Association of urethral toxicity with dose exposure in combined high-dose-rate brachytherapy and intensity-modulated radiation therapy in intermediate- and high-risk prostate cancer

INTRODUCTION: To report acute and late toxicities in patients with intermediate- and high-risk prostate cancer treated with combined high-dose-rate brachytherapy (HDR-B) and intensity-modulated radiation therapy (IMRT). MATERIALS AND METHODS: From March 2003 to September 2005, 64 men were treated with a single implant HDR-B with 21 Gy given in three fractions, followed by 50 Gy IMRT along with organ tracking. Median age was 66.1 years, and risk of recurrence was intermediate in 47% of the patients or high in 53% of the patients. Androgen deprivation therapy was received by 69% of the patients. Toxicity was scored according to the CTCAE version 3.0. Median follow-up was 3.1 years. RESULTS: Acute grade 3 genitourinary (GU) toxicity was observed in 7.8% of the patients, and late grades 3 and 4 GU toxicity was observed in 10.9% and 1.6% of the patients. Acute grade 3 gastrointestinal (GI) toxicity was experienced by 1.6% of the patients, and late grade 3 GI toxicity was absent. The urethral V(120) (urethral volume receiving > or =120% of the prescribed HDR-B dose) was associated with acute (P=.047) and late > or = grade 2 GU toxicities (P=.049). CONCLUSIONS: Late grades 3 and 4GU toxicity occurred in 10.9% and 1.6% of the patients after HDR-B followed by IMRT in association with the irradiated urethral volume. The impact of V(120) on GU toxicity should be validated in further studies.

The platelet protein kinase C substrate pleckstrin binds directly to SDPR protein

Pleckstrin is a modular platelet protein consisting of N- and C-terminal pleckstrin homology (PH) domains, a central dishevelled egl10 and pleckstrin (DEP) domain and a phosphorylation region. Following agonist-induced platelet stimulation, dimeric pleckstrin translocates to the plasma membrane, is phosphorylated and then monomerizes. A recent study found that pleckstrin null platelets from a knockout mouse have a defect in granule secretion, actin polymerization and aggregation. However, the mechanism of pleckstrin signaling for this function is unknown. Our recent studies have led to the identification of a novel pleckstrin-binding protein, serum deprivation response protein (SDPR), by co-immunoprecipitation, GST-pulldowns and nanospray quadruple time of flight mass spectrometry. We show that this interaction occurs directly through N-terminal sequences of pleckstrin. Both pleckstrin and SDPR are phosphorylated by protein kinase C (PKC), but the interaction between pleckstrin and SDPR was shown to be independent of PKC inhibition or activation. These results suggest that SDPR may facilitate the translocation of nonphosphorylated pleckstrin to the plasma membrane in conjunction with phosphoinositides that bind to the C-terminal PH domain. After binding of pleckstrin to the plasma membrane, its phosphorylation by PKC exerts downstream effects on platelet aggregation/secretion.

Embedding Moose Facilities Directly in IDEs

Moose is a powerful reverse engineering platform, but its facilities and means to analyze software are separated from the tools developers typically use to develop and maintain their software systems: development environments such as Eclipse, VisualWorks, or Squeak. In practice, this requires developers to work with two distinct environments, one to actually develop the software, and another one (e.g., Moose) to analyze it. We worked on several different techniques, using both dynamic and static analyzes to provide software analysis capabilities to developers directly in the IDE. The immediate availability of analysis tools in an IDE significantly increases the likelihood that developers integrate software analysis in their daily work, as we discovered by conducting user studies with developers. Finally, we identified several important aspect of integrating software analysis in IDEs that need to be addressed in the future to increase the adoption of these techniques by developers.

Der mittelfristige Einfluss von Feedback auf die Leistung von Mastery oder Performance motivierten Personen

In vielen Situationen bekommen Personen beim Lernen neuer Aufgaben in einer ersten Phase Feedback, doch in einer zweiten Phase arbeiten sie ohne Feedback. Bislang gibt es einige Befunde zu der Auswirkung eines Feedbacks auf die unmittelbare Leistung, nicht jedoch auf die mittelfristige Leistung in einer Phase ohne Feedback. Es ist zu erwarten, dass die Form der Leistungsmotivation hier eine entscheidende Rolle spielt. Für Personen, die das Ziel haben, besser zu sein als andere, kann ein negatives Feedback eine Bedrohung des Selbstwertes darstellen und daher demotivieren. Mittelfristig sollte jedoch die Bedrohung des Selbstwertes abnehmen. Daher ist zu erwarten, dass Feedback mittelfristig die Leistung steigert. Für Personen, die das Ziel haben, ihre Kenntnisse zu verbessern, stellt ein negatives Feedback keine Bedrohung des Selbstwertes da. Daher sollte sich Feedback anfänglich positiv auf die Leistung auswirken. Diese Personen lieben jedoch das Gefühl, sich Kenntnisse selbst zu erarbeitet zu haben. Feedback verdirbt den Spass am selbstständigen Explorieren und Lösungen finden. Feedback sollte daher - nach einer anfänglichen Leistungssteigerung- mittelfristig zu einer Verringerung der Leistung führen. Wir zeigen in einer Studie in der Tangram Puzzles gelöst wurden, dass beide Prozesse stattfinden.

Learning by the Dendritic Prediction of Somatic Spiking

Recent modeling of spike-timing-dependent plasticity indicates that plasticity involves as a third factor a local dendritic potential, besides pre- and postsynaptic firing times. We present a simple compartmental neuron model together with a non-Hebbian, biologically plausible learning rule for dendritic synapses where plasticity is modulated by these three factors. In functional terms, the rule seeks to minimize discrepancies between somatic firings and a local dendritic potential. Such prediction errors can arise in our model from stochastic fluctuations as well as from synaptic input, which directly targets the soma. Depending on the nature of this direct input, our plasticity rule subserves supervised or unsupervised learning. When a reward signal modulates the learning rate, reinforcement learning results. Hence a single plasticity rule supports diverse learning paradigms.

Purchase decision-making is modulated by vestibular stimulation

Purchases are driven by consumers’ product preferences and price considerations. Using caloric vestibular stimulation (CVS), we investigated the role of vestibular-affective circuits in purchase decision-making. CVS is an effective noninvasive brain stimulation method, which activates vestibular and overlapping emotional circuits (e.g., the insular cortex and the anterior cingulate cortex (ACC)). Subjects were exposed to CVS and sham stimulation while they performed two purchase decision-making tasks. In Experiment 1 subjects had to decide whether to purchase or not. CVS significantly reduced probability of buying a product. In Experiment 2 subjects had to rate desirability of the products and willingness to pay (WTP) while they were exposed to CVS and sham stimulation. CVS modulated desirability of the products but not WTP. The results suggest that CVS interfered with emotional circuits and thus attenuated the pleasant and rewarding effect of acquisition, which in turn reduced purchase probability. The present findings contribute to the rapidly growing literature on the neural basis of purchase decision-making.