The Study of the Optimal Parameter Settings in a Hospital Supply Chain System in Taiwan

This study proposed the optimal parameter settings for the hospital supply chain system (HSCS) when either the total system cost (TSC) or patient safety level (PSL) (or both simultaneously) was considered as the measure of the HSCS’s performance. Four parameters were considered in the HSCS: safety stock, maximum inventory level, transportation capacity, and the reliability of the HSCS. A full-factor experimental design was used to simulate an HSCS for the purpose of collecting data. The response surface method (RSM) was used to construct the regression model, and a genetic algorithm (GA) was applied to obtain the optimal parameter settings for the HSCS. The results show that the best method of obtaining the optimal parameter settings for the HSCS is the simultaneous consideration of both the TSC and the PSL to measure performance. Also, the results of sensitivity analysis based on the optimal parameter settings were used to derive adjustable strategies for the decision-makers

A HO-IRT BASED DIAGNOSTIC ASSESSMENT SYSTEM WITH CONSTRUCTED RESPONSE ITEMS

ABSTRACT The aim of the present study was to develop an on-line assessment system with constructed response items in the context of elementary mathematics curriculum. The system recorded the problem solving process of constructed response items and transfered the process to response codes for further analyses. An inference mechanism based on artificial intelligence was implemented with the system to diagnose the bugs in the problem solving process automatically. To examine the performance of the system, a "Multiplication of Fraction" test was constructed and administered to 158 six graders in Taiwan. The results showed that the mean of classification accuracies of the bugs is above 97%, which implies that the proposed system identifies leaning bugs accurately and efficiently. In addition to bug identification, a high-order item response theory (HO-IRT) was applied to estimate the overall and domain abilities. The correlations between the abilities estimated with HO-IRT and the number of bugs were highly correlated, which suggests that the more learning bugs children possessed the lower his/her mathematic abilities would be. Keywords: constructed response item, computerized test, automated scoring, high-order item response theory INTRODUCTION Constructed response (CR) items are open ended, short answer questions that elicit students' higher-level cognitive abilities and are beneficial to evaluate complex concepts or skills such as problem solvin

Molecular events associated with epithelial to mesenchymal transition of nasopharyngeal carcinoma cells in the absence of Epstein-Barr virus genome

Epithelial-mesenchymal transition (EMT) is an important process in tumor metastasis. The EMT-related events associated with metastasis of NPC in the absence of EBV have not been elucidated. We established an EBV-negative NPC cell line from a bone marrow biopsy of an NPC patient. Using a Matrigel system we isolated an invasive and non-invasive sublines, designated NPC-BM29 and NPC-BM00. NPC-BM29 acquired an invasive-like phenotype characterized by EMT, marked by down-regulation of E-cadherin and β-catenin with concomitant increased expression of Ets1. NPC-BM29 cells expressed ≥ 10-fold higher of MMP-9 than NPC-BM00 cells. NPC-BM29 cells grew better in 2% serum than NPC-BM00 cells, with a population doubling-time of 26.8 h and 30.7 h, respectively. A marked reduction in colony-formation ability of NPC-BM00 cells compared to NPC-BM29 was observed. Wound-healing assay revealed that NPC-BM29 cells displayed higher motility than NPC-BM00 and the motility was further enhanced by cell treatment with TPA, a PKC activator. Cell surface markers and tumor-associated molecules, AE3, MAK6 and sialyl-Tn, were up-regulated in NPC-BM29 cells, whereas the expression of HLA-DR and CD54 was significantly increased in NPC-BM00 cells. NPC-BM29 consistently released higher levels of IL-8 and IL-10 than NPC-BM00, with low levels of IL-1α expression in both cell lines. Higher level of VEGF production was detected in NPC-BM00 than NPC-BM29 cells. These data show that EBV is not required for exhibiting multiple metastatic phenotypes associated with EMT. More studies that target right molecules/signalings associated with the EMT may offer new therapeutic intervention options for NPC invasion and metastasis

Apoptosis induction in BEFV-infected Vero and MDBK cells through Src-dependent JNK activation regulates caspase-3 and mitochondria pathways

Our previous report demonstrated that bovine ephemeral fever virus (BEFV)-infected cultured cells could induce caspase-dependent apoptosis. This study aims to further elucidate how BEFV activates the caspase cascade in bovine cells. BEFV replicated and induced apoptosis in Vero and Madin-Darby bovine kidney (MDBK) cells, and a kinetic study showed a higher efficiency of replication and a greater apoptosis induction ability of BEFV in Vero cells. Src and c-Jun N-terminal kinase (JNK) inhibitor, but not extracellular signal-regulated kinase (ERK) or p38 inhibitor, alleviated BEFV-mediated cytopathic effect and apoptosis. In BEFV-infected Vero and MDBK cells, BEFV directly induced Src tyrosine-418 phosphorylation and JNK phosphorylation and kinase activity, which was inhibited specifically by SU6656 and SP600125, respectively. The caspase cascade and its downstream effectors, Poly (ADP-ribose) polymerase (PARP) and DFF45, were also activated simultaneously upon BEFV infection. In addition, cytochrome c, but not Smac/DIABLO, was released gradually from mitochondria after BEFV infection. SU6656 suppressed Src, JNK, and caspase-3 and -9 activation, as well as PARP and DFF45 cleavage; SP600125 reduced JNK and caspase-3 and -9 activation, as well as PARP and DFF45 cleavage. Taken together, these results strongly support the hypothesis that a Src-dependent JNK signaling pathway plays a key role in BEFV-induced apoptosis. The molecular mechanism identified in our study may provide useful information for the treatment of BEFV

A Chinese Herbal Decoction, Modified Yi Guan Jian, Induces Apoptosis in Hepatic Stellate Cells through an ROS-Mediated Mitochondrial/Caspase Pathway

The Chinese herb modified Yi Guan Jian (mYGJ) is an effective regimen that is usually used in outpatients with chronic liver diseases such as fibrosis and cirrhosis. However, the mechanism for the action of mYGJ on liver fibrosis is not yet clear. In this study, we found that mYGJ induced hepatic stellate cells (HSCs) apoptosis concomitant with the downregulation of Bcl-2 expression and slight elevation of Bax level. Moreover, the reactive oxygen species (ROS) were generated in the early stages of mYGJ-induced HSCs apoptosis to facilitate calcium and cytochrome c release from the mitochondria to cytosol. Subsequently, caspase 9 and caspase 3 were activated. Furthermore, the activation of ER stress-associated caspase 12 in HSCs was also evaluated. Together, we report the first evidence-based study to demonstrate that mYGJ decoction induces HSCs apoptosis through ROS accumulation and the intrinsic apoptosis pathway. These findings provide rationale for further clinical investigation of traditional Chinese medicine recipes against liver fibrosis

Association between copy number variation of complement component C4 and Graves' disease

<p>Abstract</p> <p>Background</p> <p>Gene copy number of complement component <it>C4</it>, which varies among individuals, may determine the intrinsic strength of the classical complement pathway. Presuming a major role of complement as an effecter in peptide-mediated inflammation and phagocytosis, we hypothesized that <it>C4 </it>genetic diversity may partially explain the development of Graves' disease (GD) and the variation in its outcomes.</p> <p>Methods</p> <p>A case-control study including 624 patients with GD and 160 healthy individuals were enrolled. CNV of <it>C4 </it>isotypes (<it>C4A </it>and <it>C4B</it>) genes were performed by quantitative real-time polymerase chain reaction analysis. Statistical comparison and identification of CNV of total <it>C4, C4 </it>isotypes (<it>C4A </it>and <it>C4B</it>) and <it>C4 </it>polymorphisms were estimated according to the occurrence of GD and its associated clinical features.</p> <p>Results</p> <p>Individuals with 4, 2, and 2 copies of <it>C4</it>, <it>C4A </it>and <it>C4B </it>genes, especially those with A2B2 polymorphism may associate with the development of GD (p = 0.001, OR = 10.994, 95% CI: 6.277-19.255; p = 0.008, OR = 1.732, 95% CI: 1.190-2.520; p = 2.420 × 10-5, OR = 2.621, 95% CI: 1.791-3.835; and <it>p </it>= 1.395 × 10^-4, OR = 2.671, 95% CI: 1.761-4.052, respectively). Although the distribution of copy number for total <it>C4</it>, <it>C4 </it>isotypes as well as <it>C4 </it>polymorphisms did not associate with the occurrence of goiter, nodular hyperplasia, GO and myxedema, <2 copies of <it>C4A </it>may associate with high risk toward vitiligo in patients with GD (<it>p </it>= 0.001, OR = 5.579, 95% CI: 1.659-18.763).</p> <p>Conclusions</p> <p>These results may be further estimated for its clinical application on GD and the vitiligo in patients with GD.</p

Non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients without previous oral anticoagulants or stable under warfarin: a nationwide cohort study.

AimsInvestigations on non-VKA oral anticoagulants (NOACs) for atrial fibrillation (AF) patients without taking any oral anticoagulants (OACs) or staying well on warfarin were limited. We aimed to investigate the associations between stroke prevention strategies and clinical outcomes among AF patients who were previously well without taking any OACs or stayed well on warfarin for years.Methods and resultsThe retrospective analysis included a total of 54 803 AF patients who did not experience an ischaemic stroke or intra-cranial haemorrhage (ICH) for years after AF was diagnosed. Among these patients, 32 917 patients who did not receive OACs were defined as the 'original non-OAC cohort' (group 1), and 8007 patients who continuously received warfarin were defined as the 'original warfarin cohort' (group 2). In group 1, compared to non-OAC, warfarin showed no significant difference in ischaemic stroke (aHR 0.979, 95%CI 0.863-1.110, P = 0.137) while those initiated NOACs were associated with lower risk (aHR 0.867, 95%CI 0.786-0.956, P = 0.043). When compared to warfarin, the composite of 'ischaemic stroke or ICH' and 'ischaemic stroke or major bleeding' was significantly lower in the NOAC initiator with an aHR of 0.927 (95%CI 0.865-0.994; P = 0.042) and 0.912 (95%CI 0.837-0.994; P ConclusionsThe NOACs should be considered for AF patients who were previously well without taking OACs and those who were free of ischaemic stroke and ICH under warfarin for years

Task-Dependent Differences in Operant Behaviors of Rats With Acute Exposure to High Ambient Temperature: A Potential Role of Hippocampal Dopamine Reuptake Transporters

Behavioral or cognitive functions are known to be influenced by thermal stress from the change in ambient temperature (Ta). However, little is known about how increased Ta (i.e., when the weather becomes warm or hot) may affect operant conditioned behavior and the neural substrates involved. The present study thus investigated the effects of high Ta on operant behaviors maintained on a fixed-ratio 1 (FR1) and a differential reinforcement for low-rate responding 10 s (DRL 10-s) schedule of reinforcement. The rats were randomly assigned to three groups receiving acute exposure to Ta of 23°C, 28°C, and 35°C, respectively, for evaluating the effects of high Ta exposure on four behavioral tests. Behavioral responses in an elevated T-maze and locomotor activity were not affected by Ta treatment. Regarding operant tests, while the total responses of FR1 behavior were decreased only under 35°C when compared with the control group of 23°C, those of DRL 10-s behavior were significantly reduced in both groups of 28°C and 35°C. Distinct patterns of inter-response time (IRT) distribution of DRL behavior appeared among the three groups; between-group differences of behavioral changes produced by high Ta exposure were confirmed by quantitative analyses of IRT data. Western blot assays of dopamine (DA) D1 and D2 receptor, DA transporter (DAT) and brain-derived neurotrophic factor (BDNF) were conducted for the sample tissues collected in six brain areas from all the subjects after acute high Ta exposure. Significant Ta-related effects were only revealed in the dorsal hippocampus (dHIP). In which, the DAT levels were increased in a Ta-dependent fashion that was associated with operant behavior changes under high Ta exposure. And, there as an increased level of D1 receptors in the 28°C group. In summary, these data indicate that the performance of operant behavior affected by the present high Ta exposure is task-dependent, and these changes of operant behaviors cannot be attributed to gross motor function or anxiety being affected. The regulation of dHIP DAT may be involved in this operant behavioral change under high Ta exposure