Intra-subject variability in attention-deficit hyperactivity disorder

BACKGROUND: This study is based on a comprehensive survey of the neuropsychological attention-deficit hyperactivity disorder (ADHD) literature and presents the first psychometric analyses of different parameters of intra-subject variability (ISV) in patients with ADHD compared to healthy controls, using the Continuous Performance Test, a Go-NoGo task, a Stop Signal Task, as well as N-back tasks. METHODS: Data of 57 patients with ADHD and 53 age- and gender-matched controls were available for statistical analysis. Different parameters were used to describe central tendency (arithmetic mean, median), dispersion (standard deviation, coefficient of variation, consecutive variance), and shape (skewness, excess) of reaction time distributions, as well as errors (commissions and omissions). RESULTS: Group comparisons revealed by far the strongest effect sizes for measures of dispersion, followed by measures of central tendency, and by commission errors. Statistical control of ISV reduced group differences in the other measures substantially. One (patients) or two (controls) principal components explained up to 67% of the inter-individual differences in intra-individual variability. CONCLUSIONS: Results suggest that, across a variety of neuropsychological tests, measures of ISV contribute best to group discrimination, with limited incremental validity of measures of central tendency and errors. Furthermore, increased ISV might be a unitary construct in ADHD.

Postnatal Notch1 activation induces T‑cell malignancy in conditional and inducible mouse models

The Notch1 signaling pathway is essential for hematopoietic development. However, the effects of postnatal activation of Notch1 signaling on hematopoietic system is not yet fully understood. We previously generated ZEG‑IC‑Notch1 transgenic mice that have a floxed β‑geo/stop signal between a CMV promoter and intracellular domain of Notch1 (IC‑Notch1). Constitutively active IC‑Notch1 is silent until the introduction of Cre recombinase. In this study, endothelial/hematopoietic specific expression of IC‑Notch1 in double transgenic ZEG‑IC‑Notch1/Tie2‑Cre embryos induced embryonic lethality at E9.5 with defects in vascular system but not in hematopoietic system. Inducible IC‑Notch1 expression in adult mice was achieved by using tetracycline regulated Cre system. The ZEG‑IC‑Notch1/Tie2‑tTA/tet‑O‑Cre triple transgenic mice survived embryonic development when maintained on tetracycline. Post‑natal withdrawal of tetracycline induced expression of IC‑Notch1 transgene in hematopoietic cells of adult mice. The triple transgenic mice displayed extensive T‑cell infiltration in multiple organs and T‑cell malignancy of lymph nodes. In addition, the protein levels of p53 and alternative reading frame (ARF) were decreased in lymphoma‑like neoplasms from the triple transgenic mice while their mRNA expression remained unchanged, suggesting that IC‑Notch1 might repress ARF‑p53 pathway by a post‑transcriptional mechanism. This study demonstrated that activation of constitutive Notch1 signaling after embryonic development alters adult hematopoiesis and induces T‑cell malignancy.

Diagnostic performance and accuracy of 3-D spoiled gradient-dual-echo MRI with water- and fat-signal separation in liver-fat quantification: comparison to liver biopsy

To prospectively evaluate a 3-dimensional spoiled gradient-dual-echo (3D SPGR-DE) magnetic resonance imaging (MRI) sequence for the qualitative and quantitative analysis of liver fat content (LFC) in patients with the suspicion of fatty liver disease using histopathology as the standard of reference.

Recurrent non-melanoma skin cancer: remission of field cancerization after conversion from calcineurin inhibitor- to proliferation signal inhibitor-based immunosuppression in a cardiac transplant recipient

Non-melanoma skin cancers (NMSCs) are the most common malignancies after solid organ transplantation. Their incidence increases with time after transplantation. Calcineurin-inhibitors (CNIs) and azathioprine are known as skin neoplasia-initiating and -enhancing immunosuppressants. In contrast, increasing clinical experience suggests a relevant antiproliferative effect of mammalian target of rapamycin inhibitors, also named proliferation signal inhibitors (PSIs). We report the case of a cardiac allograft recipient with an impressive and consolidated reduction of recurrent NMSC, observed after conversion from CNI-therapy to a PSI-based protocol.

Last stop expulsion - The minority question and forced migration in East-Central Europe: 1918-49

This article deals with the European minorities in the period between the two world wars and with their final expulsion from nation-states at the end of World War II. First, the tensions which arose between the organised minorities and the successor states of the Habsburg Monarchy are accounted for primarily by the argument that the various minorities located within the successor states had already undergone a comprehensive processes of nationalisation within the Habsburg Empire. Therefore they were able to resist assimilation by the political elites of the new titular nations (Czechs, Poles, Rumanians, Serbs). A second topic is that of the use made of the minorities issue by Adolf Hitler to help achieve his expansionist aims. The minorities issue was central to the international destabilisation of interwar Europe. Finally, the mass expulsion of minorities (above all, Germans) after the end of the war is explained by strategic considerations on the part of the Allied powers as well as involving the nation-state regimes. It is argued, against a commonly held view, that German atrocities during the period of occupation had little to do with the decision to expel most ethnic Germans from their territories of settlement in Poland, Czechoslovakia and Yugoslavia. The article shows that it is necessary to treat national minorities in the first half of the twentieth century as a single phenomenon which shares similar features across the various nation-states of East-Central Europe.

Dose modulated retrospective ECG-gated versus non-gated 64-row CT angiography of the aorta at the same radiation dose: Comparison of motion artifacts, diagnostic confidence and signal-to-noise-ratios

To compare ECG-gated and non-gated CT angiography of the aorta at the same radiation dose, with regard to motion artifacts (MA), diagnostic confidence (DC) and signal-to-noise-ratios (SNRs).

Does quantification of USPIO uptake-related signal loss allow differentiation of benign and malignant normal-sized pelvic lymph nodes?

Ultrasmall superparamagnetic iron oxide (USPIO) particles are promising contrast media, especially for molecular and cellular imaging besides lymph node staging owing to their superior NMR efficacy, macrophage uptake and lymphotropic properties. The goal of the present prospective clinical work was to validate quantification of signal decrease on high-resolution T(2)-weighted MR sequences before and 24-36 h after USPIO administration for accurate differentiation between benign and malignant normal-sized pelvic lymph nodes. Fifty-eight patients with bladder or prostate cancer were examined on a 3 T MR unit and their respective lymph node signal intensities (SI), signal-to-noise (SNR) and contrast-to-noise (CNR) were determined on pre- and post-contrast 3D T(2)-weighted turbo spin echo (TSE) images. Based on histology and/or localization, USPIO-uptake-related SI/SNR decrease of benign vs malignant and pelvic vs inguinal lymph nodes was compared. Out of 2182 resected lymph nodes 366 were selected for MRI post-processing. Benign pelvic lymph nodes showed a significantly higher SI/SNR decrease compared with malignant nodes (p < 0.0001). Inguinal lymph nodes in comparison to pelvic lymph nodes presented a reduced SI/SNR decrease (p < 0.0001). CNR did not differ significantly between benign and malignant lymph nodes. The receiver operating curve analysis yielded an area under the curve of 0.96, and the point with optimal accuracy was found at a threshold value of 13.5% SNR decrease. Overlap of SI and SNR changes between benign and malignant lymph nodes were attributed to partial voluming, lipomatosis, histiocytosis or focal lymphoreticular hyperplasia. USPIO-enhanced MRI improves the diagnostic ability of lymph node staging in normal-sized lymph nodes, although some overlap of SI/SNR-changes remained. Quantification of USPIO-dependent SNR decrease will enable the validation of this promising technique with the final goal of improving and individualizing patient care.