The role of the A C395 IFNGR1 mutation in determining susceptibility to intracellular infection in Malta

Background: The first human mycobacterial susceptibility gene was identified amongst four children on the island of Malta in 1995. All affected children were homozygous for a nonsense mutation at position 395 of the interferon gamma receptor 1 (IFNGR1) gene, and all but one died of overwhelming mycobacterial infection. The population of Malta has high rates of infection with intracellular pathogens; leishmania, brucellosis and tuberculosis are all endemic, while leprosy, which was previously endemic, has only recently been eradicated. We hypothesised that heterozygous carriers of the IFNGR1 gene mutation, while resistant to infection with poorly pathogenic organisms, may have increased susceptibility to infection with more virulent pathogens. Methodology and Result: Screening patients with a past history of intracellular infection and healthy newborns for the presence of the IFNGR1 A->C395 mutation, using sequence specific primer PCR, did not identify any carriers of the mutation. Conclusion: These results suggest that the IFNGR1 mutation is unlikely to be of public health significance on Malta.peer-reviewe

Mapping and Functional Role of Phosphorylation Sites in the Thyroid Transcription Factor-1 (TTF-1)

The phosphorylation of thyroid transcription factor-1 (TTF-1), a homeodomain-containing transcription factor that is required for thyroid-specific expression of the thyroglobulin and thyroperoxidase gene promoters, has been studied. Phosphorylation occurs on a maximum of seven serine residues that are distributed in three tryptic peptides. Mutant derivatives of TTF-1, with alanine residues replacing the serines in the phosphorylation sites, have been constructed and used to assess the functional relevance of TTF-1 phosphorylation. The DNA binding activity of TTF-1 appears to be phosphorylation-independent, as indicated also by the performance of TTF-1 purified from an overexpressing Escherichia coli strain. Transcriptional activation by TTF-1 could require phosphorylation only in specific cell types since in a co-transfection assay in heterologous cells both wild-type and mutant proteins show a similar transcriptional activity

Study on Council Directive 92/83/EEC on the structures of excise duty on alcohol and alcoholic beverages. Final Report Volume 1 – Main Text June

The purpose of this Study is to contribute to the Impact Assessment of a possible revision of Council Directive 1992/83/EEC on the harmonisation of the structure of excise duty on alcohol and alcoholic beverages. The Study includes a baseline assessment of a series of issues emerged from the previous evaluation of the Directive and analyses how these problems may evolve if no EU action is taken. Secondly, the Study formulates a set of possible policy options to address these problems, assesses their likely impacts (legal certainty, market functioning, administrative costs, tax revenues, alcohol control policies, fraud etc.), and compares the outcome with the baseline situation. The main issues analysed in this Study includes: the uncertainties in the excise duty classification of certain new ‘borderline’ products; the functioning of Article 27 concerning the exemptions extended to denatured alcohol; the reduced rates applicable to low-strength alcoholic beverages and to small producers; the exemption for private production and home consumption; and the disparities of methods for measuring the Plato degree of sweetened and flavoured beer. The underlying evidence is based on the triangulation of in-depth interviews with stakeholders from the Member States, the results of an open public consultation online, a quantitative analysis of the market, and the review of other literature and documentary sources

Exploring the baseline knowledge and experience of healthcare professionals in the United Kingdom on Novel Psychoactive Substances

Submitted 28 january 2020. Reviwers' comments received 11 February 2020. Accepted 26 February 2020. Published 2 March 2020.Objective: This survey aimed to explore knowledge and experience on novel psychoactive substances (NPS) of healthcare professionals (HCPs). The study also aimed to assess how HCPs would like to improve their knowledge of NPS. Methods: Seventy paper questionnaires were disseminated in 2017 within continuing education events to pharmacists, nurses and general practitioners (GPs). Additionally, 127 online surveys were completed using the Qualtrics platform by other HCPs and mental health nurses in six United Kingdom (UK) independent mental health hospitals long-stay in-patient rehabilitation services. Two educational sessions involving pharmacists and GPs were also held in late 2017 and mid-2018. Knowledge of NPS by HCPs was evaluated prior to the start of the educational events. Evaluation forms were handed out post-sessions to garner feedback, especially on areas for improvement for future sessions. Statistical analysis of data was undertaken using SPSS (V.25). Results: Most HCPs reported only 'basic' to 'intermediate' NPS knowledge. Substance misuse service staff felt more informed, were more often consulted and had greater confidence regarding NPS compared to hospital and primary care professionals. A negative association was found between the age of the HCP and knowledge of NPS. Most participants expressed a need for regular training and updates as insufficient NPS-related information is currently received. Conclusions: An improvement within the self-reported knowledge of HCPs on NPS is evident in comparison to previous studies. Continued education of HCPs on NPS is fundamental for the provision of improved harm reduction services, which can enhance overall care for NPS service users.Peer reviewedFinal Published versio

Environmental surveillance and spatio-temporal analysis of Legionella spp. In a region of northeastern Italy (2002\u20132017)

Legionella spp. are considered an important cause of potentially preventable morbidity and mortality, making environmental surveillance a crucial component of risk assessment plans. In this work, 20,319 water samples were collected in 3,983 environmental surveys during a 16-year period by ARPA, the Regional Agency for Environmental Protection, Friuli Venezia Giulia, and the results were studied to better understand the diffusion mechanisms of Legionella. The data showed a strong seasonal signal, a prevalence of L. pneumophila serogroup 2-15 in most environments (63% of positive samples), a prevalence of L. pneumophila serogroup 1 in swimming pool-associated environments (82% of positive samples), a persistent presence of Legionella in hospitals and a recurrent presence of Legionella in other facilities such as hotels, possibly years after interventions, highlighting the difficulty of eradicating the bacteria. Retrospective spatio-temporal analyses on geocoded historical data were carried out with SaTScan using an ordinal model with risk as a covariate to identify potential clusters with an excess of cases in the higher-risk categories. Although no outbreaks occurred during the period of study, such analyses identified spatially restricted zones with unusual contamination, which sometimes were also areas in which several surveys triggered by notifications of clinical cases were performed. Simulations of periodic prospective analyses permitted the assessment of the efficacy of the method in early detection of such clusters. The proposed method may be a useful tool in environmental surveillance, prevention and control of Legionella

Consistent perturbations in an imperfect fluid

We present a new prescription for analysing cosmological perturbations in a more-general class of scalar-field dark-energy models where the energy-momentum tensor has an imperfect-fluid form. This class includes Brans-Dicke models, f(R) gravity, theories with kinetic gravity braiding and generalised galileons. We employ the intuitive language of fluids, allowing us to explicitly maintain a dependence on physical and potentially measurable properties. We demonstrate that hydrodynamics is not always a valid description for describing cosmological perturbations in general scalar-field theories and present a consistent alternative that nonetheless utilises the fluid language. We apply this approach explicitly to a worked example: k-essence non-minimally coupled to gravity. This is the simplest case which captures the essential new features of these imperfect-fluid models. We demonstrate the generic existence of a new scale separating regimes where the fluid is perfect and imperfect. We obtain the equations for the evolution of dark-energy density perturbations in both these regimes. The model also features two other known scales: the Compton scale related to the breaking of shift symmetry and the Jeans scale which we show is determined by the speed of propagation of small scalar-field perturbations, i.e. causality, as opposed to the frequently used definition of the ratio of the pressure and energy-density perturbations.Comment: 40 pages plus appendices. v2 reflects version accepted for publication in JCAP (new summary of notation, extra commentary on choice of gauge and frame, extra references to literature

Defining the Value of Injection Current and Effective Electrical Contact Area for EGaIn-Based Molecular Tunneling Junctions

Analysis of rates of tunneling across self-assembled monolayers (SAMs) of n-alkanethiolates SCn (with n = number of carbon atoms) incorporated in junctions having structure AgTS-SAM//Ga2O3/EGaIn leads to a value for the injection tunnel current density J0 (i.e., the current flowing through an ideal junction with n = 0) of 103.6±0.3 A·cm–2 (V = +0.5 V). This estimation of J0 does not involve an extrapolation in length, because it was possible to measure current densities across SAMs over the range of lengths n = 1–18. This value of J0 is estimated under the assumption that values of the geometrical contact area equal the values of the effective electrical contact area. Detailed experimental analysis, however, indicates that the roughness of the Ga2O3 layer, and that of the AgTS-SAM, determine values of the effective electrical contact area that are 10–4 the corresponding values of the geometrical contact area. Conversion of the values of geometrical contact area into the corresponding values of effective electrical contact area results in J0(+0.5 V) = 107.6±0.8 A·cm–2, which is compatible with values reported for junctions using top-electrodes of evaporated Au, and graphene, and also comparable with values of J0 estimated from tunneling through single molecules. For these EGaIn-based junctions, the value of the tunneling decay factor β (β = 0.75 ± 0.02 Å–1; β = 0.92 ± 0.02 nC–1) falls within the consensus range across different types of junctions (β = 0.73–0.89 Å–1; β = 0.9–1.1 nC–1). A comparison of the characteristics of conical Ga2O3/EGaIn tips with the characteristics of other top-electrodes suggests that the EGaIn-based electrodes provide a particularly attractive technology for physical-organic studies of charge transport across SAMs.Chemistry and Chemical Biolog

Generic f(R) theories and classicality of their scalarons

We study quantum stability bound on the mass of scalaron in generic theories of $f(R)$ gravity. We show that in these scenarios, the scalaron mass increases faster with local density of the environment than one loop quantum correction to it thereby leading to violation of quantum bound on the chameleon mass. The introduction of quadratic curvature corrections in the action are shown to stabilize the model.Comment: 7 pages, no figures, typos corrected, to match with the PLB published versio

Government policy and healthcare management: proposal of a shared decision-making model

As a consequence of the current economic crisis many changes have been introduced to health systems on national levels to reduce expenditure and to introduce more cost-effective methods. Then recent developments in medical technology have led to a shift in the traditional framework of physician-patient responsibility in health care decision making. In this context, the health community urges, in any case, decision makers to ensure that all changes introduced are in accordance with Health System Values. This paper presents a new decision making platform, as a tool to facilitate shared decision making, to improve the quality and transparency of tactical and strategic decisions. This new application, based on analytic quantitative method, is a component of a wider distribute web system under development, which aims to inform the new effective health technologies supporting designers in the user need elicitation and early stage health technology assessments. A case study aiming to elicit the user needs affecting the decision of whether to adopt a new magnetic resonance imaging (MRI) is also presented

Physical non-equivalence of the Jordan and Einstein frames

We show, considering a specific f(R)-gravity model, that the Jordan frame and the Einstein frame are physically non-equivalent, although they are connected by a conformal transformation which yields a mathematical equivalence. Since all the calculations are performed analytically, this non-equivalence is shown in an unambiguous way.Comment: 7 pages, 3 figure