NIHAO project II: Halo shape, phase-space density and velocity distribution of dark matter in galaxy formation simulations

We use the NIHAO (Numerical Investigation of Hundred Astrophysical Objects) cosmological simulations to study the effects of galaxy formation on key properties of dark matter (DM) haloes. NIHAO consists of $\simeq 90$ high-resolution SPH simulations that include (metal-line) cooling, star formation, and feedback from massive stars and SuperNovae, and cover a wide stellar and halo mass range: $10^6 < M_* / M_{\odot} < 10^{11}$ ( $10^{9.5} < M_{\rm halo} / M_{\odot} < 10^{12.5}$). When compared to DM-only simulations, the NIHAO haloes have similar shapes at the virial radius, R_{\rm vir}, but are substantially rounder inside $\simeq 0.1R_{\rm vir}$. In NIHAO simulations $c/a$ increases with halo mass and integrated star formation efficiency, reaching $\sim 0.8$ at the Milky Way mass (compared to 0.5 in DM-only), providing a plausible solution to the long-standing conflict between observations and DM-only simulations. The radial profile of the phase-space $Q$ parameter ($\rho/\sigma^3$) is best fit with a single power law in DM-only simulations, but shows a flattening within $\simeq 0.1R_{\rm vir}$ for NIHAO for total masses $M>10^{11} M_{\odot}$. Finally, the global velocity distribution of DM is similar in both DM-only and NIHAO simulations, but in the solar neighborhood, NIHAO galaxies deviate substantially from Maxwellian. The distribution is more symmetric, roughly Gaussian, with a peak that shifts to higher velocities for Milky Way mass haloes. We provide the distribution parameters which can be used for predictions for direct DM detection experiments. Our results underline the ability of the galaxy formation processes to modify the properties of dark matter haloes.Comment: 19 pages, 17 figures, analysis strongly improved, main conclusions unchanged, accepted for publication in MNRA

Protective Effects of Melatonin on the Skin: Future Perspectives

When exposed to hostile environments such as radiation, physical injuries, chemicals, pollution, and microorganisms, the skin requires protective chemical molecules and pathways. Melatonin, a highly conserved ancient molecule, plays a crucial role in the maintenance of skin. As human skin has functional melatonin receptors and also acts as a complete system that is capable of producing and regulating melatonin synthesis, melatonin is a promising candidate for its maintenance and protection. Below, we review the studies of new metabolic pathways involved in the protective functions of melatonin in dermal cells. We also discuss the advantages of the topical use of melatonin for therapeutic purposes and skin protection. In our view, endogenous intracutaneous melatonin production, together with topically-applied exogenous melatonin and its metabolites, represent two of the most potent defense systems against external damage to the skin.Part of this review was co-funded by the Spanish Ministry of the Economy and Competitiveness, the FEDER Regional Development Fund (nos. SAF2013-49019 and SAF2017-85903), the Charles III Institute (no. CB/10/00238), and the Economy, Innovation, Science and Employment Council of the Junta de Andalucía (CTS-101). JF and LM are FPU (Professional University formation) Fellows of the Spanish Ministry of Education, Culture and Sport

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose

Consumption Risk Sharing over the Business Cycle: The Role of Small Firms' Access to Credit Markets

Consumption risk sharing among U.S. states increases in booms and decreases in recessions. These business cycle fluctuations in interstate risk sharing are driven mainly by states in which small businesses account for a large share of income or employment. State-level banking deregulation during the 1980s loosened the dependence of interstate risk sharing on the business cycle, mainly through its impact on states with many small firms. Our results establish a major benefit from bank deregulation: small firms' access to credit and, with it, interstate risk sharing have improved mainly when it is most urgently needed: in nationwide economic downturns. © 2011 The President and Fellows of Harvard College and the Massachusetts Institute of Technology.

Experience of GIS Technology Application in the Surveillance of Tick-Borne Infections

ObjectiveThe main aim of this work is to estimate the projected risks based on the incidence rate of natural foci infections and to expand the list of criteria for the characterization of natural foci of tick-borne infections.IntroductionThe epidemiological situation of natural foci of tick-borne infections (TBI) in Ukraine, as well as globally, is characterized by significant activation of processes due to global climate change, growing human-induced factor and shortcomings in the organization and running of epidemiological surveillance [1]. For the Western region of Ukraine, among all tick-borne zoonoses the most important are tick-borne viral encephalitis (TBVE), Lyme disease (LD), human granulocytic anaplasmosis (HGA) and some others [2-4]. Taking into account the increased incidence rate for these infections, we have developed baseline criteria (indicators of natural contamination of the main carriers and levels of the serum layer among the population in relation to the TBI pathogens in the endemic areas) to identify areas with different risk of contamination through GIS-technologies [5].MethodsEpi Info 7.1.1.14 software was used to analyze patient questionnaires with tick-borne infections (TBI) for 2010-2015. Prevalence maps of vector-borne infections were created by means of GIS technology using the QGIS 2.0.1. software to assess the risks of infection. Maps demonstrating the distribution of TBVE, LD and HGA were also developed based on contamination risk assessment criteria.ResultsRetrospective epidemiological analysis of incidence rates for TBVE, LD and HGA was conducted based on laboratory tests that were performed in the laboratory of vector-borne viral infections of the State Institution Lviv Research Institute of Epidemiology and Hygiene of the Ministry of Health of Ukraine. A direct correlation between the infection of I. ricinus, B. burgdorferi and LB (P &lt;0.05) and infections of I. ricinus ticks, anaplasma and incidence of HGA (P &lt;0.05) was established. However, this connection has not been confirmed for indicators with TBE.Data was obtained during the assessment of possible risks of tick-borne infections. For TBVE, the indicator of predicted risks based on the basic criteria was 60.3%, taking into account the cases of the disease. This was based on indicators of natural infection of the main carriers and the level of the serum layer among the population on the TBI activators in the endemic areas. The data obtained can be explained by the low level of morbidity and the detection of TBVE cases. The predicted risk for LD according to these criteria is 88.9%, due to the high level of clinical and laboratory diagnosis.As for the HGA, the predicted risk indicator reaches 66.7% due to the fact that the study of human anaplasmosis in Ukraine is at the initial level (the incidence rate and incidence are not included in the official reporting system).Taking into account the results obtained, it is advisable to supplement the list of criteria for determining the degree of activity of natural foci of tick-borne infections and the identification of areas with high risk of morbidity. These calculations were made by grouping statistical data (indicators) [5]. The reliability of the difference between the same indicators for individual zones was 95% (Table 1).ConclusionsTick-borne zoonoses are a serious problem for the public health system of the Western region of Ukraine. Extending the list of criteria for the characterization of natural foci of tick-borne infections will improve epidemiological surveillance and focus on key measures in high and medium-risk areas for the rational use of funds.References1. Nordberg M. Tick-Borne Infections in Humans. Aspects of immunopathogenesis, diagnosis and co-infections with Borrelia burgdorferi and Anaplasma phagocytophilum. Linköping University Medical Dissertations No.1315. Linköping, Sweden 2012.2. Morochkovsky R. Clinical characteristic of tick-borne encephalitis in Volhynia and optimization of treatment. Ternopil State Medical Academy I. Gorbachevsky Dissertations. Ternopil, Ukraine 2003.3. Zinchuk O. Lime borreliosis: Clinical and immunopathogenetic features and emergency preventive treatment. Lviv National Medical University D. Galitsky Dissertations. Lviv, Ukraine 2010.4. Ben I., Biletska H. Epidemiologic aspects of human granulocytic anaplasmosis in the Western region of Ukraine. Lik Sprava. 2015 Oct-Dec;(7-8).5. Ben I., Lozynsky I. Application of GIS-technologies for risk assessment of areas with tick-borne infections. Materials of the Regional Scientific Symposium within the framework of the concept of "Unified Health" and a review and Selection of scientific works with the support of CCDD in Ukraine. 2017 April 24-28, Kyiv

Exploring factors influencing US millennial consumers' use of tap-and-go payment technology

Although mobile payment (MP) represents a possibility for traditional brick-and-mortar US retailers to enhance the quality of customer service, mobile payment adoption in the US has lagged, with research regarding this phenomenon in the US seemingly in its embryonic stage. The current study contributes to the literature on mobile payment adoption in the US by investigating the factors on US millennial consumers' use of mobile payment technology, operationalized in the study as tap-and-go payment systems. The study mirrors a study of the acceptance of mobile shopping technology among German consumers, with some extension. The study incorporated mobile payment risk perception, system trust, and socio-cultural influence into an extended technology acceptance model (TAM) to explore this issue. Results from a survey conducted among 357 US Millennials indicate that perceived ease of use of MP (PEOUMP); perceived usefulness (PUMP); and risk perception all influence attitude toward mobile payment (AttMP). System trust, socio-cultural influence, and AttMP all influence MP use intention. The paper discussed the limitations of the study and future research directions. - 2019, - 2019 Informa UK Limited, trading as Taylor & Francis Group.Scopu