Intensified Antituberculosis Therapy in Adults with Tuberculous Meningitis

BACKGROUND Tuberculous meningitis is often lethal. Early antituberculosis treatment and adjunctive treatment with glucocorticoids improve survival, but nearly one third of patients with the condition still die. We hypothesized that intensified antituberculosis treatment would enhance the killing of intracerebral Mycobacterium tuberculosis organisms and decrease the rate of death among patients. METHODS We performed a randomized, double-blind, placebo-controlled trial involving human immunodeficiency virus (HIV)-infected adults and HIV-uninfected adults with a clinical diagnosis of tuberculous meningitis who were admitted to one of two Vietnamese hospitals. We compared a standard, 9-month antituberculosis regimen (which included 10 mg of rifampin per kilogram of body weight per day) with an intensified regimen that included higher-dose rifampin (15 mg per kilogram per day) and levofloxacin (20 mg per kilogram per day) for the first 8 weeks of treatment. The primary outcome was death by 9 months after randomization. RESULTS A total of 817 patients (349 of whom were HIV-infected) were enrolled; 409 were randomly assigned to receive the standard regimen, and 408 were assigned to receive intensified treatment. During the 9 months of follow-up, 113 patients in the intensified-treatment group and 114 patients in the standard-treatment group died (hazard ratio, 0.94; 95% confidence interval, 0.73 to 1.22; P=0.66). There was no evidence of a significant differential effect of intensified treatment in the overall population or in any of the subgroups, with the possible exception of patients infected with isoniazid-resistant M. tuberculosis. There were also no significant differences in secondary outcomes between the treatment groups. The overall number of adverse events leading to treatment interruption did not differ significantly between the treatment groups (64 events in the standard-treatment group and 95 events in the intensified-treatment group, P=0.08). CONCLUSIONS Intensified antituberculosis treatment was not associated with a higher rate of survival among patients with tuberculous meningitis than standard treatment. (Funded by the Wellcome Trust and the Li Ka Shing Foundation; Current Controlled Trials number, ISRCTN61649292.)

The production of the new gauge boson BHB_{H} via e−γe^{-}\gamma collision in the littlest Higgs model

The new lightest gauge boson $B_H$ with mass of a few hundred GeV is predicted in the littlest Higgs model. $B_H$ should be accessible in the planed ILC and the observation of such particle can strongly support the littlest Higgs model. The realization of $\gamma\gamma$ and $e\gamma$ collision will open a wider window to probe $B_H$. In this paper, we study the new gauge boson $B_{H}$ production processes $e^{-}\gamma\to e^{-}\gamma B_{H}$ and $e^{-}\gamma\to e^{-}Z B_{H}$ at the ILC. Our results show that the production cross section of the process $e^{-}\gamma\to e^{-}Z B_{H}$ is less than one fb in the most parameter spaces while the production cross section of the process $e^{-}\gamma\to e^{-}\gamma B_{H}$ can reach the level of tens fb and even hundreds of fb in the sizable parameter spaces allowed by the electroweak precision data. With the high luminosity, the sufficient typical signals could be produced, specially via $e^{-}\gamma\to e^{-}\gamma B_{H}$. Because the final electron and photon beams can be easily identified and the signal can be easily distinguished from the background produced by $Z$ and $H$ decaying, $B_H$ should be detectable via $e\gamma$ collision at the ILC. Therefore, the processes $e^{-}\gamma\to e^{-}\gamma B_{H}$ and $e^{-}\gamma\to e^{-}Z B_{H}$ provide a useful way to detect $B_{H}$ and test the littlest Higgs model.Comment: 15 pages, 3 figures. Some typos have been corrected, we have added some new references, and there are also some changes in equation 1

Sources of Multidrug Resistance in Patients With Previous Isoniazid-Resistant Tuberculosis Identified Using Whole Genome Sequencing: A Longitudinal Cohort Study

Background Meta-analysis of patients with isoniazid-resistant tuberculosis given standard first-line anti-tuberculosis treatment indicated an increased risk of multi-drug resistant tuberculosis (MDR-TB) emerging (8%), compared to drug-sensitive tuberculosis (0.3%). Here we use whole genome sequencing (WGS) to investigate whether treatment of patients with pre-existing isoniazid resistant disease with first-line anti-tuberculosis therapy risks selecting for rifampicin resistance, and hence MDR-TB. Methods Patients with isoniazid-resistant pulmonary TB were recruited and followed up for 24 months. Drug-susceptibility testing was performed by Microscopic observation drug-susceptibility assay (MODS), Mycobacterial Growth Indicator Tube (MGIT) and by WGS on isolates at first presentation and in the case of re-presentation. Where MDR-TB was diagnosed, WGS was used to determine the genomic relatedness between initial and subsequent isolates. De novo emergence of MDR-TB was assumed where the genomic distance was five or fewer single nucleotide polymorphisms (SNPs) whereas reinfection with a different MDR-TB strain was assumed where the distance was 10 or more SNPs. Results 239 patients with isoniazid-resistant pulmonary tuberculosis were recruited. Fourteen (14/239, 5.9%) patients were diagnosed with a second episode of tuberculosis that was multi-drug resistant. Six (6/239, 2.5%) were identified as having evolved MDR-TB de novo and six as having been re-infected with a different strain. In two cases the genomic distance was between 5-10 SNPs and therefore indeterminate. Conclusions In isoniazid-resistant TB, de novo emergence and reinfection of MDR-TB strains equally contributed to MDR development. Early diagnosis and optimal treatment of isoniazid resistant TB are urgently needed to avert the de novo emergence of MDR-TB during treatment

Probing the lightest new gauge boson BHB_H in the littlest Higgs model via the processes γγ→ffˉBH\gamma\gamma \to f\bar{f}B_H at the ILC

The neutral gauge boson $B_H$ with the mass of hundreds GeV, is the lightest particle predicted by the littlest Higgs(LH) model, and such particle should be the first signal of the LH model at the planed ILC if it exists indeed. In this paper, we study some processes of the $B_H$ production associated with the fermion pair at the ILC, i.e., $\gamma\gamma\to f\bar{f}B_{H}$. The studies show that the most promising processes to detect $B_H$ among $\gamma\gamma\to f\bar{f}B_{H}$ are $\gamma\gamma\to l'^+l'^-B_{H}(l'=e,\mu)$, and they can produce the sufficient signals in most parameter space preferred by the electroweak precision data at the ILC. On the other hand, the signal produced via the certain $B_H$ decay modes is typical and such signal can be easily identified from the SM background. Therefore, $B_H$, the lightest gauge boson in the LH model would be detectable at the photon collider realized at the ILC.Comment: 12 pages, 4 figure

Regulation of SOX11 expression through CCND1 and STAT3 in mantle cell lymphoma

The neural transcription factor SOX11 is usually highly expressed in typical mantle cell lymphoma (MCL), but it is absent in the more indolent form of MCL. Despite being an important diagnostic marker for this hard-to-treat malignancy, the mechanisms of aberrant SOX11 expression are largely unknown. Herein, we describe 2 modes of SOX11 regulation by the cell-cycle regulator cyclin D1 (CCND1) and the signal transducer and activator of transcription 3 (STAT3). We found that ectopic expression of CCND1 in multiple human MCL cell lines resulted in increased SOX11 transcription, which correlated with increased acetylated histones H3K9 and H3K14 (H3K9/14Ac). Increased H3K9/14Ac and SOX11 expression was also observed after histone deacetylase 1 (HDAC1) or HDAC2 was depleted by RNA interference or inhibited by the HDAC inhibitor vorinostat. Mechanistically, we showed that CCND1 interacted with and sequestered HDAC1 and HDAC2 from the SOX11 locus, leading to SOX11 upregulation. Interestingly, our data revealed a potential inverse relationship between phosphorylated Y705 STAT3 and SOX11 expression in MCL cell lines, primary tumors, and patient-derived xenografts. Functionally, inactivation of STAT3 by inhibiting the upstream Janus kinase (JAK) 1 or JAK2 or by STAT3 knockdown was found to increase SOX11 expression, whereas interleukin-21 (IL-21)–induced STAT3 activation or overexpression of the constitutively active form of STAT3 decreased SOX11 expression. In addition, targeting SOX11 directly by RNA interference or indirectly by IL-21 treatment induced toxicity in SOX11^+ MCL cells. Collectively, we demonstrate the involvement of CCND1 and STAT3 in the regulation of SOX11 expression, providing new insights and therapeutic implications in MCL

Formation of ionospheric irregularities over Southeast Asia during the 2015 St. Patrickˈs Day storm

We investigate the geospace response to the 2015 St. Patrickˈs Day storm leveraging on instruments spread over Southeast Asia (SEA), covering a wide longitudinal sector of the low-latitude ionosphere. A regional characterization of the storm is provided, identifying the peculiarities of ionospheric irregularity formation. The novelties of this work are the characterization in a broad longitudinal range and the methodology relying on the integration of data acquired by Global Navigation Satellite System (GNSS) receivers, magnetometers, ionosondes, and Swarm satellites. This work is a legacy of the project EquatoRial Ionosphere Characterization in Asia (ERICA). ERICA aimed to capture the features of both crests of the equatorial ionospheric anomaly (EIA) and trough (EIT) by means of a dedicated measurement campaign. The campaign lasted from March to October 2015 and was able to observe the ionospheric variability causing effects on radio systems, GNSS in particular. The multiinstrumental and multiparametric observations of the region enabled an in-depth investigation of the response to the largest geomagnetic storm of the current solar cycle in a region scarcely reported in literature. Our work discusses the comparison between northern and southern crests of the EIA in the SEA region. The observations recorded positive and negative ionospheric storms, spread F conditions, scintillation enhancement and inhibition, and total electron content variability. The ancillary information on the local magnetic field highlights the variety of ionospheric perturbations during the different storm phases. The combined use of ionospheric bottomside, topside, and integrated information points out how the storm affects the F layer altitude and the consequent enhancement/suppression of scintillations.Published12211–122331A. Geomagnetismo e Paleomagnetismo2A. Fisica dell'alta atmosfera1IT. Reti di monitoraggio e Osservazioni5IT. Osservazioni satellitariJCR Journalope

Scalar Bilepton Dark Matter

In this work we show that 3-3-1 model with right-handed neutrinos has a natural weakly interacting massive particle (WIMP) dark mater candidate. It is a complex scalar with mass of order of some hundreds of GeV which carries two units of lepton number, a scalar bilepton. This makes it a very peculiar WIMP, very distinct from Supersymmetric or Extra-dimension candidates. Besides, although we have to make some reasonable assumptions concerning the several parameters in the model, no fine tunning is required in order to get the correct dark matter abundance. We also analyze the prospects for WIMP direct detection by considering recent and projected sensitivities for WIMP-nucleon elastic cross section from CDMS and XENON Collaborations.Comment: 21 pages, 8 figures, uses iopart.cls, same text as published version with a small different arrangement of figure

Gas Accretion in Star-Forming Galaxies

Cold-mode gas accretion onto galaxies is a direct prediction of LCDM simulations and provides galaxies with fuel that allows them to continue to form stars over the lifetime of the Universe. Given its dramatic influence on a galaxy's gas reservoir, gas accretion has to be largely responsible for how galaxies form and evolve. Therefore, given the importance of gas accretion, it is necessary to observe and quantify how these gas flows affect galaxy evolution. However, observational data have yet to conclusively show that gas accretion ubiquitously occurs at any epoch. Directly detecting gas accretion is a challenging endeavor and we now have obtained a significant amount of observational evidence to support it. This chapter reviews the current observational evidence of gas accretion onto star-forming galaxies.Comment: Invited review to appear in Gas Accretion onto Galaxies, Astrophysics and Space Science Library, eds. A. J. Fox & R. Dav\'e, to be published by Springer. This chapter includes 22 pages with 7 Figure

Spatial optical solitons in nonlinear photonic crystals

We study spatial optical solitons in a one-dimensional nonlinear photonic crystal created by an array of thin-film nonlinear waveguides, the so-called Dirac-comb nonlinear lattice. We analyze modulational instability of the extended Bloch-wave modes and also investigate the existence and stability of bright, dark, and ``twisted'' spatially localized modes in such periodic structures. Additionally, we discuss both similarities and differences of our general results with the simplified models of nonlinear periodic media described by the discrete nonlinear Schrodinger equation, derived in the tight-binding approximation, and the coupled-mode theory, valid for shallow periodic modulations of the optical refractive index.Comment: 15 pages, 21 figure