The future of the UK IPO

IPOs have long played a central role in how most companies go public, but the dominance of classic IPO models in UK markets has been significantly threatened over the last two decades. Companies are ever more reluctant to go public—and those that do so increasingly gravitate towards methods that reformulate or entirely depart from traditional IPO structures. The UK’s exit from the EU on 31 December 2020, which removed the requirement to follow EU regulations, has provided the UK with the opportunity to assess whether its rules still offer the right regulatory regime for IPOs. This paper examines what the right balance for the UK IPO might be. First, it analyses how traditional IPO structures have been evolving in the UK; second, it considers how the development of alternative investment models has been impinging on the classic IPO model; finally, it examines the extent to which new and proposed regulatory changes have learned from these developments in order to strike a satisfactory regulatory balance between issuers and investors. Ultimately, it is argued that the changes to date are modest and stay largely within the confines of existing frameworks, despite the claims that they comprise a fundamental overhaul of the regime. Although some caution is desirable particularly where investor protection concerns arise, the limited nature of these changes means that the reforms to the UK regime may fail to achieve the much-needed revitalisation of the UK IPO

Updating the relationship of the Ne/ERN to task-related behavior: A brief review and suggestions for future research

The error negativity/error-related negativity (Ne/ERN) is one of the most well-studied event-related potential (ERP) components in the electroencephalography (EEG) literature. Peaking about 50 ms after the commission of an error, the Ne/ERN is a negative deflection in the ERP waveform that is thought to reflect error processing in the brain. While its relationships to trait constructs such as anxiety are well-documented, there is still little known about how the Ne/ERN may subsequently influence task-related behavior. In other words, does the occurrence of the Ne/ERN trigger any sort of error corrective process, or any other behavioral adaptation to avoid errors? Several theories have emerged to explain how the Ne/ERN may implement or affect behavior on a task, but evidence supporting each has been mixed. In the following manuscript, we review these theories, and then systematically discuss the reasons that there may be discrepancies in the literature. We review both the inherent biological factors of the neural regions that underlie error-processing in the brain, and some of the researcher-induced factors in analytic and experimental choices that may be exacerbating these discrepancies. We end with a table of recommendations for future researchers who aim to understand the relationship between the Ne/ERN and behavior

GABA receptor associated protein changes the electrostatic environment around the GABA type A receptor.

Funder: Science and Technology Facilities Council; Id: http://dx.doi.org/10.13039/501100000271We have performed fully atomistic molecular dynamics simulations of the intracellular domain of a model of the GABAA receptor with and without the GABA receptor associated protein (GABARAP) bound. We have also calculated the electrostatic potential due to the receptor, in the absence and presence of GABARAP. We find that GABARAP binding changes the electrostatic properties around the GABAA receptor and could lead to increased conductivity of chloride ions through the receptor. We also find that ion motions that would result in conducting currents are observed nearly twice as often when GABARAP binds. These results are consistent with data from electrophysiological experiments

On positivity of Ehrhart polynomials

Ehrhart discovered that the function that counts the number of lattice points in dilations of an integral polytope is a polynomial. We call the coefficients of this polynomial Ehrhart coefficients, and say a polytope is Ehrhart positive if all Ehrhart coefficients are positive (which is not true for all integral polytopes). The main purpose of this article is to survey interesting families of polytopes that are known to be Ehrhart positive and discuss the reasons from which their Ehrhart positivity follows. We also include examples of polytopes that have negative Ehrhart coefficients and polytopes that are conjectured to be Ehrhart positive, as well as pose a few relevant questions.Comment: 40 pages, 7 figures. To appear in in Recent Trends in Algebraic Combinatorics, a volume of the Association for Women in Mathematics Series, Springer International Publishin

Cost-effectiveness of intermittent preventive treatment of malaria in infants (IPTi) for averting anaemia in Gabon: a comparison between intention to treat and according to protocol analyses

ABSTRACT: BACKGROUND: In Gabon, the impact of intermittent preventive treatment of malaria in infants (IPTi) was not statistically significant on malaria reduction, but the impact on moderate anaemia was, with some differences between the intention to treat (ITT) and the according to protocol (ATP) trial analyses. Specifically, ATP was statistically significant, while ITT analysis was borderline. The main reason for the difference between ITT and ATP populations was migration. METHODS: This study estimates the cost-effectiveness of IPTi on the reduction of anaemia in Gabon, comparing results of the ITT and the ATP clinical trial analyses. Threshold analysis was conducted to identify when the intervention costs and protective efficacy of IPTi for the ATP cohort equalled the ITT cost-effectiveness ratio. RESULTS: Based on IPTi intervention costs, the cost per episode of moderate anaemia averted was US$12.88 (CI 95$11.30 (CI 95% 4.56, 26.66) using the ATP analysis. In order for the ATP results to equal the cost-effectiveness of ITT, total ATP intervention costs should rise from US$118.38 to US$134 or the protective efficacy should fall from 27% to 18.1%. The uncertainty surrounding the cost-effectiveness ratio using ITT trial results was higher than using the ATP results. CONCLUSIONS: Migration implies great challenges in the organization of health interventions that require repeat visits in Gabon. This was apparent in the study as the cost-effectiveness of IPTp-SP worsened when drop out from the prevention was taken into account. Despite such challenges, IPTi was both inexpensive and efficacious in averting cases of moderate anaemia in infant

Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukemia

Chromosomal rearrangements are initiating events in acute lymphoblastic leukaemia (ALL). Here using RNA sequencing of 560 ALL cases, we identify rearrangements between MEF2D (myocyte enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL (B-ALL) cases with a distinct gene expression profile, the most common of which is MEF2DBCL9. Examination of an extended cohort of 1,164 B-ALL cases identified 30 cases with MEF2D rearrangements, which include an additional fusion partner, FOXJ2; thus, MEF2D-rearranged cases comprise 5.3% of cases lacking recurring alterations. MEF2D-rearranged ALL is characterized by a distinct immunophenotype, DNA copy number alterations at the rearrangement sites, older diagnosis age and poor outcome. The rearrangements result in enhanced MEF2D transcriptional activity, lymphoid transformation, activation of HDAC9 expression and sensitive to histone deacetylase inhibitor treatment. Thus, MEF2D-rearranged ALL represents a distinct form of high-risk leukaemia, for which new therapeutic approaches should be considered.This work was supported in part by the American Lebanese Syrian Associated Charities of St. Jude Children’s Research Hospital; by a Stand Up to Cancer Innovative Research Grant and St. Baldrick’s Foundation Scholar Award (to C.G.M.); by a St. Baldrick’s Consortium Award (S.P.H.), by a Leukemia and Lymphoma Society Specialized Center of Research grant (S.P.H. and C.G.M.), by a Lady Tata Memorial Trust Award (I.I.), by a Leukemia and Lymphoma Society Special Fellow Award and Alex’s Lemonade Stand Foundation Young Investigator Awards (K.R.), by an Alex’s Lemonade Stand Foundation Award (M.L.) and by National Cancer Institute Grants CA21765 (St Jude Cancer Center Support Grant), U01 CA157937 (C.L.W. and S.P.H.), U24 CA114737 (to Dr Gastier-Foster), NCI Contract HHSN261200800001E (to Dr Gastier-Foster), U10 CA180820 (ECOG-ACRIN Operations) and CA180827 (E.P.); U10 CA180861 (C.D.B. and G.M.); U24 CA196171 (The Alliance NCTN Biorepository and Biospecimen Resource); CA145707 (C.L.W. and C.G.M.); and grants to the COG: U10 CA98543 (Chair’s grant and supplement to support the COG ALL TARGET project), U10 CA98413 (Statistical Center) and U24 CA114766 (Specimen Banking). This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract Number HHSN261200800001E

Deregulation of DUX4 and ERG in acute lymphoblastic leukemia

Chromosomal rearrangements deregulating hematopoietic transcription factors are common in acute lymphoblastic leukemia (ALL).1,2 Here, we show that deregulation of the homeobox transcription factor gene DUX4 and the ETS transcription factor gene ERG are hallmarks of a subtype of B-progenitor ALL that comprises up to 7% of B-ALL. DUX4 rearrangement and overexpression was present in all cases, and was accompanied by transcriptional deregulation of ERG, expression of a novel ERG isoform, ERGalt, and frequent ERG deletion. ERGalt utilizes a non-canonical first exon whose transcription was initiated by DUX4 binding. ERGalt retains the DNA-binding and transactivating domains of ERG, but inhibits wild-type ERG transcriptional activity and is transforming. These results illustrate a unique paradigm of transcription factor deregulation in leukemia, in which DUX4 deregulation results in loss-of-function of ERG, either by deletion or induction of expression of an isoform that is a dominant negative inhibitor of wild type ERG function