A note on the uniqueness of D=4 N=1 Supergravity

We investigate in 4 spacetime dimensions, all the consistent deformations of the lagrangian ${\cal L}_2+{\cal L}_{{3/2}}$, which is the sum of the Pauli-Fierz lagrangian ${\cal L}_2$ for a free massless spin 2 field and the Rarita-Schwinger lagrangian ${\cal L}_{{3/2}}$ for a free massless spin 3/2 field. Using BRST cohomogical techniques, we show, under the assumptions of locality, Poincar\'e invariance, conservation of the number of gauge symmetries and the number of derivatives on each fields, that N=1 D=4 supergravity is the only consistent interaction between a massless spin 2 and a massless spin 3/2 field. We do not assume general covariance. This follows automatically, as does supersymmetry invariance. Various cohomologies related to conservations laws are also given.Comment: 22+1 pages, LaTeX. References adde

Half-BPS cosmic string in N=2 supergravity in the presence of a dilaton

We construct new half-BPS cosmic string solutions in D=4 N=2 supergravity compatible with a consistent truncation to N=1 supergravity where they describe D-term cosmic strings. The constant Fayet-Iliopoulos term in the N=1 D-term is not put in by hand but is geometrically engineered by a gauging in the mother N=2 supergravity theory. The coupling of the N=2 vector multiplets is characterized by a cubic prepotential admitting an axion-dilaton field, a common property of many compactifications of string theory. The axion-dilaton field survives the truncation to N=1 supergravity. On the string configuration the BPS equations constrain the dilaton to be an arbitrary constant. All the cosmic string solutions with different values of the dilaton have the same energy per unit length but different lenght scales.Comment: 52 pages; typos correcte

D-term cosmic strings from N=2 Supergravity

We describe new half-BPS cosmic string solutions in N=2, d=4 supergravity coupled to one vector multiplet and one hypermultiplet. They are closely related to D-term strings in N=1 supergravity. Fields of the N=2 theory that are frozen in the solution contribute to the triplet moment map of the quaternionic isometries and leave their trace in N=1 as a constant Fayet-Iliopoulos term. The choice of U(1) gauging and of special geometry are crucial. The construction gives rise to a non-minimal Kaehler potential and can be generalized to higher dimensional quaternionic-Kaehler manifolds.Comment: 37 pages, LaTeX, v2: minor corrections, references added, version to be published in JHE

Tate Form and Weak Coupling Limits in F-theory

We consider the weak coupling limit of F-theory in the presence of non-Abelian gauge groups implemented using the traditional ansatz coming from Tate's algorithm. We classify the types of singularities that could appear in the weak coupling limit and explain their resolution. In particular, the weak coupling limit of SU(n) gauge groups leads to an orientifold theory which suffers from conifold singulaties that do not admit a crepant resolution compatible with the orientifold involution. We present a simple resolution to this problem by introducing a new weak coupling regime that admits singularities compatible with both a crepant resolution and an orientifold symmetry. We also comment on possible applications of the new limit to model building. We finally discuss other unexpected phenomena as for example the existence of several non-equivalent directions to flow from strong to weak coupling leading to different gauge groups.Comment: 34 page

Stability of warped AdS3 vacua of topologically massive gravity

AdS3 vacua of topologically massive gravity (TMG) have been shown to be perturbatively unstable for all values of the coupling constant except the chiral point \mu l=1. We study the possibility that the warped vacua of TMG, which exist for all values of \mu, are stable under linearized perturbations. In this paper, we show that spacelike warped AdS3 vacua with Compere-Detournay boundary conditions are indeed stable in the range \mu l > 3. This is precisely the range in which black hole solutions arise as discrete identifications of the warped AdS3 vacuum. The situation somewhat resembles chiral gravity: although negative energy modes do exist, they are all excluded by the boundary conditions, and the perturbative spectrum solely consists of boundary (pure large gauge) gravitons.Comment: 30 pages, 1 figur

D-brane Deconstructions in IIB Orientifolds

With model building applications in mind, we collect and develop basic techniques to analyze the landscape of D7-branes in type IIB compact Calabi-Yau orientifolds, in three different pictures: F-theory, the D7 worldvolume theory and D9-anti-D9 tachyon condensation. A significant complication is that consistent D7-branes in the presence of O7^- planes are generically singular, with singularities locally modeled by the Whitney Umbrella. This invalidates the standard formulae for charges, moduli space and flux lattice dimensions. We infer the correct formulae by comparison to F-theory and derive them independently and more generally from the tachyon picture, and relate these numbers to the closed string massless spectrum of the orientifold compactification in an interesting way. We furthermore give concrete recipes to explicitly and systematically construct nontrivial D-brane worldvolume flux vacua in arbitrary Calabi-Yau orientifolds, illustrate how to read off D-brane flux content, enhanced gauge groups and charged matter spectra from tachyon matrices, and demonstrate how brane recombination in general leads to flux creation, as required by charge conservation and by equivalence of geometric and gauge theory moduli spaces.Comment: 49 pages, v2: two references adde

Adjunctive host-directed therapies for pulmonary tuberculosis: a prospective, open-label, phase 2, randomised controlled trial.

BACKGROUND: Current tuberculosis treatments leave patients with clinically significant lung injury and increased all-cause mortality post-cure. Adjunctive host-directed therapies could protect the lungs, improve long-term survival, and shorten treatment duration; however, few have been tested clinically. Therefore, we aimed to assess the safety and preliminary efficacy of four host-directed therapies for tuberculosis. METHODS: In this prospective, open-label, phase 2, randomised controlled trial, patients with pulmonary tuberculosis were recruited at three clinical sites in South Africa. Eligible patients were aged 18-65 years, HIV-1-negative, and had rifampicin-susceptible Mycobacterium tuberculosis, a sputum Xpert cycle threshold of less than 20, and moderately advanced or far advanced disease on chest radiography. By use of numbers generated in blocks of ten and stratification by site, eligible patients were randomly assigned (1:1:1:1:1) to receive one of the four oral host-directed treatments plus standard tuberculosis treatment or standard treatment alone (the control group). Host-directed treatments were: CC-11050 (200 mg twice daily, taken with food; day 1-112); everolimus (0·5 mg/day; day 1-112); auranofin (3 mg/day for seven doses, then 6 mg/day; day 1-112); and ergocalciferol (5 mg on day 1, then 2·5 mg on day 28 and day 56). All study participants received oral rifabutin-substituted standard tuberculosis treatment for 180 days. Patients and clinicians were not masked to treatment assignment. Spirometry and sputum culture with solid and liquid media were done at baseline and up to 180 days at specified intervals throughout treatment. The primary endpoint was safety and tolerability up to day 210. Secondary preliminary efficacy endpoints were treatment effects on sputum microbiology (culture status at day 56 and the hazard ratio for stable culture conversion up to day 180) and lung function (FEV1 and forced vital capacity [FVC]) measured by spirometry at day 56, day 180, and day 540. Safety was analysed in the intention-to-treat population and preliminary efficacy primarily in the per-protocol population. The trial is registered at ClinicalTrials.gov, NCT02968927. Post-treatment follow-up was completed in 2020. FINDINGS: Between Nov 18, 2016, and Sept 27, 2018, 200 patients were screened and randomly assigned to different treatment groups (n=40 per group, apart from n=39 in the everolimus group after one patient withdrew consent). 11 treatment-emergent serious adverse events occurred either during treatment or within 30 days after treatment discontinuation, of which three were attributable to a host-directed treatment. Life-threatening thrombocytopenia occurred in an auranofin recipient; apparent intra-abdominal sepsis leading to death occurred in another auranofin recipient and was classified as a suspected unexpected serious adverse reaction. Tuberculous spondylitis occurred as an apparent paradoxical reaction in a patient receiving ergocalciferol. Two patients in the control group had life-threatening, treatment-attributable liver injury. No treatment-emergent, treatment-attributable serious adverse events occurred in patients receiving CC-11050 or everolimus. Mean FEV1 in the control group was 61·7% of predicted (95% CI 56·3-67·1) at baseline and 69·1% (62·3-75·8) at day 180. Patients treated with CC-11050 and everolimus had increased recovery of FEV1 at day 180 relative to the control group (mean difference from control group 6·30%, 95% CI 0·06-12·54; p=0·048; and 6·56%, 0·18-12·95; p=0·044, respectively), whereas auranofin and ergocalciferol recipients did not. None of the treatments had an effect on FVC during 180 days of follow-up or on measures of sputum culture status over the course of the study. INTERPRETATION: CC-11050 and everolimus were safe and reasonably well tolerated as adjunctive therapies for tuberculosis, and analysis of preliminary efficacy suggests they might also enhance the recovery of FEV1, a key measure of lung function and predictor of all-cause mortality. Further studies of these candidates are warranted. FUNDING: The Bill & Melinda Gates Foundation and the South African Medical Research Council

Adjunctive host-directed therapies for pulmonary tuberculosis : a prospective, open-label, phase 2, randomised controlled trial

BACKGROUND : Current tuberculosis treatments leave patients with clinically significant lung injury and increased all-cause mortality post-cure. Adjunctive host-directed therapies could protect the lungs, improve long-term survival, and shorten treatment duration; however, few have been tested clinically. Therefore, we aimed to assess the safety and preliminary efficacy of four host-directed therapies for tuberculosis. METHODS : In this prospective, open-label, phase 2, randomised controlled trial, patients with pulmonary tuberculosis were recruited at three clinical sites in South Africa. Eligible patients were aged 18–65 years, HIV-1-negative, and had rifampicin-susceptible Mycobacterium tuberculosis , a sputum Xpert cycle threshold of less than 20, and moderately advanced or far advanced disease on chest radiography. By use of numbers generated in blocks of ten and stratification by site, eligible patients were randomly assigned (1:1:1:1:1) to receive one of the four oral host-directed treatments plus standard tuberculosis treatment or standard treatment alone (the control group). Host-directed treatments were: CC-11050 (200 mg twice daily, taken with food; day 1–112); everolimus (0·5 mg/day; day 1–112); auranofin (3 mg/day for seven doses, then 6 mg/day; day 1–112); and ergocalciferol (5 mg on day 1, then 2·5 mg on day 28 and day 56). All study participants received oral rifabutin-substituted standard tuberculosis treatment for 180 days. Patients and clinicians were not masked to treatment assignment. Spirometry and sputum culture with solid and liquid media were done at baseline and up to 180 days at specified intervals throughout treatment. The primary endpoint was safety and tolerability up to day 210. Secondary preliminary efficacy endpoints were treatment effects on sputum microbiology (culture status at day 56 and the hazard ratio for stable culture conversion up to day 180) and lung function (FEV 1 and forced vital capacity [FVC]) measured by spirometry at day 56, day 180, and day 540. Safety was analysed in the intention-to-treat population and preliminary efficacy primarily in the per-protocol population. The trial is registered at ClinicalTrials.gov , NCT02968927 . Post-treatment follow-up was completed in 2020. FINDINGS : Between Nov 18, 2016, and Sept 27, 2018, 200 patients were screened and randomly assigned to different treatment groups (n=40 per group, apart from n=39 in the everolimus group after one patient withdrew consent). 11 treatment-emergent serious adverse events occurred either during treatment or within 30 days after treatment discontinuation, of which three were attributable to a host-directed treatment. Life-threatening thrombocytopenia occurred in an auranofin recipient; apparent intra-abdominal sepsis leading to death occurred in another auranofin recipient and was classified as a suspected unexpected serious adverse reaction. Tuberculous spondylitis occurred as an apparent paradoxical reaction in a patient receiving ergocalciferol. Two patients in the control group had life-threatening, treatment-attributable liver injury. No treatment-emergent, treatment-attributable serious adverse events occurred in patients receiving CC-11050 or everolimus. Mean FEV 1 in the control group was 61·7% of predicted (95% CI 56·3–67·1) at baseline and 69·1% (62·3–75·8) at day 180. Patients treated with CC-11050 and everolimus had increased recovery of FEV 1 at day 180 relative to the control group (mean difference from control group 6·30%, 95% CI 0·06–12·54; p=0·048; and 6·56%, 0·18–12·95; p=0·044, respectively), whereas auranofin and ergocalciferol recipients did not. None of the treatments had an effect on FVC during 180 days of follow-up or on measures of sputum culture status over the course of the study. INTERPRETATION : CC-11050 and everolimus were safe and reasonably well tolerated as adjunctive therapies for tuberculosis, and analysis of preliminary efficacy suggests they might also enhance the recovery of FEV 1 , a key measure of lung function and predictor of all-cause mortality. Further studies of these candidates are warranted.The Bill & Melinda Gates Foundation and the South African Medical Research Council.https://www.thelancet.com/journals/lanreshj2022Medical Microbiolog