The Euromelanoma skin cancer prevention campaign in Europe: characteristics and results of 2009 and 2010.

Background  Euromelanoma is a skin cancer education and prevention campaign that started in 1999 in Belgium as 'Melanoma day'. Since 2000, it is active in a large and growing number of European countries under the name Euromelanoma. Objective  To evaluate results of Euromelanoma in 2009 and 2010 in 20 countries, describing characteristics of screenees, rates of clinically suspicious lesions for skin cancer and detection rates of melanomas. Methods  Euromelanoma questionnaires were used by 20 countries providing their data in a standardized database (Belgium, Croatia, Cyprus, Czech Republic, FYRO Macedonia, Germany, Greece, Hungary, Italy, Lithuania, Luxembourg, Malta, Moldavia, Portugal, Serbia, Slovenia, Spain, Sweden, Switzerland and Ukraine). Results  In total, 59 858 subjects were screened in 20 countries. Most screenees were female (64%), median ages were 43 (female) and 46 (male) and 33% had phototype I or II. The suspicion rates ranged from 1.1% to 19.4% for melanoma (average 2.8%), from 0.0% to 10.7% for basal cell carcinoma (average 3.1%) and from 0.0% to 1.8% for squamous cell carcinoma (average 0.4%). The overall positive predictive value of countries where (estimation of) positive predictive value could be determined was 13.0%, melanoma detection rates varied from 0.1% to 1.9%. Dermoscopy was used in 78% of examinations with clinically suspected melanoma; full body skin examination was performed in 72% of the screenees. Conclusion  Although the population screened during Euromelanoma was relatively young, high rates of clinically suspected melanoma were found. The efficacy of Euromelanoma could be improved by targeting high-risk populations and by better use of dermoscopy and full body skin examination.

Immunohistochemical expression of fibronectin and C5b-9 in the myocardium in cases of carbon monoxide poisoning.

Even if there is clinical evidence that carbon monoxide poisoning determines cardiac damage, the literature on the cardiac pathomorphology in such cases is scarce. We investigated the immunohistochemical expression of two known markers of fresh cardiac damage, fibronectin and the terminal complement complex C5b-9, in both cardiac ventricles in 26 cases of CO intoxication (study group, 15 ♀, 11 ♂, mean age 47 years, mean COHb level 65.9%, min. 51%, max. 85%) compared to a group of 23 cases of hanging (n = 23, 4♀, 19♂, mean age 42 years) as well as to 25 cases of myocardial infarction (n = 25, 13♀, 12♂, mean age 64 years). Fresh cardiac damage was detected with the antibody fibronectin in cases of CO poisoning and was prevalently localised at the right ventricle.

Implications of the serpentine phase transition on the behaviour of beryllium and lithium-boron of subducted ultramafic rocks

The Totalp-Platta-Malenco ophiolites in the Eastern Central Alps offer a unique opportunity to study the behaviour of Li, Be and B in ultramafic rocks in response to serpentinization and to progressive Alpine metamorphism. These units represent the remnants of a former ocean-continent transition that was intensely serpentinized during exposure on the Jurassic seafloor of the Ligurian Tethys. From north to the south, three isograd reactions (lizardite double right arrow antigorite + brucite; lizardite + talc double right arrow antigorite; lizardite + tremolite double right arrow antigorite + diopside) have been used to quantify the evolution of the light element content of metamorphic minerals. We determined the Li, Be and B concentrations in major silicate minerals from the ultramafic bodies of Totalp, Platta and Malenco by secondary ion mass spectrometry. Mantle minerals have Be concentrations (e.g. <0.001-0.009 mu g/g in olivine) similar to the metamorphic minerals that replace them (e.g. <0.001-0.016 mu g/g in serpentine). The mantle signature of Be is thus neither erased during seafloor alteration nor by progressive metamorphism from prehnite-pumpellyite to epidote-amphibolite facies. In contrast, the Li and B inventories of metamorphic minerals are related to the lizardite-to-antigorite transition. Both elements display higher concentrations in the low-temperature serpentine polymorph lizardite (max. 156 mu/g Li, max. 318 mu g/g B) than in antigorite (max. 0.11 mu g/g Li, max. 12 mu g/g B). Calculated average B/Li ratios for lizardite (similar to 1395) and antigorite (similar to 115) indicate that Li fractionates from B during the lizardite-to-antigorite transition during prograde metamorphism in ultramafic rocks. In subduction zones, this signature is likely to be recorded in the B-rich nature of forearc fluids. Relative to oceanic mantle the Be content of mantle clinopyroxene is much higher, but similar to Be values from mantle xenoliths and subduction-related peridotite massifs. These data support previous hypothesis that the mantle rocks from the Eastern Central Alps have a subcontinental origin. We conclude that Be behaves conservatively during subduction metamorphism of ultramafic rocks, at least at low-temperature, and thus retains the fingerprint of ancient subduction-related igneous events in mantle peridotites. (C) 2010 Elsevier Ltd. All rights reserved.

Cell disposition of raltegravir and newer antiretrovirals in HIV-infected patients: high inter-individual variability in raltegravir cellular penetration.

Objectives The site of pharmacological activity of raltegravir is intracellular. Our aim was to determine the extent of raltegravir cellular penetration and whether raltegravir total plasma concentration (C(tot)) predicts cellular concentration (C(cell)). Methods Open-label, prospective, pharmacokinetic study on HIV-infected patients on a stable raltegravir-containing regimen. Plasma and peripheral blood mononuclear cells were simultaneously collected during a 12 h dosing interval after drug intake. C(tot) and C(cell) of raltegravir, darunavir, etravirine, maraviroc and ritonavir were measured by liquid chromatography coupled to tandem mass spectrometry after protein precipitation. Longitudinal mixed effects analysis was applied to the C(cell)/C(tot) ratio. Results Ten HIV-infected patients were included. The geometric mean (GM) raltegravir total plasma maximum concentration (C(max)), minimum concentration (C(min)) and area under the time-concentration curve from 0-12 h (AUC(0-12)) were 1068 ng/mL, 51.1 ng/mL and 4171 ng·h/mL, respectively. GM raltegravir cellular C(max), C(min) and AUC(0-12) were 27.5 ng/mL, 2.9 ng/mL and 165 ng·h/mL, respectively. Raltegravir C(cell) corresponded to 5.3% of C(tot) measured simultaneously. Both concentrations fluctuate in parallel, with C(cell)/C(tot) ratios remaining fairly constant for each patient without a significant time-related trend over the dosing interval. The AUC(cell)/AUC(tot) GM ratios for raltegravir, darunavir and etravirine were 0.039, 0.14 and 1.55, respectively. Conclusions Raltegravir C(cell) correlated with C(tot) (r = 0.86). Raltegravir penetration into cells is low overall (∼5% of plasma levels), with distinct raltegravir cellular penetration varying by as much as 15-fold between patients. The importance of this finding in the context of development of resistance to integrase inhibitors needs to be further investigated.

What is the value of joint processing of pilots and data in block-fading channels?

The spectral efficiency achievable with joint processing of pilot and data symbol observations is compared with that achievable through the conventional (separate) approach of first estimating the channel on the basis of the pilot symbols alone, and subsequently detecting the datasymbols. Studied on the basis of a mutual information lower bound, joint processing is found to provide a non-negligible advantage relative to separate processing, particularly for fast fading. It is shown that, regardless of the fading rate, only a very small number of pilot symbols (at most one per transmit antenna and per channel coherence interval) shouldbe transmitted if joint processing is allowed.

Toxicokinetics of captan and folpet biomarkers in orally exposed volunteers

The time courses of key biomarkers of exposure to captan and folpet was assessed in accessible biological matrices of orally exposed volunteers. Ten volunteers ingested 1 mg kg(-1) body weight of captan or folpet. Blood samples were withdrawn at fixed time periods over the 72 h following ingestion and complete urine voids were collected over 96 h post-dosing. The tetrahydrophthalimide (THPI) metabolite of captan along with the phthalimide (PI) and phthalic acid metabolites of folpet were then quantified in these samples. Plasma levels of THPI and PI increased progressively after ingestion, reaching peak values ~10 and 6 h post-dosing, respectively; subsequent elimination phase appeared monophasic with a mean elimination half-life (t(½) ) of 15.7 and 31.5 h, respectively. In urine, elimination rate time courses of PI and phthalic acid evolved in parallel, with respective t(½) of 27.3 and 27.6 h; relatively faster elimination was found for THPI, with mean t(½) of 11.7 h. However, phthalic acid was present in urine in 1000-fold higher amounts than PI. In the 96 h period post-treatment, on average 25% of folpet dose was excreted in urine as phthalic acid as compared with only 0.02% as PI. The corresponding value for THPI was 3.5%. Overall, THPI and PI appear as interesting biomarkers of recent exposure, with relatively short half-lives; their sensitivity to assess exposure in field studies should be further verified. Although not a metabolite specific to folpet, the concomitant use of phthalic acid as a major biomarker of exposure to folpet should also be considered. Copyright © 2011 John Wiley & Sons, Ltd.

Genetic differentiation of continental and island populations of Bombus terrestris (Hymenoptera: Apidae) in Europe.

Ten microsatellite loci and a partial sequence of the COII mitochondrial gene were used to investigate genetic differentiation in B. terrestris, a bumble bee of interest for its high-value crop pollination. The analysis included eight populations from the European continent, five from Mediterranean islands (six subspecies altogether) and one from Tenerife (initially described as a colour form of B. terrestris but recently considered as a separate species, B. canariensis). Eight of the 10 microsatellite loci displayed high levels of polymorphism in most populations. In B. terrestris populations, the total number of alleles detected per polymorphic locus ranged from 3 to 16, with observed allelic diversity from 3.8 +/- 0.5 to 6.5 +/- 1.4 and average calculated heterozygosities from 0.41 +/- 0.09 to 0.65 +/- 0.07. B. canariensis showed a significantly lower average calculated heterozygosity (0.12 +/- 0.08) and observed allelic diversity (1.5 +/- 0.04) as compared to both continental and island populations of B. terrestris. No significant differentiation was found among populations of B. terrestris from the European continent. In contrast, island populations were all significantly and most of them strongly differentiated from continental populations. B. terrestris mitochondrial DNA is characterized by a low nucleotide diversity: 0.18% +/- 0.07%, 0.20% +/- 0.04% and 0.27% +/- 0.04% for the continental populations, the island populations and all populations together, respectively. The only haplotype found in the Tenerife population differs by a single nucleotide substitution from the most common continental haplotype of B. terrestris. This situation, identical to that of Tyrrhenian islands populations and quite different from that of B. lucorum (15 substitutions between terrestris and lucorum mtDNA) casts doubts on the species status of B. canariensis. The large genetic distance between the Tenerife and B. terrestris populations estimated from microsatellite data result, most probably, from a severe bottleneck in the Canary island population. Microsatellite and mitochondrial DNA data call for the protection of the island populations of B. terrestris against importation of bumble bees of foreign origin which are used as crop pollinators.

Changing healthcare: stakeholder perceptions of the burden of chronic disease and the value of teams, measurements and communication.

Canadian healthcare is changing. Over the course of the past decade, the Health Care in Canada Survey (HCIC) has annually measured the reactions of the public and professional stakeholders to many of these change forces. In HCIC 2008, for the first time, the public's perception of their health status and all stakeholders' views of the burden and effective management of chronic diseases were sought. Overall, Canadians perceive themselves as healthy, with 84% of adults reporting good-to-excellent health. However, good health decreased with age as the occurrence of chronic illness rose, from 12% in the age group 18-24 to 65% for the population =65 years. More than 70% of all stakeholders were strongly or somewhat supportive of the implementation of coordinated care, or disease management programs, to improve the care of patients with chronic illnesses. Concordant support was also expressed for key disease management components, including coordinated interventions to improve home, community and self-care; increased wellness promotion; and increased use of clinical measurements and feedback to all stakeholders. However, there were also important areas of non-concordance. For example, the public and doctors consistently expressed less support than other stakeholders for the value of team care, including the use of non-physician professionals to provide patient care; increased patient involvement in decision-making; and the use of electronic health records to facilitate communication. The actual participation in disease management programs averaged 34% for professionals and 25% for the public. We conclude that chronic diseases are common, age-related and burdensome in Canada. Disease management or coordinated intervention often delivered by teams is also relatively common, despite its less-than-universal acceptance by all stakeholders. Further insights are needed, particularly into the variable perceptions of the value and efficacy of team-delivered healthcare and its important components.

A modular magnetic anastomotic device for minimally invasive digestive anastomosis: proof of concept and preliminary data in the pig model.

BACKGROUND: The aim of our study was to assess the feasibility of minimally invasive digestive anastomosis using a modular flexible magnetic anastomotic device made up of a set of two flexible chains of magnetic elements. The assembly possesses a non-deployed linear configuration which allows it to be introduced through a dedicated small-sized applicator into the bowel where it takes the deployed form. A centering suture allows the mating between the two parts to be controlled in order to include the viscerotomy between the two magnetic rings and the connected viscera. METHODS AND PROCEDURES: Eight pigs were involved in a 2-week survival experimental study. In five colorectal anastomoses, the proximal device was inserted by a percutaneous endoscopic technique, and the colon was divided below the magnet. The distal magnet was delivered transanally to connect with the proximal magnet. In three jejunojejunostomies, the first magnetic chain was injected in its linear configuration through a small enterotomy. Once delivered, the device self-assembled into a ring shape. A second magnet was injected more distally through the same port. The centering sutures were tied together extracorporeally and, using a knot pusher, magnets were connected. Ex vivo strain testing to determine the compression force delivered by the magnetic device, burst pressure of the anastomosis, and histology were performed. RESULTS: Mean operative time including endoscopy was 69.2 ± 21.9 min, and average time to full patency was 5 days for colorectal anastomosis. Operative times for jejunojejunostomies were 125, 80, and 35 min, respectively. The postoperative period was uneventful. Burst pressure of all anastomoses was ≥ 110 mmHg. Mean strain force to detach the devices was 6.1 ± 0.98 and 12.88 ± 1.34 N in colorectal and jejunojejunal connections, respectively. Pathology showed a mild-to-moderate inflammation score. CONCLUSIONS: The modular magnetic system showed enormous potential to create minimally invasive digestive anastomoses, and may represent an alternative to stapled anastomoses, being easy to deliver, effective, and low cost.

Semiclassical evaluation of average nuclear one- and two-body matrix elements

Thomas-Fermi theory is developed to evaluate nuclear matrix elements averaged on the energy shell, on the basis of independent particle Hamiltonians. One- and two-body matrix elements are compared with the quantal results, and it is demonstrated that the semiclassical matrix elements, as function of energy, well pass through the average of the scattered quantum values. For the one-body matrix elements it is shown how the Thomas-Fermi approach can be projected on good parity and also on good angular momentum. For the two-body case, the pairing matrix elements are considered explicitly.

Chemoendocrine compared with endocrine adjuvant therapies for node-negative breast cancer: predictive value of centrally reviewed expression of estrogen and progesterone receptors--International Breast Cancer Study Group.

PURPOSE: To centrally assess estrogen receptor (ER) and progesterone receptor (PgR) levels by immunohistochemistry and investigate their predictive value for benefit of chemo-endocrine compared with endocrine adjuvant therapy alone in two randomized clinical trials for node-negative breast cancer. PATIENTS AND METHODS: International Breast Cancer Study Group Trial VIII compared cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy for 6 cycles followed by endocrine therapy with goserelin with either modality alone in pre- and perimenopausal patients. Trial IX compared three cycles of CMF followed by tamoxifen for 5 years versus tamoxifen alone in postmenopausal patients. Central Pathology Office reviewed 883 (83%) of 1,063 patients on Trial VIII and 1,365 (82%) of 1,669 on Trial IX and determined ER and PgR by immunohistochemistry. Disease-free survival (DFS) was compared across the spectrum of expression of each receptor using the Subpopulation Treatment Effect Pattern Plot methodology. RESULTS: Both receptors displayed a bimodal distribution, with substantial proportions showing no staining (receptor absent) and most of the remainder showing a high percentage of stained cells. Chemo-endocrine therapy yielded DFS superior to endocrine therapy alone for patients with receptor-absent tumors, and in some cases also for those with low levels of receptor expression. Among patients with ER-expressing tumors, additional prediction of benefit was suggested in absent or low PgR in Trial VIII but not in Trial IX. CONCLUSION: Low levels of ER and PgR are predictive of the benefit of adding chemotherapy to endocrine therapy. Low PgR may add further prediction among pre- and perimenopausal but not postmenopausal patients whose tumors express ER.

Timing of primary growth harvest affects the yield and nutritive value of timothy-red clover mixtures

Selostus: Ensimmäisen sadon korjuuaika vaikuttaa timotein ja puna-apilan seosnurmen satoon ja rehuarvoon

Effects of genetics and environment on isoflavone content of soybean from different regions of Brazil

The effects of genetics and environmental factors on isoflavone content of soybean (Glycine max L.) cultivars grown in different locations in Brazil in 1993/94 were evaluated. Seeds of different cultivars were analised by high performance liquid chromatography (HPLC). In Rio Grande do Sul (RS), Paraná (PR), and Mato Grosso do Sul (MS) States, a significant difference in the isoflavone total content average of the cultivars IAS 5 and FT-Abyara (163.9, 116.4 and 79.5 mg/100 g, respectively) was observed. In general, IAS 5 contained higher isoflavone than FT-Abyara. Cultivars IAS 5 and FT-Abyara grown at Vacaria, RS (28°30' S latitude) with temperature average of 19°C, had the highest isoflavone concentrations (218.7 and 163.8 mg/100 g, respectively). In Palotina, PR (24°27' S latitude), where temperature average was 24°C, the isoflavone concentrations were 105.9 and 86.8 mg/100 g, respectively. The lowest isoflavone contents were observed for FT-Estrela and FT-Cristalina, (27.6 and 46.5 mg/100 g, repectively) at Rondonópolis, MT (16°20' S latitude), where the temperature was 27°C.