Two Types of K⁺ Channel Subunit, Erg1 and KCNQ2/3, Contribute to the M-Like Current in a Mammalian Neuronal Cell

The potassium M current was originally identified in sympathetic ganglion cells, and analogous currents have been reported in some central neurons and also in some neural cell lines. It has recently been suggested that the M channel in sympathetic neurons comprises a heteromultimer of KCNQ2 and KCNQ3 (Wang et al., 1998) but it is unclear whether all other M-like currents are generated by these channels. Here we report that the M-like current previously described in NG108–15 mouse neuroblastoma x rat glioma cells has two components, “fast” and “slow”, that may be differentiated kinetically and pharmacologically. We provide evidence from PCR analysis and expression studies to indicate that these two components are mediated by two distinct molecular species of K+ channel: the fast component resembles that in sympathetic ganglia and is probably carried byKCNQ2/3 channels, whereas the slow component appears to be carried by merg1a channels. Thus, the channels generating M-like currents in different cells may be heterogeneous in molecular composition

From FinTech to TechFin: The Regulatory Challenges of Data-Driven Finance

Financial technology (‘FinTech’) is transforming finance and challenging its regulation at an unprecedented rate. Two major trends stand out in the current period of FinTech development. The first is the speed of change driven by the commoditization of technology, Big Data analytics, machine learning and artificial intelligence. The second is the increasing number and variety of new entrants into the financial sector, including pre-existing technology and e-commerce companies. This paper considers the impact of these new entrants with their typically large pre-existing non-financial services customer bases. These firms (loosely termed ‘TechFins’) may be characterised by their capacity to leverage the data gathered in their primary business into financial services. In other words, TechFins represent an Uber moment in finance. This shift from financial intermediary (FinTech) to data intermediary (TechFin) raises implications for incumbent financial services firms, FinTech startups and regulators. This seachange calls for analysis to underpin regulatory approaches with a view to balancing the competing interests of innovation, development, financial stability and consumer protection.postprin

Sustainability, FinTech & Financial Inclusion

We argue financial technology (FinTech) is the key driver for financial inclusion, which in turn underlies sustainable balanced development, as embodied in the UN Sustainable Development Goals (SDGs). The full potential of FinTech to support the SDGs may be realized with a progressive approach to the development of underlying infrastructure to support digital financial transformation. Our research suggests that the best way to think about such a strategy is to focus on four primary pillars. The first pillar requires the building of digital identity, simplified account opening and e-KYC systems, supported by the second pillar of open interoperable electronic payments systems. The third pillar involves using the infrastructure of the first and second pillars to underpin electronic provision of government services and payments. The fourth pillar—design of digital financial markets and systems—supports broader access to finance and investment. Implementing the four pillars is a major journey for any economy, but one which has tremendous potential to transform not only finance but economies and societies, through FinTech, financial inclusion and sustainable balanced development

Node-node distance distribution for growing networks

We present the simulation of the time evolution of the distance matrix. The result is the node-node distance distribution for various kinds of networks. For the exponential trees, analytical formulas are derived for the moments of the distance distribution.Comment: presented during the 37-th Polish Physicists' Meeting, Gdansk, Poland, 15-19 Sep. 2003, 6 pages, 3 figure

The ICO Gold Rush: It's a Scam, It's a Bubble, It's a Super Challenge for Regulators

Initial coin offerings typically use blockchain technology to offer tokens that confer some rights in return, most often, for cryptocurrency. They can be seen as effectively a conjunction of crowdfunding and blockchain. Based on a handselected database comprising more than a hundred ICOs we provide a taxonomy of ICOs to facilitate thinking clearly about them, analyse the various regulatory challenges they pose, and suggest the first steps regulators should consider in responding to them. At the moment, many ICOs are offered on the basis of utterly inadequate disclosure of information, and the decision to invest in them often cannot be the outcome of a rational calculus. Many of the hallmarks of a classic speculative bubble are present in many, but certainly not all, ICOs. At the same time, ICOs provide a new and innovative structure for raising funds to support new and innovative ideas and ventures, with the potential for aspects of the underlying structures to have an important impact on fundraising systems and structures in future.published_or_final_versio

A two-component jet model for the optical plateau in the afterglow of GRB 191221B

The long gamma-ray burst GRB 191221B has abundant observations in X-ray, optical and radio bands. In the literature, the observed optical light curve of GRB 191221B displays a plateau around 0.1-day, which is rather peculiar in gamma-ray bursts. Here we performed detailed analysis of the observational data from Swift/UVOT, VLT and LCO, obtained the light curve of the multi-band afterglow of GRB 191221B. By examining optical, ultraviolet, X-ray, and radio data for this event, we demonstrate that an on-axis two-component jet model can explain the observations. Our analysis suggests that the narrow component has an initial Lorentz factor of 400 and a jet opening half-angle of $1.4^{\circ}$, while the wide component has an initial Lorentz factor of 25 and a jet opening half-angle of $2.8^{\circ}$. The narrow jet dominates the early decay, whereas the wider jet causes the optical plateau and dominates late decay. According to this model, the reason for the absence of the X-ray plateau is due to the steeper spectral index of the wide component, resulting in a less significant flux contribution from the wide jet in the X-ray bands than in the optical bands. Moreover, we have explained the inconsistency in the decay indices of the UVOT and Rc-band data around 2000 seconds using reverse shock emission.Comment: 10 pages, 7 figures, Accepted by the Monthly Notices of the Royal Astronomical Societ

Catheter ablation and lower risk of incident dementia and mortality in older adults with atrial fibrillation.

Background Atrial fibrillation (AF) has consistently been associated with a higher risk of incident dementia. Observational evidence has suggested catheter ablation may be associated with a lower risk of dementia in patients with AF, but further research is needed. The objectives of this study were to use a global health research network to examine associations between catheter ablation, incident dementia and mortality in older adults with AF, and amongst subgroups by age, sex, co-morbidity status, and oral anticoagulant use.Methods The research network primarily included healthcare organizations in the United States. This network was searched on 28th September 2022 for patients aged ≥65 years with a diagnosis of AF received at least 5 years prior to the search date. Cox proportional hazard models were run on propensity-score matched cohorts. Results After propensity score matching, 20,746 participants (mean age 68 years; 59% male) were included in each cohort with and without catheter ablation. The cohorts were well balanced for age, sex, ethnicity, co-morbidities, and cardiovascular medications received. The risk of dementia was significantly lower in the catheter ablation cohort (Hazard Ratio 0.52, 95% confidence interval: 0.45-0.61). The catheter ablation cohort also had a lower risk of all-cause mortality (Hazard Ratio 0.58, 95% confidence interval: 0.55-0.61). These associations remained in subgroup analyses in individuals aged 65-79 years, ≥80 years, males, females, participants who received OACs during follow-up, participants with paroxysmal and non-paroxysmal AF, and participants with and without hypertension, diabetes mellitus, ischemic stroke, chronic kidney disease and heart failure, including heart failure with preserved ejection fraction and heart failure with reduced ejection fraction.Conclusion The observed lower risk of dementia and mortality with catheter ablation could be an important consideration when determining appropriate patient-centered rhythm control strategies for patients with AF. Further studies including data on the success of ablation are required

Associations between COVID-19 and 30-day thromboembolic events and mortality in people with dementia receiving antipsychotic medications

Background: Antipsychotic medications are frequently prescribed to people with dementia to manage behavioural and psychological symptoms. Using a global federated research network, the objectives were to determine: 1) if COVID-19 is associated with 30-day thromboembolic events and mortality for people with dementia receiving antipsychotic medications; and 2) if the proportion of people with dementia receiving antipsychotics is higher during the COVID-19 pandemic compared to 2019. Methods: A retrospective cohort study was conducted using TriNetX, a global federated health research network. The network was searched for people aged ≥ 65 years with dementia, COVID-19 and use of antipsychotics in the 30-days prior to COVID-19 recorded in electronic medical records between 20/01/2020 and 05/12/2020. These individuals were compared to historical controls from 2019 with dementia and use of antipsychotics in the 30-days before a visit to a participating healthcare organisation. Propensity score matching for age, sex, race, co-morbidities and use of antidepressants and anticonvulsants was used to balance cohorts with and without COVID-19. Results: Within the TriNetX network, 8414 individuals with COVID-19, dementia and use of antipsychotics and 31,963 historical controls were identified. After propensity score matching there were 8396 individuals with COVID-19 and 8396 historical controls. The cohorts were well balanced for age, sex, race, co-morbidities and use of antidepressants and anticonvulsants. The odds of 30-day thromboembolic events and all-cause mortality were significantly higher in adults with COVID-19 (Odds Ratios: 1.36 (95% confidence interval (CI): 1.21–1.52) and 1.93 (1.71–2.17), respectively). The number of people with dementia with a visit to a participating healthcare organisation was lower between 20/01/2020 and 05/12/2020 (n = 165,447) compared to the same period in 2019 (n = 217,391), but the proportion receiving antipsychotics increased from 14.7% (95%CI: 14.6–14.9%) to 16.4% (95%CI: 16.2–16.5%), P < .0001. Conclusions: These findings add to the evidence base that during the COVID-19 pandemic there was an increase in the proportion of people with dementia receiving antipsychotics. The negative effects of antipsychotics in patients with dementia may be compounded by concomitant COVID-19