European multicentre experience with the sutureless Perceval valve: clinical and haemodynamic outcomes up to 5 years in over 700 patients†.

OBJECTIVES This report summarizes the 5-year clinical and haemodynamic data from three prospective, European multicentre trials with the Perceval sutureless aortic valve. METHODS From April 2007 to August 2012, 731 consecutive patients (mean age: 78.5 years; 68.1% females; mean logistic EuroSCORE 10.9%) underwent AVR with the Perceval valve in 25 European centres. Isolated AVR was performed in 498 (68.1%) patients. A minimally invasive approach was performed in 189 (25.9%) cases. The cumulative follow-up was 729 patients-years. RESULTS In isolated AVR, mean cross-clamp and cardiopulmonary bypass times were 30.8 and 50.8 min in full sternotomy, and 37.6 and 64.4 min in the minimally invasive approach, respectively. Early cardiac-related deaths occurred in 1.9%. Overall survival rates at 1 and 5 years were 92.1 and 74.7%, respectively. Major paravalvular leak occurred in 1.4% and 1% at early and late follow-up, respectively. Significant improvement in clinical status was observed postoperatively in the majority of patients. Mean and peak gradients decreased from 42.9 and 74.0 mmHg preoperatively, to 7.8 and 16 mmHg at the 3-year follow-up. LV mass decreased from 254.5 to 177.4 g at 3 years. CONCLUSIONS This European multicentre experience, with the largest cohort of patients with sutureless valves to date, shows excellent clinical and haemodynamic results that remain stable even up to the 5-year follow-up. Even in this elderly patient cohort with 40% octogenarians, both early and late mortality rates were very low. There were no valve migrations, structural valve degeneration or valve thrombosis in the follow-up. The sutureless technique is a promising alternative to biological aortic valve replacement.

Normal Thyroid Function and the Risk of Atrial Fibrillation: the Rotterdam Study

CONTEXT Hyperthyroidism is an established risk factor for atrial fibrillation (AF), but information concerning the association with variations within the normal range of thyroid function and subgroups at risk is lacking. OBJECTIVE This study aimed to investigate the association between normal thyroid function and AF prospectively and explore potential differential risk patterns. DESIGN, SETTING, AND PARTICIPANTS From the Rotterdam Study we included 9166 participants ≥ 45 y with TSH and/or free T4 (FT4) measurements and AF assessment (1997-2012 median followup, 6.8 y), with 399 prevalent and 403 incident AF cases. MAIN OUTCOME MEASURES Outcome measures were 3-fold: 1) hazard ratios (HRs) for the risk of incident AF by Cox proportional-hazards models, 2) 10-year absolute risks taking competing risk of death into account, and 3) discrimination ability of adding FT4 to the CHARGE-AF simple model, an established prediction model for AF. RESULTS Higher FT4 levels were associated with higher risks of AF (HR 1.63, 95% confidence interval, 1.19-2.22), when comparing those in the highest quartile to those in lowest quartile. Absolute 10-year risks increased with higher FT4 in participants ≤ 65 y from 1-9% and from 6-12% in subjects ≥ 65 y. Discrimination of the prediction model improved when adding FT4 to the simple model (c-statistic, 0.722 vs 0.729; P = .039). TSH levels were not associated with AF. CONCLUSIONS There is an increased risk of AF with higher FT4 levels within the normal range, especially in younger subjects. Adding FT4 to the simple model slightly improved discrimination of risk prediction.

Evaluation of a Commercial ELISA for the Detection of Antibodies to Sarcoptes scabiei in Wild Boar (Sus scrofa).

Sarcoptic mange occurs in free-ranging wild boar (Sus scrofa) but has been poorly described in this species. We evaluated the performance of a commercial indirect enzyme-linked immunosorbent assay (ELISA) for serodiagnosis of sarcoptic mange in domestic swine when applied to wild boar sera. We tested 96 sera from wild boar in populations without mange history ("truly noninfected") collected in Switzerland between December 2012 and February 2014, and 141 sera from free-ranging wild boar presenting mange-like lesions, including 50 live animals captured and sampled multiple times in France between May and August 2006 and three cases submitted to necropsy in Switzerland between April 2010 and February 2014. Mite infestation was confirmed by skin scraping in 20 of them ("truly infected"). We defined sensitivity of the test as the proportion of truly infected that were found ELISA-positive, and specificity as the proportion of truly noninfected that were found negative. Sensitivity and specificity were 75% and 80%, respectively. Success of antibody detection increased with the chronicity of lesions, and seroconversion was documented in 19 of 27 wild boar sampled multiple times that were initially negative or doubtful. In conclusion, the evaluated ELISA has been successfully applied to wild boar sera. It appears to be unreliable for early detection in individual animals but may represent a useful tool for population surveys.

PCSK9 Plasma Concentrations Are Independent of GFR and Do Not Predict Cardiovascular Events in Patients with Decreased GFR.

BACKGROUND Impaired renal function causes dyslipidemia that contributes to elevated cardiovascular risk in patients with chronic kidney disease (CKD). The proprotein convertase subtilisin/kexin type 9 (PCSK9) is a regulator of the LDL receptor and plasma cholesterol concentrations. Its relationship to kidney function and cardiovascular events in patients with reduced glomerular filtration rate (GFR) has not been explored. METHODS Lipid parameters including PCSK9 were measured in two independent cohorts. CARE FOR HOMe (Cardiovascular and Renal Outcome in CKD 2-4 Patients-The Forth Homburg evaluation) enrolled 443 patients with reduced GFR (between 90 and 15 ml/min/1.73 m2) referred for nephrological care that were prospectively followed for the occurrence of a composite cardiovascular endpoint. As a replication cohort, PCSK9 was quantitated in 1450 patients with GFR between 90 and 15 ml/min/1.73 m2 enrolled in the Ludwigshafen Risk and Cardiovascular Health Study (LURIC) that were prospectively followed for cardiovascular deaths. RESULTS PCSK9 concentrations did not correlate with baseline GFR (CARE FOR HOMe: r = -0.034; p = 0.479; LURIC: r = -0.017; p = 0.512). 91 patients in CARE FOR HOMe and 335 patients in LURIC reached an endpoint during a median follow-up of 3.0 [1.8-4.1] years and 10.0 [7.3-10.6] years, respectively. Kaplan-Meier analyses showed that PCSK9 concentrations did not predict cardiovascular events in either cohort [CARE FOR HOMe (p = 0.622); LURIC (p = 0.729)]. Sensitivity analyses according to statin intake yielded similar results. CONCLUSION In two well characterized independent cohort studies, PCSK9 plasma levels did not correlate with kidney function. Furthermore, PCSK9 plasma concentrations were not associated with cardiovascular events in patients with reduced renal function.

Ueber das Alter der jüdischen Proselyten-Taufe und deren Zusammenhang mit dem johanneischen und christlichen Ritus : nebst einer Beilage über die Irrlehrer zu Colossä

von Matthias Schneckenburger

Gene-gene interaction and gene-pathway analysis of genome-wide association for schizophrenia

Schizophrenia (SZ) is a complex disorder with high heritability and variable phenotypes that has limited success in finding causal genes associated with the disease development. Pathway-based analysis is an effective approach in investigating the molecular mechanism of susceptible genes associated with complex diseases. The etiology of complex diseases could be a network of genetic factors and within the genes, interaction may occur. In this work we argue that some genes might be of small effect that by itself are neither sufficient nor necessary to cause the disease however, their effect may induce slight changes to the gene expression or affect the protein function, therefore, analyzing the gene-gene interaction mechanism within the disease pathway would play crucial role in dissecting the genetic architecture of complex diseases, making the pathway-based analysis a complementary approach to GWAS technique. ^ In this study, we implemented three novel linkage disequilibrium based statistics, the linear combination, the quadratic, and the decorrelation test statistics, to investigate the interaction between linked and unlinked genes in two independent case-control GWAS datasets for SZ including participants of European (EA) and African (AA) ancestries. The EA population included 1,173 cases and 1,378 controls with 729,454 genotyped SNPs, while the AA population included 219 cases and 288 controls with 845,814 genotyped SNPs. We identified 17,186 interacting gene-sets at significant level in EA dataset, and 12,691 gene-sets in AA dataset using the gene-gene interaction method. We also identified 18,846 genes in EA dataset and 19,431 genes in AA dataset that were in the disease pathways. However, few genes were reported of significant association to SZ. ^ Our research determined the pathways characteristics for schizophrenia through the gene-gene interaction and gene-pathway based approaches. Our findings suggest insightful inferences of our methods in studying the molecular mechanisms of common complex diseases.^

Solar radiation over and under sea ice and photographic quantification of Ice algal aggregates during the POLARSTERN cruise ARK-XXVII/3 (IceArc) in summer 2012

The ice cover of the Arctic Ocean has been changing dramatically in the last decades and the consequences for the sea-ice associated ecosystem remain difficult to assess. Algal aggregates underneath sea ice have been described sporadically but the frequency and distribution of their occurrence is not well quantified. We used upward looking images obtained by a remotely operated vehicle (ROV) to derive estimates of ice algal aggregate biomass and to investigate their spatial distribution. During the IceArc expedition (ARK-XXVII/3) of RV Polarstern in late summer 2012, different types of algal aggregates were observed floating underneath various ice types in the Central Arctic basins. Our results show that the floe scale distribution of algal aggregates in late summer is very patchy and determined by the topography of the ice underside, with aggregates collecting in dome shaped structures and at the edges of pressure ridges. The buoyancy of the aggregates was also evident from analysis of the aggregate size distribution. Different approaches used to estimate aggregate biomass yield a wide range of results. This highlights that special care must be taken when upscaling observations and comparing results from surveys conducted using different methods or on different spatial scales.

Solar irradiance over and under seasonal land-fast sea ice off Barrow, Alaska, in 2010

The amount of solar radiation transmitted through Arctic sea ice is determined by the thickness and physical properties of snow and sea ice. Light transmittance is highly variable in space and time since thickness and physical properties of snow and sea ice are highly heterogeneous on variable time and length scales. We present field measurements of under-ice irradiance along transects under undeformed land-fast sea ice at Barrow, Alaska (March, May, and June 2010). The measurements were performed with a spectral radiometer mounted on a floating under-ice sled. The objective was to quantify the spatial variability of light transmittance through snow and sea ice, and to compare this variability along its seasonal evolution. Along with optical measurements, snow depth, sea ice thickness, and freeboard were recorded, and ice cores were analyzed for chlorophyll a and particulate matter. Our results show that snow cover variability prior to onset of snow melt causes as much relative spatial variability of light transmittance as the contrast of ponded and white ice during summer. Both before and after melt onset, measured transmittances fell in a range from one third to three times the mean value. In addition, we found a twentyfold increase of light transmittance as a result of partial snowmelt, showing the seasonal evolution of transmittance through sea ice far exceeds the spatial variability. However, prior melt onset, light transmittance was time invariant and differences in under-ice irradiance were directly related to the spatial variability of the snow cover.

Geochemistry and mineralogy at DSDP Holes 61-462, 61-462A and 33-315A

Sedimentary rocks of Barremian through early Maestrichtian age recovered on Deep Sea Drilling Project Leg 61 had their principal source in the complex of igneous rocks with which they are interlayered in the Nauru Basin. Relict textures and primary sedimentary structures show these Cretaceous sediments to be of hyaloclastic origin, in part reworked and redeposited by slumps and currents. The dominant composition now is smectite, but locally iron, titanium, and manganese oxides, plagioclase, pyroxene, analcime, clinoptilolite, chalcedonic quartz, cristobalite, amphibole, nontronite, celadonite, and pyrite are also present. The mineral assemblages and the geochemistry reflect the original basaltic composition and its subsequent alteration by one or more processes of submarine weathering, authigenesis, hydrothermal circulation, and contact metamorphism. Hyaloclastitic sandstone, siltstone, and breccia within the sheet flows below 729 meters sub-bottom depth have Barremian fossils, thus establishing the age of the lower, or extrusive, complex of post-ridge-crest volcanism. Similar hyaloclastites between 564 and 729 meters are invaded by hypabyssal sills of the upper igneous complex, and fossil ages of Albian or Cenomanian set an older limit to the age of that second post-ridge-crest episode. Cenomanian to early Campanian sedimentary rocks between 490 and 564 meters have a substantial contribution of clays of submarine-weathered-basalt origin, as well as hydrothermal and pelagic components. The interval of reworked hyaloclastitic siltstone, sandstone, and breccias between 450 and 490 meters is of late Campanian and early Maestrichtian age. These sediments probably formed from glassy basalt that fragmented upon eruption nearby, when sills were being emplaced. In addition to pelagic elements, these Upper Cretaceous volcanogenic sediments include redeposited material of shallow-water origin, apparently derived from the Marshall Islands.