Is the Climate Sensitivity Even More Uncertain?

Uncertainty in climate sensitivity is a fundamental problem for projections of the future climate. Climate sensitivity is defined as the equilibrium response of global-mean surface air temperature to a doubling of the atmospheric CO2 concentration from the preindustrial level (. 280 ppm). In spite of various efforts to estimate its value, climate sensitivity is still not well constrained (IPCC, 2007, pp.718-727 and pp.798-799; Gerard and Baker, 2007), posing a difficulty to informing climate change policy. Here we show that the climate sensitivity is in fact even more uncertain than has been found by earlier studies (Andronova and Schlesinger, 2001; Gregory et al., 2002; Knutti et al., 2002; Forest et al., 2006; Hegerl et al., 2006). Our results suggest that uncertainty in historical radiative forcing has not been sufficiently considered and that including a carbon cycle feedback, which in principle offers an additional constraint on climate sensitivity, does not reduce the uncertainty in climate sensitivity due to the poor knowledge of the global carbon budget before the year 1850

Das Eigenmittelsystem der Europaeischen Union

Die Finanzierung der Europäischen Union ist seit Beginn der europäischen Integration ein fortwährender Konfliktpunkt zwischen den Mitgliedstaaten. Das heutige Eigenmittelsystem, mit dem die EU den überwiegenden Teil ihrer Einnahmen von den Mitgliedstaaten erhält, ist vor allem als Ergebnis politischer Verhandlungs- und Kompromißfindungskunst zu sehen. Transparenz, Bürgernähe und ökonomische Effizienz blieben dabei immer wieder auf der Strecke. Ausgehend von der Frage, welche Einnahmenkompetenzen der europäischen Ebene zugeordnet werden sollten, analysiert der Autor Stärken und Schwächen des Eigenmittelsystems und formuliert die wichtigsten Reformerfordernisse. Dazu gehört beispielsweise die Abschaffung des inzwischen verfehlten Korrekturmechanismus zugunsten des Vereinigten Königreichs

Das Eigenmittelsystem der Europaeischen Union

Die Finanzierung der Europäischen Union ist seit Beginn der europäischen Integration ein fortwährender Konfliktpunkt zwischen den Mitgliedstaaten. Das heutige Eigenmittelsystem, mit dem die EU den überwiegenden Teil ihrer Einnahmen von den Mitgliedstaaten erhält, ist vor allem als Ergebnis politischer Verhandlungs- und Kompromißfindungskunst zu sehen. Transparenz, Bürgernähe und ökonomische Effizienz blieben dabei immer wieder auf der Strecke. Ausgehend von der Frage, welche Einnahmenkompetenzen der europäischen Ebene zugeordnet werden sollten, analysiert der Autor Stärken und Schwächen des Eigenmittelsystems und formuliert die wichtigsten Reformerfordernisse. Dazu gehört beispielsweise die Abschaffung des inzwischen verfehlten Korrekturmechanismus zugunsten des Vereinigten Königreichs

Influence of grape rot on the contents of sulfur binding compounds in wine after automated optical grape sorting

In the last years, climate change has played an important role in some wine growing regions because of the increasing hazard of different kinds of bunch rot. Botrytis cinerea is the most important kind of rot on grapes. Beside sensory effects, this rot can influence the content of yeast nutrients, e.g. thiamine, in the must and thus affect the alcoholic fermentation. To get insight into the influence of Botrytis cinerea on the content of sulfur binding compounds formed during the fermentation process in wine, tons of grapes from the Mosel valley were sorted by an automated optical grape sorter, an innovative possibility of grape sorting, in 2011. Wine samples before sulfurisation of the four sorting fractions, namely control (unsorted berries), free-run (juice from opened berries), positive (healthy, intact berries) and negative (rotten berries) were analysed for the sulfur-binding compounds acetaldehyde, pyruvic acid, 2-oxoglutaric acid and for bound sulfur dioxide. The results show that acetaldehyde concentrations were not affected by rot, while pyruvic acid and 2-oxoglutaric acid levels were significantly higher in the negative fractions and lower in the positive fractions. Accordingly, bound sulfur levels were significantly higher in wines from the negative fraction. In conclusion, it could be shown that fractionation of the berries can efficiently help to reduce sulfur binding compounds in wine and thus reduce the addition of sulfur dioxide

Sensitivity of a coupled climate-carbon cycle model to large volcanic eruptions

The sensitivity of the climate-biogeochemistry system to volcanic eruptions is investigated using the comprehensive Earth System Model developed at the Max Planck Institute for Meteorology. The model includes an interactive carbon cycle with modules for terrestrial biosphere as well as ocean biogeochemistry. The volcanic forcing is based on a recent reconstruction for the last 1200 yr. An ensemble of five simulations is performed and the averaged response of the system is analysed in particular for the largest eruption of the last millennium in the year 1258. After this eruption, the global annual mean temperature drops by 1 K and recovers slowly during 10 yr. Atmospheric CO2 concentration declines during 4 yr after the eruption by ca. 2 ppmv to its minimum value and then starts to increase towards the pre-eruption level. This CO2 decrease is explained mainly by reduced heterotrophic respiration on land in response to the surface cooling, which leads to increased carbon storage in soils, mostly in tropical and subtropical regions. The ocean acts as a weak carbon sink, which is primarily due to temperature-induced solubility. This sink saturates 2 yr after the eruption, earlier than the land uptake. © 2010 The Authors Tellus B © 2010 International Meteorological Institute in Stockholm

How reliable is MRI in diagnosing cartilaginous lesions in patients with first and recurrent lateral patellar dislocations?

<p>Abstract</p> <p>Background</p> <p>Lateral dislocation of the patella (LPD) leads to cartilaginous injuries, which have been reported to be associated with retropatellar complaints and the development of patellofemoral osteoarthritis. Therefore, the purpose of this study was to determine the reliability of MRI for cartilage diagnostics after a first and recurrent LPD.</p> <p>Methods</p> <p>After an average of 4.7 days following an acute LPD, 40 patients (21 with first LPDs and 19 with recurrent LPDs) underwent standardized 1.5 Tesla MRI (sagittal T1-TSE, coronal STIR-TSE, transversal fat-suppressed PD-TSE, sagittal fat-suppressed PD-TSE). MRI grading was compared to arthroscopic assessment of the cartilage.</p> <p>Results</p> <p>Sensitivities and positive predictive values for grade 3 and 4 lesions were markedly higher in the patient group with first LPDs compared to the group with recurrent LPDs. Similarly, intra- and inter-observer agreement yielded higher kappa values in patients with first LPDs compared to those with recurrent LPDs. All grade 4 lesions affecting the subchondral bone (osteochondral defects), such as a fissuring or erosion, were correctly assessed on MRI.</p> <p>Conclusions</p> <p>This study demonstrated a comparatively good diagnostic performance for MRI in the evaluation of first and recurrent LPDs, and we therefore recommend MRI for the cartilage assessment after a LPD.</p

Validation of New Gene Variant Classification Methods:a Field-Test in Diagnostic Cardiogenetics

Background: In the molecular genetic diagnostics of Mendelian disorders, solutions are needed for the major challenge of dealing with the large number of variants of uncertain significance (VUSs) identified using next-generation sequencing (NGS). Recently, promising approaches using constraint metrics to calculate case excess scores (CE), etiological fractions (EF), and gnomAD-derived constraint scores have been reported that estimate the likelihood of rare variants in specific genes or regions that are pathogenic. Our objective is to study the usability of these constraint data into variant interpretation in a diagnostic setting, using our cardiomyopathy cohort. Methods and Results: Patients (N = 2002) referred for clinical genetic diagnostics underwent NGS testing of 55–61 genes associated with cardiomyopathies. Previously classified likely pathogenic (LP) and pathogenic (P) variants were used to validate the use of data from CE, EF, and gnomAD constraint analyses for (re)classification of associated variant types in specific cardiomyopathy subtype-related genes. The classifications corroborated in 94% (354/378) of cases. Next, we reclassified 23 unique VUSs to LP, increasing the diagnostic yield by 1.2%. In addition, 106 unique VUSs (5.3% of patients) were prioritized for co-segregation or functional analyses. Conclusions: Our analysis confirms that the use of constraint metrics data can improve variant interpretation, and we, therefore, recommend using constraint scores on other cohorts and disorders and its inclusion in variant interpretation protocols

Urine E-cadherin: A Marker for early detection of kidney injury in diabetic patients.

Diabetic nephropathy (DN) is the main reason for end-stage renal disease. Microalbuminuria as the non-invasive available diagnosis marker lacks specificity and gives high false positive rates. To identify and validate biomarkers for DN, we used in the present study urine samples from four patient groups: diabetes without nephropathy, diabetes with microalbuminuria, diabetes with macroalbuminuria and proteinuria without diabetes. For the longitudinal validation, we recruited 563 diabetic patients and collected 1363 urine samples with the clinical data during a follow-up of 6 years. Comparative urinary proteomics identified four proteins Apolipoprotein A-I (APOA1), Beta-2-microglobulin (B2M), E-cadherin (CDH1) and Lithostathine-1-alpha (REG1A), which differentiated with high statistical strength (p < 0.05) between DN patients and the other groups. Label-free mass spectrometric quantification of the candidates confirmed the discriminatory value of E-cadherin and Lithostathine-1-alpha (p < 0.05). Immunological validation highlighted E-cadherin as the only marker able to differentiate significantly between the different DN stages with an area under the curve (AUC) of 0.85 (95%-CI: [0.72, 0.97]). The analysis of the samples from the longitudinal study confirmed the prognostic value of E-cadherin, the critical increase in urinary E-cadherin level was measured 20 ± 12.5 months before the onset of microalbuminuria and correlated significantly (p < 0.05) with the glomerular filtration rate measured by estimated glomerular filtration rate (eGFR)

Strategies in Rapid Genetic Diagnostics of Critically Ill Children:Experiences From a Dutch University Hospital

Background: Genetic disorders are a substantial cause of infant morbidity and mortality and are frequently suspected in neonatal intensive care units. Non-specific clinical presentation or limitations to physical examination can result in a plethora of genetic testing techniques, without clear strategies on test ordering. Here, we review our 2-years experiences of rapid genetic testing of NICU patients in order to provide such recommendations. Methods: We retrospectively included all patients admitted to the NICU who received clinical genetic consultation and genetic testing in our University hospital. We documented reasons for referral for genetic consultation, presenting phenotypes, differential diagnoses, genetic testing requested and their outcomes, as well as the consequences of each (rapid) genetic diagnostic approach. We calculated diagnostic yield and turnaround times (TATs). Results: Of 171 included infants that received genetic consultation 140 underwent genetic testing. As a result of testing as first tier, 13/14 patients received a genetic diagnosis from QF-PCR; 14/115 from SNP-array; 12/89 from NGS testing, of whom 4/46 were diagnosed with a small gene panel and 8/43 with a large OMIM-morbid based gene panel. Subsequent secondary or tertiary analysis and/or additional testing resulted in five more diagnoses. TATs ranged from 1 day (QF-PCR) to a median of 14 for NGS and SNP-array testing, with increasing TAT in particular when many consecutive tests were performed. Incidental findings were detected in 5/140 tested patients (3.6%). Conclusion: We recommend implementing a broad NGS gene panel in combination with CNV calling as the first tier of genetic testing for NICU patients given the often unspecific phenotypes of ill infants and the high yield of this large panel