Radiative corrections to all charge assignments of heavy quark baryon semileptonic decays

In semileptonic decays of spin-1/2 baryons containing heavy quarks up to six charge assignments for the baryons and lepton are possible. We show that the radiative corrections to four of these possibilities can be directly obtained from the final results of the two possibilities previously studied. There is no need to recalculate integrals over virtual or real photon momentum or any traces.Comment: 15 pages, 2 figures, RevTex. Extended discussion. Final version to appear in Physical Review

Clinical evaluation of two dark blood methods of late gadolinium quantification of ischemic scar

BACKGROUND: Late gadolinium enhancement (LGE) imaging was validated for diagnosis and quantification of myocardial infarction (MI). Despite good contrast between scar and normal myocardium, contrast between blood pool and myocardial scar can be limited. Dark blood LGE sequences attempt to overcome this issue. PURPOSE: To evaluate T1 rho (T1 ρ)-prepared dark blood sequence and compare to blood nulled (BN) phase sensitive inversion recovery (PSIR) and standard myocardium nulled (MN) PSIR for detection and quantification of scar. STUDY TYPE: Prospective. POPULATION: Thirty patients with prior MI. FIELD STRENGTH/SEQUENCE: Patients underwent identical 1.5 T MRI protocols. Following routine LGE imaging, a slice with scar, remote myocardium, and blood pool was selected. PSIR LGE was repeated with inversion time set to MN, to BN, and T1 ρ FIDDLE (flow-independent dark-blood delayed enhancement) in random order. ASSESSMENT: Three observers. Qualitative assessment of confidence scores in scar detection and degree of transmurality. Quantitative assessment of myocardial scar mass (grams), and contrast-to-noise ratio (CNR) measurements between scar, blood pool, and myocardium. STATISTICAL TESTS: Repeated-measures analysis of variance (ANOVA) with Bonferroni correction, coefficient of variation, and the Cohen κ statistic. RESULTS: CNRscar-blood was significantly increased for both BN (27.1 ± 10.4) and T1 ρ (30.2 ± 15.1) compared with MN (15.3 ± 8.4 P < 0.001 for both sequences). There was no significant difference in CNRscar-myo between BN (55.9 ± 17.3) and MN (51.1 ± 17.8 P = 0.512); both had significantly higher CNRscar-myo compared with the T1 ρ (42.6 ± 16.9 P = 0.007 and P = 0.014, respectively). No significant difference in scar size between LGE methods: MN (2.28 ± 1.58 g) BN (2.16 ± 1.57 g) and T1 ρ (2.29 ± 2.5 g). Confidence scores were significantly higher for BN (3.87 ± 0.346) compared with MN (3.1 ± 0.76 P < 0.001) and T1 ρ (3.20 ± 0.71 P < 0.001). DATA CONCLUSION: PSIR with inversion time (TI) set for blood nulling and the T1 ρ LGE sequence demonstrated significantly higher scar to blood CNR compared with routine MN. PSIR with TI set for blood nulling demonstrated significantly higher reader confidence scores compared with routine MN and T1 ρ LGE, suggesting routine adoption of a BN PSIR approach might be appropriate for LGE imaging. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018

Vector meson production and nucleon resonance analysis in a coupled-channel approach for energies m_N < sqrt(s) < 2 GeV II: photon-induced results

We present a nucleon resonance analysis by simultaneously considering all pion- and photon-induced experimental data on the final states gamma N, pi N, 2 pi N, eta N, K Lambda, K Sigma, and omega N for energies from the nucleon mass up to sqrt(s) = 2 GeV. In this analysis we find strong evidence for the resonances P_{31}(1750), P_{13}(1900), P_{33}(1920), and D_{13}(1950). The omega N production mechanism is dominated by large P_{11}(1710) and P_{13}(1900) contributions. In this second part we present the results on the photoproduction reactions and the electromagnetic properties of the resonances. The inclusion of all important final states up to sqrt(s) = 2 GeV allows for estimates on the importance of the individual states for the GDH sum rule.Comment: 41 pages, 26 figures, discussion extended, typos corrected, references updated, to appear in Phys. Rev.

Neutron structure function and inclusive DIS from H-3 and He-3 at large Bjorken-x

A detailed study of inclusive deep inelastic scattering (DIS) from mirror A = 3 nuclei at large values of the Bjorken variable x is presented. The main purpose is to estimate the theoretical uncertainties on the extraction of the neutron DIS structure function from such nuclear measurements. On one hand, within models in which no modification of the bound nucleon structure functions is taken into account, we have investigated the possible uncertainties arising from: i) charge symmetry breaking terms in the nucleon-nucleon interaction, ii) finite Q**2 effects neglected in the Bjorken limit, iii) the role of different prescriptions for the nucleon Spectral Function normalization providing baryon number conservation, and iv) the differences between the virtual nucleon and light cone formalisms. Although these effects have been not yet considered in existing analyses, our conclusion is that all these effects cancel at the level of ~ 1% for x < 0.75 in overall agreement with previous findings. On the other hand we have considered several models in which the modification of the bound nucleon structure functions is accounted for to describe the EMC effect in DIS scattering from nuclei. It turns out that within these models the cancellation of nuclear effects is expected to occur only at a level of ~ 3%, leading to an accuracy of ~ 12 % in the extraction of the neutron to proton structure function ratio at x ~ 0.7 -0.8$. Another consequence of considering a broad range of models of the EMC effect is that the previously suggested iteration procedure does not improve the accuracy of the extraction of the neutron to proton structure function ratio.Comment: revised version to appear in Phys. Rev. C; main modifications in Section 4; no change in the conclusion

Effective Lagrangian Approach to the Theory of Eta Photoproduction in the N∗(1535)N^{*}(1535) Region

We investigate eta photoproduction in the $N^{*}(1535)$ resonance region within the effective Lagrangian approach (ELA), wherein leading contributions to the amplitude at the tree level are taken into account. These include the nucleon Born terms and the leading $t$-channel vector meson exchanges as the non-resonant pieces. In addition, we consider five resonance contributions in the $s$- and $u$- channel; besides the dominant $N^{*}(1535)$, these are: $N^{*}(1440),N^{*}(1520),N^{*}(1650)$ and $N^{*}(1710)$. The amplitudes for the $\pi^\circ$ and the $\eta$ photoproduction near threshold have significant differences, even as they share common contributions, such as those of the nucleon Born terms. Among these differences, the contribution to the $\eta$ photoproduction of the $s$-channel excitation of the $N^{*}(1535)$ is the most significant. We find the off-shell properties of the spin-3/2 resonances to be important in determining the background contributions. Fitting our effective amplitude to the available data base allows us to extract the quantity $\sqrt{\chi \Gamma_\eta} A_{1/2}/\Gamma_T$, characteristic of the photoexcitation of the $N^{*}(1535)$ resonance and its decay into the $\eta$-nucleon channel, of interest to precise tests of hadron models. At the photon point, we determine it to be $(2.2\pm 0.2)\times 10^{-1} GeV^{-1}$ from the old data base, and $(2.2\pm 0.1) \times 10^{-1} GeV^{-1}$ from a combination of old data base and new Bates data. We obtain the helicity amplitude for $N^{*}(1535)\rightarrow \gamma p$ to be $A_{1/2}=(97\pm 7)\times 10^{-3} GeV^{-1/2}$ from the old data base, and $A_{1/2}=(97\pm 6)\times 10^{-3} GeV^{-1/2}$ from the combination of the old data base and new Bates data, compared with the results of the analysis of pion photoproduction yielding $74\pm 11$, in the same units.Comment: 43 pages, RevTeX, 9 figures available upon request, to appear in Phys. Rev.

Modeling the emergence of viral resistance for SARS-CoV-2 during treatment with an anti-spike monoclonal antibody

To mitigate the loss of lives during the COVID-19 pandemic, emergency use authorization was given to several anti-SARS-CoV-2 monoclonal antibody (mAb) therapies for the treatment of mild-to-moderate COVID-19 in patients with a high risk of progressing to severe disease. Monoclonal antibodies used to treat SARS-CoV-2 target the spike protein of the virus and block its ability to enter and infect target cells. Monoclonal antibody therapy can thus accelerate the decline in viral load and lower hospitalization rates among high-risk patients with variants susceptible to mAb therapy. However, viral resistance has been observed, in some cases leading to a transient viral rebound that can be as large as 3-4 orders of magnitude. As mAbs represent a proven treatment choice for SARS-CoV-2 and other viral infections, evaluation of treatment-emergent mAb resistance can help uncover underlying pathobiology of SARS-CoV-2 infection and may also help in the development of the next generation of mAb therapies. Although resistance can be expected, the large rebounds observed are much more difficult to explain. We hypothesize replenishment of target cells is necessary to generate the high transient viral rebound. Thus, we formulated two models with different mechanisms for target cell replenishment (homeostatic proliferation and return from an innate immune response antiviral state) and fit them to data from persons with SARS-CoV-2 treated with a mAb. We showed that both models can explain the emergence of resistant virus associated with high transient viral rebounds. We found that variations in the target cell supply rate and adaptive immunity parameters have a strong impact on the magnitude or observability of the viral rebound associated with the emergence of resistant virus. Both variations in target cell supply rate and adaptive immunity parameters may explain why only some individuals develop observable transient resistant viral rebound. Our study highlights the conditions that can lead to resistance and subsequent viral rebound in mAb treatments during acute infection

Cardiac reverse remodeling in primary mitral regurgitation: mitral valve replacement vs. mitral valve repair

Background When feasible, guidelines recommend mitral valve repair (MVr) over mitral valve replacement (MVR) to treat primary mitral regurgitation (MR), based upon historic outcome studies and transthoracic echocardiography (TTE) reverse remodeling studies. Cardiovascular magnetic resonance (CMR) offers reference standard biventricular assessment with superior MR quantification compared to TTE. Using serial CMR in primary MR patients, we aimed to investigate cardiac reverse remodeling and residual MR post-MVr vs MVR with chordal preservation. Methods 83 patients with ≥ moderate-severe MR on TTE were prospectively recruited. 6-min walk tests (6MWT) and CMR imaging including cine imaging, aortic/pulmonary through-plane phase contrast imaging, T1 maps and late-gadolinium-enhanced (LGE) imaging were performed at baseline and 6 months after mitral surgery or watchful waiting (control group). Results 72 patients completed follow-up (Controls = 20, MVr = 30 and MVR = 22). Surgical groups demonstrated comparable baseline cardiac indices and co-morbidities. At 6-months, MVr and MVR groups demonstrated comparable improvements in 6MWT distances (+ 57 ± 54 m vs + 64 ± 76 m respectively, p = 1), reduced indexed left ventricular end-diastolic volumes (LVEDVi; − 29 ± 21 ml/m2 vs − 37 ± 22 ml/m2 respectively, p = 0.584) and left atrial volumes (− 23 ± 30 ml/m2 and − 39 ± 26 ml/m2 respectively, p = 0.545). At 6-months, compared with controls, right ventricular ejection fraction was poorer post-MVr (47 ± 6.1% vs 53 ± 8.0% respectively, p = 0.01) compared to post-MVR (50 ± 5.7% vs 53 ± 8.0% respectively, p = 0.698). MVR resulted in lower residual MR-regurgitant fraction (RF) than MVr (12 ± 8.0% vs 21 ± 11% respectively, p = 0.022). Baseline and follow-up indices of diffuse and focal myocardial fibrosis (Native T1 relaxation times, extra-cellular volume and quantified LGE respectively) were comparable between groups. Stepwise multiple linear regression of indexed variables in the surgical groups demonstrated baseline indexed mitral regurgitant volume as the sole multivariate predictor of left ventricular (LV) end-diastolic reverse remodelling, baseline LVEDVi as the most significant independent multivariate predictor of follow-up LVEDVi, baseline indexed LV end-systolic volume as the sole multivariate predictor of follow-up LV ejection fraction and undergoing MVR (vs MVr) as the most significant (p < 0.001) baseline multivariate predictor of lower residual MR. Conclusion In primary MR, MVR with chordal preservation may offer comparable cardiac reverse remodeling and functional benefits at 6-months when compared to MVr. Larger, multicenter CMR studies are required, which if the findings are confirmed could impact future surgical practice

Investigating the composition and recruitment of the mycobacterial ImuA'-ImuB-DnaE2 mutasome

A DNA damage-inducible mutagenic gene cassette has been implicated in the emergence of drug resistance in Mycobacterium tuberculosis during anti-tuberculosis (TB) chemotherapy. However, the molecular composition and operation of the encoded 'mycobacterial mutasome' - minimally comprising DnaE2 polymerase and ImuA ' and ImuB accessory proteins - remain elusive. Following exposure of mycobacteria to DNA damaging agents, we observe that DnaE2 and ImuB co-localize with the DNA polymerase III beta subunit (beta clamp) in distinct intracellular foci. Notably, genetic inactivation of the mutasome in an imuB(AAAAGG) mutant containing a disrupted beta clamp-binding motif abolishes ImuB-beta clamp focus formation, a phenotype recapitulated pharmacologically by treating bacilli with griselimycin and in biochemical assays in which this beta clamp-binding antibiotic collapses pre-formed ImuB-beta clamp complexes. These observations establish the essentiality of the ImuB-beta clamp interaction for mutagenic DNA repair in mycobacteria, identifying the mutasome as target for adjunctive therapeutics designed to protect anti-TB drugs against emerging resistance.Microscopic imaging and technolog

Safety and efficacy of inhaled interferon-β1a (SNG001) in adults with mild-to-moderate COVID-19: a randomized, controlled, phase II trial

Background: With the emergence of SARS-CoV-2 variants resistant to monoclonal antibody therapies and limited global access to therapeutics, the evaluation of novel therapeutics to prevent progression to severe COVID-19 remains a critical need. Methods: Safety, clinical and antiviral efficacy of inhaled interferon-β1a (SNG001) were evaluated in a phase II randomized controlled trial on the ACTIV-2/A5401 platform (ClinicalTrials.gov NCT04518410). Adult outpatients with confirmed SARS-CoV-2 infection within 10 days of symptom onset were randomized and initiated either orally inhaled nebulized SNG001 given once daily for 14 days (n = 110) or blinded pooled placebo (n = 110) between February 10 and August 18, 2021. Findings: The proportion of participants reporting premature treatment discontinuation was 9% among SNG001 and 13% among placebo participants. There were no differences between participants who received SNG001 or placebo in the primary outcomes of treatment emergent Grade 3 or higher adverse events (3.6% and 8.2%, respectively), time to symptom improvement (median 13 and 9 days, respectively), or proportion with unquantifiable nasopharyngeal SARS-CoV-2 RNA at days 3 (28% [26/93] vs. 39% [37/94], respectively), 7 (65% [60/93] vs. 66% [62/94]) and 14 (91% [86/95] vs. 91% [83/81]). There were fewer hospitalizations with SNG001 (n = 1; 1%) compared with placebo (n = 7; 6%), representing an 86% relative risk reduction (p = 0.07). There were no deaths in either arm. Interpretation: In this trial, SNG001 was safe and associated with a non-statistically significant decrease in hospitalization for COVID-19 pneumonia. Funding: The ACTIV-2 platform study is funded by the NIH. Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1 AI068634, UM1 AI068636 and UM1 AI106701. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health

4D Flow Cardiac MR in Primary Mitral Regurgitation

Background Four-dimensional-flow cardiac MR (4DF-MR) offers advantages in primary mitral regurgitation. The relationship between 4DF-MR-derived mitral regurgitant volume (MR-Rvol) and the post-operative left ventricular (LV) reverse remodeling has not yet been established. Purpose To ascertain if the 4DF-MR-derived MR-Rvol correlates with the LV reverse remodeling in primary mitral regurgitation. Study Type Prospective, single-center, two arm, interventional vs. nonintervention observational study. Population Forty-four patients (male N = 30; median age 68 [59–75]) with at least moderate primary mitral regurgitation; either awaiting mitral valve surgery (repair [MVr], replacement [MVR]) or undergoing “watchful waiting” (WW). Field Strength/Sequence 5 T/Balanced steady-state free precession (bSSFP) sequence/Phase contrast imaging/Multishot echo-planar imaging pulse sequence (five shots). Assessment Patients underwent transthoracic echocardiography (TTE), phase-contrast MR (PMRI), 4DF-MR and 6-minute walk test (6MWT) at baseline, and a follow-up PMRI and 6MWT at 6 months. MR-Rvol was quantified by PMRI, 4DF-MR, and TTE by one observer. The pre-operative MR-Rvol was correlated with the post-operative decrease in the LV end-diastolic volume index (LVEDVi). Statistical Tests Included Student t-test/Mann–Whitney test/Fisher's exact test, Bland–Altman plots, linear regression analysis and receiver operating characteristic curves. Statistical significance was defined as P < 0.05. Results While Bland–Altman plots demonstrated similar bias between all the modalities, the limits of agreement were narrower between 4DF-MR and PMRI (bias 15; limits of agreement −36 mL to 65 mL), than between 4DF-MR and TTE (bias −8; limits of agreement −106 mL to 90 mL) and PMRI and TTE (bias −23; limits of agreement −105 mL to 59 mL). Linear regression analysis demonstrated a significant association between the MR-Rvol and the post-operative decrease in the LVEDVi, when the MR-Rvol was quantified by PMRI and 4DF-MR, but not by TTE (P = 0.73). 4DF-MR demonstrated the best diagnostic performance for reduction in the post-operative LVEDVi with the largest area under the curve (4DF-MR 0.83; vs. PMRI 0.78; and TTE 0.51; P = 0.89). Data Conclusion This study demonstrates the potential clinical utility of 4DF-MR in the assessment of primary mitral regurgitation