CP asymmetries in B0 decays in the left-right model

We study time dependent CP asymmetries in B^0_{d,s} decays in the left-right model with spontaneous breakdown of CP. Due to the new contributions to B^0-\bar B^0 mixing the CP asymmetries can be substantially modified. Moreover, there can be significant new contributions to the $B$-meson decay amplitudes from the magnetic penguins. Most promising for detection of the new physics in the planned $B$ factories is that the CP asymmetries in the decays B--> J/\psi K_S and B--> \phi K_S which are supposed to be equal in the standard model can differ significantly in this class of models independently of the results in the measurements of B--> X_s \gamma.Comment: Revised version, to appear in PR

Lattice Matrix Elements and CP Violation in B and K Physics: Status and Outlook

Status of lattice calculations of hadron matrix elements along with CP violation in B and in K systems is reviewed. Lattice has provided useful input which, in conjunction with experimenatl data, leads to the conclusion that CP-odd phase in the CKM matrix plays the dominant role in the observed asymmetry in $B \to \psi K_s$. It is now quite likely that any beyond the SM, CP-odd, phase will cause only small deviations in B-physics. Search for the effects of the new phase(s) will consequently require very large data samples as well as very precise theoretical predictions. Clean determination of {\it all} the angles of the unitarity triangle therefore becomes essential. In this regard $B \to K D^0$ processes play a unique role. Regarding K-decays, remarkable progress made by theory with regard to maintenance of chiral symmetry on the lattice is briefly discussed. First application already provide quantitaive information on $B_K$ and the $\Delta I=1/2$ rule. The enhancement in $Re A_0$ appears to arise solely from tree operators, esp. $Q_2$; penguin contribution to $Re A_0$ appears to be very small. However, improved calculations are necessary for \epsilon^'/epsilon as there the contributions of QCD penguins and electroweak penguins largely seem to cancel. There are good reasons, though, to believe that these cancellations will not survive improvements that are now underway. Importance of determining the unitarity triangle purely from K-decays is also emphasized.Comment: Invited talk at the 9th International Symposium on Particles, Strings and Cosmology (PASCOS 03), Mumbai (Bombay) India,3-8 Jan 200

Immune correlates of CD4 decline in HIV-infected patients experiencing virologic failure before undergoing treatment interruption

<p>Abstract</p> <p>Background</p> <p>The advantage of treatment interruptions (TIs) in salvage therapy remains controversial. Regardless, characterizations of the correlates of CD4 count fall during TI are important to identify since patients with virologic failure commonly stop antiretroviral (ARV) therapy. The objective of this study was to determine the predictive value of pre-TI proliferative capacity and cell surface markers for CD4 count change in HIV-infected patients experiencing virologic failure before undergoing TI.</p> <p>Methods</p> <p>Peripheral blood mononuclear cells (PBMCs) from 13 HIV-infected patients experiencing virologic failure at baseline time points before the TI were tested for proliferation using the 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) dilution assay and a Gag p55 peptide pool, staphylococcus enterotoxin B (SEB), cytomegalovirus (CMV) recall antigen, and anti-CD3 antibody as stimuli. CD28 and CD57 expression on CD4+ and CD8+ T-cells was measured.</p> <p>Results</p> <p>The median changes in the CD4+ T-cell count and viral load from baseline to the TI time point corresponding to the CD4 count nadir were -44 cells/mm³{Interquartile range (IQR) -17, -104} and +85,332 copies/mL (IQR +11,198, +283,327), respectively. CD4+ T-cell proliferation to CMV, pre-TI CD4+ T-cell count, and percent CD4+CD57+ cells correlated negatively with CD4 count change during TI (r = -0.59, p = 0.045, r = -0.61, p = 0.030 and r = -0.69, p = 0.0095, respectively; Spearman correlation). The presence of HIV-specific proliferative responses was not associated with a reduced decline in CD4 count during TI.</p> <p>Conclusion</p> <p>The use of pre-TI immune proliferative responses and cell surface markers may have predictive value for CD4 count decline during TI.</p

CP Asymmetries in B_s Decays and Spontaneous CP violation

We study possible effects of new physics in CP asymmetries in two-body $B_s$ decays in left-right models with spontaneous CP violation. Considering the contributions of new CP phases to the $B_s$ mixing as well as to the penguin dominated decay amplitudes we show that, with the present constraints, large deviations from the standard model predictions in CP asymmetries are allowed in both cases. Detection of the new physics can be done by measuring non-zero asymmetries which are predicted to vanish in the standard model or by comparing two measurements which are predicted to be equal in the standard model. In particular, we show that the measurement of the CKM angle $\gamma$ in electroweak penguin dominated processes $B_s^0\to\rho^0\eta^{(')}, \rho^0\phi$ can largely be affected by the new physics.Comment: References and discussion added, version to be published in PR

Discriminating Active from Latent Tuberculosis in Patients Presenting to Community Clinics

BACKGROUND Because of the high global prevalence of latent TB infection (LTBI), a key challenge in endemic settings is distinguishing patients with active TB from patients with overlapping clinical symptoms without active TB but with co-existing LTBI. Current methods are insufficiently accurate. Plasma proteomic fingerprinting can resolve this difficulty by providing a molecular snapshot defining disease state that can be used to develop point-of-care diagnostics. METHODS Plasma and clinical data were obtained prospectively from patients attending community TB clinics in Peru and from household contacts. Plasma was subjected to high-throughput proteomic profiling by mass spectrometry. Statistical pattern recognition methods were used to define mass spectral patterns that distinguished patients with active TB from symptomatic controls with or without LTBI. RESULTS 156 patients with active TB and 110 symptomatic controls (patients with respiratory symptoms without active TB) were investigated. Active TB patients were distinguishable from undifferentiated symptomatic controls with accuracy of 87% (sensitivity 84%, specificity 90%), from symptomatic controls with LTBI (accuracy of 87%, sensitivity 89%, specificity 82%) and from symptomatic controls without LTBI (accuracy 90%, sensitivity 90%, specificity 92%). CONCLUSIONS We show that active TB can be distinguished accurately from LTBI in symptomatic clinic attenders using a plasma proteomic fingerprint. Translation of biomarkers derived from this study into a robust and affordable point-of-care format will have significant implications for recognition and control of active TB in high prevalence settings

Distinct Effector Memory CD4+ T Cell Signatures in Latent Mycobacterium tuberculosis Infection, BCG Vaccination and Clinically Resolved Tuberculosis

Two billion people worldwide are estimated to be latently infected with Mycobacterium tuberculosis (Mtb) and are at risk for developing active tuberculosis since Mtb can reactivate to cause TB disease in immune-compromised hosts. Individuals with latent Mtb infection (LTBI) and BCG-vaccinated individuals who are uninfected with Mtb, harbor antigen-specific memory CD4+ T cells. However, the differences between long-lived memory CD4+ T cells induced by latent Mtb infection (LTBI) versus BCG vaccination are unclear. In this study, we characterized the immune phenotype and functionality of antigen-specific memory CD4+ T cells in healthy BCG-vaccinated individuals who were either infected (LTBI) or uninfected (BCG) with Mtb. Individuals were classified into LTBI and BCG groups based on IFN-γ ELISPOT using cell wall antigens and ESAT-6/CFP-10 peptides. We show that LTBI individuals harbored high frequencies of late-stage differentiated (CD45RA−CD27−) antigen-specific effector memory CD4+ T cells that expressed PD-1. In contrast, BCG individuals had primarily early-stage (CD45RA−CD27+) cells with low PD-1 expression. CD27+ and CD27− as well as PD-1+ and PD-1− antigen-specific subsets were polyfunctional, suggesting that loss of CD27 expression and up-regulation of PD-1 did not compromise their capacity to produce IFN-γ, TNF-α and IL-2. PD-1 was preferentially expressed on CD27− antigen-specific CD4+ T cells, indicating that PD-1 is associated with the stage of differentiation. Using statistical models, we determined that CD27 and PD-1 predicted LTBI versus BCG status in healthy individuals and distinguished LTBI individuals from those who had clinically resolved Mtb infection after anti-tuberculosis treatment. This study shows that CD4+ memory responses induced by latent Mtb infection, BCG vaccination and clinically resolved Mtb infection are immunologically distinct. Our data suggest that differentiation into CD27−PD-1+ subsets in LTBI is driven by Mtb antigenic stimulation in vivo and that CD27 and PD-1 have the potential to improve our ability to evaluate true LTBI status

Potential of Host Markers Produced by Infection Phase-Dependent Antigen-Stimulated Cells for the Diagnosis of Tuberculosis in a Highly Endemic Area

CITATION: Chegou, N. N. et al. 2012. Potential of host markers produced by infection phase-dependent antigen-stimulated cells for the diagnosis of tuberculosis in a highly endemic area. PLoS ONE, 7(6): e38501, doi:10.1371/journal.pone.0038501.The original publication is available at http://journals.plos.org/plosoneBackground: Recent interferon gamma (IFN-γ)-based studies have identified novel Mycobacterium tuberculosis (M.tb) infection phase-dependent antigens as diagnostic candidates. In this study, the levels of 11 host markers other than IFN-γ, were evaluated in whole blood culture supernatants after stimulation with M.tb infection phase-dependent antigens, for the diagnosis of TB disease. Methodology and Principal Findings: Five M.tb infection phase-dependent antigens, comprising of three DosR-regulon-encoded proteins (Rv2032, Rv0081, Rv1737c), and two resucitation promoting factors (Rv0867c and Rv2389c), were evaluated in a case-control study with 15 pulmonary TB patients and 15 household contacts that were recruited from a high TB incidence setting in Cape Town, South Africa. After a 7-day whole blood culture, supernatants were harvested and the levels of the host markers evaluated using the Luminex platform. Multiple antigen-specific host markers were identified with promising diagnostic potential. Rv0081-specific levels of IL-12(p40), IP-10, IL-10 and TNF-α were the most promising diagnostic candidates, each ascertaining TB disease with an accuracy of 100%, 95% confidence interval for the area under the receiver operating characteristics plots, (1.0 to 1.0). Conclusions: Multiple cytokines other than IFN-γ in whole blood culture supernatants after stimulation with M.tb infection phase-dependent antigens show promise as diagnostic markers for active TB. These preliminary findings should be verified in well-designed diagnostic studies employing short-term culture assays. © 2012 Chegou et al.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0038501Publisher's versio

Psychological well-being in Europe after the outbreak of war in Ukraine

The Russian invasion of Ukraine on February 24, 2022, has had devastating effects on the Ukrainian population and the global economy, environment, and political order. However, little is known about the psychological states surrounding the outbreak of war, particularly the mental well-being of individuals outside Ukraine. Here, we present a longitudinal experience-sampling study of a convenience sample from 17 European countries (total participants = 1,341, total assessments = 44,894, countries with >100 participants = 5) that allows us to track well-being levels across countries during the weeks surrounding the outbreak of war. Our data show a significant decline in well-being on the day of the Russian invasion. Recovery over the following weeks was associated with an individual’s personality but was not statistically significantly associated with their age, gender, subjective social status, and political orientation. In general, well-being was lower on days when the war was more salient on social media. Our results demonstrate the need to consider the psychological implications of the Russo-Ukrainian war next to its humanitarian, economic, and ecological consequences