Is scale-up worth it? Challenges in economic analysis of diagnostic tests for tuberculosis.

David Dowdy and colleagues discuss the complexities of costing new TB diagnostic tests, including GeneXpert, and argue that flexible analytic tools are needed for decision-makers to adapt large-sample cost-effectiveness data to local conditions

INTEGRATION OF CAD AND CAE IN SME’S FOR PRODUCT DEVELOPMENT

Small manufacturing enterprises face a number of challenges when integrating computer aided design (CAD) tools and computer-aided engineering (CAE) tools into their design processes. One of the most significant challenges is interoperability across the wide range of commercial CAD and CAE tools. Although many of these tools support industry data standards and claim to be interoperable, the connection between them is not seamless. This paper summarizes studies of tool integration activities at one small manufacturer. The paper shows the enhancement of the product development process resulting from replacement of a two dimensional CAD system with a three-dimensional CAD system and creation of an inhouse capability to perform finite element analysis (FEA), replacing analysis that had previously been outsourced. As a result of these experiences, the manufacturer learned that improved productivity and superior designs could be obtained by integrating analysis into the design process at the earlier stages of conceptual and preliminary design

Constant Approximation for kk-Median and kk-Means with Outliers via Iterative Rounding

In this paper, we present a new iterative rounding framework for many clustering problems. Using this, we obtain an $(\alpha_1 + \epsilon \leq 7.081 + \epsilon)$-approximation algorithm for $k$-median with outliers, greatly improving upon the large implicit constant approximation ratio of Chen [Chen, SODA 2018]. For $k$-means with outliers, we give an $(\alpha_2+\epsilon \leq 53.002 + \epsilon)$-approximation, which is the first $O(1)$-approximation for this problem. The iterative algorithm framework is very versatile; we show how it can be used to give $\alpha_1$- and $(\alpha_1 + \epsilon)$-approximation algorithms for matroid and knapsack median problems respectively, improving upon the previous best approximations ratios of $8$ [Swamy, ACM Trans. Algorithms] and $17.46$ [Byrka et al, ESA 2015]. The natural LP relaxation for the $k$-median/$k$-means with outliers problem has an unbounded integrality gap. In spite of this negative result, our iterative rounding framework shows that we can round an LP solution to an almost-integral solution of small cost, in which we have at most two fractionally open facilities. Thus, the LP integrality gap arises due to the gap between almost-integral and fully-integral solutions. Then, using a pre-processing procedure, we show how to convert an almost-integral solution to a fully-integral solution losing only a constant-factor in the approximation ratio. By further using a sparsification technique, the additive factor loss incurred by the conversion can be reduced to any $\epsilon > 0$

The importance of implementation strategy in scaling up Xpert MTB/RIF for diagnosis of tuberculosis in the Indian health-care system: a transmission model.

BACKGROUND: India has announced a goal of universal access to quality tuberculosis (TB) diagnosis and treatment. A number of novel diagnostics could help meet this important goal. The rollout of one such diagnostic, Xpert MTB/RIF (Xpert) is being considered, but if Xpert is used mainly for people with HIV or high risk of multidrug-resistant TB (MDR-TB) in the public sector, population-level impact may be limited. METHODS AND FINDINGS: We developed a model of TB transmission, care-seeking behavior, and diagnostic/treatment practices in India and explored the impact of six different rollout strategies. Providing Xpert to 40% of public-sector patients with HIV or prior TB treatment (similar to current national strategy) reduced TB incidence by 0.2% (95% uncertainty range [UR]: -1.4%, 1.7%) and MDR-TB incidence by 2.4% (95% UR: -5.2%, 9.1%) relative to existing practice but required 2,500 additional MDR-TB treatments and 60 four-module GeneXpert systems at maximum capacity. Further including 20% of unselected symptomatic individuals in the public sector required 700 systems and reduced incidence by 2.1% (95% UR: 0.5%, 3.9%); a similar approach involving qualified private providers (providers who have received at least some training in allopathic or non-allopathic medicine) reduced incidence by 6.0% (95% UR: 3.9%, 7.9%) with similar resource outlay, but only if high treatment success was assured. Engaging 20% of all private-sector providers (qualified and informal [providers with no formal medical training]) had the greatest impact (14.1% reduction, 95% UR: 10.6%, 16.9%), but required >2,200 systems and reliable treatment referral. Improving referrals from informal providers for smear-based diagnosis in the public sector (without Xpert rollout) had substantially greater impact (6.3% reduction) than Xpert scale-up within the public sector. These findings are subject to substantial uncertainty regarding private-sector treatment patterns, patient care-seeking behavior, symptoms, and infectiousness over time; these uncertainties should be addressed by future research. CONCLUSIONS: The impact of new diagnostics for TB control in India depends on implementation within the complex, fragmented health-care system. Transformative strategies will require private/informal-sector engagement, adequate referral systems, improved treatment quality, and substantial resources. Please see later in the article for the Editors' Summary

A Pilot Study of Short-Duration Sputum Pretreatment Procedures for Optimizing Smear Microscopy for Tuberculosis

Direct sputum smear microscopy for tuberculosis (TB) lacks sensitivity for the detection of acid fast bacilli. Sputum pretreatment procedures may enhance sensitivity. We did a pilot study to compare the diagnostic accuracy and incremental yield of two short-duration (<1 hour) sputum pretreatment procedures to optimize direct smears among patients with suspected TB at a referral hospital in India.Blinded laboratory comparison of bleach and universal sediment processing (USP) pretreated centrifuged auramine smears to direct Ziehl-Neelsen (ZN) and direct auramine smears and to solid (Loweinstein-Jensen (LJ)) and liquid (BACTEC 460) culture. 178 pulmonary and extrapulmonary TB suspects were prospectively recruited during a one year period. Thirty six (20.2%) were positive by either solid or liquid culture. Direct ZN smear detected 22 of 36 cases and direct auramine smears detected 26 of 36 cases. Bleach and USP centrifugation detected 24 cases each, providing no incremental yield beyond direct smears. When compared to combined culture, pretreated smears were not more sensitive than direct smears (66.6% vs 61.1 (ZN) or 72.2 (auramine)), and were not more specific (92.3% vs 93.0 (ZN) or 97.2 (auramine).Short duration sputum pretreatment with bleach and USP centrifugation did not increase yield as compared to direct sputum smears. Further work is needed to confirm this in a larger study and also determine if longer duration pre-treatment might be effective in optimizing smear microscopy for TB

Commercial Serological Tests for the Diagnosis of Active Pulmonary and Extrapulmonary Tuberculosis: An Updated Systematic Review and Meta-Analysis

An up-to-date systematic review and meta-analysis by Karen Steingart and colleagues confirms that commercially available serological tests do not provide an accurate diagnosis of tuberculosis

Synthesis and insecticidal activity of organophosphorus compounds containing substituted s-triazole and fused ring heterocycles

199-20

simultaneous determination of metronidazole and miconazole nitrate in gel by

ABSTRACT A new, simple, precise, rapid and selective high-performance thin-layer chromatographic (HPTLC) method for the simultaneous quantification of Metronidazole (MTZ) and Miconazole nitrate (MCZ) in gel has been developed. It was performed on silica gel 60 GF 254 Thin Layer Chromatographic plates using mobile phase comprising of Toluene: Chloroform: Methanol (3.0:2.0:0.6 v/v) and the detection was carried out at 240 nm using densitometer. The retention factors of MTZ and MCZ were 0.34 and 0.55 respectively. Calibration curves were linear in the range of 300-700 ng/spot of MTZ and 600-1400 ng/spot of MCZ both by height and by area. The percent recovery of the drugs from gel carried out by standard addition method was found to be 100.13±1.59 (by height) and 98.92±0.76 (by area) for MTZ and 99.49±1.58 (by height) and 99.63±1.46 (by area) for MCZ indicative of accuracy and precision of simultaneous determination of MTZ and MCZ nitrate