Optimal procurement policy for cost conscious retailer

Manufacturers whose products primarily relay on expensive raw materials need to make well informed procurement decisions in order to reduce their production costs. Decision making is especially difficult when there is uncertainty about the raw material cost as well as the product demand. This research considers an optimum procurement and production planning problem under uncertainty. Basic raw material is a rare metal with a dynamically and stochastically changing price. The manufacturer has the dual sourcing option: buy from the spot market; or to sign long term contracts. Long term contracts can be signed only at the beginning of every year with a yearly duration. In addition, the contract price depends on the average spot price during some interval. We first consider a simplified version of the problem without long-term contract, and assume a base-stock procurement and inventory control policy. We model the problem as a Markov chain and present some numerical examples demonstrating the effect of various parameters on the optimum base-stock value. Then, we investigate a case with dual procurement option, and present our results.M.S.Includes bibliographical referencesby Sicong Ho

Prognostic, Diagnostic, and Clinicopathological Significance of Circular RNAs in Pancreatic Cancer: A Systematic Review and Meta-Analysis

Pancreatic cancer (PC) is a highly aggressive malignant tumor with a high mortality rate. It is urgent to find optimal molecular targets for the early diagnosis and treatment of PC. Here, we aimed to systematically analyze the prognostic, diagnostic, and clinicopathological significance of circular RNAs (circRNAs) in PC. Relevant studies were screened through PubMed, Web of Science, and other databases. The prognostic value of PC-associated circRNAs was assessed using the composite hazard ratio (HR), the diagnostic performance was assessed using the area under the summary receiver operator characteristic (SROC) curve (AUC), and the correlation with clinicopathological characteristics using the composite odds ratio (OR) was explored. In our study, 48 studies were included: 34 for prognosis, 11 for diagnosis, and 30 for correlation with clinicopathological characteristics. For prognosis, upregulated circRNAs were associated with poorer overall survival (OS) (HR = 2.02) and disease-free survival/progression-free survival (HR = 1.84) while downregulated circRNAs were associated with longer OS (HR = 0.55). Notably, the combination of circRNAs, including hsa_circ_0064288, hsa_circ_0000234, hsa_circ_0004680, hsa_circ_0071036, hsa_circ_0000677, and hsa_circ_0001460, was associated with worse OS (HR = 2.35). For diagnosis, the AUC was 0.83, and the pooled sensitivity and specificity were 0.79 and 0.73, respectively. For clinicopathologic characteristics, upregulated circRNAs were associated with poorer tumor differentiation, more nerve and vascular invasion, higher T stage, lymphatic metastasis, distant metastasis, advanced TNM stage, and higher preoperative CA19-9 level. In contrast, downregulated circRNAs were negatively associated with PC differentiation and lymphatic metastasis. Overall, our results showed that circRNAs are closely related to the prognosis and clinicopathological characteristics of PC patients and could be utilized for early diagnosis; thus, they are promising biomarkers for clinical application in PC

Recent Progress in the Neoadjuvant Treatment Strategy for Locally Advanced Esophageal Cancer

Neoadjuvant therapies, primarily chemotherapy and chemoradiotherapy, are able to improve the overall survival (OS) in patients with locally advanced resectable esophageal cancer (EC) based on the results of several randomized clinical trials. The advantage of neoadjuvant therapy is chiefly attributed to the decreased risk of local–regional recurrence and distant metastasis. Thus, it has been recommended as standard treatment for patients with resectable EC. However, several fundamental problems remain. First, the combination of neoadjuvant chemotherapy (nCT), neoadjuvant chemoradiotherapy (nCRT), and surgery for EC patients with different histological types remain controversial. Furthermore, to reduce the toxicity of preoperative chemotherapy and the risk of complications caused by preoperative radiation therapy, the treatment protocols of nCT and nCRT still need to be investigated and optimized by prospective trials. Moreover, for patients with complete clinical response following neoadjuvant therapy, it is worth ascertaining whether a “watch and wait” surveillance plus surgery-as-needed policy is more favorable, as well as, in addition to preoperative chemoradiotherapy, whether immunotherapy, especially when combined with the traditional neoadjuvant therapy regimens, brings new prospects for EC treatment. In this review, we summarize the recent insights into the research progress and existing problems of neoadjuvant therapy for locally advanced resectable EC

Long Non-Coding RNAs in Pancreatic Cancer: Biologic Functions, Mechanisms, and Clinical Significance

Despite tremendous efforts devoted to research in pancreatic cancer (PC), the mechanism underlying the tumorigenesis and progression of PC is still not completely clear. Additionally, ideal biomarkers and satisfactory therapeutic strategies for clinical application in PC are still lacking. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) might participate in the pathogenesis of diverse cancers, including PC. The abnormal expression of lncRNAs in PC is considered a vital factor during tumorigenesis that affects tumor cell proliferation, migration, invasion, apoptosis, angiogenesis, and drug resistance. With this review of relevant articles published in recent years, we aimed to summarize the biogenesis mechanism, classifications, and modes of action of lncRNAs and to review the functions and mechanisms of lncRNAs in PC. Additionally, the clinical significance of lncRNAs in PC was discussed. Finally, we pointed out the questions remaining from recent studies and anticipated that further investigations would address these gaps in knowledge in this field

Colorectal Cancer in Ulcerative Colitis: Mechanisms, Surveillance and Chemoprevention

Patients with ulcerative colitis (UC) are at a two- to three-fold increased risk of developing colorectal cancer (CRC) than the general population based on population-based data. UC-CRC has generated a series of clinical problems, which are reflected in its worse prognosis and higher mortality than sporadic CRC. Chronic inflammation is a significant contributor to the development of UC-CRC, so comprehending the relationship between the proinflammatory factors and epithelial cells together with downstream signaling pathways is the core to elucidate the mechanisms involved in developing of CRC. Clinical studies have shown the importance of early prevention, detection and management of CRC in patients with UC, and colonoscopic surveillance at regular intervals with multiple biopsies is considered the most effective way. The use of endoscopy with targeted biopsies of visible lesions has been supported in most populations. In contrast, random biopsies in patients with high-risk characteristics have been suggested during surveillance. Some of the agents used to treat UC are chemopreventive, the effects of which will be examined in cancers in UC in a population-based setting. In this review, we outline the current state of potential risk factors and chemopreventive recommendations in UC-CRC, with a specific focus on the proinflammatory mechanisms in promoting CRC and evidence for personalized surveillance

Integrin β1 in Pancreatic Cancer: Expressions, Functions, and Clinical Implications

Pancreatic cancer (PC) is characterized by rapid progression and a high mortality rate. The current treatment is still based on surgical treatment, supplemented by radiotherapy and chemotherapy, and new methods of combining immune and molecular biological treatments are being explored. Despite this, the survival rate of PC patients is still very disappointing. Therefore, clarifying the molecular mechanism of PC pathogenesis and developing precisely targeted drugs are key to improving PC prognosis. As the most common β subunit of the integrin family, integrin β1 has been proved to be closely related to the vascular invasion, distant metastasis, and survival of PC patients, and treatment targeting integrin β1 in PC has gained initial success in animal models. In this review, we summarize the various signaling pathways by which integrins are involved in PC, focusing on the roles of integrin β1 in the malignant behaviors of PC. Additionally, recent studies regarding the feasibility of integrin β1 as a diagnostic and prognostic biomarker in PC are also discussed. Finally, we present the progress of several integrin β1-based clinical trials to highlight the potential of integrin β1 as a target for personalized therapy in PC

Combined use of CDAI and blood indices for assessing endoscopic activity in ileocolic Crohn’s disease

Abstract Background Mucosal healing has become the primary treatment target for patients with Crohn’s disease (CD). We aimed to develop a noninvasive and convenient tool to evaluate the endoscopic activity in patients with ileocolic CD. Methods A retrospective multicenter study including 300 CD patients (training, 210 patients; test, 90 patients) was conducted at two tertiary referral centers. Independent risk factors associated with endoscopic activity were explored, which were then combined into a comprehensive index. The predictive performance was evaluated with the area under receiver operating characteristic curve (ROC). Cohen’s Kappa was adopted to examine the consistency between each indicator and endoscopic activity. Results A total of 210 CD patients were recruited in the training cohort. We found that Crohn’s Disease Activity Index (CDAI), C-reactive protein (CRP) and platelet-to-lymphocyte percentage ratio (PLpR) were independently associated with endoscopic activity. Additionally, the comprehensive index generated from the above three indices achieved good discrimination and performed better than CDAI in AUC (0.849 vs. 0.769, P < 0.05). This was further well demonstrated by the external test cohort, which showed good discrimination (AUC: 0.84, 95% CI: 0.744–0.936). Intra-individual comparison revealed the comprehensive index to be superior in the prediction of endoscopic activity. In the subgroup analysis, the AUC of comprehensive index was significantly higher than CDAI especially in inflammatory phenotype (0.824 vs. 0.751, P < 0.05). Conclusion Combining CDAI, CRP and PLpR significantly improved the accuracy for predicting endoscopic activity in ileocolic CD, which can help better monitor an endoscopic flare

Beam Control in an Intracavity Frequency-Doubling Semiconductor Disk Laser

In this paper, we have demonstrated a 1.3 W green laser using a V-shaped intracavity frequency doubling 1036 nm semiconductor disk laser. The beam quality of the fundamental and second harmonic generation (SHG) laser is investigated. It has been found that the output lasers at the fundamental and SHG wavelength both suffer from reduced beam quality along with power scaling. The measured beam profile is elliptical under high power operation. In order to improve the SHG laser beam, an intracavity aperture is employed to control the mode characteristics of fundamental frequency light. By fine-tuning the aperture, a nearly circular beam profile with improving beam quality and brightness is realized