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ObjectivesThe province of Ontario, Canada, banned the use of menthol-flavoured tobacco products as of 1 January 2017. The long-term impact of a menthol ban on smoking behaviour has not been previously evaluated.MethodsPopulation cohort study with baseline survey conducted September–December 2016 and follow-up January–August 2018 among residents of Ontario, Canada, 16 years old and over who reported current smoking (past 30 days) at baseline survey and completed follow-up (n=913) including 187 reporting smoking menthol cigarettes daily, 420 reported smoking menthol cigarettes occasionally, and 306 were non-menthol cigarette smokers. Relative rates of making a quit attempt and being a non-smoker at follow-up were estimated with Poisson regression controlling for smoking and demographic characteristics at baseline.ResultsAt follow-up, 63% of daily menthol smokers reported making a quit attempt since the ban compared with 62% of occasional menthol smokers and 43% of non-menthol smokers (adjusted relative rate (ARR) for daily menthol smokers compared with non-menthol smokers: 1.25; 95% CI 1.03 to 1.50). At follow-up, 24% of daily menthol smokers reported making a quit since the ban compared with 20% of occasional menthol smokers and 14% of non-menthol smokers (ARR for daily menthol smokers compared with non-menthol smokers: 1.62; 95% CI 1.08 to 2.42).ConclusionsThe study found higher rates of quitting among daily and occasional menthol smokers in Ontario 1 year after the implementation of a menthol ban compared with non-menthol smokers. Our findings suggest that restrictions on menthol may lead to substantial improvements in public health.

BackgroundMajor depressive disorder (MDD) may be present in 10%–20% of patients in medical settings. Routine depression screening is sometimes recommended to improve depression management. However, studies of the diagnostic accuracy of depression screening tools have typically used data-driven, exploratory methods to select optimal cutoffs. Often, these studies report results from a small range of cutoff points around whatever cutoff score is most accurate in that given study. When published data are combined in meta-analyses, estimates of accuracy for different cutoff points may be based on data from different studies, rather than data from all studies for each possible cutoff point. As a result, traditional meta-analyses may generate exaggerated estimates of accuracy. Individual patient data (IPD) meta-analyses can address this problem by synthesizing data from all studies for each cutoff score to obtain diagnostic accuracy estimates. The nine-item Patient Health Questionnaire-9 (PHQ-9) and the shorter PHQ-2 and PHQ-8 are commonly recommended for depression screening. Thus, the primary objectives of our IPD meta-analyses are to determine the diagnostic accuracy of the PHQ-9, PHQ-8, and PHQ-2 to detect MDD among adults across all potentially relevant cutoff scores. Secondary analyses involve assessing accuracy accounting for patient factors that may influence accuracy (age, sex, medical comorbidity).Methods/designData sources will include MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, PsycINFO, and Web of Science. We will include studies that included a Diagnostic and Statistical Manual or International Classification of Diseases diagnosis of MDD based on a validated structured or semi-structured clinical interview administered within 2 weeks of the administration of the PHQ. Two reviewers will independently screen titles and abstracts, perform full article review, and extract study data. Disagreements will be resolved by consensus. Risk of bias will be assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Bivariate random-effects meta-analysis will be conducted for the full range of plausible cutoff values.DiscussionThe proposed IPD meta-analyses will allow us to obtain estimates of the diagnostic accuracy of the PHQ-9, PHQ-8, and PHQ-2.Systematic review registrationPROSPERO CRD42014010673

intervention schedules or strategies may be required to maximise the possibility of eradicating bacterial colonisation. Are peripheral microscopy centres ready for next generation molecular tuberculosis diagnostics?To the Editor:Sputum smear microscopy is the primary test for tuberculosis (TB) in most high-burden countries. Direct Ziehl-Neelsen (ZN) microscopy is routinely implemented in these countries via a vast network of decentralised, peripheral microscopy centres (as opposed to centralised reference laboratories), often located within primary or community health centres. This decentralised approach increases access in primary care settings and may help reduce diagnostic delays [1]. However, microscopy has limitations and novel diagnostics are urgently needed, particularly in settings with high prevalence of drug resistance and HIV [1,2].While Xpert1 MTB/RIF (Cepheid, Sunnyvale, CA, USA), a World Health Organization-endorsed test, is already being rolled out in many countries, it is intended for district or sub-district laboratories [3], and not peripheral microscopy centres. In contrast, at least four next-generation nucleic-acid amplification tests (NAATs) are now on the market, with the goal of point-of-care (POC) use in peripheral laboratories [4,5]. Can these so-called ''POC-NAATs'' actually be implemented in peripheral microscopy centres? Is there sufficient expertise (e.g. to extract DNA) and biosafety (e.g. to process sputum)? Will the necessary infrastructure (e.g. stable power supply) be present? Will environmental conditions (e.g. high temperature) limit their use?The introduction of novel diagnostics that aim to replace smear microscopy in peripheral laboratories is more likely to succeed if the new tests are designed with real world conditions in mind. However, there are limited data on landscape of microscopy centres in high-burden countries. We addressed this gap with a survey of 22 high-burden countries. We designed a one-page, 12-question survey. We focused on the most important requirements and considerations for the next generation of TB diagnostics. We included questions about ambient temperature and humidity conditions, safety, infrastructure, availability of equipment and expertise, and communication infrastructure.We contacted at least three experts in each country. If the responses were discrepant, we attempted to obtain at least one additional response from another expert. All contacts had extensive field experience and were either working for the national TB programme or non-governmental organisations, or were carrying out diagnostics or implementation research in the respective countries. Respondents were instructed to focus on the ''typical'' most peripheral microscopy laboratory in the country.We were able to obtain at least three responses from 17 of 22 (77%) high-burden countries. For four countries, we received two responses that were consistent and matched well with other countries of comparable purchasing power parity. For one country, we received only one response; however...

To respond to metal surpluses, cells have developed intricate ways of defense against the excessive metallic ions. To understand the ways in which cells sense the presence of toxic concentration in the environment, the role of Ca in mediating the cell response to high Cu was investigated in Saccharomyces cerevisiae cells. It was found that the cell exposure to high Cu was accompanied by elevations in cytosolic Ca with patterns that were influenced not only by Cu concentration but also by the oxidative state of the cell. When Ca channel deletion mutants were used, it was revealed that the main contributor to the cytosolic Ca pool under Cu stress was the vacuolar Ca channel, Yvc1, also activated by the Cch1-mediated Ca influx. Using yeast mutants defective in the Cu transport across the plasma membrane, it was found that the Cu-dependent Ca elevation could correlate not only with the accumulated metal, but also with the overall oxidative status. Moreover, it was revealed that Cu and HO acted in synergy to induce Ca-mediated responses to external stress.

The involvement of Ca2+ in the response to high Mn2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, and Hg2+ was investigated in Saccharomyces cerevisiae. The yeast cells responded through a sharp increase in cytosolic Ca2+ when exposed to Cd2+, and to a lesser extent to Cu2+, but not to Mn2+, Co2+, Ni2+, Zn2+, or Hg2+. The response to high Cd2+ depended mainly on external Ca2+ (transported through the Cch1p/Mid1p channel) but also on vacuolar Ca2+ (released into the cytosol through the Yvc1p channel). The adaptation to high Cd2+ was influenced by perturbations in Ca2+ homeostasis. Thus, the tolerance to Cd2+ often correlated with sharp Cd2+‐induced cytosolic Ca2+ pulses, while the Cd2+ sensitivity was accompanied by the incapacity to rapidly restore the low cytosolic Ca2+.

A retrospective cohort design was used to study the impact of a multiplex respiratory virus panel polymerase chain reaction test in 186 adult patients with suspected influenza-like illness. Decisions regarding continuation of empirical antiviral therapy appear to be impacted by the test. However, the impact on reducing antibiotic use remains unclear.

BackgroundSystematic reviews are increasingly informing policies in tuberculosis (TB) care and control. They may also be a source of questions for future research. As part of the process of developing the International Roadmap for TB Research, we did a systematic review of published systematic reviews on TB, to identify research priorities that are most frequently suggested in reviews.Methodology/Principal FindingsWe searched EMBASE, MEDLINE, Web of Science, and the Cochrane Library for systematic reviews and meta-analyses on any aspect of TB published between 2005 and 2010. One reviewer extracted data and a second reviewer independently extracted data from a random subset of included studies. In total, 137 systematic reviews, with 141 research questions, were included in this review. We used the UK Health Research Classification System (HRCS) to help us classify the research questions and priorities. The three most common research topics were in the area of detection, screening and diagnosis of TB (32.6%), development and evaluation of treatments and therapeutic interventions (23.4%), and TB aetiology and risk factors (19.9%). The research priorities determined were mainly focused on the discovery and evaluation of bacteriological TB tests and drug-resistant TB tests and immunological tests. Other important topics of future research were genetic susceptibility linked to TB and disease determinants attributed to HIV/TB. Evaluation of drug treatments for TB, drug-resistant TB and HIV/TB were also frequently proposed research topics.ConclusionsSystematic reviews are a good source of key research priorities. Findings from our survey have informed the development of the International Roadmap for TB Research by the TB Research Movement.