Clinical Practice Recommendations on Genetic Testing of CYP2C9 and VKORC1 Variants in Warfarin Therapy

OBJECTIVE To systematically review evidence on genetic variants influencing outcomes during warfarin therapy and provide practice recommendations addressing the key questions: (1) Should genetic testing be performed in patients with an indication for warfarin therapy to improve achievement of stable anticoagulation and reduce adverse effects? (2) Are there subgroups of patients who may benefit more from genetic testing compared with others? (3) How should patients with an indication for warfarin therapy be managed based on their genetic test results? METHODS A systematic literature search was performed for VKORC1 and CYP2C9 and their association with warfarin therapy. Evidence was critically appraised, and clinical practice recommendations were developed based on expert group consensus. RESULTS Testing of VKORC1 (-1639G>A), CYP2C9*2, and CYP2C9*3 should be considered for all patients, including pediatric patients, within the first 2 weeks of therapy or after a bleeding event. Testing for CYP2C9*5, *6, *8, or *11 and CYP4F2 (V433M) is currently not recommended. Testing should also be considered for all patients who are at increased risk of bleeding complications, who consistently show out-of-range international normalized ratios, or suffer adverse events while receiving warfarin. Genotyping results should be interpreted using a pharmacogenetic dosing algorithm to estimate the required dose. SIGNIFICANCE This review provides the latest update on genetic markers for warfarin therapy, clinical practice recommendations as a basis for informed decision making regarding the use of genotype-guided dosing in patients with an indication for warfarin therapy, and identifies knowledge gaps to guide future research.

Zwischen Rigidität und Flexibilität: Der Verpflichtungsgrad internationaler Menschenrechte. Ein Beitrag zum Zusammenspiel von Menschenrechten, humanitärem Völkerrecht und dem Recht der Staatenverantwortlichkeit.

Die Bedrohungssituation für Menschenrechte hat sich in den letzten Jahren gewandelt. Stellte früher meist ein zu mächtiger Staat die Hauptgefahr für Menschenrechte dar, resultieren Probleme heute oft aus dessen Schwäche, z. B. in Bürgerkriegen. Dies hat zwei Auswirkungen: Zum einen erlebt das humanitäre Völkerrecht eine Renaissance, zum anderen sind es zunehmend nichtstaatliche Gebilde, welche für Rechtsverletzungen verantwortlich sind. Dogmatisch wirft diese Konstellation verschiedenste Probleme auf: Menschenrechtliche Verpflichtungen mit unterschiedlichem Geltungsgrad überlappen sich mit solchen des humanitären Völkerrechts, staatliche Verpflichtungen verlangen vermehrt auch aktives Handeln, und in Folge der unterschiedlichen beteiligten Akteure lassen sich Lösungen oft nur unter Berücksichtigung der Regeln der Staatenverantwortlichkeit finden. Ziel des Autors ist es, aus diesem Gewirr anwendbarer Normen ein integrales Modell des Geltungsgrades, d. h. der Verpflichtungen aus Menschenrechten, zu entwickeln.

VIRTOPSY--scientific documentation, reconstruction and animation in forensic: individual and real 3D data based geo-metric approach including optical body/object surface and radiological CT/MRI scanning.

Until today, most of the documentation of forensic relevant medical findings is limited to traditional 2D photography, 2D conventional radiographs, sketches and verbal description. There are still some limitations of the classic documentation in forensic science especially if a 3D documentation is necessary. The goal of this paper is to demonstrate new 3D real data based geo-metric technology approaches. This paper present approaches to a 3D geo-metric documentation of injuries on the body surface and internal injuries in the living and deceased cases. Using modern imaging methods such as photogrammetry, optical surface and radiological CT/MRI scanning in combination it could be demonstrated that a real, full 3D data based individual documentation of the body surface and internal structures is possible in a non-invasive and non-destructive manner. Using the data merging/fusing and animation possibilities, it is possible to answer reconstructive questions of the dynamic development of patterned injuries (morphologic imprints) and to evaluate the possibility, that they are matchable or linkable to suspected injury-causing instruments. For the first time, to our knowledge, the method of optical and radiological 3D scanning was used to document the forensic relevant injuries of human body in combination with vehicle damages. By this complementary documentation approach, individual forensic real data based analysis and animation were possible linking body injuries to vehicle deformations or damages. These data allow conclusions to be drawn for automobile accident research, optimization of vehicle safety (pedestrian and passenger) and for further development of crash dummies. Real 3D data based documentation opens a new horizon for scientific reconstruction and animation by bringing added value and a real quality improvement in forensic science.

Mass spectrometric study of molecular and ionic sublimation of lanthanum triiodide

The molecular and ionic composition of saturated vapor over lanthanum triiodide was studied by Knudsen effusion mass spectrometry. The (LaI3)n molecules (n = 1–3) and the [I(LaI3)n]− ions (n = 0–4) were observed. The partial pressures of the molecules were determined and the enthalpies of sublimation, ΔsH° (298.15 K) in kJ mol−1, in the form of monomers (304 ± 7), dimers (428 ± 25), and trimers (455 ± 50) were obtained by the second and third laws of thermodynamics. The enthalpy of formation, ΔfH° (298.15 K) in kJ mol−1, of the LaI3 (−376 ± 10), La2I6 (−932 ± 25), La3I9 (−1585 ± 50) molecules and the LaI4− (−841 ± 24), La2I7− (−1486 ± 32) ions were determined. The electron work function, φe = 3.5 ± 0.3 eV, for the LaI3 crystal was calculated from the thermochemical cycle.

Meta-analysis identifies seven susceptibility loci involved in the atopic march.

Eczema often precedes the development of asthma in a disease course called the 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P=2.1 × 10(-8)) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P=5.3 × 10(-9)). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.

Light intensity selectively influences the distribution and further redistribution of macro- and micronutrients in hydroponically grown wheat ( Triticum aestivum L.)

Investigations were focused on light effects on allocation of root-borne macronutrients (calcium, magnesium and potassium) and micronutrients (iron, manganese, zinc and copper) in roots, shoots and harvested grains of wheat (Triticum aestivum L.). Plants were exposed to low (100 μmol photons m−2 s−1) or high light (380 μmol photons m−2 s−1). High light stimulated both root and shoot growth. While the total contents per plant of some nutrients were markedly higher (calcium and potassium) or lower (copper) under high light, no major differences were observed for other nutrients. The distribution of nutrients and the further redistribution within the shoot were influenced by the light intensity in an element-specific manner. Nutrients were selectively directed to the leaves of the main shoot (low light) or to the tillers (high light). The quality of the harvested grains was also affected by the light intensity.

Aus schmelzendem Eis. Funde vom Schnidejoch.

Am Ende des Hitzesommers 2003 entdeckten Wanderer am Rande eines kleinen Eisfeldes erstmals prähistorische Objekte. Die Fundstelle liegt am Schnidejoch, einem alpinen Übergang, der das Simmental mit dem Rhônetal verbindet. Bis heute liegen von dieser außergewöhnlichen Fundstelle rund 900 Funde vom Neolithikum bis zum Mittelalter vor. Die Forschungen am Schnidejoch können auch als „Archäologie zwischen Gletschern und Gipfeln“ bezeichnet werden. Die Fundstelle befindet sich auf 2750 m Höhe und wird von der höchsten Erhebung der westlichen Berner Alpen, dem 3248 m hohen Wildhorn, überragt. Die ältesten Objekte werden in die Zeitspanne von 4800 bis 4300 v. Chr. datiert. Es handelt sich um Fragmente von Pfeilen und um eine Schale aus Ulmenholz. Weitere Leder- und Pfeilfragmente zeigen, dass der Pass auch in der zweiten Hälfte des 4. Jahrtausends v. Chr. benutzt wurde. Eine ganze Serie von Objekten stammt aus dem Zeitraum um 2800 v. Chr.: eine komplette Bogenausrüstung, bestehend aus Pfeilbogen, Bogensehne, Bogenfutteral, Pfeilschäften und Pfeilspitzen. Ebenfalls zu diesem Ensemble gehören Bekleidungsreste: Teile eines Grasumhangs, Schuhfragmente und ein Hosenbein aus Leder. Es ist wenig wahrscheinlich, dass die in den Bergen lebensnotwendige Bekleidung und die Bewaffnung einfach verloren wurden. Es ist deshalb zu vermuten, dass am Schnidejoch vor fast 5000 Jahren jemand zu Tode kam; eine Leiche wurde aber – anders als beim „Ötzi“ – nicht gefunden. Möglicherweise wurde die am Schnidejoch umgekommene Person geborgen und in einem zeitgleich errichteten Kollektivgrab im Tal bestattet.