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The nutritional properties of seaweeds are incompletely known, and studies on nutrient bioavailability are scarce, although such information is required to evaluate seaweed as a foodstuff. In the present study, samples of wakame (Undaria pinnatifida) and nori (Porphyra purpurea) were analysed to determine their chemical composition. To evaluate the algae as dietary supplements, the effects on rats of the inclusion of these seaweeds in a standard rodent diet were investigated. The control rats were fed a diet containing 100 % standard rodent diet. The wakame diet was obtained by mixing 10 % dried wakame with 90 % standard rodent diet, and the nori diet was obtained by mixing 10 % dried nori with 80 % standard rodent diet and 10 % starch. Food intake and the body weight were measured. Nitrogen ingested and excreted were determined to calculate true digestibility, biological value, net protein utilization and nitrogen balance. Biochemical determinations were made on serum blood samples. The protein content was high (16.8 % for wakame and 33.2 % for nori), the fat content was low (1 % for wakame and 2.8 % for nori) and the carbohydrates comprised 37 % for both seaweeds. The fibre and ash contents in wakame were 16.9 and 28.3 %, respectively, and in nori, they were 7.5 and 21.3 %, respectively. Both seaweeds contain high concentrations of calcium, sodium, potassium, iron and magnesium, and the most abundant vitamin was vitamin A. Few changes were observed in the nutritional parameters, but LDL cholesterol levels were significantly lower in rats fed with seaweed-supplemented diets than in the control rats. Wakame and nori are excellent sources of nutrients and are well accepted by experimental animals.

The development of multiphase steels to obtain an optimum balance between strength and ductility is a very active topic of research. In particular, carbide-free bainitic steels have shown promising mechanical properties, making them good candidates for replacing well-established first-generation steels in the automotive industry. In this work, a detailed analysis of the microstructures attainable through overaging treatments is tackled in two bainitic steels with different Si contents. The focus has been put onto the mechanical characterization, via nanoindentation, of the phases that are generated as a consequence of the change in the bainitic treatment conditions and the final cooling to room temperature. The results show the suitability of the nanoindentation technique for gaining knowledge about the underlying transformation-related phenomena and for measuring the relative difference in hardness of the various micro-constituents. The latter is a key factor in understanding the origin of the damage in this kind of steels.

New trends focused on achieving higher performance steels has led to a so-called 3rd Generation Advanced High Strength Steels (AHSS), in which the typical polygonal ferrite found in TRIP steels as a matrix phase is replaced by harder phases as Carbide-Free Bainite (CFB) and/or (tempered) martensite. Besides, large volume fractions of retained austenite (R.A.) with adequate stability are aimed for to improve the formability of the steels. Si containing steels are regarded as the most suitable to retard cementite formation and consequently reach high volume fractions of RA. In this work, CFB annealing schedules were applied to dilatometer samples of Fe-0.22C-2.0Mn-1.3Si. The overaging temperature TB was varied between 390 oC and 480 oC, and other processing variables investigated were the austenitizing temperature Taus, and the overaging holding time tB. The annealed samples analyzed with LOM, FEG-SEM, EBSD and X-ray diffraction techniques show that markedly different complex microstructures made up of bainite, ferrite, MA phase and retained austenite (R.A) are accomplished depending on the specific thermal cycle. These results are described in detail and discussed in relation to the dilatometry measurements.

Two groups of rats were fed on diets with protein from a marine specie holothuria (Holothuria forskali) or casein (for the control group) during 16 days with the aim of assessing the nutritional value of the holothuria protein. Several serum lipid levels were also determined. The results of the nutritive parameters indicate that except for True Digestibility (which did not differ significantly between the two groups) all other indicators were significantly lower for the holothuria fed group. HDL-cholesterol level was significantly higher in the holothuria fed group, while triglyceride level was lower.

To investigate the effects of pectin on cholesterol metabolism, normal rats were fed for three weeks a diet containing 2.5 or 5 % apple or orange pectin, or without pectin (control). Cholesterol concentrations were determined in faeces after 1, 2 and 3 weeks of treatment, and in liver and serum at the end of the experimental trials. Cholesterol concentration in faeces showed a significant increase by week 3 in rats fed 5 % orange or apple pectin. Hepatic cholesterol concentration declined significantly in all pectin-fed groups. Serum cholesterol only declined significantly in apple-fed groups. The decrease of cholesterol levels in liver and serum, and its increase in faeces could explain the beneficial effect of including these fibers in the diet to prevent some nowadays very frequent diseases.

The dietary effects of two high protein diets from two species of sea urchin (Paracentrotus lividus and Echinus esculentus) as compared to a reference protein such as casein on serum lipid levels and on intestinal disaccharidases and alkaline phosphatase were studied. After 23 days, the containing the two sea urchins as diets compared to casein decreased the cholesterol level and significantly increased the HDL-cholesterol in serum. The consumption of Echinus esculentus meal produced a significant decrease in lactase activity. The intestinal alkaline phosphatase activity increased not significantly in animals fed on the sea urchin meal.

This book analyses the cultural elements of 21st-century tourism. The structure of the book is based on four main issues, which will help further the reader's understanding of present-day experiential tourism: namely urban and cultural tourism on a global scale; specific studies of new products linked to reappraising the landscape; heritage; and nature. It also examines the influence of branding and of the images projected in order to promote this new type of tourism, using both theoretical and general approaches. Finally, the Camino de Santiago is analysed as a paradigm of the new pilgrimage routes all over the world, with their implications and polysemic nature. Culture, nature, spirituality and urbanism are brought together in a series of studies of contemporary tourist activities. Tourism is, in short, an activity that marks the return of slow movement, of calm and relaxation, of the landscape and of self-rediscovery as a reappraised counterpoint to the frenetic pace of life in modern-day societies.

In patients with locally advanced non–small-cell lung cancer who have undergone concurrent chemotherapy and radiation therapy, the use of durvalumab in the year after completing treatment significantly prolonged disease-free and overall survival as compared with placebo.

Objectives To compare the effectiveness of rituximab versus an alternative tumour necrosis factor (TNF) inhibitor (TNFi) in patients with rheumatoid arthritis (RA) with an inadequate response to one previous TNFi. Methods SWITCH-RA was a prospective, global, observational, real-life study. Patients non-responsive or intolerant to a single TNFi were enrolled ≤4 weeks after starting rituximab or a second TNFi. Primary end point: change in Disease Activity Score in 28 joints excluding patient's global health component (DAS28-3)–erythrocyte sedimentation rate (ESR) over 6 months. Results 604 patients received rituximab, and 507 an alternative TNFi as second biological therapy. Reasons for discontinuing the first TNFi were inefficacy (n=827), intolerance (n=263) and other (n=21). A total of 728 patients were available for primary end point analysis (rituximab n=405; TNFi n=323). Baseline mean (SD) DAS28-3–ESR was higher in the rituximab than the TNFi group: 5.2 (1.2) vs 4.8 (1.3); p<0.0001. Least squares mean (SE) change in DAS28-3–ESR at 6 months was significantly greater in rituximab than TNFi patients: −1.5 (0.2) vs −1.1 (0.2); p=0.007. The difference remained significant among patients discontinuing the initial TNFi because of inefficacy (−1.7 vs −1.3; p=0.017) but not intolerance (−0.7 vs −0.7; p=0.894). Seropositive patients showed significantly greater improvements in DAS28-3–ESR with rituximab than with TNFi (−1.6 (0.3) vs −1.2 (0.3); p=0.011), particularly those switching because of inefficacy (−1.9 (0.3) vs −1.5 (0.4); p=0.021). The overall incidence of adverse events was similar between the rituximab and TNFi groups. Conclusions These real-life data indicate that, after discontinuation of an initial TNFi, switching to rituximab is associated with significantly improved clinical effectiveness compared with switching to a second TNFi. This difference was particularly evident in seropositive patients and in those switched because of inefficacy.

New therapeutic strategies for malignant mesothelioma are urgently needed. In the DETERMINE study, we investigated the effects of the cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibody tremelimumab in patients with previously treated advanced malignant mesothelioma. DETERMINE was a double-blind, placebo-controlled, phase 2b trial done at 105 study centres across 19 countries in patients with unresectable pleural or peritoneal malignant mesothelioma who had progressed after one or two previous systemic treatments for advanced disease. Eligible patients were aged 18 years or older with Eastern Cooperative Oncology Group performance status of 0 or 1 and measurable disease as defined in the modified Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0 for pleural mesothelioma or RECIST version 1.1 for peritoneal mesothelioma. Patients were randomly assigned (2:1) in blocks of three, stratified by European Organisation for Research and Treatment of Cancer status (low risk vs high risk), line of therapy (second line vs third line), and anatomic site (pleural vs peritoneal), by use of an interactive voice or web system, to receive intravenous tremelimumab (10 mg/kg) or placebo every 4 weeks for 7 doses and every 12 weeks thereafter until a treatment discontinuation criterion was met. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study drug. The trial is ongoing but no longer recruiting participants, and is registered with ClinicalTrials.gov, number NCT01843374. Between May 17, 2013, and Dec 4, 2014, 571 patients were randomly assigned to receive tremelimumab (n=382) or placebo (n=189), of whom 569 patients received treatment (two patients in the tremelimumab group were excluded from the safety population because they did not receive treatment). At the data cutoff date (Jan 24, 2016), 307 (80%) of 382 patients had died in the tremelimumab group and 154 (81%) of 189 patients had died in the placebo group. Median overall survival in the intention-to-treat population did not differ between the treatment groups: 7·7 months (95% CI 6·8–8·9) in the tremelimumab group and 7·3 months (5·9–8·7) in the placebo group (hazard ratio 0·92 [95% CI 0·76–1·12], p=0·41). Treatment-emergent adverse events of grade 3 or worse occurred in 246 (65%) of 380 patients in the tremelimumab group and 91 (48%) of 189 patients in the placebo group; the most common were dyspnoea (34 [9%] patients in the tremelimumab group vs 27 [14%] patients in the placebo group), diarrhoea (58 [15%] vs one [<1%]), and colitis (26 [7%] vs none). The most common serious adverse events were diarrhoea (69 [18%] patients in the tremelimumab group vs one [<1%] patient in the placebo group), dyspnoea (29 [8%] vs 24 [13%]), and colitis (24 [6%] vs none). Treatment-emergent events leading to death occurred in 36 (9%) of 380 patients in the tremelimumab group and 12 (6%) of 189 in the placebo group; those leading to the death of more than one patient were mesothelioma (three [1%] patients in the tremelimumab group vs two [1%] in the placebo group), dyspnoea (three [1%] vs two [1%]); respiratory failure (one [<1%] vs three [2%]), myocardial infarction (three [1%] vs none), lung infection (three [1%] patients vs none), cardiac failure (one [<1%] vs one [<1%]), and colitis (two [<1%] vs none). Treatment-related adverse events leading to death occurred in five (1%) patients in the tremelimumab group and none in the placebo group. The causes of death were lung infection in one patient, intestinal perforation and small intestinal obstruction in one patient; colitis in two patients, and neuritis and skin ulcer in one patient. Tremelimumab did not significantly prolong overall survival compared with placebo in patients with previously treated malignant mesothelioma. The safety profile of tremelimumab was consistent with the known safety profile of CTLA-4 inhibitors. Investigations into whether immunotherapy combination regimens can provide greater efficacy than monotherapies in malignant mesothelioma are ongoing. AstraZeneca.