Early and efficient detection of Mycobacterium tuberculosis in sputum by microscopic observation of broth cultures.

Early, efficient and inexpensive methods for the detection of pulmonary tuberculosis are urgently needed for effective patient management as well as to interrupt transmission. These methods to detect M. tuberculosis in a timely and affordable way are not yet widely available in resource-limited settings. In a developing-country setting, we prospectively evaluated two methods for culturing and detecting M. tuberculosis in sputum. Sputum samples were cultured in liquid assay (micro broth culture) in microplate wells and growth was detected by microscopic observation, or in Löwenstein-Jensen (LJ) solid media where growth was detected by visual inspection for colonies. Sputum samples were collected from 321 tuberculosis (TB) suspects attending Bugando Medical Centre, in Mwanza, Tanzania, and were cultured in parallel. Pulmonary tuberculosis cases were diagnosed using the American Thoracic Society diagnostic standards. There were a total of 200 (62.3%) pulmonary tuberculosis cases. Liquid assay with microscopic detection detected a significantly higher proportion of cases than LJ solid culture: 89.0% (95% confidence interval [CI], 84.7% to 93.3%) versus 77.0% (95% CI, 71.2% to 82.8%) (p = 0.0007). The median turn around time to diagnose tuberculosis was significantly shorter for micro broth culture than for the LJ solid culture, 9 days (interquartile range [IQR] 7-13), versus 21 days (IQR 14-28) (p<0.0001). The cost for micro broth culture (labor inclusive) in our study was US $4.56 per sample, versus US$11.35 per sample for the LJ solid culture. The liquid assay (micro broth culture) is an early, feasible, and inexpensive method for detection of pulmonary tuberculosis in resource limited settings

S4 Flavor Symmetry and Fermion Masses: Towards a Grand Unified theory of Flavor

Pursuing a bottom-up approach to explore which flavor symmetry could serve as an explanation of the observed fermion masses and mixings, we discuss an extension of the standard model (SM) where the flavor structure for both quarks and leptons is determined by a spontaneously broken S4 and the requirement that its particle content is embeddable simultaneously into the conventional SO(10) grand unified theory (GUT) and a continuous flavor symmetry G_f like SO(3)_f or SU(3)_f. We explicitly provide the Yukawa and the Higgs sector of the model and show its viability in two numerical examples which arise as small deviations from rank one matrices. In the first case, the corresponding mass matrix is democratic and in the second one only its 2-3 block is non-vanishing. We demonstrate that the Higgs potential allows for the appropriate vacuum expectation value (VEV) configurations in both cases, if CP is conserved. For the first case, the chosen Yukawa couplings can be made natural by invoking an auxiliary Z2 symmetry. The numerical study we perform shows that the best-fit values for the lepton mixing angles theta_12 and theta_23 can be accommodated for normal neutrino mass hierarchy. The results for the quark mixing angles turn out to be too small. Furthermore the CP-violating phase delta can only be reproduced correctly in one of the examples. The small mixing angle values are likely to be brought into the experimentally allowed ranges by including radiative corrections. Interestingly, due to the S4 symmetry the mass matrix of the right-handed neutrinos is proportional to the unit matrix.Comment: 27 pages, published version with minor change

Validation of techniques to mitigate copper surface contamination in CUORE

In this article we describe the background challenges for the CUORE experiment posed by surface contamination of inert detector materials such as copper, and present three techniques explored to mitigate these backgrounds. Using data from a dedicated test apparatus constructed to validate and compare these techniques we demonstrate that copper surface contamination levels better than 10E-07 - 10E-08 Bq/cm2 are achieved for 238U and 232Th. If these levels are reproduced in the final CUORE apparatus the projected 90% C.L. upper limit on the number of background counts in the region of interest is 0.02-0.03 counts/keV/kg/y depending on the adopted mitigation technique.Comment: 10 pages, 6 figures, 6 table

Search for 14.4 keV solar axions from M1 transition of Fe-57 with CUORE crystals

We report the results of a search for axions from the 14.4 keV M1 transition from Fe-57 in the core of the sun using the axio-electric effect in TeO2 bolometers. The detectors are 5x5x5 cm3 crystals operated at about 10 mK in a facility used to test bolometers for the CUORE experiment at the Laboratori Nazionali del Gran Sasso in Italy. An analysis of 43.65 kg d of data was made using a newly developed low energy trigger which was optimized to reduce the detectors energy threshold. An upper limit of 0.63 c kg-1 d-1 was established at 95% C.L.. From this value, a lower bound at 95% C.L. was placed on the Peccei-Quinn energy scale of fa >= 0.76 10**6 GeV for a value of S=0.55 for the flavor-singlet axial vector matrix element. Bounds are given for the interval 0.15 < S < 0.55.Comment: 14 pages, 6 figures, submitted to JCA

The low energy spectrum of TeO2 bolometers: results and dark matter perspectives for the CUORE-0 and CUORE experiments

We collected 19.4 days of data from four 750 g TeO2 bolometers, and in three of them we were able to set the energy threshold around 3 keV using a new analysis technique. We found a background rate ranging from 25 cpd/keV/kg at 3 keV to 2 cpd/keV/kg at 25 keV, and a peak at 4.7 keV. The origin of this peak is presently unknown, but its presence is confirmed by a reanalysis of 62.7 kg.days of data from the finished CUORICINO experiment. Finally, we report the expected sensitivities of the CUORE0 (52 bolometers) and CUORE (988 bolometers) experiments to a WIMP annual modulation signal.Comment: 9 pages, 10 figure

Omnichannel Value Chain: Mapping Digital Technologies for Channel Integration Activities

In order to provide a seamless customer experience, researchers and practitioners have proposed creation of an omnichannel retailing environment by integrating online and offline channels. Channel integration necessitates use of digital technologies and there are myriads of technological solutions available. However, retailers are struggling with selection and implementation of suitable technologies to add value through channel integration. Despite the strong practical need, this issue has not been effectively addressed in the academic literature. This paper presents an omnichannel value chain underpinned by Porter’s value chain model. We identify ten channel integration activities for value creation by carrying out a synthesis of current research on omnichannel retailing. Enabling digital technologies are then mapped to these activities using technology implementation examples and provide a guideline for retailers to select appropriate technologies for the identified value creation activities

An active-shield method for the reduction of surface contamination in CUORE

The main goal of the CUORE experiment is to search for the neutrinoless double beta decay of 130Te. As it is a rare nuclear decay, the sensitivity of the experiment strongly depends on the background level in the transition energy region. In this paper we describe the R&D work performed to develop an active method for the reduction of radioactive background in CUORE. The idea is to reject events originated by surface contamination in large mass bolometric detectors by using bolometers sensitive to surface events. Results obtained with the first prototypes and tests made with large mass surface sensitive bolometers will be reported

Effects of cytokine blocking agents on hospital mortality in patients admitted to ICU with acute respiratory distress syndrome by SARS-CoV-2 infection: Retrospective cohort study

Background: The use of cytokine-blocking agents has been proposed to modulate the inflammatory response in patients with COVID-19. Tocilizumab and anakinra were included in the local protocol as an optional treatment in critically ill patients with acute respiratory distress syndrome (ARDS) by SARS-CoV-2 infection. This cohort study evaluated the effects of therapy with cytokine blocking agents on in-hospital mortality in COVID-19 patients requiring mechanical ventilation and admitted to intensive care unit. Methods: The association between therapy with tocilizumab or anakinra and in-hospital mortality was assessed in consecutive adult COVID-19 patients admitted to our ICU with moderate to severe ARDS. The association was evaluated by comparing patients who received to those who did not receive tocilizumab or anakinra and by using different multivariable Cox models adjusted for variables related to poor outcome, for the propensity to be treated with tocilizumab or anakinra and after patient matching. Results: Sixty-six patients who received immunotherapy (49 tocilizumab, 17 anakinra) and 28 patients who did not receive immunotherapy were included. The in-hospital crude mortality was 30,3% in treated patients and 50% in non-treated (OR 0.77, 95% CI 0.56-1.05, p=0.069). The adjusted Cox model showed an association between therapy with immunotherapy and in-hospital mortality (HR 0.40, 95% CI 0.19-0.83, p=0.015). This protective effect was further confirmed in the analysis adjusted for propensity score, in the propensity-matched cohort and in the cohort of patients with invasive mechanical ventilation within 2 hours after ICU admission. Conclusions: Although important limitations, our study showed that cytokine-blocking agents seem to be safe and to improve survival in COVID-19 patients admitted to ICU with ARDS and the need for mechanical ventilation