Global tuberculosis targets and milestones set for 2016-2035: definition and rationale.

BACKGROUND: Global tuberculosis (TB) targets were set as part of the World Health Organization's End TB Strategy (2016-2035) and the Sustainable Development Goals (2016-2030). OBJECTIVE: To define and explain the rationale for these targets. DESIGN: Scenarios for plausible reductions in TB deaths and cases were developed using empirical evidence from best-performing countries and modelling of the scale-up of under-used interventions and hypothetical TB vaccines. Results were discussed at consultations in 2012 and 2013. A final proposal was presented to the World Health Assembly in 2014 and unanimously endorsed by all Member States. RESULTS: The 2030 targets are a 90% reduction in TB deaths and 80% reduction in TB incidence compared with 2015 levels. The 2035 targets are for reductions of 95% and 90%, respectively. A third target-that no TB-affected households experience catastrophic costs due to the disease by 2020-was also agreed. CONCLUSION: The global TB targets and milestones set for the period 2016-2035 are ambitious. Achieving them requires concerted action on several fronts, but two things are fundamental: 1) progress towards universal health coverage to ensure that everyone with TB can access high-quality treatment; and 2) substantial investment in research and development for new tools to prevent TB disease among the approximately 1.7 billion people infected

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

Systematic review of mathematical models exploring the epidemiological impact of future TB vaccines

Mathematical models are useful for assessing the potential epidemiological impact of future tuberculosis (TB) vaccines. We conducted a systematic review of mathematical models estimating the epidemiological impact of future human TB vaccines. PubMed, Embase and WHO Global Health Library were searched, 3-stage manual sifted, and citation- and reference-tracked, identifying 23 papers. An adapted quality assessment tool was developed, with a resulting median study quality score of 20/28. The literature remains divided as to whether vaccines effective pre- or post-infection would provide greatest epidemiological impact. However, all-age or adolescent/adult targeted prevention of disease vaccines achieve greater and more rapid impact than neonatal vaccines. Mass campaigns alongside routine neonatal vaccination can have profound additional impact. Economic evaluations found TB vaccines overwhelmingly cost-effective, particularly when targeted to adolescents/adults. The variability of impact by setting, age group and vaccine characteristics must be accounted for in the development and delivery of future TB vaccines

Radiogenic and muon-induced backgrounds in the LUX dark matter detector

The Large Underground Xenon (LUX) dark matter experiment aims to detect rare low-energy interactions from Weakly Interacting Massive Particles (WIMPs). The radiogenic backgrounds in the LUX detector have been measured and compared with Monte Carlo simulation. Measurements of LUX high-energy data have provided direct constraints on all background sources contributing to the background model. The expected background rate from the background model for the 85.3 day WIMP search run is (2.6±0.2stat±0.4sys)×10-3 events keVee-1kg-1day-1 in a 118 kg fiducial volume. The observed background rate is (3.6±0.4stat)×10-3 events keVee-1kg-1day-1 , consistent with model projections. The expectation for the radiogenic background in a subsequent one-year run is presented

Identification of Radiopure Titanium for the LZ Dark Matter Experiment and Future Rare Event Searches

The LUX-ZEPLIN (LZ) experiment will search for dark matter particle interactions with a detector containing a total of 10 tonnes of liquid xenon within a double-vessel cryostat. The large mass and proximity of the cryostat to the active detector volume demand the use of material with extremely low intrinsic radioactivity. We report on the radioassay campaign conducted to identify suitable metals, the determination of factors limiting radiopure production, and the selection of titanium for construction of the LZ cryostat and other detector components. This titanium has been measured with activities of $^{238}$U$_{e}$~$<$1.6~mBq/kg, $^{238}$U$_{l}$~$<$0.09~mBq/kg, $^{232}$Th$_{e}$~$=0.28\pm 0.03$~mBq/kg, $^{232}$Th$_{l}$~$=0.25\pm 0.02$~mBq/kg, $^{40}$K~$<$0.54~mBq/kg, and $^{60}$Co~$<$0.02~mBq/kg (68\% CL). Such low intrinsic activities, which are some of the lowest ever reported for titanium, enable its use for future dark matter and other rare event searches. Monte Carlo simulations have been performed to assess the expected background contribution from the LZ cryostat with this radioactivity. In 1,000 days of WIMP search exposure of a 5.6-tonne fiducial mass, the cryostat will contribute only a mean background of $0.160\pm0.001$(stat)$\pm0.030$(sys) counts

Five years of searches for point sources of astrophysical neutrinos with the AMANDA-II neutrino telescope

We report the results of a five-year survey of the northern sky to search for point sources of high energy neutrinos. The search was performed on the data collected with the AMANDA-II neutrino telescope in the years 2000 to 2004, with a live time of 1001 days. The sample of selected events consists of 4282 upward going muon tracks with high reconstruction quality and an energy larger than about 100 GeV. We found no indication of point sources of neutrinos and set 90% confidence level flux upper limits for an all-sky search and also for a catalog of 32 selected sources. For the all-sky search, our average (over declination and right ascension) experimentally observed upper limit Phi(0)=(E/1 TeV)(gamma)center dot d Phi/dE to a point source flux of muon and tau neutrino (detected as muons arising from taus) is Phi(nu mu)+nu(0)(mu)+Phi(nu tau)+nu(0)(tau)=11.1x 10(-11) TeV-1 cm(-2) s(-1), in the energy range between 1.6 TeV and 2.5 PeV for a flavor ratio Phi(nu mu)+nu(0)(mu)/Phi(nu tau)+nu(0)(tau)=1 and assuming a spectral index gamma=2. It should be noticed that this is the first time we set upper limits to the flux of muon and tau neutrinos. In previous papers we provided muon neutrino upper limits only neglecting the sensitivity to a signal from tau neutrinos, which improves the limits by 10% to 16%. The value of the average upper limit presented in this work corresponds to twice the limit on the muon neutrino flux Phi(nu mu)+nu(0)(mu)=5.5x10(-11) TeV-1 cm(-2) s(-1). A stacking analysis for preselected active galactic nuclei and a search based on the angular separation of the events were also performed. We report the most stringent flux upper limits to date, including the results of a detailed assessment of systematic uncertainties

LUX-ZEPLIN (LZ) Technical Design Report

In this Technical Design Report (TDR) we describe the LZ detector to be built at the Sanford Underground Research Facility (SURF). The LZ dark matter experiment is designed to achieve sensitivity to a WIMP-nucleon spin-independent cross section of three times ten to the negative forty-eighth square centimeters

Evidence-informed policy making at country level: lessons learned from the South African Tuberculosis Think Tank.

BACKGROUND: National Tuberculosis Programmes (NTPs) require specialist input to support the development of policy and practice informed by evidence, typically against tight deadlines. OBJECTIVE: To describe lessons learned from establishing a dedicated tuberculosis (TB) think tank to advise the South African NTP on TB policy. INTERVENTION AND EVALUATION METHODS: A national TB think tank was established to advise the NTP in support of evidence-informed policy. Support was provided for activities, including meetings, modelling and regular telephone calls, with a wider network of unpaid expert advisers under an executive committee and working groups. Intervention evaluation used desktop analysis of documentary evidence, interviews and direct observation. RESULTS: The TB Think Tank evolved over time to acquire three key roles: an 'institution', a 'policy dialogue forum' and an 'interface'. Although enthusiasm was high, motivating participation among the NTP and external experts proved challenging. Motivation of working groups was most successful when aligned to a specific need for NTP decision making. Despite challenges, the TB Think Tank contributed to South Africa's first ever TB and human immunodeficiency virus (HIV) investment case, and the decision to create South Africa's first ever ring-fenced grant for TB. The TB Think Tank also assisted the NTP in formulating strategy to accelerate progress towards reaching World Health Organization targets. DISCUSSION: With partners, the TB Think Tank achieved major successes in supporting evidence-informed decision making, and garnered increased funding for TB in South Africa. Identifying ways to increase the involvement of NTP staff and other experts, and keeping the scope of the Think Tank well defined, could facilitate greater impact. Think tank initiatives could be replicated in other settings to support evidence-informed policy making