Eine Theorie des Erzählens außerhalb der Erzähltheorie: Zur Analyse des psychotherapeutischen „Narrativs“

Brigitte Boothe: Das Narrativ. Biografisches Erzählen im psychotherapeutischen Prozess. Mit einem Geleitwort von Jörg Frommer. Stuttgart: Schattauer 2011. 260 S. EUR 36,99. ISBN 978-3-7945-2801-

Allosteric inhibition enhances the efficacy of ABL kinase inhibitors to target unmutated BCR-ABL and BCR-ABL-T315I

Background: Chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphatic leukemia (Ph + ALL) are caused by the t(9;22), which fuses BCR to ABL resulting in deregulated ABL-tyrosine kinase activity. The constitutively activated BCR/ABL-kinase "escapes" the auto-inhibition mechanisms of c-ABL, such as allosteric inhibition. The ABL-kinase inhibitors (AKIs) Imatinib, Nilotinib or Dasatinib, which target the ATP-binding site, are effective in Ph + leukemia. Another molecular therapy approach targeting BCR/ABL restores allosteric inhibition. Given the fact that all AKIs fail to inhibit BCR/ABL harboring the 'gatekeeper' mutation T315I, we investigated the effects of AKIs in combination with the allosteric inhibitor GNF2 in Ph + leukemia. Methods: The efficacy of this approach on the leukemogenic potential of BCR/ABL was studied in Ba/F3 cells, primary murine bone marrow cells, and untransformed Rat-1 fibroblasts expressing BCR/ABL or BCR/ABL-T315I as well as in patient-derived long-term cultures (PDLTC) from Ph + ALL-patients. Results: Here, we show that GNF-2 increased the effects of AKIs on unmutated BCR/ABL. Interestingly, the combination of Dasatinib and GNF-2 overcame resistance of BCR/ABL-T315I in all models used in a synergistic manner. Conclusions: Our observations establish a new approach for the molecular targeting of BCR/ABL and its resistant mutants using a combination of AKIs and allosteric inhibitors

New age and petrological constraints on Lower Silesian basaltoids, SW Poland

Fifteen samples of basaltoid rocks were analysed from Lower Silesia, SW Poland, all of them situated close to the Sudetic Marginal Fault. K-Ar datings were made on whole rock samples, using the methodology applied by the Institute of Nuclear Research, Hungarian Academy of Sciences, Debrecen, Hungary. Most of the samples gave dates ranging between 21-38 Ma, whereas that derived from a borehole in the Mokrzeszów graben was dated to 44 Ma. Another borehole sample (Jeżów Sudecki B-5) is of 59 Ma age. On the other hand, the supposedly “Quaternary” basalts from the Dębowiec area fall into the interval of 29-30 Ma.The southeasternmost occurrences of the Lower Silesian basalts at Nowa Cerekiew display two generations of effusive activity: the older lava flows (26 Ma) are cut by plugs dated to 22 Ma. The Oligocene-Lower Miocene (26-33 Ma, 20-24 Ma) rocks represent alkali basalts and basanites. Most of the samples studied show properties typical of the two phases of volcanic activity, hitherto recorded in the Opole area by other authors

Disulfiram-ethanol reaction and disulfiram-like reaction – not fully explained ethanol-drug interactions

Disulfiram-ethanol reaction (DER) and disulfiram-like reaction (DLR) are defined as acute intoxication with acetaldehyde after exposure to ethanol with disulfiram or a specific drug. The reaction is still considered as a problem of modern pharmacotherapy. The name of the reaction comes from a drug called disulfiram. In the 1940s, in United States disulfiram was registered for the treatment of alcoholism. DER is the effect of disulfiram’s mechanism of action consisting in inhibition of acetaldehyde dehydrogenase (ALDH), which causes accumulation of acetaldehyde, with accompanying alcohol intolerance and aversion to alcohol consumption. Many commonly used drugs have an ability to interact with ethanol and produce the DLR. The reaction can vary in severity of clinical course and can rarely be fatal. Specific for DER mechanism and symptoms have been observed for drugs such as abacavir, several cephalosporins and procarbazine. Based on clinical symptoms, many active agents such as chloramphenicol, griseofulvin, metronidazole and propranolol were considered as active agents increasing the risk of DLR occurrence. However no increase of acetaldehyde level in blood serum was observed, and the mechanism of interaction was different, often including changes in the level of neurotransmitters within the central nervous system. According to other drugs discussed in the article the mechanism of interaction remains unknown. For these reasons reported interactions of drugs (other than disulfiram) have been referred as DLR. For many drugs the available data is limited to only few clinical cases of acute alcohol intolerance. Furthermore, in these cases the mechanism of interaction has not been studied which limits the conclusions and indicates the need for further research in this area. The description of selected drugs also includes information on the potential risk of disulfiram-like reaction obtained from the Summary of Product Characteristics (SmPC) of drugs registered in Poland

Retrieval of Salt Marsh Above-ground Biomass From High-spatial Resolution Hyperspectral Imagery Using PROSAIL

Salt marsh vegetation density varies considerably on short spatial scales, complicating attempts to evaluate plant characteristics using airborne remote sensing approaches. In this study, we used a mast-mounted hyperspectral imaging system to obtain cm-scale imagery of a salt marsh chronosequence on Hog Island, VA, where the morphology and biomass of the dominant plant species, Spartina alterniflora, varies widely. The high-resolution hyperspectral imagery allowed the detailed delineation of variations in above-ground biomass, which we retrieved from the imagery using the PROSAIL radiative transfer model. The retrieved biomass estimates correlated well with contemporaneously collected in situ biomass ground truth data ( R2=0.73 ). In this study, we also rescaled our hyperspectral imagery and retrieved PROSAIL salt marsh biomass to determine the applicability of the method across spatial scales. Histograms of retrieved biomass changed considerably in characteristic marsh regions as the spatial scale of the imagery was progressively degraded. This rescaling revealed a loss of spatial detail and a shift in the mean retrieved biomass. This shift is indicative of the loss of accuracy that may occur when scaling up through a simple averaging approach that does not account for the detail found in the landscape at the natural scale of variation of the salt marsh system. This illustrated the importance of developing methodologies to appropriately scale results from very fine scale resolution up to the more coarse-scale resolutions commonly obtained in airborne and satellite remote sensing

New data on age and petrological properties of Lower Silesian Cenozoic basaltoids, SW Poland

Fifteen samples of basaltoid rocks have been analysed from the Lower Silesia, SW Poland, some of them from localities close to the Sudetic Marginal Fault. K-Ar datings have been made on whole rock samples, using the methodology applied by the Institute of Nuclear Research, Hungarian Academy of Sciences, Debrecen, Hungary. Most of the samples give ages ranging between 21- 38 Ma, whereas that derived from a borehole in the Mokrzeszów Graben has been dated to 44 Ma. Another borehole sample (Jeżów Sudecki B-5), close to the Intrasudetic Fault, is of 59 Ma age. On the other hand, the supposedly "Quaternary" basaltoids from Dębowiec area fall into the interval of 29–30 Ma. The southeasternmost occurrences of the Lower Silesian basaltoids at Nowa Cerekiew display two generations of effusive activity: the older lava flows (26 Ma) are cut by plugs dated to 22 Ma. The Oligocene–Lower Miocene (26-33 Ma, 20'24 Ma) rocks represent alkali basalts and basanites. The alkali basalts consist of phenocrysts of olivine (chrysolite), altered to a different degree, and clinopyroxene (salite). In the matrix, clinopyroxene (Ti-salite), olivine (hyalosiderite), plagioclases (labradorite–andesine), and opaque minerals (titanomagnetite, ilmenite) occur. The basanites contain phenocrysts of altered olivine (chrysolite) and clinopyroxene (salite). Their matrix consists of clinopyroxene (Ti-salites), olivine (hyalosiderite), nepheline, plagioclases (bytownite–andesine), and opaque minerals. On the TAS diagram, samples of the studied basaltoids plot mainly in the fields of basalts and basanites/tephrites. The bimodality of some samples falling into two fields of basalts and basanites/nephelinites on the TiO2/Zr-Nb/y diagram results from their distinct geochemical signature

Validating the early phototherapy prediction tool across cohorts

Background: Hyperbilirubinemia of the newborn infant is a common disease worldwide. However, recognized early and treated appropriately, it typically remains innocuous. We recently developed an early phototherapy prediction tool (EPPT) by means of machine learning (ML) utilizing just one bilirubin measurement and few clinical variables. The aim of this study is to test applicability and performance of the EPPT on a new patient cohort from a different population. Materials and methods: This work is a retrospective study of prospectively recorded neonatal data from infants born in 2018 in an academic hospital, Regensburg, Germany, meeting the following inclusion criteria: born with 34 completed weeks of gestation or more, at least two total serum bilirubin (TSB) measurement prior to phototherapy. First, the original EPPT—an ensemble of a logistic regression and a random forest—was used in its freely accessible version and evaluated in terms of the area under the receiver operating characteristic curve (AUROC). Second, a new version of the EPPT model was re-trained on the data from the new cohort. Third, the predictive performance, variable importance, sensitivity and specificity were analyzed and compared across the original and re-trained models. Results: In total, 1,109 neonates were included with a median (IQR) gestational age of 38.4 (36.6–39.9) and a total of 3,940 bilirubin measurements prior to any phototherapy treatment, which was required in 154 neonates (13.9%). For the phototherapy treatment prediction, the original EPPT achieved a predictive performance of 84.6% AUROC on the new cohort. After re-training the model on a subset of the new dataset, 88.8% AUROC was achieved as evaluated by cross validation. The same five variables as for the original model were found to be most important for the prediction on the new cohort, namely gestational age at birth, birth weight, bilirubin to weight ratio, hours since birth, bilirubin value. Discussion: The individual risk for treatment requirement in neonatal hyperbilirubinemia is robustly predictable in different patient cohorts with a previously developed ML tool (EPPT) demanding just one TSB value and only four clinical parameters. Further prospective validation studies are needed to develop an effective and safe clinical decision support system

Epidemiologic characteristics of amniotic band sequence with limb malformations without body wall defect: data from the Polish Registry of Congenital Malformations

Abstract Amniotic Band Sequence (ABS) is a rare disruptive condition, with a variable spectrum of congenital defects caused by fibrous bands emerging as a result of amniotic rupture in the first trimester of gestation. Several factors, such as young parental age, primigravidity, febrile maternal illness, and drug use in the first trimester, were postulated to have substantial influence on ABS prevalence rate. We aimed our study to determine the prevalence of ABS with limb defects, but no body wall affectation, in a Polish population. We also examined the influence of different parental, gestational and environmental factors on the ABS prevalence value, and assessed the rate of gestational complications associated with this disorder. Among 1 706 639 births surveilled between 1998 and 2005, 36 liveborn infants with ABS-L were reported to the Polish Registry of Congenital Malformations, giving a global prevalence for a Polish population of 1 per 47 619 livebirths. We found that young maternal age, young paternal age, and primigravidity significantly increase the risk of ABS-L, when their effect was analyzed independently. However, because of a close relationship of these variables, we analyzed their mutually adjusted effect using conditional logistic regression models, and found that young maternal age proved the strongest risk factor for ABS-L (p = 0.0508). The condition was also more prevalent in infants with low birthweight (OR = 5.71; p < 0.0001). Since gestational complications are often relevant to maternal age and birth order, we introduced an adjustment for these variables, and found that respiratory tract infections and vaginal bleeding/spotting convey approximately fourfold increased risk of ABS-L (OR = 3.72/p = 0.0058 and OR = 3.70/p = 0.0014 respectively)

Frequency of 22q11.2 microdeletion in children with congenital heart defects in western poland

<p>Abstract</p> <p>Background</p> <p>The 22q11.2 microdeletion syndrome (22q11.2 deletion syndrome -22q11.2DS) refers to congenital abnormalities, including primarily heart defects and facial dysmorphy, thymic hypoplasia, cleft palate and hypocalcaemia. Microdeletion within chromosomal region 22q11.2 constitutes the molecular basis of this syndrome. The 22q11.2 microdeletion syndrome occurs in 1/4000 births. The aim of this study was to determine the frequency of 22q11.2 microdeletion in 87 children suffering from a congenital heart defect (conotruncal or non-conotruncal) coexisting with at least one additional 22q11.2DS feature and to carry out 22q11.2 microdeletion testing of the deleted children's parents. We also attempted to identify the most frequent heart defects in both groups and phenotypic traits of patients with microdeletion to determine selection criteria for at risk patients.</p> <p>Methods</p> <p>The analysis of microdeletions was conducted using fluorescence <it>in situ </it>hybridization (FISH) on metaphase chromosomes and interphase nuclei isolated from venous peripheral blood cultures. A molecular probe (Tuple) specific to the <it>HIRA (TUPLE1, DGCR1</it>) region at 22q11 was used for the hybridisation.</p> <p>Results</p> <p>Microdeletions of 22q11.2 region were detected in 13 children with a congenital heart defect (14.94% of the examined group). Microdeletion of 22q11.2 occurred in 20% and 11.54% of the conotruncal and non-conotruncal groups respectively. Tetralogy of Fallot was the most frequent heart defect in the first group of children with 22q11.2 microdeletion, while ventricular septal defect and atrial septal defect/ventricular septal defect were most frequent in the second group. The microdeletion was also detected in one of the parents of the deleted child (6.25%) without congenital heart defect, but with slight dysmorphism. In the remaining children, 22q11.2 microdeletion originated <it>de novo</it>.</p> <p>Conclusions</p> <p>Patients with 22q11.2DS exhibit wide spectrum of phenotypic characteristics, ranging from discreet to quite strong. The deletion was inherited by one child. Our study suggests that screening for 22q11.2 microdeletion should be performed in children with conotruncal and non-conotruncal heart defects and with at least one typical feature of 22q11.2DS as well as in the deleted children's parents.</p