The Proposed OECD Multilateral Instrument Amending Tax Treaties

In this article, the authors consider some of the practical issues relating to the introduction of the OECD multilateral instrument amending tax treaties, which has been proposed within the context of the OECD/G20 Base Erosion and Profit Shifting Project

COVID-19 and its consequences on mental health (Review).

As one year is approaching since the beginning of the Coronavirus disease 2019 (COVID-19) pandemic, it is important to acknowledge the detrimental effect that it is having on mental health at the individual, societal and public health levels. The current review presents the direct and indirect psychological impact of COVID-19 on the general public, as well as on vulnerable groups, including the elderly, the young, healthcare professionals, people with pre-existing mental health issues, those infected by COVID-19, homeless people and refugees. Important findings are discussed in the present review, including the social stigma in older people associated with portraying COVID-19 as the disease of the elderly, and the limited psychological impact of COVID-19 in the severely mentally ill, alongside the response of the mental healthcare systems globally to this unparalleled public health crisis. The important lessons to be learnt so far can help formulate individual mental health recommendations, as well as improved intervention and prevention public health strategies

Some Reflections on the Proposed Revisions to the OECD Model and Commentaries, and on the Multilateral Instrument, with Respect to Fiscally Transparent Entities

This material was first published by Sweet & Maxwell Limited in Angelo Nikolakakis, Stephane Austry, John Avery Jones, Philip Baker, Peter Blessing, Robert Danon, Shefali Goradia, Johann Hattingh, Koichi Inoue, Juergen Luedicke, Guglielmo Maisto, Toshio Miyatake, Kees van Raad, Richard Vann and Bertil Wiman, “Some Reflections on the Proposed Revisions to the OECD Model and Commentaries, and on the Multilateral Instrument, With Respect to Fiscally Transparent Entities”, British Tax Review, Vol. 2017, No. 3, pp. 295-373, 2017 and is reproduced by agreement with the Publishers. This article sets out some reflections of the authors on those aspects of the OECD’s October 2015 final report on Neutralising the Effects of Hybrid Mismatch Arrangements (the Hybrids Report) that relate to revisions to the OECD Model to add a specific provision on fiscally transparent entities (as a new Article 1(2)), and to build on the Commentaries already in place in this regard (the HR Proposals). It also considers the similar and related provisions contained in the multilateral instrument to implement the tax treaty related BEPS measures (the MLI) that was released on 24 November 2016. The authors conduct an extensive review of the issues and raise a number of interpretive and technical questions, as well as policy considerations. This review is set against the backdrop of an examination of similar provisions (or provisions with similar purposes) in the US Models and in various existing bilateral treaties, as well as under domestic laws, of the countries represented by the authors. The authors also provide some observations with respect to potential scope and drafting or implementation of alternatives, with a view to contributing to the ongoing international debate and reform project

A barrier to homologous recombination between sympatric strains of the cooperative soil bacterium Myxococcus xanthus

The bacterium Myxococcus xanthus glides through soil in search of prey microbes, but when food sources run out, cells cooperatively construct and sporulate within multicellular fruiting bodies. M. xanthus strains isolated from a 16 × 16-cm-scale patch of soil were previously shown to have diversified into many distinct compatibility types that are distinguished by the failure of swarming colonies to merge upon encounter. We sequenced the genomes of 22 isolates from this population belonging to the two most frequently occurring multilocus sequence type (MLST) clades to trace patterns of incipient genomic divergence, specifically related to social divergence. Although homologous recombination occurs frequently within the two MLST clades, we find an almost complete absence of recombination events between them. As the two clades are very closely related and live in sympatry, either ecological or genetic barriers must reduce genetic exchange between them. We find that the rate of change in the accessory genome is greater than the rate of amino-acid substitution in the core genome. We identify a large genomic tract that consistently differs between isolates that do not freely merge and therefore is a candidate region for harbouring gene(s) responsible for self/non-self discrimination

Frequent COL4 mutations in familial microhematuria accompanied by later-onset Alport nephropathy due to focal segmental glomerulosclerosis

Familial microscopic hematuria (FMH) is associated with a genetically heterogeneous group of conditions including the collagen-IV nephropathies, the heritable C3/CFHR5 nephropathy and the glomerulopathy with fibronectin deposits. The clinical course varies widely, ranging from isolated benign familial hematuria to end-stage renal disease (ESRD) later in life. We investigated 24 families using Next Generation Sequencing (NGS) for five genes: COL4A3, COL4A4, COL4A5, CFHR5 and FN1. In 17 families (71%), we found 15 pathogenic mutations in COL4A3/A4/A5, nine of them novel. In five families patients inherited classical AS with hemizygous X-linked COL4A5 mutations. Even more patients developed later-onset Alport-related nephropathy having inherited heterozygous COL4A3/A4 mutations that cause thin basement membranes. Amongst 62 heterozygous or hemizygous patients, eight (13%) reached ESRD, while 25% of patients with heterozygous COL4A3/A4 mutations, aged >50-yrs, reached ESRD. In conclusion, COL4A mutations comprise a frequent cause of FMH. Heterozygous COL4A3/A4 mutations predispose to renal function impairment, supporting that thin basement membrane nephropathy is not always benign. The molecular diagnosis is essential for differentiating the X-linked from the autosomal recessive and dominant inheritance. Finally, NGS technology is established as the gold standard for the diagnosis of FMH and associated collagen-IV glomerulopathies, frequently averting the need for invasive renal biopsies

Association between happiness and psychopathology in an elderly regional rural population in Crete

Research has shown that socio-demographic profile and psychopathology symptoms are related to levels of happiness in old age. The aims of this cross-sectional study were: 1) to investigate the effect of recent stressful life events and socio-demographic factors on psychopathological symptoms in elderly residents in mountain regions of Crete, Greece and 2) to explore the mechanism which underlies the relationship between socio-demographic factors and psychopathological symptoms, with levels of happiness in old age. To this end, we used the nine psychopathology dimensions of symptoms as defined in the Symptom Checklist-90-R (SCL-90), while the Holmes and Rahe stress inventory was administered to quantify the stressful life events. A sample of 205 elderly men and women (age=77.1±6.7 years) living in 10 remote rural and isolated villages participated in this study. Data was collected through questionnaires completed upon individual meetings with each participant, with the interviewer's assistance. Each questionnaire included the two aforesaid scales alongside questions on individual socio-demographic characteristics. Analysis of variance was applied to detect socio-demographic factors that have a significant effect on specific psychopathological symptoms. Then, path analysis was applied to quantify the direct and indirect effect of the selected socio-demographic factors on happiness levels. Stressful life events were found to have no statistically significant effect on the presence of specific symptoms (somatization, psychoticism, anxiety) in elderly adults. Furthermore, certain socio-demographic factors (marital status, smoking, family income and social activity) were found to influence happiness, which varied according to the level of psycho-emotional tension. The results suggest that somatization, psychoticism, and phobic anxiety symptoms are psychic reactions independent of recent stressful life events. Our study,despite its regional character, may contribute in the development of appropriate clinical assessment tools and interventions, helping primary care practitioners to approach elderly people living in remote villages in a more appropriate and holistic manner, improving thereby the effectiveness of their interventions

Co-Spray Drying of Paracetamol and Propyphenazone with Polymeric Binders for Enabling Compaction and Stability Improvement in a Combination Tablet

Paracetamol (PCT) and propyphenazone (PRP) are analgesic drugs that are often combined in a single dosage form for enhanced pharmacological action. In this work, PCT and PRP were co-spray dried separately with hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC) using drug suspensions in polymer solutions as feed liquids. It was thought that because of polymer adherence to the surface of drug particles, the risk of PCT–PRP contact and interaction could be reduced. Such interaction may be caused by localized temperature gradients due to frictional forces during tableting, or during storage under harsh conditions. A worst-case scenario would be eutectic formation due to variations in powder mixture homogeneity since eutectic and therapeutic mass PCT/PRP ratios are close (65:35 and 60:40, respectively) and eutectic temperature is low (~56 °C). Uniform particle size, round shape, compaction improvement and faster release of the analgesics were important additional benefits of co-spray drying. Experimental design was first applied for each drug to optimize the polymer concentration on the yield of spray drying and melting point separation (Δmp) of heated binary mixtures of co-spray dried PCT/neat PRP, and vice versa, with the two drugs always included at their therapeutic 60:40 ratio. Optimal combinations with largest Δmp and production yield were: co-spray dried PCT (15% HPC) with neat PRP and co-spray dried PRP (10% HPMC) with neat PCT. Compression studies of these combinations showed tableting improvement due to the polymers, as reflected in greater work of compaction and solid fraction, greater fracture toughness and tablet strength, easier tablet detachment from the punch surface and ejectability. Faster release of both drugs was obtained from the tablet of co-spray dried PCT (15% HPC) with neat PRP. A one-month stability test (75% RH/40 °C) showed moisture-induced alteration tablet strength

Delivery of CdiA nuclease toxins into target cells during contact-dependent growth inhibition.

Bacterial contact-dependent growth inhibition (CDI) is mediated by the CdiB/CdiA family of two-partner secretion proteins. CDI systems deploy a variety of distinct toxins, which are contained within the polymorphic C-terminal region (CdiA-CT) of CdiA proteins. Several CdiA-CTs are nucleases, suggesting that the toxins are transported into the target cell cytoplasm to interact with their substrates. To analyze CdiA transfer to target bacteria, we used the CDI system of uropathogenic Escherichia coli 536 (UPEC536) as a model. Antibodies recognizing the amino- and carboxyl-termini of CdiA(UPEC536) were used to visualize transfer of CdiA from CDI(UPEC536+) inhibitor cells to target cells using fluorescence microscopy. The results indicate that the entire CdiA(UPEC536) protein is deposited onto the surface of target bacteria. CdiA(UPEC536) transfer to bamA101 mutants is reduced, consistent with low expression of the CDI receptor BamA on these cells. Notably, our results indicate that the C-terminal CdiA-CT toxin region of CdiA(UPEC536) is translocated into target cells, but the N-terminal region remains at the cell surface based on protease sensitivity. These results suggest that the CdiA-CT toxin domain is cleaved from CdiA(UPEC536) prior to translocation. Delivery of a heterologous Dickeya dadantii CdiA-CT toxin, which has DNase activity, was also visualized. Following incubation with CDI(+) inhibitor cells targets became anucleate, showing that the D.dadantii CdiA-CT was delivered intracellularly. Together, these results demonstrate that diverse CDI toxins are efficiently translocated across target cell envelopes