Role of Quasiparticles in an Electric Circuit with Josephson Junctions.

Although Josephson junctions can be viewed as highly nonlinear impedances for superconducting quantum technologies, they also possess internal dynamics that may strongly affect their behavior. Here, we construct a computational framework that includes a microscopic description of the junction (full fledged treatment of both the superconducting condensate and the quasiparticles) in the presence of a surrounding electrical circuit. Our approach generalizes the standard resistor capacitor Josephson model to arbitrary junctions (including, e.g., multiterminal geometries and/or junctions that embed topological or magnetic elements) and arbitrary electric circuits treated at the classical level. By treating the superconducting condensate and quasiparticles on equal footings, we capture nonequilibrium phenomena such as multiple Andreev reflection. We show that the interplay between the quasiparticle dynamics and the electrical environment leads to the emergence of new phenomena. In a RC circuit connected to single channel Josephson junction, we find out-of-equilibrium current-phase relations that are strongly distorted with respect to the (almost sinusoidal) equilibrium one, revealing the presence of the high harmonic ac Josephson effect. In an RLC circuit connected to a junction, we find that the shape of the resonance is strongly modified by the quasiparticle dynamics: close to resonance, the current can be smaller than without the resonator. Our approach provides a route for the quantitative modeling of superconducting-based circuits.

High-dose chemotherapy with carmustine, etoposide, cytarabine and melphalan followed by autologous stem cell transplant is an effective treatment for elderly patients with poor-prognosis lymphoma.

Autologous stem cell transplant (ASCT) after high-dose chemotherapy (HDT) increases overall survival when used in relapsed non-Hodgkin lymphoma (NHL) in patients under 65 years old. Limited experience is available for older patients. We present a retrospective analysis of 73 consecutive patients aged over 65 years treated for aggressive or relapsed lymphoma by HDT with carmustine, etoposide, cytarabine and melphalan (BEAM) at full dosage followed by ASCT. Patient data were obtained from medical charts from two institutions. Median age was 67 years (65-74). Significant comorbidities were present in 24.7% of patients. The median number of days for grade 4 neutropenia was 9 (5-18). The early treatment-related mortality rate (<100 days) was 2.7%. The estimated 2-year progression-free survival and overall survival rates were 67.2% and 78.5%, respectively. In conclusion, the full-dose HDT-ASCT regimen is feasible, safe and efficient in selected patients over 65 years old.

Effects of chronic sepsis on contractile properties of fast twitch muscle in an experimental model of critical illness neuromyopathy in the rat.

OBJECTIVE: Critical illness polyneuromyopathy has been extensively studied in various animal models regarding electrophysiological aspects or molecular mechanisms involved in its physiopathology; however, little data are available on its main clinical feature, that is, muscular weakness. We have studied the effects of chronic sepsis in rats with special consideration to contractile and neuromuscular blockade properties in relation with the level of messenger RNA (mRNA) coding for ryanodine and acetylcholine receptors. DESIGN: This was an experimental animal study. SETTING: This study was conducted at a university laboratory. SUBJECTS: Subjects consisted of Wistar rats. INTERVENTIONS: Chronic sepsis was achieved by cecal ligation and needle perforation. Ten days after surgery, fast twitch extensor digitorum longus was excised for extraction and assays of mRNA coding for ryanodine and acetylcholine receptor subunits and contralateral muscle was tested in vivo on a mechanical bench. A fatigability index was measured and neuromuscular blockade properties using atracurium were evaluated. MEASUREMENTS AND MAIN RESULTS: A decrease in active force developed by extensor digitorum longus associated with an increase in passive force is induced by chronic sepsis. Maximal force at optimal length during twitch contraction was significantly reduced (0.25 +/- 0.09 N vs. 0.17 +/- 0.06 N); contraction and relaxation speeds were higher as shown by the decrease of respective time constants (3.75 +/- 0.01 msec vs. 2.70 +/- 0.0 msec, 10.76 +/- 0.03 msec vs. 7.62 +/- 0.03 msec) in the control group compared with the septic group. Fatigability index was significantly lower (23 +/- 0.11% vs. 59 +/- 0.19%) in septic rats. These rats also showed quicker blockade and shorter recovery after atracurium administration. Sepsis induced a significant increase of the expression of ryanodine receptor (RyR) RyR1 along with a steady expression of RyR3 mRNA, leading to a 5.6-fold increase of RyR1/RyR3 ratio with a steadiness of mRNA corresponding to acetylcholine-receptors. CONCLUSIONS: Chronic inflammation and sepsis induced a decrease in contractile performances of extensor digitorum longus along with accelerated kinetics of atracurium possibly induced by modified expression of RyR1 receptors and not acetylcholine-receptors.

Effects of chronic sepsis on rat motor units: experimental study of critical illness polyneuromyopathy.

Critical illness polyneuromyopathy (CIP) leads to major muscle weakness correlated with peripheral nerve and/or muscle alterations. Because sepsis seems to be the main factor, we used an experimental model of chronic sepsis in rats to study the localization of the first alterations on isolated motor units of soleus muscle. Seven days of chronic sepsis leads to a decrease in muscle force and an increase in muscle fatigability. Muscle twitch contraction time is also slower and all the motor units exhibit a slow profile in septic rats. Motor axon conduction velocity remains normal. We observed a significant increase in the latency between nerve and muscle action potentials but no modifications in the electromechanical delay. The first action of sepsis on motor units seems to be a delayed trigger of muscle action potential along with a muscle weakness but without nerve conduction impairment.

Effects of chronic sepsis on the voltage-gated sodium channel in isolated rat muscle fibers.

OBJECTIVE: Physiopathology of critical illness polyneuromyopathy was investigated in several animal-based models. Electrophysiologic approach was achieved in denervated and corticosteroid-induced myopathy; other models based on sepsis or inflammatory factors (zymosan, cytokines) were also used but did not consider voltage-gated sodium channel implication in neuromuscular weakness. We have studied electrophysiologic effects of chronic sepsis on an intact neuromuscular rat model with special consideration to the subtypes of sodium channels involved. DESIGN: Experimental animal study. SETTING: University laboratory. SUBJECTS: Wistar rats. INTERVENTIONS: Chronic sepsis was achieved by a technique of cecal ligature and needle perforation. Ten days after surgery, the rats were killed. Fast-twitch flexor digitorum brevis was excised and dissociated in 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid-buffered saline supplemented with 3.0 mg/mL collagenase. Fast sodium currents were recorded by a macropatch clamp technique at room temperature (22+/-2 degrees C) in a cell-attached configuration. MEASUREMENTS AND MAIN RESULTS: A decrease in maximal sodium current and in conductance was evidenced without modification of the sodium Nernst potential. A shift of the voltage inactivation curve toward more negative potentials could explain the observed decrease in excitability. In parallel, we observed an up-regulation of NaV 1.5-type sodium channels. CONCLUSIONS: Chronic inflammation and sepsis induced modifications of sodium channel properties that could contribute to muscular inexcitability. This inexcitability can be elicited by a modification of properties or type of voltage-gated sodium channels. Our results lead us to explain this inexcitability by an up-regulation of NaV 1.5 sodium channel.