Outcome of ACHD patients with non-inducible versus inducible IART undergoing cavo-tricuspid isthmus ablation: the role of empiric ablation

Purpose: Catheter ablation for supraventricular tachycardia (SVT) in adults with congenital heart disease (ACHD) is an important therapeutic option. Cavo-tricuspid isthmus (CTI)-dependent intraatrial re-entrant tachycardia (IART) is common. However, induction of sustained tachycardia at the time of ablation is not always possible. We hypothesised that performing an empiric CTI line in case of non-inducibility leads to good outcomes. Long-term outcomes of empiric versus entrained CTI ablation in ACHD patients were examined. / Methods: Retrospective, single-centre, case-control study over 7 years. Arrhythmia-free survival after empiric versus entrained CTI ablation was compared. / Results: Eighty-seven CTI ablations were performed in 85 ACHD patients between 2010 and 2017. The mean age of the cohort was 43 years and 48% were male. Underlying aetiology included ASD (31%), VSD (11.4%), AVSD (9.1%), AVR (4.8%), Fallot’s (18.4%), Ebstein’s (2.3%), Fontan’s palliation (9.2%) and atrial switch (13.8%). CTI-dependent IART was entrained in 59 patients whereas it was non-inducible in 28. The latter had an empiric CTI ablation. Forty-three percent of procedures were performed under general anaesthesia. There were no reported procedural complications. There was no significant difference in the mean procedure or fluoroscopy times between the groups (empiric vs entrained CTI; 169.1 vs 183.3 and 28.1 vs 19.9 min). Arrhythmia-free survival was 64.3% versus 72.8% (p value 0.44) in the empiric and entrained groups at 21 months follow-up. / Conclusions: Long-term outcomes after empiric and entrained CTI ablation for IART in ACHD patients are comparable. This is a safe and effective therapeutic option. In the case of non-inducibility of IART, an empiric CTI line should be considered in this cohort

Quantum Point Contacts and Coherent Electron Focusing

I. Introduction II. Electrons at the Fermi level III. Conductance quantization of a quantum point contact IV. Optical analogue of the conductance quantization V. Classical electron focusing VI. Electron focusing as a transmission problem VII. Coherent electron focusing (Experiment, Skipping orbits and magnetic edge states, Mode-interference and coherent electron focusing) VIII. Other mode-interference phenomenaComment: #3 of a series of 4 legacy reviews on QPC'

The Buffer Gas Beam: An Intense, Cold, and Slow Source for Atoms and Molecules

Beams of atoms and molecules are stalwart tools for spectroscopy and studies of collisional processes. The supersonic expansion technique can create cold beams of many species of atoms and molecules. However, the resulting beam is typically moving at a speed of 300-600 m/s in the lab frame, and for a large class of species has insufficient flux (i.e. brightness) for important applications. In contrast, buffer gas beams can be a superior method in many cases, producing cold and relatively slow molecules in the lab frame with high brightness and great versatility. There are basic differences between supersonic and buffer gas cooled beams regarding particular technological advantages and constraints. At present, it is clear that not all of the possible variations on the buffer gas method have been studied. In this review, we will present a survey of the current state of the art in buffer gas beams, and explore some of the possible future directions that these new methods might take

Effectiveness and safety of opicapone in Parkinson's disease patients with motor fluctuations: The OPTIPARK open-label study

BACKGROUND: The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. METHODS: OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). RESULTS: Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. CONCLUSIONS: Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. TRIAL REGISTRATION: Registered in July 2016 at clinicaltrials.gov (NCT02847442)

Interventions for acute stroke management in Africa: a systematic review of the evidence

Abstract Background The past decades have witnessed a rapid evolution of research on evidence-based acute stroke care interventions worldwide. Nonetheless, the evidence-to-practice gap in acute stroke care remains variable with slow and inconsistent uptake in low-middle income countries (LMICs). This review aims to identify and compare evidence-based acute stroke management interventions with alternative care on overall patient mortality and morbidity outcomes, functional independence, and length of hospital stay across Africa. Methods This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. An electronic search was conducted in six databases comprising MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, Academic Search Complete and Cochrane Library for experimental and non-experimental studies. Eligible studies were abstracted into evidence tables and their methodological quality appraised using the Joanna Briggs Institute checklist. Data were analysed and presented narratively with reference to observed differences in patient outcomes, reporting p values and confidence intervals for any possible relationship. Results Initially, 1896 articles were identified and 37 fully screened. Four non-experimental studies (three cohort and one case series studies) were included in the final review. One study focused on the clinical efficacy of a stroke unit whilst the remaining three reported on thrombolytic therapy. The results demonstrated a reduction in patient deaths attributed to stroke unit care and thrombolytic therapy. Thrombolytic therapy was also associated with reductions in symptomatic intracerebral haemorrhage (SICH). However, the limited eligible studies and methodological limitations compromised definitive conclusions on the extent of and level of efficacy of evidence-based acute stroke care interventions across Africa. Conclusion Evidence from this review confirms the widespread assertion of low applicability and uptake of evidence-based acute stroke care in LMICs. Despite the limited eligible studies, the overall positive patient outcomes following such interventions demonstrate the applicability and value of evidence-based acute stroke care interventions in Africa. Health policy attention is thus required to ensure widespread applicability of such interventions for improved patients’ outcomes. The review findings also emphasises the need for further research to unravel the reasons for low uptake. Systematic review registration PROSPERO CRD4201605156

Investigating translaminar signaling from layer 5 Pyramidal subpopulations to layer 2/3 in Somatosensory Cortex

Information processing in the mammalian cortex is achieved via a precise arrangement of synaptic connections between different neuronal subtypes. The excitatory neurons of the cortex are arranged in a laminar manner across six layers and form specific intralaminar and translaminar connections with one another. In addition, these excitatory neurons interact with a series of inhibitory interneuron subtypes, such that the relative levels and timing of excitatory and inhibitory synaptic transmission determine how information is processed by the cortical network. This thesis examines the translaminar signaling from layer 5 (L5) to layer 2/3 (L2/3) of cortex. Considered the principal output layer, L5 is populated by intratelencephalic (IT) and pyramidal tract (PT) pyramidal neurons, which form long-range projections to other cortical and subcortical regions, respectively. These long-range axons of L5 pyramidal neurons also branch locally and form ascending collaterals that extend to more superficial layers, including L2/3. An unanswered question in the field, is what sorts of translaminar signals do these local collaterals deliver. I have used the mouse somatosensory cortex in order to address this question. In the first series of experiments, transgenic mice expressing the optogenetic activator, channelrhodopsin-2 (ChR2), were used to stimulate a non-specific population of L5 pyramidal neurons. This was shown to elicit both monosynaptic excitation and disynaptic inhibition within L2/3, and to modulate the action potential activity of L2/3 pyramidal neurons in vitro and in vivo. I then used retrograde labelling strategies in order to distinguish between IT and PT L5 pyramidal neurons, revealing that the long-range target of the L5 neuron is associated with morphological differences in its local ascending collaterals. To investigate whether the functional consequences, I used a retrograde viral system to deliver ChR2 to each of the projection-defined L5 subtypes. Patch clamp recordings revealed that IT L5 neurons evoked robust excitation but little inhibition within L2/3. In contrast, PT L5 neurons elicited significant levels of synaptic inhibition, which was shown to result from the selective targeting of L2/3 parvalbumin-expressing interneurons. Finally, I was able to demonstrate that this differential recruitment of excitation and inhibition by the L5 subtypes results in opposing modulatory effects upon L2/3 pyramidal neuron activity in vitro and during sensory-driven input in vivo. The work supports growing evidence that L5 plays a significant role in modulating ongoing local cortical activity. It also suggests that projection-defined L5 subpopulations provide opposing translaminar signals to L2/3, which could be important for sensory processing, sensory-motor integration and synaptic plasticity.</p