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Background Ibrutinib and acalabrutinib are Bruton tyrosine kinase inhibitors used in the treatment of B‐cell lymphoproliferative disorders. Ibrutinib is associated with new‐onset atrial fibrillation. Cases of sinus bradycardia and sinus arrest have also been reported following ibrutinib treatment. Conversely, acalabrutinib is less arrhythmogenic. The basis for these different effects is unclear. Methods and Results The effects of ibrutinib and acalabrutinib on atrial electrophysiology were investigated in anesthetized mice using intracardiac electrophysiology, in isolated atrial preparations using high‐resolution optical mapping, and in isolated atrial and sinoatrial node (SAN) myocytes using patch‐clamping. Acute delivery of acalabrutinib did not affect atrial fibrillation susceptibility or other measures of atrial electrophysiology in mice in vivo. Optical mapping demonstrates that ibrutinib dose‐dependently impaired atrial and SAN conduction and slowed beating rate. Acalabrutinib had no effect on atrial and SAN conduction or beating rate. In isolated atrial myocytes, ibrutinib reduced action potential upstroke velocity and Na+ current. In contrast, acalabrutinib had no effects on atrial myocyte upstroke velocity or Na+ current. Both drugs increased action potential duration, but these effects were smaller for acalabrutinib compared with ibrutinib and occurred by different mechanisms. In SAN myocytes, ibrutinib impaired spontaneous action potential firing by inhibiting the delayed rectifier K+ current, while acalabrutinib had no effects on SAN myocyte action potential firing. Conclusions Ibrutinib and acalabrutinib have distinct effects on atrial electrophysiology and ion channel function that provide insight into the basis for increased atrial fibrillation susceptibility and SAN dysfunction with ibrutinib, but not with acalabrutinib.

Abstract Background The Collaboration of Practitioners and Researchers Seminar Series is student-led program comprised of seminars delivered jointly by medical and graduate students on a topic in medicine of mutual interest to an audience of both medical and graduate students. Methods Following its inaugural year in 2016–2017, we evaluated changes in attendees’ perceived understanding of translational research through an electronic survey and semi-structured interviews with attendees. Results Study participants rated their understanding of translational research and comfort with interacting with students from the other program higher following attending seminars. Participants believed that the seminars helped in breaking barriers between medical and graduate students. Conclusions We conclude that this seminar series positively impacted attendees’ understanding of translational research and attitudes towards collaboration between medical and graduate students. We believe that similar initiatives may be of value in fostering new opportunities for collaboration between medical and graduate students at other institutions.

The heart receives both sympathetic and parasympathetic efferent innervation as well as having the ability to process information internally via an intrinsic cardiac autonomic nervous system (ICANS). For over a century, the role of the parasympathetic innervation via vagal acetylcholine release was related to controlling the tone primarily via heart rate. Although subsequently in the late 1800’s, shown to play a role in atrial arrhythmia, the myocardium took precedence from the mid-1950s until a resurgence of interest in the autonomics in the last decade. Originally ignored as being benign and thus left untreated, recent emphasis has focused on atrial arrhythmia as atrial fibrillation is the most common arrhythmia seen by the general practitioner. It is now recognized to have significant mortality and morbidity due to resultant stroke and heart failure, and with the aging population, there will be an unprecedented increased burden on health care resources. Although it has been known for more than half a century that cholinergic stimulation can initiate atrial fibrillation, the classical concept focused on the M2 receptor and its signalling cascade including RGS4, as these had been shown to have predominant effects on nodal function (heart rate and conduction block) as well as contractility. However, recent evidence suggests that the M3 receptor may have a major role in initiation and perpetuation of atrial fibrillation and RGS2, a putative regulator of the M3 receptor, may be a target for therapeutic intervention. Mice lacking RGS2 (RGS2--), were found to have significantly altered electrophysiological atrial responses and were more susceptible to electrically-induced atrial fibrillation. Vagally-induced or programmed stimulation-induced atrial fibrillation could also be blocked by the selective M3R antagonist, darifenacin. These results suggest a potential surgical target (ICANS) and pharmacological targets (M3R, RGS2) for the management of atrial fibrillation

The V-BLAST wireless communication architecture, space-time block code (STBC), and space-frequency block code (SFBC) techniques are strong candidates for achieving very high data rates in 4G broadband wireless communications. This paper extends the efficient Active Constellation Extension Smart Gradient-Project (ACE-SGP) peak-to-average power (PAPR) reduction method to STBC, SFBC, and V-BLAST systems. Simulation results show 4.19 and 3.57 dB of PAPR reduction for the Alamouti STBC and SFBC, respectively.

The majority of optimal rules derived for different decentralized detection application scenarios are based on an assumption that the sensors' observations are statistically independent. Deriving the optimal decision rule in the canonical decentralized setting with correlated observations was shown to be complicated even for the simple case of two sensors. We introduce an alternative suboptimal rule to deal with correlated observations in decentralized detection with censoring sensors using a modified generalized likelihood ratio test (mGLRT). In the censoring scheme, sensors either send or do not send their complete observations to the fusion center. Using ML estimation to estimate the censored values, the decentralized problem is converted to a centralized problem. Our simulation results indicate that, when sensor observations are correlated, the mGLRT gives considerably better performance in terms of probability of detection than does the optimal decision rule derived for uncorrelated observations.