TIME Impact - a new user-friendly tuberculosis (TB) model to inform TB policy decisions.

Tuberculosis (TB) is the leading cause of death from infectious disease worldwide, predominantly affecting low- and middle-income countries (LMICs), where resources are limited. As such, countries need to be able to choose the most efficient interventions for their respective setting. Mathematical models can be valuable tools to inform rational policy decisions and improve resource allocation, but are often unavailable or inaccessible for LMICs, particularly in TB. We developed TIME Impact, a user-friendly TB model that enables local capacity building and strengthens country-specific policy discussions to inform support funding applications at the (sub-)national level (e.g. Ministry of Finance) or to international donors (e.g. the Global Fund to Fight AIDS, Tuberculosis and Malaria).TIME Impact is an epidemiological transmission model nested in TIME, a set of TB modelling tools available for free download within the widely-used Spectrum software. The TIME Impact model reflects key aspects of the natural history of TB, with additional structure for HIV/ART, drug resistance, treatment history and age. TIME Impact enables national TB programmes (NTPs) and other TB policymakers to better understand their own TB epidemic, plan their response, apply for funding and evaluate the implementation of the response.The explicit aim of TIME Impact's user-friendly interface is to enable training of local and international TB experts towards independent use. During application of TIME Impact, close involvement of the NTPs and other local partners also builds critical understanding of the modelling methods, assumptions and limitations inherent to modelling. This is essential to generate broad country-level ownership of the modelling data inputs and results. In turn, it stimulates discussions and a review of the current evidence and assumptions, strengthening the decision-making process in general.TIME Impact has been effectively applied in a variety of settings. In South Africa, it informed the first South African HIV and TB Investment Cases and successfully leveraged additional resources from the National Treasury at a time of austerity. In Ghana, a long-term TIME model-centred interaction with the NTP provided new insights into the local epidemiology and guided resource allocation decisions to improve impact

Modelling of photonic wire Bragg Gratings

Some important properties of photonic wire Bragg grating structures have been investigate. The design, obtained as a generalisation of the full-width gap grating, has been modelled using 3D finite-difference time-domain simulations. Different types of stop-band have been observed. The impact of the grating geometry on the lowest order (longest wavelength) stop-band has been investigated - and has identified deeply indented configurations where reduction of the stop-bandwidth and of the reflectivity occurred. Our computational results have been substantially validated by an experimental demonstration of the fundamental stop-band of photonic wire Bragg gratings fabricated on silicon-on-insulator material. The accuracy of two distinct 2D computational models based on the effective index method has also been studied - because of their inherently much greater rapidity and consequent utility for approximate initial designs. A 2D plan-view model has been found to reproduce a large part of the essential features of the spectral response of full 3D models

Nonlinear Optical Properties Of GeSbS Chalcogenide Waveguides

We characterize the nonlinear optical properties of GeSbS chalcogenide glasses with fiber-based experiments. A waveguide nonlinear parameter of 7 W-1/m and nonlinear refractive index of 3.71 x 10-18 m2/W are estimated by self-phase modulation. A GeSbS waveguide could also generate a supercontinuum from 1280 to 2120 nm at the -30 dB level for maximum coupled power of 340 W, showing a 14-fold spectral broadening of the input spectrum explained by cascaded stimulated Raman scattering

Effect of antiretroviral therapy on the diagnostic accuracy of symptom screening for intensified tuberculosis case finding in a South African HIV clinic.

BACKGROUND: Current symptom screening algorithms for intensified tuberculosis case finding or prior to isoniazid preventive therapy (IPT) in patients infected with human immunodeficiency virus (HIV) were derived from antiretroviral-naive cohorts. There is a need to validate screening algorithms in patients on antiretroviral therapy (ART). METHODS: We performed cross-sectional evaluation of the diagnostic accuracy of symptom screening, including the World Health Organization (WHO) algorithm, to rule out tuberculosis in HIV-infected individuals pre-ART and on ART undergoing screening prior to IPT. RESULTS: A total of 1429 participants, 54% on ART, had symptom screening and a sputum culture result available. Culture-positive tuberculosis was diagnosed in 126 patients (8.8%, 95% confidence interval [CI], 7.4%-10.4%). The WHO symptom screen in the on-ART compared with the pre-ART group had a lower sensitivity (23.8% vs 47.6%), but higher specificity (94.4% vs 79.8%). The effect of ART was independent of CD4(+) count in multivariable analyses. The posttest probability of tuberculosis following a negative WHO screen was 8.9% (95% CI, 7.4%-10.8%) and 4.4% (95% CI, 3.7%-5.2%) for the pre-ART and on-ART groups, respectively. Addition of body mass index to the WHO screen significantly improved discriminatory ability in both ART groups, which was further improved by adding CD4 count and ART duration. CONCLUSIONS: The WHO symptom screen has poor sensitivity, especially among patients on ART, in a clinic where regular tuberculosis screening is practiced. Consequently, a significant proportion of individuals with tuberculosis would inadvertently be placed on isoniazid monotherapy despite high negative predictive values. Until more sensitive methods of ruling out tuberculosis are established, it would be prudent to do a sputum culture prior to IPT where this is feasible

220 fs Er-Yb:glass laser mode-locked by a broadband low-loss Si/Ge saturable absorber

We demonstrate femtosecond performance of an ultra-broadband high-index-contrast saturable Bragg reflector consisting of a silicon/silicon-dioxide/germanium structure that is fully compatible with CMOS processing. This device offers a reflectivity bandwidth of over 700 nm and sub-picosecond recovery time of the saturable loss. It is used to achieve mode-locking of an Er-Yb:glass laser centered at 1540 nm, generating 220 fs pulses, with the broadest output spectrum to date

Skin-Test Screening and Tuberculosis Transmission among the Homeless1

We describe the implementation of a mandatory tuberculosis (TB) screening program that uses symptom screening and tuberculin skin testing in homeless shelters. We used the results of DNA fingerprinting of Mycobacterium tuberculosis isolates to evaluate the effect of the program on TB incidence and transmission. After the program was implemented, the proportion of cases among homeless persons detected by screening activities increased, and the estimated TB incidence decreased from 510 to 121 cases per 100,000 population per year. Recent transmission, defined by DNA fingerprinting analysis as clustered patterns occurring within 2 years, decreased from 49% to 14% (p=0.03). Our results suggest that the shelter-based screening program decreased the incidence of TB by decreasing its transmission among the homeless

Defining the research agenda to measure and reduce tuberculosis stigmas

This is an Open Access article, © 2017 International Union Against Tuberculosis and Lung Disease. Content in the UH Research Archive is made available for personal research, educational, and non-commercial purposes only. Unless otherwise stated, all content is protected by copyright, and in the absence of an open license, permissions for further re-use should be sought from the publisher, the author, or other copyright holder.Crucial to finding and treating the 4 million tuberculosis (TB) patients currently missed by National TB Programs, TB stigma is receiving well-deserved and long-delayed attention at the global level. However, the ability to measure and evaluate the success of TB stigma reduction efforts is limited by the need for additional tools. At a 2016 TB stigma measurement meeting held in The Hague, stigma experts discussed and proposed a research agenda around four themes: (1) Drivers: What are the main drivers and domains of TB stigma(s)?; (2) Consequences: How consequential are TB stigmas? How are negative impacts most felt?; (3) Burden: What is the global prevalence and distribution of TB stigma(s)? What explains any variation? (4): Intervention: What can be done to reduce the extent and impact of TB stigma(s)? Each theme was further subdivided into research topics to be addressed to move the agenda forward. These include more clarity on what causes TB stigmas to emerge and thrive, the difficulty of measuring the complexity of stigma, and the improbability of a universal stigma ‘cure’. Notwithstanding, these challenges should not hinder investments in TB stigma measurement and reduction. We believe it is time to focus on how and not whether the global community should measure and reduce TB stigma.Peer reviewedFinal Published versio

Development of a Standardized Screening Rule for Tuberculosis in People Living with HIV in Resource-Constrained Settings: Individual Participant Data Meta-analysis of Observational Studies

Haileyesus Getahun and colleagues report the development of a simple, standardized tuberculosis (TB) screening rule for resource-constrained settings, to identify people living with HIV who need further investigation for TB disease