In this work we explored metabolic aspects of human primary leukemic lymphocytes that hold a potential impact on the treatment of Bruton tyrosine kinase (BTK)-driven diseases. Our results suggest that there is crosstalk between Bruton tyrosine kinase (BTK) signaling and bioenergetic stress responses. In primary chronic lymphocytic leukemia (CLL) lymphocytes, pharmacological interference with mitochondrial ATP synthesis or glucose metabolism affects BTK activity. Conversely, an inhibitor of BTK used clinically (ibrutinib) induces bioenergetic stress responses that in turn affect ibrutinib resistance. Although the detailed molecular mechanisms are still to be defined, our work shows for the first time that in primary B cells, metabolic stressors enhance BTK signaling and suggest that metabolic rewiring to hyperglycemia affects ibrutinib resistance in TP53 deficient chronic lymphocytic leukemia (CLL) lymphocytes.

Although accident investigation has significantly contributed to safety and reliability improvement of airplanes over decades, its contribution has not been quantified and compared to that of other safety measures. In this paper, a cost effectiveness measure is proposed in terms of the cost and the number of likely future accidents in similar aircraft which could potentially be prevented by the investigation. We concluded that a crucial role of an investigation is to distinguish accidents caused by errors (such as failure to consider a failure mode) a rare combination of circumstances, such as an extremely strong gust hitting a damaged plane on its way to the repair depot. Errors are common to a large number of airplanes and the same accident is likely to happen to other airplanes, while a rare event is unlikely to happen again. We first analyzed past accidents in order to shed light on a key factor-the probability of reoccurrence of an accident. Then, we introduced a concept of cost effectiveness measurement, cost per life saved, and threshold of cost effectiveness. Past accidents with different types of cause were selected as examples, and we examined how the probability of reoccurrence affects cost effectiveness. Finally, we performed a comparison in cost effectiveness between accident investigation and structural design change intended to reduce the probability of failure due to fatigue of a fuselage panel. We found that for the example the safety improvement implemented by the accident investigation was clearly more cost effective.

Portal vein and its two branches were evaluated by ultrasound in 12 children (14 months to eight years) with portal cavernomas; the cavernomas appeared idiopathic (five cases) or were secondary either to a catherization of umbilical vein in the neonatal period (six cases) or to trauma (one case). Angiographic confirmation of cavernoma was obtained in all patients. Twelve patients with intrahepatic portal hypertension were used as controls. The following abnormal patterns were observed: (1) absence of normal portal vein; (2) absence of normal portal division; (3) tortuous, small and irregular appearance and/or abnormal sagittal division of the venous system; (4) presence of small linear echoes dotting the portal vein; (5) presence of small linear echoes dotting the porta hepatis area. Ultrasonogram was normal in the 12 controls. Thus, ultrasound appears to be a procedure of choice in the evaluation of portal cavernomas, permitting postponement of invasive angiographic examination until surgical treatment is anticipated.

A bipolar electrode for transcatheter electrocoagulation with alternating current is described. This electrode avoids the problem of variation of the electric impedance of the monopolar electrode/ground plate system. It allows quick, safe, and reliable endovascular occlusion of vessels.

Selective catheterization of coronary vein. Early (..), bidirectional flow: hepatopetal toward portal trunk (white arrow) and hepatofugal toward esophageal varices (black arrow). Later (D) , gastrorenal shunt opacified (black arrow) .Cat heter tip (arrowhead).