediastinal mass with multiple pulmonary nodules.</p

The Acid Test of Fluoride: How pH Modulates Toxicity

Background: It is not known why the ameloblasts responsible for dental enamel formation are uniquely sensitive to fluoride ($F^−$). Herein, we present a novel theory with supporting data to show that the low pH environment of maturating stage ameloblasts enhances their sensitivity to a given dose of $F^−$. Enamel formation is initiated in a neutral pH environment (secretory stage); however, the pH can fall to below 6.0 as most of the mineral precipitates (maturation stage). Low pH can facilitate entry of $F^−$ into cells. Here, we asked if $F^−$ was more toxic at low pH, as measured by increased cell stress and decreased cell function. Methodology/Principal Findings: Treatment of ameloblast-derived LS8 cells with $F^−$ at low pH reduced the threshold dose of $F^−$ required to phosphorylate stress-related proteins, PERK, eIF2α, JNK and c-jun. To assess protein secretion, LS8 cells were stably transduced with a secreted reporter, Gaussia luciferase, and secretion was quantified as a function of $F^−$ dose and pH. Luciferase secretion significantly decreased within 2 hr of $F^−$ treatment at low pH versus neutral pH, indicating increased functional toxicity. Rats given 100 ppm $F^−$ in their drinking water exhibited increased stress-mediated phosphorylation of eIF2α in maturation stage ameloblasts (pH<6.0) as compared to secretory stage ameloblasts (pH∼7.2). Intriguingly, $F^−$-treated rats demonstrated a striking decrease in transcripts expressed during the maturation stage of enamel development (Klk4 and Amtn). In contrast, the expression of secretory stage genes, AmelX, Ambn, Enam and Mmp20, was unaffected. Conclusions: The low pH environment of maturation stage ameloblasts facilitates the uptake of $F^−$, causing increased cell stress that compromises ameloblast function, resulting in dental fluorosis

Rapid response of Helheim Glacier in Greenland to climate variability over the past century

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Geoscience 5 (2012): 37-41, doi:10.1038/ngeo1349.During the early 2000s the Greenland Ice Sheet experienced the largest ice mass loss observed on the instrumental record1, largely as a result of the acceleration, thinning and retreat of major outlet glaciers in West and Southeast Greenland2-5. The quasi-simultaneous change in the glaciers suggests a common climate forcing and increasing air6 and ocean7-8 temperatures have been indicated as potential triggers. Here, we present a new record of calving activity of Helheim Glacier, East Greenland, extending back to c. 1890 AD. This record was obtained by analysing sedimentary deposits from Sermilik Fjord, where Helheim Glacier terminates, and uses the annual deposition of sand grains as a proxy for iceberg discharge. The 120 year long record reveals large fluctuations in calving rates, but that the present high rate was reproduced only in the 1930s. A comparison with climate indices indicates that high calving activity coincides with increased Atlantic Water and decreased Polar Water influence on the shelf, warm summers and a negative phase of the North Atlantic Oscillation. Our analysis provides evidence that Helheim Glacier responds to short-term (3-10 years) large-scale oceanic and atmospheric fluctuations.This study has been supported by Geocenter Denmark in financial support to the SEDIMICE project. CSA was supported by the Danish Council for Independent Research│Nature and Universe (Grant no. 09-064954/FNU). FSt was supported by NSF ARC 0909373 and by WHOI’s Ocean and Climate Change Institute and MHRI was supported by the Danish Agency for Science, Technology and Innovation.2012-06-1

An evolutionary approach to a combined mixed integer programming model of seaside operations as arise in container ports

This paper puts forward an integrated optimisation model that combines three distinct problems, namely berth allocation, quay crane assignment, and quay crane scheduling that arise in container ports. Each one of these problems is difficult to solve in its own right. However, solving them individually leads almost surely to sub-optimal solutions. Hence, it is desirable to solve them in a combined form. The model is of the mixed-integer programming type with the objective being to minimize the tardiness of vessels and reduce the cost of berthing. Experimental results show that relatively small instances of the proposed model can be solved exactly using CPLEX. Large scale instances, however, can only be solved in reasonable times using heuristics. Here, an implementation of the genetic algorithm is considered. The effectiveness of this implementation is tested against CPLEX on small to medium size instances of the combined model. Larger size instances were also solved with the genetic algorithm, showing that this approach is capable of finding the optimal or near optimal solutions in realistic times

Enhancer of zeste homolog 2 (EZH2) expression is an independent prognostic factor in renal cell carcinoma

Background: The enhancer of zeste homolog 2 (EZH2) gene exerts oncogene-like activities and its (over)expression has been linked to several human malignancies. Here, we studied a possible association between EZH2 expression and prognosis in patients with renal cell carcinoma (RCC). Methods: EZH2 protein expression in RCC specimens was analyzed by immunohistochemistry using a tissue microarray (TMA) containing RCC tumor tissue and corresponding normal tissue samples of 520 patients. For immunohistochemical assessment of EZH2 expression, nuclear staining quantity was evaluated using a semiquantitative score. The effect of EZH2 expression on cancer specific survival (CSS) was assessed by univariate and multivariate Cox regression analyses. Results: During follow-up, 147 patients (28%) had died of their disease, median follow-up of patients still alive was 6.0 years (range 0 - 16.1 years). EZH2 nuclear staining was present in tumor cores of 411 (79%) patients. A multivariate Cox regression analysis revealed that high nuclear EZH2 expression was an independent predictor of poor CSS (>25-50% vs. 0%: HR 2.72, p = 0.025) in patients suffering from non-metastatic RCC. Apart from high nuclear EZH2 expression, tumor stage and Fuhrman's grading emerged as significant prognostic markers. In metastatic disease, nuclear EZH2 expression and histopathological subtype were independent predictive parameters of poor CSS (EZH2: 1-5%: HR 2.63, p = 0.043, >5-25%: HR 3.35, p = 0.013, >25%-50%: HR 4.92, p = 0.003, all compared to 0%: HR 0.36, p = 0.025, respectively). Conclusions: This study defines EZH2 as a powerful independent unfavourable prognostic marker of CSS in patients with metastatic and non-metastatic RCC