Classical and Quantum Equations of Motion for a BTZ Black String in AdS Space

We investigate gravitational collapse of a $(3+1)$-dimensional BTZ black string in AdS space in the context of both classical and quantum mechanics. This is done by first deriving the conserved mass per unit length of the cylindrically symmetric domain wall, which is taken as the classical Hamiltonian of the black string. In the quantum mechanical context, we take primary interest in the behavior of the collapse near the horizon and near the origin (classical singularity) from the point of view of an infalling observer. In the absence of radiation, quantum effects near the horizon do not change the classical conclusions for an infalling observer, meaning that the horizon is not an obstacle for him/her. The most interesting quantum mechanical effect comes in when investigating near the origin. First, quantum effects are able to remove the classical singularity at the origin, since the wave function is non-singular at the origin. Second, the Schr\"odinger equation describing the behavior near the origin displays non-local effects, which depend on the energy density of the domain wall. This is manifest in that derivatives of the wavefunction at one point are related to the value of the wavefunction at some other distant point.Comment: 9 pages, 1 figure. Minor Clarification and corrections. Accepted for Publication in JHE

Social determinants of pertussis and influenza vaccine uptake in pregnancy: a national cohort study in England using electronic health records.

OBJECTIVE: To examine the social determinants of influenza and pertussis vaccine uptake among pregnant women in England. DESIGN: Nationwide population-based cohort study. SETTING: The study used anonymised primary care data from the Clinical Practice Research Datalink and linked Hospital Episode Statistics secondary care data. PARTICIPANTS: Pregnant women eligible for pertussis (2012-2015, n=68 090) or influenza (2010/2011-2015/2016, n=152 132) vaccination in England. MAIN OUTCOME MEASURES: Influenza and pertussis vaccine uptake. RESULTS: Vaccine uptake was 67.3% for pertussis and 39.1% for influenza. Uptake of both vaccines varied by region, with the lowest uptakes in London and the North East. Lower vaccine uptake was associated with greater deprivation: almost 10% lower in the most deprived quintiles compared with the least deprived for influenza (34.5% vs 44.0%), and almost 20% lower for pertussis (57.7% vs 76.0%). Lower uptake for both vaccines was also associated with non-white ethnicity (lowest among women of black ethnicity), maternal age under 20 years and a greater number of children in the household. The associations between all social factors and vaccine uptake were broadly unchanged in fully adjusted models, suggesting the social determinants of uptake were largely independent of one another. Among 3111 women vaccinated against pertussis in their first eligible pregnancy and pregnant again, 1234 (40%) were not vaccinated in their second eligible pregnancy. CONCLUSIONS: Targeting promotional campaigns to pregnant women who are younger, of non-white ethnicity, with more children, living in areas of greater deprivation or the London or North East regions, has potential to reduce vaccine-preventable disease among infants and pregnant women, and to reduce health inequalities. Vaccination promotion needs to be sustained across successive pregnancies. Further research is needed into whether the effectiveness of vaccine promotion strategies may vary according to social factors

Quantum Gravity in 2+1 Dimensions: The Case of a Closed Universe

In three spacetime dimensions, general relativity drastically simplifies, becoming a ``topological'' theory with no propagating local degrees of freedom. Nevertheless, many of the difficult conceptual problems of quantizing gravity are still present. In this review, I summarize the rather large body of work that has gone towards quantizing (2+1)-dimensional vacuum gravity in the setting of a spatially closed universe.Comment: 61 pages, draft of review for Living Reviews; comments, criticisms, additions, missing references welcome; v2: minor changes, added reference

Preclinical Development of an In Vivo BCG Challenge Model for Testing Candidate TB Vaccine Efficacy

There is an urgent need for an immunological correlate of protection against tuberculosis (TB) with which to evaluate candidate TB vaccines in clinical trials. Development of a human challenge model of Mycobacterium tuberculosis (M.tb) could facilitate the detection of such correlate(s). Here we propose a novel in vivo Bacille Calmette-Guérin (BCG) challenge model using BCG immunization as a surrogate for M.tb infection. Culture and quantitative PCR methods have been developed to quantify BCG in the skin, using the mouse ear as a surrogate for human skin. Candidate TB vaccines have been evaluated for their ability to protect against a BCG skin challenge, using this model, and the results indicate that protection against a BCG skin challenge is predictive of BCG vaccine efficacy against aerosol M.tb challenge. Translation of these findings to a human BCG challenge model could enable more rapid assessment and down selection of candidate TB vaccines and ultimately the identification of an immune correlate of protection

Restoration of Hepatic Glucokinase Expression Corrects Hepatic Glucose Flux and Normalizes Plasma Glucose in Zucker Diabetic Fatty Rats

OBJECTIVE—We examined in 20-week-old Zucker diabetic fatty (ZDF) rats whether restoration of hepatic glucokinase (GK) expression would alter hepatic glucose flux and improve hyperglycemia

Acute maternal infection and risk of pre-eclampsia: a population-based case-control study.

BACKGROUND: Infection in pregnancy may be involved in the aetiology of pre-eclampsia. However, a clear association between acute maternal infection and pre-eclampsia has not been established. We assessed whether acute urinary tract infection, respiratory tract infection, and antibiotic drug prescriptions in pregnancy (a likely proxy for maternal infection) are associated with an increased risk of pre-eclampsia. METHODS AND FINDINGS: We used a matched nested case-control design and data from the UK General Practice Research Database to examine the association between maternal infection and pre-eclampsia. Primiparous women aged at least 13 years and registered with a participating practice between January 1987 and October 2007 were eligible for inclusion. We selected all cases of pre-eclampsia and a random sample of primiparous women without pre-eclampsia (controls). Cases (n=1533) were individually matched with up to ten controls (n=14236) on practice and year of delivery. We calculated odds ratios and 95% confidence intervals for pre-eclampsia comparing women exposed and unexposed to infection using multivariable conditional logistic regression. After adjusting for maternal age, pre-gestational hypertension, diabetes, renal disease and multifetal gestation, the odds of pre-eclampsia were increased in women prescribed antibiotic drugs (adjusted odds ratio 1.28;1.14-1.44) and in women with urinary tract infection (adjusted odds ratio 1.22;1.03-1.45). We found no association with maternal respiratory tract infection (adjusted odds ratio 0.91;0.72-1.16). Further adjustment for maternal smoking and pre-pregnancy body mass index made no difference to our findings. CONCLUSIONS: Women who acquire a urinary infection during pregnancy, but not those who have a respiratory infection, are at an increased risk of pre-eclampsia. Maternal antibiotic prescriptions are also associated with an increased risk. Further research is required to elucidate the underlying mechanism of this association and to determine whether, among women who acquire infections in pregnancy, prompt treatment or prophylaxis against infection might reduce the risk of pre-eclampsia

Lack of association between gene polymorphisms of Angiotensin converting enzyme, Nod-like receptor 1, Toll-like receptor 4, FAS/FASL and the presence of Helicobacter pylori-induced premalignant gastric lesions and gastric cancer in Caucasians

<p>Abstract</p> <p>Background</p> <p>Several polymorphisms of genes involved in the immunological recognition of <it>Helicobacter pylori </it>and regulating apoptosis and proliferation have been linked to gastric carcinogenesis, however reported data are partially conflicting. The aim of our study was to evaluate potential associations between the presence of gastric cancer (GC) and high risk atrophic gastritis (HRAG) and polymorphisms of genes encoding <it>Angiotensin converting enzyme </it>(<it>ACE</it>), <it>Nod-like receptor 1 </it>(<it>NOD1</it>), <it>Toll-like receptor 4 </it>(<it>TLR4</it>) and <it>FAS/FASL</it>.</p> <p>Methods</p> <p>Gene polymorphisms were analyzed in 574 subjects (GC: n = 114; HRAG: n = 222, controls: n = 238) of Caucasian origin. <it>ACE I/D </it>(rs4646994), <it>NOD1 796G>A </it>(rs5743336), <it>TLR4 3725G>C </it>(rs11536889), <it>FAS 1377G>A </it>(rs2234767), <it>FAS 670A>G </it>(rs1800682) and <it>FASL 844T>C </it>(rs763110) were genotyped by different PCR approaches and restriction fragment length polymorphism analysis.</p> <p>Results</p> <p>Frequencies of genotypes in our study are similar to the data reported on subjects of Caucasian ethnicity. There was a tendency for <it>NOD1 796G/G </it>genotype to be associated with increased risk of HRAG (62.4% <it>vs</it>. 54.5% in controls, <it>p </it>= 0.082). <it>FAS 670G/G </it>genotype was more frequent in HRAG when compared to controls, 23.9% and 17.2% respectively, however it failed to reach significance level (<it>p </it>= 0.077). We did not find any significant associations for all polymorphisms in relation to GC or HRAG. <it>NOD1 796G>A </it>and <it>TLR4 3725G>C </it>gene polymorphisms were also not associated with <it>Helicobacter pylori </it>infection.</p> <p>Conclusions</p> <p><it>ACE, NOD1, TRL4 </it>and <it>FAS/FASL </it>gene polymorphisms are not linked with gastric carcinogenesis in Caucasians, and therefore they should not be considered as potential biomarkers for identifying individuals with higher risk for GC.</p

Entropy-driven liquid-liquid separation in supercooled water

Twenty years ago Poole et al. (Nature 360, 324, 1992) suggested that the anomalous properties of supercooled water may be caused by a critical point that terminates a line of liquid-liquid separation of lower-density and higher-density water. Here we present an explicit thermodynamic model based on this hypothesis, which describes all available experimental data for supercooled water with better quality and with fewer adjustable parameters than any other model suggested so far. Liquid water at low temperatures is viewed as an 'athermal solution' of two molecular structures with different entropies and densities. Alternatively to popular models for water, in which the liquid-liquid separation is driven by energy, the phase separation in the athermal two-state water is driven by entropy upon increasing the pressure, while the critical temperature is defined by the 'reaction' equilibrium constant. In particular, the model predicts the location of density maxima at the locus of a near-constant fraction (about 0.12) of the lower-density structure.Comment: 7 pages, 6 figures. Version 2 contains an additional supplement with tables for the mean-field equatio

A Novel, Non-Apoptotic Role for Scythe/BAT3: A Functional Switch between the Pro- and Anti-Proliferative Roles of p21 during the Cell Cycle

BACKGROUND: Scythe/BAT3 is a member of the BAG protein family whose role in apoptosis has been extensively studied. However, since the developmental defects observed in Bat3-null mouse embryos cannot be explained solely by defects in apoptosis, we investigated whether BAT3 is also involved in cell-cycle progression. METHODS/PRINCIPAL FINDINGS: Using a stable-inducible Bat3-knockdown cellular system, we demonstrated that reduced BAT3 protein level causes a delay in both G1/S transition and G2/M progression. Concurrent with these changes in cell-cycle progression, we observed a reduction in the turnover and phosphorylation of the CDK inhibitor p21, which is best known as an inhibitor of DNA replication; however, phosphorylated p21 has also been shown to promote G2/M progression. Our findings indicate that in Bat3-knockdown cells, p21 continues to be synthesized during cell-cycle phases that do not normally require p21, resulting in p21 protein accumulation and a subsequent delay in cell-cycle progression. Finally, we showed that BAT3 co-localizes with p21 during the cell cycle and is required for the translocation of p21 from the cytoplasm to the nucleus during the G1/S transition and G2/M progression. CONCLUSION: Our study reveals a novel, non-apoptotic role for BAT3 in cell-cycle regulation. By maintaining a low p21 protein level during the G1/S transition, BAT3 counteracts the inhibitory effect of p21 on DNA replication and thus enables the cells to progress from G1 to S phase. Conversely, during G2/M progression, BAT3 facilitates p21 phosphorylation by cyclin A/Cdk2, an event required for G2/M progression. BAT3 modulates these pro- and anti-proliferative roles of p21 at least in part by regulating cyclin A abundance, as well as p21 translocation between the cytoplasm and the nucleus to ensure that it functions in the appropriate intracellular compartment during each phase of the cell cycle.Dissertatio

Persistence of immune responses after heterologous and homologous third COVID-19 vaccine dose schedules in the UK: eight-month analyses of the COV-BOOST trial

Background: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose in June 2021. Monovalent messenger RNA (mRNA) COVID-19 vaccines were subsequently widely used for the third and fourth-dose vaccination campaigns in high-income countries. Real-world vaccine effectiveness against symptomatic infections following third doses declined during the Omicron wave. This report compares the immunogenicity and kinetics of responses to third doses of vaccines from day (D) 28 to D242 following third doses in seven study arms. Methods: The trial initially included ten experimental vaccine arms (seven full-dose, three half-dose) delivered at three groups of six sites. Participants in each site group were randomised to three or four experimental vaccines, or MenACWY control. The trial was stratified such that half of participants had previously received two primary doses of ChAdOx1 nCov-19 (Oxford–AstraZeneca; hereafter referred to as ChAd) and half had received two doses of BNT162b2 (Pfizer–BioNtech, hereafter referred to as BNT). The D242 follow-up was done in seven arms (five full-dose, two half-dose). The BNT vaccine was used as the reference as it was the most commonly deployed third-dose vaccine in clinical practice in high-income countries. The primary analysis was conducted using all randomised and baseline seronegative participants who were SARS-CoV-2 naïve during the study and who had not received a further COVID-19 vaccine for any reason since third dose randomisation. Results: Among the 817 participants included in this report, the median age was 72 years (IQR: 55–78) with 50.7% being female. The decay rates of anti-spike IgG between vaccines are different among both populations who received initial doses of ChAd/ChAd and BNT/BNT. In the population that previously received ChAd/ChAd, mRNA vaccines had the highest titre at D242 following their vaccine dose although Ad26. COV2. S (Janssen; hereafter referred to as Ad26) showed slower decay. For people who received BNT/BNT as their initial doses, a slower decay was also seen in the Ad26 and ChAd arms. The anti-spike IgG became significantly higher in the Ad26 arm compared to the BNT arm as early as 3 months following vaccination. Similar decay rates were seen between BNT and half-BNT; the geometric mean ratios ranged from 0.76 to 0.94 at different time points. The difference in decay rates between vaccines was similar for wild-type live virus-neutralising antibodies and that seen for anti-spike IgG. For cellular responses, the persistence was similar between study arms. Conclusions: Heterologous third doses with viral vector vaccines following two doses of mRNA achieve more durable humoral responses compared with three doses of mRNA vaccines. Lower doses of mRNA vaccines could be considered for future booster campaigns