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D. Pamučar, Željko Stević, S. Sremac

In this paper, a new multi-criteria problem solving method—the Full Consistency Method (FUCOM)—is proposed. The model implies the definition of two groups of constraints that need to satisfy the optimal values of weight coefficients. The first group of constraints is the condition that the relations of the weight coefficients of criteria should be equal to the comparative priorities of the criteria. The second group of constraints is defined on the basis of the conditions of mathematical transitivity. After defining the constraints and solving the model, in addition to optimal weight values, a deviation from full consistency (DFC) is obtained. The degree of DFC is the deviation value of the obtained weight coefficients from the estimated comparative priorities of the criteria. In addition, DFC is also the reliability confirmation of the obtained weights of criteria. In order to illustrate the proposed model and evaluate its performance, FUCOM was tested on several numerical examples from the literature. The model validation was performed by comparing it with the other subjective models (the Best Worst Method (BWM) and Analytic Hierarchy Process (AHP)), based on the pairwise comparisons of the criteria and the validation of the results by using DFC. The results show that FUCOM provides better results than the BWM and AHP methods, when the relation between consistency and the required number of the comparisons of the criteria are taken into consideration. The main advantages of FUCOM in relation to the existing multi-criteria decision-making (MCDM) methods are as follows: (1) a significantly smaller number of pairwise comparisons (only n − 1), (2) a consistent pairwise comparison of criteria, and (3) the calculation of the reliable values of criteria weight coefficients, which contribute to rational judgment.

Yilong Li, Nicola D. Roberts, J. Wala, Ofer Shapira, S. Schumacher, K. Kumar, Ekta Khurana, Sebastian M. Waszak et al.

Edin Smailhodzic, Wyanda Hooijsma, A. Boonstra, D. Langley

BackgroundSince the emergence of social media in 2004, a growing percentage of patients use this technology for health related reasons. To reflect on the alleged beneficial and potentially harmful effects of social media use by patients, the aim of this paper is to provide an overview of the extant literature on the effects of social media use for health related reasons on patients and their relationship with healthcare professionals.MethodsWe conducted a systematic literature review on empirical research regarding the effects of social media use by patients for health related reasons. The papers we included met the following selection criteria: (1) published in a peer-reviewed journal, (2) written in English, (3) full text available to the researcher, (4) contain primary empirical data, (5) the users of social media are patients, (6) the effects of patients using social media are clearly stated, (7) satisfy established quality criteria.ResultsInitially, a total of 1,743 articles were identified from which 22 were included in the study. From these articles six categories of patients’ use of social media were identified, namely: emotional, information, esteem, network support, social comparison and emotional expression. The types of use were found to lead to seven identified types of effects on patients, namely improved self-management and control, enhanced psychological well-being, and enhanced subjective well-being, diminished subjective well-being, addiction to social media, loss of privacy, and being targeted for promotion. Social media use by patients was found to affect the healthcare professional and patient relationship, by leading to more equal communication between the patient and healthcare professional, increased switching of doctors, harmonious relationships, and suboptimal interaction between the patient and healthcare professional.ConclusionsOur review provides insights into the emerging utilization of social media in healthcare. In particular, it identifies types of use by patients as well as the effects of such use, which may differ between patients and doctors. Accordingly, our results framework and propositions can serve to guide future research, and they also have practical implications for healthcare providers and policy makers.

K. Michailidou, J. Beesley, S. Lindstrom, S. Canisius, J. Dennis, M. Lush, M. Maranian, M. Bolla et al.

J. Smerage, W. Barlow, G. Hortobagyi, E. Winer, B. Leyland-Jones, G. Srkalović, S. Tejwani, A. Schott et al.

PURPOSE Increased circulating tumor cells (CTCs; five or more CTCs per 7.5 mL of whole blood) are associated with poor prognosis in metastatic breast cancer (MBC). A randomized trial of patients with persistent increase in CTCs tested whether changing chemotherapy after one cycle of first-line chemotherapy would improve the primary outcome of overall survival (OS). PATIENTS AND METHODS Patients with MBC who did not have increased CTCs at baseline remained on initial therapy until progression (arm A). Patients with initially increased CTCs that decreased after 21 days of therapy remained on initial therapy (arm B). Patients with persistently increased CTCs after 21 days of therapy were randomly assigned to continue initial therapy (arm C1) or change to an alternative chemotherapy (arm C2). RESULTS Of 595 eligible and evaluable patients, 276 (46%) did not have increased CTCs (arm A). Of those with initially increased CTCs, 31 (10%) were not retested, 165 were assigned to arm B, and 123 were randomly assigned to arm C1 or C2. No difference in median OS was observed between arm C1 and C2 (10.7 and 12.5 months, respectively; P = .98). CTCs were strongly prognostic. Median OS for arms A, B, and C (C1 and C2 combined) were 35 months, 23 months, and 13 months, respectively (P < .001). CONCLUSION This study confirms the prognostic significance of CTCs in patients with MBC receiving first-line chemotherapy. For patients with persistently increased CTCs after 21 days of first-line chemotherapy, early switching to an alternate cytotoxic therapy was not effective in prolonging OS. For this population, there is a need for more effective treatment than standard chemotherapy.

K. Litchfield, J. Reading, C. Puttick, Krupa Thakkar, C. Abbosh, R. Bentham, T. Watkins, R. Rosenthal et al.

Sofia Khan, Dario Greco, K. Michailidou, R. Milne, T. Muranen, T. Heikkinen, Kirsimari Aaltonen, J. Dennis et al.

Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88–0.96), rs1052532 (OR 0.97; 95% CI: 0.95–0.99), rs10719 (OR 0.97; 95% CI: 0.94–0.99), rs4687554 (OR 0.97; 95% CI: 0.95–0.99, and rs3134615 (OR 1.03; 95% CI: 1.01–1.05) located in the 3′ UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects.

W. Becker, F. Grasbon, R. Kopold, D. Milošević, G. Paulus, H. Walther

Ana Marija Škoda, Dora Šimović, Valentina Karin, V. Kardum, S. Vranić, L. Serman

The Hedgehog (Hh) signaling pathway was first identified in the common fruit fly. It is a highly conserved evolutionary pathway of signal transmission from the cell membrane to the nucleus. The Hh signaling pathway plays an important role in the embryonic development. It exerts its biological effects through a signaling cascade that culminates in a change of balance between activator and repressor forms of glioma-associated oncogene (Gli) transcription factors. The components of the Hh signaling pathway involved in the signaling transfer to the Gli transcription factors include Hedgehog ligands (Sonic Hh [SHh], Indian Hh [IHh], and Desert Hh [DHh]), Patched receptor (Ptch1, Ptch2), Smoothened receptor (Smo), Suppressor of fused homolog (Sufu), kinesin protein Kif7, protein kinase A (PKA), and cyclic adenosine monophosphate (cAMP). The activator form of Gli travels to the nucleus and stimulates the transcription of the target genes by binding to their promoters. The main target genes of the Hh signaling pathway are PTCH1, PTCH2, and GLI1. Deregulation of the Hh signaling pathway is associated with developmental anomalies and cancer, including Gorlin syndrome, and sporadic cancers, such as basal cell carcinoma, medulloblastoma, pancreatic, breast, colon, ovarian, and small-cell lung carcinomas. The aberrant activation of the Hh signaling pathway is caused by mutations in the related genes (ligand-independent signaling) or by the excessive expression of the Hh signaling molecules (ligand-dependent signaling - autocrine or paracrine). Several Hh signaling pathway inhibitors, such as vismodegib and sonidegib, have been developed for cancer treatment. These drugs are regarded as promising cancer therapies, especially for patients with refractory/advanced cancers.

Honor Bixby, J. Bentham, Bin Zhou, M. Di Cesare, C. Paciorek, J. Bennett, C. Taddei, Gretchen A. Stevens et al.

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities1,2. This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity3–6. Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017—and more than 80% in some low- and middle-income regions—was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing—and in some countries reversal—of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories. Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.

P. Salières, B. Carré, L. L. Déroff, F. Grasbon, G. Paulus, H. Walther, R. Kopold, W. Becker et al.

Atoms interacting with intense laser fields can emit electrons and photons of very high energies. An intuitive and quantitative explanation of these highly nonlinear processes can be found in terms of a generalization of classical Newtonian particle trajectories, the so-called quantum orbits. Very few quantum orbits are necessary to reproduce the experimental results. These orbits are clearly identified, thus opening the way for an efficient control as well as previously unknown applications of these processes.

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