In-house nucleic acid amplification tests for the detection of Mycobacterium tuberculosis in sputum specimens: meta-analysis and meta-regression

BACKGROUND: More than 200 studies related to nucleic acid amplification (NAA) tests to detect Mycobacterium tuberculosis directly from clinical specimens have appeared in the world literature since this technology was first introduced. NAA tests come as either commercial kits or as tests designed by the reporting investigators themselves (in-house tests). In-house tests vary widely in their accuracy, and factors that contribute to heterogeneity in test accuracy are not well characterized. Here, we used meta-analytical methods, including meta-regression, to identify factors related to study design and assay protocols that affect test accuracy in order to identify those factors associated with high estimates of accuracy. RESULTS: By searching multiple databases and sources, we identified 2520 potentially relevant citations, and analyzed 84 separate studies from 65 publications that dealt with in-house NAA tests to detect M. tuberculosis in sputum samples. Sources of heterogeneity in test accuracy estimates were determined by subgroup and meta-regression analyses. Among 84 studies analyzed, the sensitivity and specificity estimates varied widely; sensitivity varied from 9.4% to 100%, and specificity estimates ranged from 5.6% to 100%. In the meta-regression analysis, the use of IS6110 as a target, and the use of nested PCR methods appeared to be significantly associated with higher diagnostic accuracy. CONCLUSION: Estimates of accuracy of in-house NAA tests for tuberculosis are highly heterogeneous. The use of IS6110 as an amplification target, and the use of nested PCR methods appeared to be associated with higher diagnostic accuracy. However, the substantial heterogeneity in both sensitivity and specificity of the in-house NAA tests rendered clinically useful estimates of test accuracy difficult. Future development of NAA-based tests to detect M. tuberculosis from sputum specimens should take into consideration these findings in improving accuracy of in-house NAA tests

pp-sdsd shell gap reduction in neutron-rich systems and cross-shell excitations in 20^{20}O

Excited states in $^{20}$O were populated in the reaction $^{10}$Be($^{14}$C,$\alpha$) at Florida State University. Charged particles were detected with a particle telescope consisting of 4 annularly segmented Si surface barrier detectors and $\gamma$ radiation was detected with the FSU $\gamma$ detector array. Five new states were observed below 6 MeV from the $\alpha$-$\gamma$ and $\alpha$-$\gamma$-$\gamma$ coincidence data. Shell model calculations suggest that most of the newly observed states are core-excited 1p-1h excitations across the $N = Z = 8$ shell gap. Comparisons between experimental data and calculations for the neutron-rich O and F isotopes imply a steady reduction of the $p$-$sd$ shell gap as neutrons are added

Identification of culturable vaginal Lactobacillus species among reproductive age women in Mysore, India

A healthy vaginal environment is predominated by certain Lactobacillus species, which lead to the prevention of infections of the reproductive tract. This study examined the characteristics of cultivable Lactobacillus species in both healthy women and women with bacterial vaginosis (BV). Between November 2011 and September 2013, 139 women attending a women\u27s clinic in Mysore, India, were evaluated for BV in a cross-sectional study. BV was diagnosed using Amsel\u27s criteria: homogeneous vaginal discharge, vaginal pH \u3e4.5, production of amines, and presence of “clue” cells. Those with three or more of the characteristics were considered to have BV. Vaginal swabs were then cultured in Rogosa agar and de Man-Rogosa-Sharpe broth. Gram-positive lactobacilli generating 600–800 bp amplicons by16 sRNA were further characterized by sequencing. Cultivable vaginal samples were obtained from 132 women (94.9 %). According to the Amsel criteria, 83 women (62.1 %) were healthy, and 49 (37.1 %) had BV. Eleven different Lactobacillus species were isolated from 47 women. The common lactobacilli species found in this sample included L. crispatus (39.6 %), L. gasseri (45.8 %), and L. jensenii (14.6 %). Lactobacilli were isolated from 39 healthy women and eight with BV. L. gasseri was cultured from 18.8 % of healthy women and 6.1 % with BV. The presence of L. reuteri was significantly associated with normal vaginal microbiota (P-value = 0.026). These results further our understanding of vaginal lactobacilli colonization and richness in this particular population. Our findings showed that lactobacilli species present in the vaginas of healthy women in India do not differ from those reported from other countries

Criteria for the diagnosis of corticobasal degeneration

Current criteria for the clinical diagnosis of pathologically confirmed corticobasal degeneration (CBD) no longer reflect the expanding understanding of this disease and its clinicopathologic correlations. An international consortium of behavioral neurology, neuropsychology, and movement disorders specialists developed new criteria based on consensus and a systematic literature review. Clinical diagnoses (early or late) were identified for 267 nonoverlapping pathologically confirmed CBD cases from published reports and brain banks. Combined with consensus, 4 CBD phenotypes emerged: corticobasal syndrome (CBS), frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA), and progressive supranuclear palsy syndrome (PSPS). Clinical features of CBD cases were extracted from descriptions of 209 brain bank and published patients, providing a comprehensive description of CBD and correcting common misconceptions. Clinical CBD phenotypes and features were combined to create 2 sets of criteria: more specific clinical research criteria for probable CBD and broader criteria for possible CBD that are more inclusive but have a higher chance to detect other tau-based pathologies. Probable CBD criteria require insidious onset and gradual progression for at least 1 year, age at onset ≥50 years, no similar family history or known tau mutations, and a clinical phenotype of probable CBS or either FBS or naPPA with at least 1 CBS feature. The possible CBD category uses similar criteria but has no restrictions on age or family history, allows tau mutations, permits less rigorous phenotype fulfillment, and includes a PSPS phenotype. Future validation and refinement of the proposed criteria are needed

First Observation of the Rare Decay Mode K-long -> e+ e-

In an experiment designed to search for and study very rare two-body decay modes of the K-long, we have observed four examples of the decay K-long -> e+ e-, where the expected background is 0.17+-0.10 events. This observation translates into a branching fraction of 8.7^{+5.7}_{-4.1} X 10^{-12}, consistent with recent theoretical predictions. This result represents by far the smallest branching fraction yet measured in particle physics.Comment: 9 pages, 3 figure

Retrospective analysis of risk factors and gaps in prevention strategies for mother-to-child HIV transmission in Rio de Janeiro, Brazil

Background Despite great progress made in methods to prevent mother-to-child transmission of HIV (MTCT), delivery and uptake of these measures remains a challenge in many countries. Although the Brazilian Ministry of Health aimed to eliminate MTCT by 2015, infection still occured in 15–24% of infants born to HIV-infected mothers. We sought to identify remaining factors that constrain MTCT elimination. Methods We conducted a retrospective, matched case-control study by reviewing hospital charts of infants born to HIV-infected mothers between 1997 and 2014 at three MTCT reference hospitals in the Rio de Janeiro metropolitan area. Cases were defined as HIV-exposed children with two positive HIV tests before 18 months of age; controls were defined as HIV-exposed children with two negative HIV tests before 18 months of age. We performed bivariate and MTCT cascade analyses to identify risk factors for MTCT and gaps in prevention services. Results We included 435 infants and their mothers (145 cases, 290 controls). Bivariate analyses of MTCT preventative care (PMTCT) indicated that cases were less likely to complete all individual measures in the antenatal, delivery, and postnatal period (p < 0.05). Assessing completion of the PMTCT cascade, the sequential steps of PMTCT interventions, we found inadequate retention in care among both cases and controls, and cases were significantly less likely than controls to continue receiving care throughout the cascade (p < 0.05). Motives for incompletion of PMTCT measures included infrastructural issues, such as HIV test results not being returned, but were most often due to lack of care-seeking. Over the course of the study period, PMTCT completion improved, although it remained below the 95% target for antenatal care, HIV testing, and antenatal ART set by the WHO. Adding concern, evaluation of co-infections indicated that case infants were also more likely to have congenital syphilis (OR: 4.29; 95% CI: 1.66 to 11.11). Conclusions While PMTCT coverage has improved over the years, completion of services remains insufficient. Along with interventions to promote care-seeking behaviour, increased infrastructural support for PMTCT services is needed to meet the HIV MTCT elimination goal in Brazil as well as address rising national rates of congenital syphilis

Mitochondrial uncoupling links lipid catabolism to Akt inhibition and resistance to tumorigenesis

To support growth, tumour cells reprogramme their metabolism to simultaneously upregulate macromolecular biosynthesis while maintaining energy production. Uncoupling proteins (UCPs) oppose this phenotype by inducing futile mitochondrial respiration that is uncoupled from ATP synthesis, resulting in nutrient wasting. Here using a UCP3 transgene targeted to the basal epidermis, we show that forced mitochondrial uncoupling inhibits skin carcinogenesis by blocking Akt activation. Similarly, Akt activation is markedly inhibited in UCP3 overexpressing primary human keratinocytes. Mechanistic studies reveal that uncoupling increases fatty acid oxidation and membrane phospholipid catabolism, and impairs recruitment of Akt to the plasma membrane. Overexpression of Akt overcomes metabolic regulation by UCP3, rescuing carcinogenesis. These findings demonstrate that mitochondrial uncoupling is an effective strategy to limit proliferation and tumorigenesis through inhibition of Akt, and illuminate a novel mechanism of crosstalk between mitochondrial metabolism and growth signalling

De Jure Determinants of New Firm Formation: How the Pillars of Constitutions Influence Entrepreneurship

This paper provides empirical evidence supporting the view that constitutions may influence the organization of economic activities. Dealing with the issue of the institutional determinants of entrepreneurship, it shows that some of the provisions contained in national constitutions are positively and significantly associated to a standard measure of entrepreneurial dynamics, namely the rate of new business density. Using a novel dataset containing the characteristics of the constitutions enacted in the world and a sample of 115 countries, the paper finds that provisions about the right to conduct/establish a business, the right to strike, consumer protection, protection of trademarks, and education promote higher rates of new firm formation

System size and energy dependence of near-side di-hadron correlations

Two-particle azimuthal ($\Delta\phi$) and pseudorapidity ($\Delta\eta$) correlations using a trigger particle with large transverse momentum ($p_T$) in $d$+Au, Cu+Cu and Au+Au collisions at $\sqrt{s_{{NN}}}$ =\xspace 62.4 GeV and 200~GeV from the STAR experiment at RHIC are presented. The \ns correlation is separated into a jet-like component, narrow in both $\Delta\phi$ and $\Delta\eta$, and the ridge, narrow in $\Delta\phi$ but broad in $\Delta\eta$. Both components are studied as a function of collision centrality, and the jet-like correlation is studied as a function of the trigger and associated $p_T$. The behavior of the jet-like component is remarkably consistent for different collision systems, suggesting it is produced by fragmentation. The width of the jet-like correlation is found to increase with the system size. The ridge, previously observed in Au+Au collisions at $\sqrt{s_{{NN}}}$ = 200 GeV, is also found in Cu+Cu collisions and in collisions at $\sqrt{s_{{NN}}}$ =\xspace 62.4 GeV, but is found to be substantially smaller at $\sqrt{s_{{NN}}}$ =\xspace 62.4 GeV than at $\sqrt{s_{{NN}}}$ = 200 GeV for the same average number of participants ($\langle N_{\mathrm{part}}\rangle$). Measurements of the ridge are compared to models.Comment: 17 pages, 14 figures, submitted to Phys. Rev.