Tourist destinations around the world are trying to cope with the needs of visitors which are very susceptible to change. Nowadays, tourists are becoming more sophisticated and knowledgeable, and their needs for extensive  and diverse experiences are increasing. As opposed to the destinations whose tourism development depends on the natural resources that are difficult to influence, and whose business is susceptible to the negative impacts of seasonality, destinations of city and cultural tourism have more space to design their offers and contents that can satisfy the needs of travelers of the modern age. Content that can make a destination unique and well-known, is the cultural heritage created in the Art Nouveau style. The secessionist architectural masterpieces can represent a major tourist attractions in some destinations. For example, many attractive tourist cities such as Aveiro, Barcelona, Prague and Hamburg tourists visit just in order to feel and experience these works of art. For this reason it is very important to point out Art Nouveau as an essential part of the cultural heritage of the destination and enable informing and introducing tourists with this valuable tourism potential. The initial hypothesis of this paper is that Aveiro has authentic cultural heritage in the Art Nouveau style that enriches the tourist offer of the city and that attracts a certain segment of the tourism market. Aim of the paper is to percieve the participation and influence of Art Nouveau heritage in the tourism industry of Aveiro. Keywords: Secession, Art direction, Tourism, Aveiro

Relevant for various areas of human genetics, Y‐chromosomal short tandem repeats (Y‐STRs) are commonly used for testing close paternal relationships among individuals and populations, and for male lineage identification. However, even the widely used 17‐loci Yfiler set cannot resolve individuals and populations completely. Here, 52 centers generated quality‐controlled data of 13 rapidly mutating (RM) Y‐STRs in 14,644 related and unrelated males from 111 worldwide populations. Strikingly, >99% of the 12,272 unrelated males were completely individualized. Haplotype diversity was extremely high (global: 0.9999985, regional: 0.99836–0.9999988). Haplotype sharing between populations was almost absent except for six (0.05%) of the 12,156 haplotypes. Haplotype sharing within populations was generally rare (0.8% nonunique haplotypes), significantly lower in urban (0.9%) than rural (2.1%) and highest in endogamous groups (14.3%). Analysis of molecular variance revealed 99.98% of variation within populations, 0.018% among populations within groups, and 0.002% among groups. Of the 2,372 newly and 156 previously typed male relative pairs, 29% were differentiated including 27% of the 2,378 father–son pairs. Relative to Yfiler, haplotype diversity was increased in 86% of the populations tested and overall male relative differentiation was raised by 23.5%. Our study demonstrates the value of RM Y‐STRs in identifying and separating unrelated and related males and provides a reference database.

The authors assessed the overall response rate, including confirmed complete response (CR) and partial response, in patients with relapsed/refractory multiple myeloma treated with sorafenib. Qualitative and quantitative toxicities associated with this regimen were evaluated. Patients were eligible if they had a confirmed diagnosis of refractory or relapsed (RR) multiple myeloma (MM) with measurable monoclonal protein. Patients had to have adequate renal, hepatic, hematologic, and cardiac function with a Zubrod performance status of 0–2. Patients were given 400 mg sorafenib by mouth twice daily for 28‐day treatment cycles. These patients were followed up for a maximum of 3 years to assess responses and adverse events. Twenty‐three patients were enrolled. Of these, five were found to be ineligible for the following reasons: four had insufficient documentation of the baseline disease and one patient did not have measurable disease. All eighteen eligible patients were evaluable for toxicities. Three patients experienced grade 4 toxicities: one with thrombocytopenia, one with anemia, and one with renal failure. Four of the eighteen eligible patients were not assessable for response due to removal from protocol treatment prior to adequate disease assessment. Specifically, three were removed for either grade 4 toxicity or progression of disease and one was removed per patient choice (due to reasons unrelated to treatment). Of the 18 patients who were assessed for toxicities, 5 (27.8%) received at least one fully dosed cycle, 2 (11.1%) of whom had all cycles fully dosed. No responses were observed on this study of the 14 patients who were assessable for response. All patients have discontinued protocol treatment as of August 2008. Overall survival at 12 months was 50% (95% CI 27–73%) and median progression‐free survival was 1.2 months (95% CI 1.0–5.4). The trial did not exhibit activity by the International Uniform Response Criteria for MM. Further research should focus on combination therapy of sorafenib with standard treatments in selected patients with RR MM.

Background Decline in cognitive performance is associated with gait deterioration. Our objectives were: 1) to determine, from an original study in older community-dwellers without diagnosis of dementia, which gait parameters, among slower gait speed, higher stride time variability (STV) and Timed Up & Go test (TUG) delta time, were most strongly associated with lower performance in two cognitive domains (i.e., episodic memory and executive function); and 2) to quantitatively synthesize, with a systematic review and meta-analysis, the association between gait performance and cognitive decline (i.e., mild cognitive impairment (MCI) and dementia). Methods Based on a cross-sectional design, 934 older community-dwellers without dementia (mean±standard deviation, 70.3±4.9years; 52.1% female) were recruited. A score at 5 on the Short Mini-Mental State Examination defined low episodic memory performance. Low executive performance was defined by clock-drawing test errors. STV and gait speed were measured using GAITRite system. TUG delta time was calculated as the difference between the times needed to perform and to imagine the TUG. Then, a systematic Medline search was conducted in November 2013 using the Medical Subject Heading terms “Delirium,” “Dementia,” “Amnestic,” “Cognitive disorders” combined with “Gait” OR “Gait disorders, Neurologic” and “Variability.” Findings A total of 294 (31.5%) participants presented decline in cognitive performance. Higher STV, higher TUG delta time, and slower gait speed were associated with decline in episodic memory and executive performances (all P-values <0.001). The highest magnitude of association was found for higher STV (effect size  =  −0.74 [95% Confidence Interval (CI): −1.05;−0.43], among participants combining of decline in episodic memory and in executive performances). Meta-analysis underscored that higher STV represented a gait biomarker in patients with MCI (effect size  =  0.48 [95% CI: 0.30;0.65]) and dementia (effect size  = 1.06 [95% CI: 0.40;1.72]). Conclusion Higher STV appears to be a motor phenotype of cognitive decline.

Let G be a simple connected graph. The distance between the edges g and f ∈ E(G) is defined as the distance between the corresponding vertices g and f in the line graph of G. The edge-Wiener index of G is defined as the sum of such distances between all pairs of edges of the graph. Let G1+G2 and G1◦G2 be the join and the corona of graphs G1 and G2, respectively. In this paper, we present explicit formulas for the edge-Wiener index for these graphs. Then we apply our results to compute the edge-Wiener index of suspensions, bottlenecks, and thorny graphs.

In this paper we deal with quadratic metric-affine gravity, which we briefly introduce, explain and give historical and physical reasons for using this particular theory of gravity. We then introduce a generalisation of well known spacetimes, namely pp-waves. A classical pp-wave is a 4-dimensional Lorentzian spacetime which admits a nonvanishing parallel spinor field; here the connection is assumed to be Levi-Civita. This definition was generalised in our previous work to metric compatible spacetimes with torsion and used to construct new explicit vacuum solutions of quadratic metric-affine gravity, namely generalised pp-waves of parallel Ricci curvature. The physical interpretation of these solutions we propose in this article is that they represent a conformally invariant metric-affine model for a massless elementary particle. We give a comparison with the classical model describing the interaction of gravitational and massless neutrino fields, namely Einstein–Weyl theory and construct pp-wave type solutions of this theory. We point out that generalised pp-waves of parallel Ricci curvature are very similar to pp-wave type solutions of the Einstein–Weyl model and therefore propose that our generalised pp-waves of parallel Ricci curvature represent a metric-affine model for the massless neutrino.