Explore the vast range of titles available.

Fracture liaison services (FLS), implemented in different ways and countries, are reported to be a cost-effective or even a cost-saving secondary fracture prevention strategy. This presumed favorable cost-benefit relationship is encouraging and lends support to expanded implementation of FLS per International Osteoporosis Foundation Best Practice Standards. This study summarizes the economic impact and cost-effectiveness of FLS implemented to reduce subsequent fractures in individuals with osteoporosis. This systematic review identified studies reporting economic outcomes for FLS in osteoporotic patients aged 50 and older through a comprehensive search of MEDLINE, EMBASE, Cochrane Central, and PubMed of studies published January, 2000 to December, 2016. Grey literature (e.g., Google scholar, conference abstracts/posters) were also hand searched through February 2017. Two independent reviewers screened titles and abstracts and conducted full-text review on qualified articles. All disagreements were resolved by discussion between reviewers to reach consensus or by a third reviewer. In total, 23 qualified studies that evaluated the economic aspects of FLS were included: 16 cost-effectiveness studies, 2 cost-benefit analyses, and 5 studies of cost savings. Patient populations varied (prior fragility fracture, non-vertebral fracture, hip fracture, wrist fracture), and FLS strategies ranged from mail-based interventions to comprehensive nurse/physician-coordinated programs. Cost-effectiveness studies were conducted in Canada, Australia, USA, UK, Japan, Taiwan, and Sweden. FLS was cost-effective in comparisons with usual care or no treatment, regardless of the program intensity or the country in which the FLS was implemented (cost/QALY from $3023–$28,800 US dollars (USD) in Japan to $14,513–$112,877 USD in USA. Several studies documented cost savings. FLS, implemented in different ways and countries, are reported to be cost-effective or even cost-saving. This presumed favorable cost-benefit relationship is encouraging and lends support to expanded implementation of FLS per International Osteoporosis Foundation Best Practice Standards.

Several decades of research have sought to characterize tumor cell metabolism in the hope that tumor-specific activities can be exploited to treat cancer. Having originated from Warburg's seminal observation of aerobic glycolysis in tumor cells, most of this attention has focused on glucose metabolism. However, since the 1950s cancer biologists have also recognized the importance of glutamine (Q) as a tumor nutrient. Glutamine contributes to essentially every core metabolic task of proliferating tumor cells: it participates in bioenergetics, supports cell defenses against oxidative stress and complements glucose metabolism in the production of macromolecules. The interest in glutamine metabolism has been heightened further by the recent findings that c- myc controls glutamine uptake and degradation, and that glutamine itself exerts influence over a number of signaling pathways that contribute to tumor growth. These observations are stimulating a renewed effort to understand the regulation of glutamine metabolism in tumors and to develop strategies to target glutamine metabolism in cancer. In this study we review the protean roles of glutamine in cancer, both in the direct support of tumor growth and in mediating some of the complex effects on whole-body metabolism that are characteristic of tumor progression.

Hepatocellular carcinoma (HCC) cells often invade the portal venous system and subsequently develop into portal vein tumour thrombosis (PVTT). Long noncoding RNAs (lncRNAs) have been associated with HCC, but a comprehensive analysis of their specific association with HCC metastasis has not been conducted. Here, by analysing 60 clinical samples’ RNA-seq data from 20 HCC patients, we have identified and characterized 8,603 candidate lncRNAs. The expression patterns of 917 recurrently deregulated lncRNAs are correlated with clinical data in a TCGA cohort and published liver cancer data. Matched array data from the 60 samples show that copy number variations (CNVs) and alterations in DNA methylation contribute to the observed recurrent deregulation of 235 lncRNAs. Many recurrently deregulated lncRNAs are enriched in co-expressed clusters of genes related to cell adhesion, immune response and metabolic processes. Candidate lncRNAs related to metastasis, such as HAND2-AS1 , were further validated using RNAi-based loss-of-function assays. Thus, we provide a valuable resource of functional lncRNAs and biomarkers associated with HCC tumorigenesis and metastasis. Long noncoding-RNAs have been linked to hepatocellular carcinoma (HCC) and some can be used as prognostic markers. Here the authors, by analysing RNA-seq in 60 clinical samples from 20 patients, provide a resource of functional lncRNAs and biomarkers associated with HCC tumorigenesis and metastasis.

We consider a set of single-machine batch delivery scheduling problems involving two competing agents under two due date assignment models. Belonging to one of the two agents, each job is processed and delivered in a batch to its agent, where the jobs in each batch come from the same agent. The jobs in a batch are processed sequentially and the processing time of a batch is equal to the sum of the processing times of the jobs in it. A setup time is required at the start of each batch. The dispatch date of a job equals the delivery date of the batch it is in, i.e., the completion time of the last job in the batch. There is no capacity limit on each delivery batch, and the cost per batch delivery is fixed and independent of the number of jobs in the batch. The due date of each job is a decision variable, which is to be assigned by the decision maker using one of two due date models, namely the common and unrestricted due date models. Given the due date assignment model, the overall objective is to minimize one agent’s scheduling criterion, while keeping the other agent’s criterion value from exceeding a threshold given in advance. Two kinds of scheduling criteria are involved: (i) the total cost comprising the earliness, tardiness, job holding, due date assignment, and batch delivery costs; and (ii) the total cost comprising the earliness, weighted number of tardy jobs, job holding, due date assignment, and batch delivery costs. For each of the problems considered, we show that it is NP-hard in the ordinary sense and admits a fully polynomial-time approximation scheme.

This paper considers the integration of three essential seaport terminal operations: the berth allocation problem, the quay crane assignment problem (QCAP), and the quay crane scheduling problem (QCSP). The paper presents a new mathematical formulation that captures all associated operations and constraints. Different quay crane operational policies are considered, namely permitting versus not permitting bay task preemption in QCSP and static versus dynamic crane allocations in QCAP. Thus, variants of the mathematical formulation are introduced to capture the different combinations of these scenarios. Due to the preemption consideration, the models include disaggregated quay crane (QC) tasks. Specifically, QC tasks are identified by single container movements as opposed to bay or stack task allocations that are commonly used in the literature. A case study based on Abu Dhabi’s container terminal is presented where the use of the proposed mathematical models are compared against the current existing operational approach. Results show that the service times can be significantly decreased by the use of the proposed models. Moreover, the policy choice effect on the total schedule is compared through simulated examples and Abu Dhabi’s container terminal case study. The results show that the policy improvements can depend on the problem’s attributes and thus a better policy cannot be generalized.

PurposeThis paper examines the relationship between supply chain network structures and firm financial performance and the moderating role of international relations. In this study, which is grounded in social capital theory and applies the perspective of systemic risk, the authors theorize the effects of supply chain network structures on firm performance.Design/methodology/approachThe authors extracted data from two Chinese databases and constructed a supply chain network of the firms concerned based on nearly 4,300 supply chain relations between 2009 and 2018. The authors adopted the fixed effects model to investigate the relationship between supply chain network structures and firm financial performance.FindingsThe econometrics results indicate that network structures, including the degree, centrality, clustering coefficients and structural holes, are significantly related to firm financial performance. A significant and negative relationship exists between international relations and firm financial performance. The authors also find that international relations strongly weaken the relationship between supply chain network structures and firm financial performance.Originality/valueThis study, which collects secondary data from developing countries (e.g. China) and explores the impacts of supply chain network structures on firm stock performance, contributes to the existing literature and provides practical implications.

Vaccination is a well-known method to protect the public against an epidemic outbreak, e.g., COVID-19. To this end, the government of a country or region would strive to achieve its target of vaccination coverage. Limited by the total vaccine capacity of public hospitals, the government may need to cooperate with private hospitals or clinics for more vaccination. Exploring in this paper government coordination of public and private resources for vaccination, we model a vaccine system consisting of a public hospital, a profit-maximizing private clinic, and self-interested individuals, under three scenarios: (1) without information sharing (concerning vaccine inventory and vaccine price), (2) with information sharing and subsidy, and (3) with information sharing and allocation. We find that, under scenario (1), the vaccine demand is fully satisfied by the public hospital and the private clinic cannot make any profit. Under scenario (2), the private clinic is willing to enter the vaccine market with a positive profit-maximizing vaccination coverage. Under scenario (3), the socially optimal vaccination coverage may be lower than that under scenario (1). Moreover, we conduct a sensitivity analysis to generate practical implications of the research findings for vaccination policy-making. Our results provide both theoretical and managerial insights on vaccine supply decision, government intervention, and vaccination coverage.

Background RNA-binding proteins (RBPs) play essential roles in gene expression regulation through their interactions with RNA transcripts, including coding, canonical non-coding and long non-coding RNAs. Large amounts of crosslinking immunoprecipitation (CLIP)-seq data (including HITS-CLIP, PAR-CLIP, and iCLIP) have been recently produced to reveal transcriptome-wide binding sites of RBPs at the single-nucleotide level. Description Here, we constructed a database, CLIPdb, to describe RBP-RNA interactions based on 395 publicly available CLIP-seq data sets for 111 RBPs from four organisms: human, mouse, worm and yeast. We consistently annotated the CLIP-seq data sets and RBPs, and developed a user-friendly interface for rapid navigation of the CLIP-seq data. We applied a unified computational method to identify transcriptome-wide binding sites, making the binding sites directly comparable and the data available for integration across different CLIP-seq studies. The high-resolution binding sites of the RBPs can be visualized on the whole-genome scale using a browser. In addition, users can browse and download the identified binding sites of all profiled RBPs by querying genes of interest, including both protein coding genes and non-coding RNAs. Conclusion Manually curated metadata and uniformly identified binding sites of publicly available CLIP-seq data sets will be a foundation for further integrative and comparative analyses. With maintained up-to-date data sets and improved functionality, CLIPdb ( http://clipdb.ncrnalab.org ) will be a valuable resource for improving the understanding of post-transcriptional regulatory networks.

Using a ligand as a promoter enhances the reactivity of the palladium catalyst in non-directed C–H functionalization of arenes, enabling the arene to be used as the limiting reagent. The catalyst does it all The functionalization of a carbon–hydrogen (C–H) bond is one of the most useful reactions in organic synthesis as it precludes the need to install reactive groups to perform a reaction. However, the reactivity and number of C–H bonds that are present in organic molecules mean that selectively targeting one is challenging. Typically this has been achieved by 'directing groups', where proximity to a specific C–H bond guides the reaction. Now, Jin-Quan Yu and colleagues report a palladium-catalysed non-directed arene C–H functionalization method using a 2-pyridone ligand. The ligand makes the catalyst more reactive, allowing the arene to be used as the limiting reagent—overcoming a key limitation in the use of such reactions in the derivatization of complex molecules. The ligand also enhances the effects of sterics on site selectivity, in some cases improving it significantly without the need for a directing group. The directed activation of carbon–hydrogen bonds (C–H) is important in the development of synthetically useful reactions, owing to the proximity-induced reactivity and selectivity that is enabled by coordinating functional groups 1 , 2 , 3 , 4 , 5 , 6 . Palladium-catalysed non-directed C–H activation could potentially enable further useful reactions, because it can reach more distant sites and be applied to substrates that do not contain appropriate directing groups; however, its development has faced substantial challenges associated with the lack of sufficiently active palladium catalysts 7 , 8 . Currently used palladium catalysts are reactive only with electron-rich arenes, unless an excess of arene is used 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , which limits synthetic applications. Here we report a 2-pyridone ligand that binds to palladium and accelerates non-directed C–H functionalization with arene as the limiting reagent. This protocol is compatible with a broad range of aromatic substrates and we demonstrate direct functionalization of advanced synthetic intermediates, drug molecules and natural products that cannot be used in excessive quantities. We also developed C–H olefination and carboxylation protocols, demonstrating the applicability of our methodology to other transformations. The site selectivity in these transformations is governed by a combination of steric and electronic effects, with the pyridone ligand enhancing the influence of sterics on the selectivity, thus providing complementary selectivity to directed C–H functionalization.