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Black root rot (BRR) is an economically important disease of cotton and other crops, especially in cooler regions with short growing seasons. Symptoms include black discoloration of the roots, reduced number of lateral roots and stunted or slow plant growth. The cultivated tetraploid Gossypium species are susceptible to BRR. Resistance to BRR was identified in G. arboreum accession BM13H and is associated with reduced and restricted hyphal growth and less sporulation. Transcriptome analysis indicates that BM13H responds to infection at early time points 2- and 3-days post-inoculation, but by day 5, few differentially expressed genes are observed between infected and uninfected roots. Inheritance of BM13H resistance to BRR was evaluated in an F 6 recombinant inbred population and shows a single semi-dominant locus conferring resistance that was fine mapped to a region on chromosome 1, containing ten genes including five putative resistance-like genes.

Background: Targeted preventive therapy for individuals at highest risk of incident tuberculosis might impact the epidemic by interrupting transmission. We tested performance of a transcriptomic signature of tuberculosis (RISK11) and efficacy of signature-guided preventive therapy in parallel, using a hybrid three-group study design., Methods: Adult volunteers aged 18-59 years were recruited at five geographically distinct communities in South Africa. Whole blood was sampled for RISK11 by quantitative RT-PCR assay from eligible volunteers without HIV, recent previous tuberculosis (ie, <3 years before screening), or comorbidities at screening. RISK11-positive participants were block randomised (1:2; block size 15) to once-weekly, directly-observed, open-label isoniazid and rifapentine for 12 weeks (ie, RISK11 positive and 3HP positive), or no treatment (ie, RISK11 positive and 3HP negative). A subset of eligible RISK11-negative volunteers were randomly assigned to no treatment (ie, RISK11 negative and 3HP negative). Diagnostic discrimination of prevalent tuberculosis was tested in all participants at baseline. Thereafter, prognostic discrimination of incident tuberculosis was tested in the untreated RISK11-positive versus RISK11-negative groups, and treatment efficacy in the 3HP-treated versus untreated RISK11-positive groups, during active surveillance through 15 months. The primary endpoint was microbiologically confirmed pulmonary tuberculosis. The primary outcome measures were risk ratio [RR] for tuberculosis of RISK11-positive to RISK11-negative participants, and treatment efficacy. This trial is registered with ClinicalTrials.gov, NCT02735590., Findings: 20 207 volunteers were screened, and 2923 participants were enrolled, including RISK11-positive participants randomly assigned to 3HP (n=375) or no 3HP (n=764), and 1784 RISK11-negative participants. Cumulative probability of prevalent or incident tuberculosis disease was 0·066 (95% CI 0·049 to 0·084) in RISK11-positive (3HP negative) participants and 0·018 (0·011 to 0·025) in RISK11-negative participants (RR 3·69, 95% CI 2·25-6·05) over 15 months. Tuberculosis prevalence was 47 (4·1%) of 1139 versus 14 (0·78%) of 1984 in RISK11-positive compared with RISK11-negative participants, respectively (diagnostic RR 5·13, 95% CI 2·93 to 9·43). Tuberculosis incidence over 15 months was 2·09 (95% CI 0·97 to 3·19) vs 0·80 (0·30 to 1·30) per 100 person years in RISK11-positive (3HP-negative) participants compared with RISK11-negative participants (cumulative incidence ratio 2·6, 95% CI 1·2 to 5·9). Serious adverse events related to 3HP included one hospitalisation for seizures (unintentional isoniazid overdose) and one death of unknown cause (possibly temporally related). Tuberculosis incidence over 15 months was 1·94 (95% CI 0·35 to 3·50) versus 2·09 (95% CI 0·97 to 3·19) per 100 person-years in 3HP-treated RISK11-positive participants compared with untreated RISK11-positive participants (efficacy 7·0%, 95% CI -145 to 65)., Interpretation: The RISK11 signature discriminated between individuals with prevalent tuberculosis, or progression to incident tuberculosis, and individuals who remained healthy, but provision of 3HP to signature-positive individuals after exclusion of baseline disease did not reduce progression to tuberculosis over 15 months., Funding: Bill and Melinda Gates Foundation, South African Medical Research Council., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: People from ethnic minority groups experience higher rates of paranoid delusions compared with people from ethnic majority groups. Identifying with social groups has been shown to protect against mental health symptoms; however, no studies have investigated the relationship between social identification and paranoia in ethnic minority populations. Here, we investigated the association between British identification and paranoia in a sample of people from African and African Caribbean backgrounds living in the United Kingdom. We also assessed the role of potential mediating (self-esteem and locus of control) and moderating (contact with White British people) factors., Design: Cross-sectional quantitative survey design., Methods: We recruited 335 people from African and African Caribbean backgrounds who completed online self-report measures of identification with Great Britain, self-esteem, locus of control, positive and negative contact with White British people, and paranoia., Results: A parallel moderated mediation model indicated that British identification was associated with lower paranoia when participants experienced primarily positive contact with White British people. British identification was associated with higher paranoia when participants had primarily negative contact with White British people. Both effects were mediated by changes in locus of control, but self-esteem was not implicated in either pathway., Conclusions: Identification with the majority culture is associated both positively and negatively with paranoid beliefs depending on the types of social interactions people experience. The findings have implications for preventative social prescribing initiatives and for understanding the causes of the high rates of psychosis in ethnic minority populations., Practitioner Points: People from African and African Caribbean backgrounds experience high rates of paranoia, which may stem from social causes such as lack of belonging and negative social experiences. Among people from African backgrounds living in the UK, British identification is associated with lower paranoia when people's social experiences with White British people are positive and higher paranoia when their social experiences with White British people are negative. It is recommended that social interventions designed to reduce paranoia in vulnerable groups foster positive social contact and community belonging, which should enhance feelings of personal control. Understanding the complex interplay between social identity and social contact in the development of paranoia may help therapists and researchers better understand the phenomenology and risk factors of paranoid symptomology., (© 2019 The British Psychological Society.)

Background: Despite recent advances through the development pipeline, how novel tuberculosis (TB) vaccines might affect rifampicin-resistant and multidrug-resistant tuberculosis (RR/MDR-TB) is unknown. We investigated the epidemiologic impact, cost-effectiveness, and budget impact of hypothetical novel prophylactic prevention of disease TB vaccines on RR/MDR-TB in China and India., Methods: We constructed a deterministic, compartmental, age-, drug-resistance- and treatment history-stratified dynamic transmission model of tuberculosis. We introduced novel vaccines from 2027, with post- (PSI) or both pre- and post-infection (P&PI) efficacy, conferring 10 years of protection, with 50% efficacy. We measured vaccine cost-effectiveness over 2027-2050 as USD/DALY averted-against 1-times GDP/capita, and two healthcare opportunity cost-based (HCOC), thresholds. We carried out scenario analyses., Results: By 2050, the P&PI vaccine reduced RR/MDR-TB incidence rate by 71% (UI: 69-72) and 72% (UI: 70-74), and the PSI vaccine by 31% (UI: 30-32) and 44% (UI: 42-47) in China and India, respectively. In India, we found both USD 10 P&PI and PSI vaccines cost-effective at the 1-times GDP and upper HCOC thresholds and P&PI vaccines cost-effective at the lower HCOC threshold. In China, both vaccines were cost-effective at the 1-times GDP threshold. P&PI vaccine remained cost-effective at the lower HCOC threshold with 49% probability and PSI vaccines at the upper HCOC threshold with 21% probability. The P&PI vaccine was predicted to avert 0.9 million (UI: 0.8-1.1) and 1.1 million (UI: 0.9-1.4) second-line therapy regimens in China and India between 2027 and 2050, respectively., Conclusions: Novel TB vaccination is likely to substantially reduce the future burden of RR/MDR-TB, while averting the need for second-line therapy. Vaccination may be cost-effective depending on vaccine characteristics and setting.

Background: Impacts of the Covid-19 pandemic and its public health measures go beyond physical and mental health and incorporate wider well-being impacts in terms of what people are free to do or be. We explored the impacts of the Covid-19 lockdown and relevant vulnerabilities on capability well-being, mental health and social support in Austria., Methods: Adult Austrian residents (n = 560) provided responses to a cross-sectional online survey about their experiences during Covid-19 lockdown (15 March-15 April 2020). Instruments measuring capabilities (OxCAP-MH), depression and anxiety (HADS), social support (MSPSS) and mental well-being (WHO-5) were used in association with six pre-defined vulnerabilities using multivariable linear regression., Results: 31% of the participants reported low mental well-being and only 30% of those with a history of mental health treatment received treatment during lockdown. Past mental health treatment had a significant negative effect across all outcome measures with an associated capability well-being score reduction of - 6.54 (95%CI, - 9.26, - 3.82). Direct Covid-19 experience and being 'at risk' due to age and/or physical health conditions were also associated with significant capability deprivations. When adjusted for vulnerabilities, significant capability reductions were observed in association with increased levels of depression (- 1.77) and anxiety (- 1.50), and significantly higher capability levels (+ 3.75) were associated with higher levels of social support. Compared to the cohort average, individual capability impacts varied between - 9% for those reporting past mental health treatment and + 5% for those reporting one score higher on the social support scale., Conclusions: Our study is the first to assess the capability limiting aspects of lockdown and relevant vulnerabilities alongside their impacts on mental health and social support. The negative capability well-being, mental health and social support impacts of the Covid-19 lockdown were strongest for people with a history of mental health treatment. Future public health policies concerning lockdowns should pay special attention to improve social support levels in order to increase public resilience.

Previous analyses suggest that children with tuberculosis (TB) are no more or no less likely to have multidrug (MDR)- or rifampicin-resistant (RR)-TB than adults. However, the availability of new data, particularly for high MDR/RR-TB burden countries, suggest updates of country-specific estimates are warranted.We used data from population-representative surveys and surveillance collected between 2000 and 2018 to compare the odds ratio of MDR/RR-TB among children (aged <15 years) with TB, compared to the odds of MDR/RR-TB among adults (aged ≥15 years) with TB.In most settings (45 out of 55 countries), and globally as a whole, there is no evidence that age is associated with odds of MDR/RR-TB. However, in some settings, such as former Soviet Union countries in general, and Georgia, Kazakhstan, Lithuania, Tajikistan and Uzbekistan in particular, as well as Peru, MDR/RR-TB is positively associated with age ≥15 years. Meanwhile, in Western Europe in general, and the United Kingdom, Poland, Finland and Luxembourg in particular, MDR/RR-TB is positively associated with age <15 years. 16 countries had sufficient data to compare over time between 2000-2011 and 2012-2018, with evidence for decreases in the odds ratio in children compared to adults in Germany, Kazakhstan and the United States of America.Our results support findings that in most settings a child with TB is as likely as an adult with TB to have MDR/RR-TB. However, setting-specific heterogeneity requires further investigation. Furthermore, the odds ratio for MDR/RR-TB in children compared to adults is generally either stable or decreasing. There are important gaps in detection, recording and reporting of drug resistance among paediatric TB cases, limiting our understanding of transmission risks and measures needed to combat the global TB epidemic., Competing Interests: Conflict of interest: C.F. McQuaid has nothing to disclose. Conflict of interest: T. Cohen has nothing to disclose. Conflict of interest: A.S. Dean has nothing to disclose. Conflict of interest: R.M.G.J. Houben has nothing to disclose. Conflict of interest: G.M. Knight has nothing to disclose. Conflict of interest: M. Zignol has nothing to disclose. Conflict of interest: R.G. White has nothing to disclose., (Copyright ©ERS 2021.)

Background : it is widely assumed that individuals with Mycobacterium tuberculosis ( Mtb ) infection remain at lifelong risk of tuberculosis (TB) disease. However, there is substantial evidence that self-clearance of Mtb infection can occur. We infer a curve of self-clearance by time since infection and explore its implications for TB epidemiology. Methods and findings : data for self-clearance were inferred using post-mortem and tuberculin-skin-test reversion studies. A cohort model allowing for self-clearance was fitted in a Bayesian framework before estimating the lifetime risk of TB disease and the population infected with Mtb in India, China and Japan in 2019. We estimated that 24.4% (17.8-32.6%, 95% uncertainty interval (UI)) of individuals self-clear within 10 years of infection, and 73.1% (64.6-81.7%) over a lifetime. The lifetime risk of TB disease was 17.0% (10.9-22.5%), compared to 12.6% (10.1-15.0%) assuming lifelong infection. The population at risk of TB disease in India, China and Japan was 35-80% (95% UI) smaller in the self-clearance scenario. Conclusions : the population with a viable Mtb infection may be markedly smaller than generally assumed, with such individuals at greater risk of TB disease. The ability to identify these individuals could dramatically improve the targeting of preventive programmes and inform TB vaccine development, bringing TB elimination within reach of feasibility.

Developing a vaccine against the global pandemic SARS-CoV-2 is a critical area of active research. Modelling can be used to identify optimal vaccine dosing; maximising vaccine efficacy and safety and minimising cost. We calibrated statistical models to published dose-dependent seroconversion and adverse event data of a recombinant adenovirus type-5 (Ad5) SARS-CoV-2 vaccine given at doses 5.0 × 10 10 , 1.0 × 10 11 and 1.5 × 10 11 viral particles. We estimated the optimal dose for three objectives, finding: (A) the minimum dose that may induce herd immunity, (B) the dose that maximises immunogenicity and safety and (C) the dose that maximises immunogenicity and safety whilst minimising cost. Results suggest optimal dose [95% confidence interval] in viral particles per person was (A) 1.3 × 10 11 [0.8-7.9 × 10 11 ], (B) 1.5 × 10 11 [0.3-5.0 × 10 11 ] and (C) 1.1 × 10 11 [0.2-1.5 × 10 11 ]. Optimal dose exceeded 5.0 × 10 10 viral particles only if the cost of delivery exceeded £0.65 or cost per 10 11 viral particles was less than £6.23. Optimal dose may differ depending on the objectives of developers and policy-makers, but further research is required to improve the accuracy of optimal-dose estimates.

Tuberculosis remains a major source of morbidity and mortality worldwide, with 10 million cases and 1.5 million deaths in 2018. Achieving 'End TB' prevention and care goals by 2035 will likely require a new tuberculosis vaccine. The tuberculosis vaccine development pipeline has seen encouraging progress; however, questions around their population impact and implementation remain. Mathematical modelling investigates these questions to inform vaccine development and deployment strategies. We provide an update on the current vaccine development pipeline, and a systematic literature review of mathematical modelling of the epidemiological impact of new tuberculosis vaccines. Fourteen prophylactic tuberculosis vaccine candidates are currently in clinical trials. Two candidates have shown promise in phase II proof-of-concept efficacy trials: M72/AS01 E demonstrated 49.7% (95% CI; 2.1, 74.2) protection against tuberculosis disease, and BCG revaccination demonstrated 45.4% (95% CI; 6.4, 68.1) protection against sustained Mycobacterium tuberculosis infection. Since the last modelling review, new studies have investigated the epidemiological impact of differential vaccine characteristics, age targeting and spatial/risk group targeting. Critical research priorities for M72/AS01 E include completing the currently in-design trial, powered to improve the precision of efficacy estimates, include uninfected populations and further assess safety and immunogenicity in HIV-infected people. For BCG revaccination, the priority is completing the ongoing confirmation of efficacy trial. Critical modelling gaps remain on the full value proposition of vaccines, comparisons with other interventions and more realistic implementation strategies. Using carefully designed trials and modelling, we must prepare for success, to ensure that new vaccines will be promptly received by those most in need., (© 2020 The Association for the Publication of the Journal of Internal Medicine.)

Background: Following infection with Mycobacterium tuberculosis (M.tb), individuals may rapidly develop tuberculosis (TB) disease or enter a "latent" infection state with a low risk of progression to disease. Mathematical models use a variety of structures and parameterisations to represent this process. The effect of these different assumptions on the predicted impact of TB interventions has not been assessed., Methods: We explored how the assumptions made about progression from infection to disease affect the predicted impact of TB preventive therapy. We compared the predictions using three commonly used model structures, and parameters derived from two different data sources., Results: The predicted impact of preventive therapy depended on both the model structure and parameterisation. At a baseline annual TB incidence of 500/100,000, there was a greater than 2.5-fold difference in the predicted reduction in incidence due to preventive therapy (ranging from 6 to 16%), and the number needed to treat to avert one TB case varied between 67 and 157. The relative importance of structure and parameters depended on baseline TB incidence and assumptions about the efficacy of preventive therapy, with the choice of structure becoming more important at higher incidence., Conclusions: The assumptions use to represent progression to disease in models are likely to influence the predicted impact of preventive therapy and other TB interventions. Modelling estimates of TB preventive therapy should consider routinely incorporating structural uncertainty, particularly in higher burden settings. Not doing so may lead to inaccurate and over confident conclusions, and sub-optimal evidence for decision making.

Background: Refugees fleeing conflict often experience poor mental health due to experiences in their country of origin, during displacement, and in new host environments. Conditions in refugee camps and settlements, and the wider socio-political and economic context of refugees' lives, create structural conditions that compound the effects of previous adversity. Mental health and psychosocial support services must address the daily stressors and adversities refugees face by being grounded in the lived reality of refugee's lives and addressing issues relevant to them., Methods: We undertook a rapid qualitative study between March and May 2019 to understand the local prioritisation of problems facing Congolese refugees living in two refugee settings in Uganda and Rwanda. Thirty free list interviews were conducted in each setting, followed by 11 key informant interviews in Uganda and 12 in Rwanda., Results: Results from all interviews were thematically analysed following a deductive process by the in-country research teams. Free list interview findings highlight priority problems of basic needs such as food, shelter, and healthcare access; alongside contextual social problems including discrimination/inequity and a lack of gender equality. Priority problems relating to mental and psychosocial health explored in key informant interviews include discrimination and inequity; alcohol and substance abuse; and violence and gender-based violence., Conclusions: Our findings strongly resonate with models of mental health and psychosocial wellbeing that emphasise their socially determined and contextually embedded nature. Specifically, findings foreground the structural conditions of refugees' lives such as the physical organisation of camp spaces or refugee policies that are stigmatising through restricting the right to work or pursue education. This structural environment can lead to disruptions in social relationships at the familial and community levels, giving rise to discrimination/inequity and gender-based violence. Therefore, our findings foreground that one consequence of living in situations of pervasive adversity caused by experiences of discrimination, inequity, and violence is poor mental health and psychosocial wellbeing. This understanding reinforces the relevance of feasible and acceptable intervention approaches that aim to strengthening familial and community-level social relationships, building upon existing community resources to promote positive mental health and psychosocial wellbeing among Congolese refugees in these settings.

More effective tuberculosis vaccines are needed to help reach World Health Organization tuberculosis elimination goals. Insufficient evidence exists on the potential impact of future tuberculosis vaccines with varying characteristics and in different epidemiological settings. To inform vaccine development decision making, we modeled the impact of hypothetical tuberculosis vaccines in three high-burden countries. We calibrated Mycobacterium tuberculosis ( M.tb ) transmission models to age-stratified demographic and epidemiological data from China, South Africa, and India. We varied vaccine efficacy to prevent infection or disease, effective in persons M.tb uninfected or infected, and duration of protection. We modeled routine early-adolescent vaccination and 10-yearly mass campaigns from 2025. We estimated median percentage population-level tuberculosis incidence rate reduction (IRR) in 2050 compared to a no new vaccine scenario. In all settings, results suggested vaccines preventing disease in M.tb -infected populations would have greatest impact by 2050 (10-year, 70% efficacy against disease, IRR 51%, 52%, and 54% in China, South Africa, and India, respectively). Vaccines preventing reinfection delivered lower potential impact (IRR 1, 12, and 17%). Intermediate impact was predicted for vaccines effective only in uninfected populations, if preventing infection (IRR 21, 37, and 50%) or disease (IRR 19, 36, and 51%), with greater impact in higher-transmission settings. Tuberculosis vaccines have the potential to deliver substantial population-level impact. For prioritizing impact by 2050, vaccine development should focus on preventing disease in M.tb -infected populations. Preventing infection or disease in uninfected populations may be useful in higher transmission settings. As vaccine impact depended on epidemiology, different development strategies may be required., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Males are at an increased risk of tuberculosis (TB) disease compared to females. Additionally, several risk factors for multidrug-resistant (MDR) or rifampicin-resistant (RR) TB disease are more common in males, hence male TB patients may have a higher relative risk of MDR/RR-TB than female TB patients.We used sex-disaggregated data of TB patients reported to the World Health Organization for 106 countries to calculate male-to-female (M:F) risk ratios of having MDR/RR-TB.There was no evidence of either sex being more at risk of MDR/RR-TB in 81% (86 out of 106) of countries, with an overall random-effects weighted M:F risk ratio of 1.04 (95% CI 0.97-1.11). In 12% (13 out of 106) of countries there was evidence that males were more at risk, while in 7% (seven out of 106), females were more at risk. The risk of having TB that was MDR/RR increased for males compared to females as MDR/RR-TB incidence increased, and was higher for males than females in the former Soviet Union, where the risk ratio was 1.16 (1.06-1.28). Conversely, the risk increased for females compared to males as gross domestic product purchase power parity increased, and was higher for females than males in countries where the majority of TB burden was found in the foreign-born population, where the risk ratio was 0.84 (0.75-0.94).In general, the risk of MDR/RR-TB, among those with TB, is the same for males as for females. However, males in higher MDR/RR-TB burden countries, particularly the former Soviet Union, face an increased risk that their infection is MDR/RR-TB, highlighting the need for a sex-differentiated approach to TB case-finding and care., Competing Interests: Conflict of interest: C.F. McQuaid has nothing to disclose. Conflict of interest: K.C. Horton has nothing to disclose. Conflict of interest: A.S. Dean has nothing to disclose. Conflict of interest: G.M. Knight has nothing to disclose. Conflict of interest: R.G. White has nothing to disclose., (The content of this work is copyright of the authors or their employers. Design and branding are copyright ©ERS 2020.)

The impact of the COVID-19 pandemic on mental health and well-being were assessed in a convenience sample of 600 UK adults, using a cross-sectional design. Recruited over 2 weeks during the initial phase of lockdown, participants completed an online survey that included COVID-19-related questions, the Hospital Anxiety and Depression Scale, the World Health Organization (Five) Well-Being Index and the Oxford Capabilities Questionnaire for Mental Health. Self-isolating before lockdown, increased feelings of isolation since lockdown and having COVID-19-related livelihood concerns were associated with poorer mental health, well-being and quality of life. Perceiving increased kindness, community connectedness and being an essential worker were associated with better mental health and well-being outcomes.

The stressful experiences that many asylum seekers and refugees (AS&R) are exposed to during forced migration, and during resettlement in host countries, can have a profound impact on their mental health. Comparatively less research attention has been allocated to exploring other indices of quality of life (QoL) in AS&R populations. This review aimed to (i) synthesize the predictors and correlates of QoL of AS&R populations in high-income countries, and (ii) to identify the methodological strengths and weaknesses of this body of research. Fourteen databases were systematically searched (Medline, PsychINFO, CINAHL, Cochrane Library, Health Technology Assessment, National Health Service Economic Evaluation, Educational Resource Index and Abstracts, BiblioMap, Scopus, Social Sciences Citation Index, Evidence Aid, DARE, Web of Science and PubMed). Eligibility criteria included: adults seeking asylum or refuge in a high-income country, primary quantitative data, the use of a measure based on the WHO's definition of QoL, published in a peer-reviewed journal. A narrative synthesis approach was used, and the quality was assessed using the AXIS tool for cross-sectional studies and the CASP tool for longitudinal studies. Of the 13.656 papers identified, 23 met the eligibility criteria. A wide range of factors were found to have significant associations with QoL. Both positive and negative correlates of QoL were largely dominated by social (e.g. social networks) and mental health factors (e.g. depression). Although all of the cross-sectional studies met over half of the quality criteria, only 12 met 75% or more of these criteria. For the longitudinal studies, for all but one study lacked statistical precision and the results cannot be applied to the local population. Key findings across the various forms of QoL (overall, physical, psychological, social and environmental) were that having established social networks and social integration were associated with higher QoL, whereas having mental disorders (i.e. PTSD or depression) was strongly associated with reduced QoL. More research is needed into physical and environmental predictors and correlates of QoL. The findings of the review can be used to inform policies and interventions aimed at supporting AS&R and promoting the integration and wellbeing of these populations., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Social contact patterns might contribute to excess burden of tuberculosis in men. We conducted a study of social contact surveys to evaluate contact patterns relevant to tuberculosis transmission. Available data describe 21 surveys in 17 countries and show profound differences in sex-based and age-based patterns of contact. Adults reported more adult contacts than children. Children preferentially mixed with women in all surveys (median sex assortativity 58%, interquartile range [IQR] 57%-59% for boys, 61% [IQR 60%-63%] for girls). Men and women reported sex-assortative mixing in 80% and 95% of surveys (median sex assortativity 56% [IQR 54%-58%] for men, 59% [IQR 57%-63%] for women). Sex-specific patterns of contact with adults were similar at home and outside the home for children; adults reported greater sex assortativity outside the home in most surveys. Sex assortativity in adult contacts likely contributes to sex disparities in adult tuberculosis burden by amplifying incidence among men.

Background: Asylum seekers and refugees (AS&Rs) experience impaired mental health and wellbeing, related to stresses in their country of origin, experiences in transit and reception on arrival, including significant barriers to accessing mainstream services. Their contact with health care is often crisis-driven and mediated through non-governmental organisations (NGOs). Problem Management Plus (PM+) is a psychosocial intervention recommended by the World Health Organisation to address distress experienced by adults affected by humanitarian crises. We are investigating its application for the first time in a high-income country., Methods: In a pilot randomised controlled trial (RCT), PM+ will be delivered to AS&Rs in contact with NGOs in Liverpool City Region, UK by lay therapists who have lived experience of forced migration. Following systematic review and stakeholder engagement, PM+ has been adapted to the local context, and lay therapists have been trained in its delivery. We will assess the feasibility of conducting a three-arm RCT of five 90-min sessions of PM+, delivered individually or in groups by lay therapists to AS&Rs experiencing emotional distress and functional impairment, compared with each other and with usual support offered by local NGOs. Distress and impairment at baseline will be measured by the Hospital Anxiety and Depression Scale (HADS) and the WHO Disability Assessment Schedule (WHO-DAS). We aim to recruit 105 participants, 35 per arm. Primary health outcomes are anxiety and depressive symptoms at 3 months, measured by HADS. Secondary outcomes include subjective wellbeing, functional status, progress on identified problems, presence of post-traumatic stress disorder and depressive disorder and service usage. Longer-term impact will be assessed at 6 months post baseline, on the same parameters. We will assess the feasibility of conducting a full RCT in relation to the following elements: recruitment and retention of lay therapists and study participants; fidelity of delivery of PM+; and suitability of the study measures, including any linguistic or cultural barriers., Discussion: We will use these findings to specify the parameters for a full RCT to test the effectiveness and cost-effectiveness of PM+ in reducing emotional distress and health inequalities, and improving functional ability and wellbeing, amongst asylum seekers and refugees., Trial Registration: ISRCTN, ID: ISRCTN15214107. Registered on 10 September 2019.

BACKGROUND: In South Africa, it is generally estimated that only 0.5-0.6% of people's contacts occur in clinics. Both people with infectious tuberculosis and people with increased susceptibility to disease progression may spend more time in clinics, however, increasing the importance of clinic-based transmission to overall disease incidence. METHODS: We developed an illustrative mathematical model of Mycobacterium tuberculosis transmission in clinics and other settings. We assumed that 1% of contact time occurs in clinics. We varied the ratio of clinic contact time of human immunodeficiency virus (HIV) positive people compared to HIV-negative people, and of people with infectious TB compared to people without TB, while keeping the overall proportion of contact time occurring in clinics, and each person's total contact time, constant. RESULTS: With clinic contact rates respectively 10 and 5 times higher in HIV-positive people and people with TB, 10.7% (plausible range 8.5-13.4%) of TB resulted from transmission in clinics. With contact rates in HIV-positive people and people with TB respectively 5 and 2 times higher, 5.3% (plausible range 4.3-6.3%) of all TB was due to transmission in clinics. CONCLUSION: The small amount of contact time that generally occurs in clinics may greatly underestimate their contribution to TB disease in high TB-HIV burden settings.

Background: Innovative solutions are required to provide mental health support at scale in low-resource humanitarian contexts. We aimed to assess the effectiveness of a facilitator-guided, group-based, self-help intervention (Self-Help Plus) to reduce psychological distress in female refugees., Methods: We did a cluster randomised trial in rural refugee settlements in northern Uganda. Participants were female South Sudanese refugees with at least moderate levels of psychological distress (cutoff ≥5 on the Kessler 6). The intervention comprised access to usual care and five 2-h audio-recorded stress-management workshops (20-30 refugees) led by briefly trained lay facilitators, accompanied by an illustrated self-help book. Villages were randomly assigned to either intervention (Self-Help Plus or enhanced usual care) on a 1:1 basis. Within 14 villages, randomly selected households were approached. Screening of women in households continued until 20-30 eligible participants were identified per site. The primary outcome was individual psychological distress, assessed using the Kessler 6 symptom checklist 1 week before, 1 week after, and 3 months after intervention, in the intention-to-treat population. All outcomes were measured at the individual (rather than cluster) level. Secondary outcomes included personally identified problems, post-traumatic stress, depression symptoms, feelings of anger, social interactions with other ethnic groups, functional impairment, and subjective wellbeing. Assessors were masked to allocation. This trial was prospectively registered at ISRCTN, number 50148022., Findings: Of 694 eligible participants (331 Self-Help Plus, 363 enhanced usual care), 613 (88%) completed all assessments. Compared with controls, we found stronger improvements for Self-Help Plus on psychological distress 3 months post intervention (β -1·20, 95% CI -2·33 to -0·08; p=0·04; d -0·26). We also found larger improvements for Self-Help Plus 3 months post-intervention for five of eight secondary outcomes (effect size range -0·30 to -0·36). Refugees with different trauma exposure, length of time in settlements, and initial psychological distress benefited similarly. With regard to safety considerations, the independent data safety management board responded to six adverse events, and none were evaluated to be concerns in response to the intervention., Interpretation: Self-Help Plus is an innovative, facilitator-guided, group-based self-help intervention that can be rapidly deployed to large numbers of participants, and resulted in meaningful reductions in psychological distress at 3 months among South Sudanese female refugees., Funding: Research for Health in Humanitarian Crises (R2HC) Programme., (Copyright © 2020 This is an Open Access article published under the CC BY-NC-ND 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

There is growing recognition that "human development" frameworks, such as the Capabilities Approach (CA) with its emphasis on the promotion of justice, offer promise for guiding efforts aimed at enhancing mental wellbeing. This article explores challenges that might arise when there is a need to arbitrate among the competing demands of different parties in their efforts to enhance capabilities. Particular tensions can arise when the efforts of particular individuals to enhance their capabilities exert pressure on scarce resources, or threaten the safety and security of people living in precarious environmental contexts. Consideration is given to the need for "an ethos of restraint" to balance the consumption of resources aimed at facilitating human development on the one hand, with the need to promote environmental justice on the other. The paper highlights research that has investigated how environmental factors can impact on mental wellbeing, including rapid urbanization, climate change related issues (such as weather systems, drought, food insecurity and rising sea-levels), and access to "green/blue spaces". As such, the paper explores the important links that can exist between people and the ecosystems in which they live (including the way in which particular cultural beliefs and practices of indigenous groups can be tethered to the land). Elinor Ostrom's "design principles", derived from her work investigating the sustainable use of pooled resources, are presented as a helpful means of assisting members of communities to negotiate and apply "functioning constraints", which can promote environmental justice whilst not compromising efforts aimed at promoting mental wellbeing.

Mycobacterium tuberculosis (Mtb) kills more people worldwide than any single infectious pathogen, yet the only vaccine licensed against tuberculosis, Bacille Calmette Guerin (BCG) is approaching its centenary. Two recent advances in clinical tuberculosis vaccine development have invigorated the field. BCG revaccination of interferon-gamma release assay (IGRA) negative adolescents provided 45% protection against sustained Mtb infection defined by IGRA conversion; and the protein-subunit vaccine M72/AS01 E provided 50% protection against progression from Mtb infection to tuberculosis disease in IGRA-positive adults. These findings provide encouraging evidence for pre-exposure and post-exposure approaches to vaccination against tuberculosis, both of which may be necessary to rapidly interrupt the cycle of Mtb transmission and sustain long-term impact on global tuberculosis control. New trials are needed to demonstrate efficacy of M72/AS01 E with greater precision, in a wider age range, in diverse epidemic settings, and in populations that include Mtb-uninfected and HIV-infected persons. Modeling the impact of mass campaigns with M72/AS01 E and other fast-follower vaccine candidates will be crucial to make the use case and demonstrate public health value for TB endemic countries. The size and scope of the next generation of efficacy trials, and the need to expand and accelerate the existing clinical development pipeline, will require public and private consortium funding and concerted political will., (Copyright © 2020 Hatherill, White and Hawn.)

Background: BCG has been recommended at birth in countries with a high tuberculosis burden for decades, yet delayed vaccination is widespread. To support a WHO guidance review, we estimated the potential global tuberculosis mortality benefit of administering BCG on time and consequences of later administration., Methods: We estimated age-specific BCG coverage in 152 high-burden countries using data from large, nationally representative household surveys, to parameterise a static mathematical model, calibrated to global childhood tuberculosis deaths in 2016. 12 hypothetical scenarios explored the effect of BCG delivery at birth, 6 weeks, 6 months, or 9-12 months, on tuberculosis deaths per global birth cohort by age 15 years, including delivery at the time of the first diphtheria-tetanus-pertussis vaccine (DTP1) or the first measles-containing vaccine (MCV1). We assumed constant vaccine efficacy by age, but varied coverage and degree of vaccination delay, including no delay., Findings: In 152 high-burden countries, we estimated that BCG coverage in 2016 was 37% at 1 week of age, 67% at 6 weeks, and 92% at 3 years. Modelled scenarios in which 92% BCG coverage was achieved at birth reduced tuberculosis deaths in the global birth cohort by 5449 (95% uncertainty range 218-15 071) or 2·8% (0·1-7·0) by age 15 years. 100% coverage at birth reduced tuberculosis deaths by 16·5% (0·7-41·9). Later administration increased tuberculosis deaths-eg, BCG vaccination at 6 weeks, the recommended age of DTP1, increased tuberculosis deaths by 0·2% (0-0·4), even if BCG reached DTP1 coverage levels (94% at 3 years)., Interpretation: Reducing delays and increasing coverage at birth would substantially reduce global paediatric tuberculosis mortality. Modelled scenarios whereby BCG was administered later in the infant schedule were all estimated to increase tuberculosis deaths, even with increased coverage. The WHO recommendation for BCG at birth should be maintained and emphasised., Funding: WHO., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Age-mixing patterns can have substantial effects on infectious disease dynamics and intervention effects. Data on close contacts (people spoken to and/or touched) are often used to estimate age-mixing. These are not the only relevant contacts for airborne infections such as tuberculosis, where transmission can occur between anybody 'sharing air' indoors. Directly collecting data on age-mixing patterns between casual contacts (shared indoor space, but not 'close') is difficult however. We demonstrate a method for indirectly estimating age-mixing patterns between casual indoor contacts from social contact data., Methods: We estimated age-mixing patterns between close, casual, and all contacts using data from a social contact survey in South Africa. The age distribution of casual contacts in different types of location was estimated from the reported time spent in the location type by respondents in each age group., Results: Patterns of age-mixing calculated from contact numbers were similar between close and all contacts, however patterns of age-mixing calculated from contact time were more age-assortative in all contacts than in close contacts. There was also more variation by age group in total numbers of casual and all contacts, than in total numbers of close contacts. Estimates were robust to sensitivity analyses., Conclusions: Patterns of age-mixing can be estimated for all contacts using data that can be easily collected as part of social contact surveys or time-use surveys, and may differ from patterns between close contacts., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Rapid metabolite diffusion across the mesophyll (M) and bundle sheath (BS) cell interface in C 4 leaves is a key requirement for C 4 photosynthesis and occurs via plasmodesmata (PD). Here, we investigated how growth irradiance affects PD density between M and BS cells and between M cells in two C 4 species using our PD quantification method, which combines three-dimensional laser confocal fluorescence microscopy and scanning electron microscopy. The response of leaf anatomy and physiology of NADP-ME species, Setaria viridis and Zea mays to growth under different irradiances, low light (100 μmol m -2  s -1 ), and high light (1,000 μmol m -2  s -1 ), was observed both at seedling and established growth stages. We found that the effect of growth irradiance on C 4 leaf PD density depended on plant age and species. The high light treatment resulted in two to four-fold greater PD density per unit leaf area than at low light, due to greater area of PD clusters and greater PD size in high light plants. These results along with our finding that the effect of light on M-BS PD density was not tightly linked to photosynthetic capacity suggest a complex mechanism underlying the dynamic response of C 4 leaf PD formation to growth irradiance., (© 2019 John Wiley & Sons Ltd.)

Achieving the WHO End-Tuberculosis (TB) targets requires approaches to prevent progression to TB among individuals with Mycobacterium tuberculosis (M.tb) infection. Effective preventive therapy (PT) exists, but current tests have low specificity for identifying who, among those infected, is at risk of developing TB. Using mathematical models, we assessed the potential population-level impact on TB incidence of using a new more specific mRNA expression signature (COR) to target PT among HIV-uninfected adults in South Africa. We compared the results to the use of the existing interferon-γ release assay (IGRA). With annual screening coverage of 30% COR-targeted PT could reduce TB incidence in 2035 by 20% (95% CI 15-27). With the same coverage, IGRA-targeted PT could reduce TB incidence by 39% (31-48) but would require greater use of PT resulting in a higher number needed to treat per TB case averted (COR: 49 (29-77); IGRA: 84 (59-123)). The relative differences between COR and IGRA were not sensitive to screening coverage. COR-targeted PT could contribute to reducing total TB burden in high incidence countries like South Africa by allowing more efficient targeting of treatment. To maximise impact, COR-like tests may be best utilised in the highest burden regions, or sub-populations, within these countries.

Mathematical models are increasingly being used to compare strategies for tuberculosis (TB) control and inform policy decisions. Models often do not consider financial and other constraints on implementation and may overestimate the impact that can be achieved. We developed a pragmatic approach for incorporating resource constraints into mathematical models of TB. Using a TB transmission model calibrated for South Africa, we estimated the epidemiologic impact and resource requirements (financial, human resource (HR), and diagnostic) of 9 case-finding interventions. We compared the model-estimated resources with scenarios of future resource availability and estimated the impact of interventions under these constraints. Without constraints, symptom screening in public health clinics and among persons receiving care for human immunodeficiency virus infection was predicted to lead to larger reductions in TB incidence (9.5% (2.5th-97.5th percentile range (PR), 8.6-12.2) and 14.5% (2.5th-97.5th PR, 12.2-16.3), respectively) than improved adherence to diagnostic guidelines (2.7%; 2.5th-97.5th PR, 1.6-4.1). However, symptom screening required large increases in resources, exceeding future HR capacity. Even under our most optimistic HR scenario, the reduction in TB incidence from clinic symptom screening was 0.2%-0.9%-less than that of improved adherence to diagnostic guidelines. Ignoring resource constraints may result in incorrect conclusions about an intervention's impact and may lead to suboptimal policy decisions. Models used for decision-making should consider resource constraints., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

The symplastic tracer 5(6)-carboxyfluorescein diacetate (CFDA) has been widely applied in living plants to demonstrate the intercellular connection, phloem transport and vascular patterning. This protocol shows bottom-to-top carboxyfluorescein (CF) movement in the Arabidopsis by using the root-cutting and the hypocotyl-pinching procedure respectively. These two different procedures result in different efficiencies of CF movement: about 91% appearance of CF in the shoots with the hypocotyl-pinching procedure, whereas only about 70% appearance of CF with the root-cutting procedure. The simple change of loading sites, resulting in significant changes in the mobile efficiency of this symplastic dye, suggests CF movement might be subject to the symplastic regulation, most probably by the root-hypocotyl junction.

Background: Psychiatric diagnostic manuals recognise the importance of local expressions of distress in culturally diverse settings [i.e. idioms/cultural concepts of distress (CCDs)], yet there is a lack of consensus on how these should be incorporated into mental health related research., Aims: To perform a narrative synthesis and critical review of research exploring how idioms/CCDs have been integrated into assessment measures and interventions., Method: A systematic review was conducted in accordance with PRISMA guidelines. An adapted version of the COSMIN checklist was used to assess the quality of the linguistic translation of the idioms/CCDs., Results: Twenty-nine papers were included in the final review. Primary qualitative research was the most common method of gathering information about idioms/CCDs. The majority of studies described integrating idioms/CCDs into assessment measures as opposed to interventions. Some studies used information relating to idioms/CCDs to develop novel assessment measures, while others adapted pre-existing assessment measures. The measures generated moderate to high levels of validity. Information relating to the linguistic translation conducted in the completion of the studies tended to be inadequately reported., Conclusions: Integrating information about idioms/CCDs into assessment measures can enhance the validity of these assessments. Allocating greater research attention to idioms/CCDs can also promote more equitable exchanges of knowledge about mental health and wellbeing between the Global North and the Global South.

Mathematical modelling is commonly used to evaluate policy options for tuberculosis (TB) control in high-burden countries. Although major policy and funding decisions are made based on these analyses, there is concern about the variability of results produced using modelled policy analyses. We discuss new guidance for country-level TB policy modelling. The guidance was developed by the TB Modelling and Analysis Consortium in collaboration with the World Health Organization Global TB Programme, with input from a range of TB stakeholders (funders, modelling groups, country TB programme staff and subject matter experts). The guidance describes principles for country-level TB modelling, as well as good practices for operationalising the principles. The principles cover technical concerns such as model design, parameterisation and validation, as well as approaches for incorporating modelling into country-led policy making and budgeting. For modellers, this guidance suggests approaches to improve the quality and relevance of modelling undertaken to support country-level planning. For non-modellers, this guidance describes considerations for engaging modelling technical assistance, contributing to a modelling exercise and reviewing the results of modelled analyses. If routinely adopted, this guidance should improve the reliability, transparency and usefulness of modelling for country-level TB policy making. However, this guidance will not address all challenges facing modelling, and ongoing work is needed to improve the empirical evidence base for TB policy evaluation and develop stronger mechanisms for validating models. Increasing country ownership of the modelling process remains a challenge, requiring sustained engagement and capacity building.

Background: In January 2016, clinical TB guidance in the UK changed to no longer recommend screening contacts of non-pulmonary, non-laryngeal (ETB) index cases. However, no new evidence was cited for this change, and there is evidence that screening these contacts may be worthwhile. The objective of this study was to estimate the cost-effectiveness of screening contacts of adult ETB cases and adult pulmonary or laryngeal TB (PTB) cases in London, UK., Methods: We carried out a cross-sectional analysis of data collected on TB index cases and contacts in the London TB register and an economic evaluation using a static model describing contact tracing outcomes. Incremental cost-effectiveness ratios (ICERs) were calculated using no screening as the baseline comparator. All adult TB cases (≥15 years old) in London from 2012 to 2015, and their contacts, were eligible (2465/5084 PTB and 2559/6090 ETB index cases were included)., Results: Assuming each contact with PTB infects one person/month, the ICER of screening contacts of ETB cases was £78 000/quality-adjusted life-years (QALY) (95% CI 39 000 to 140 000), and screening contacts of PTB cases was £30 000/QALY (95% CI 18 000 to 50 000). The ICER of screening contacts of ETB cases was £30 000/QALY if each contact with PTB infects 3.4 people/month. Limitations of this study include the use of self-reported symptomatic periods and lack of knowledge about onward transmission from PTB contacts., Conclusions: Screening contacts of ETB cases in London was almost certainly not cost-effective at any conventional willingness-to-pay threshold in England, supporting recent changes to National Institute for Health and Care Excellence national guidelines., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Tuberculosis is the leading single-pathogen cause of death worldwide, and China has the third largest number of cases worldwide. New tools, such as new vaccines, are needed to meet WHO tuberculosis goals. Tuberculosis vaccine development strategies mostly target infants or adolescents, but given China's ageing epidemic, vaccinating older people might be important. We modelled the potential impact of new tuberculosis vaccines in China targeting adolescents (15-19 years) or older adults (60-64 years) with varying vaccine characteristics to inform strategic vaccine development., Methods: A Mycobacterium tuberculosis transmission model was calibrated to age-stratified demographic and epidemiological data from China. Varying scenarios of vaccine implementation (age targeting [adolescents or older adults] and coverage [30% or 70%]) and characteristics (efficacy [40%, 60%, or 80%], duration of protection [10 years or 20 years], and host infection status required for efficacy [pre-infection, post-infection in latency, post-infection in latency or recovered, or pre-infection and post-infection]) were assessed. Primary outcomes were tuberculosis incidence and mortality rate reduction in 2050 in each vaccine scenario compared with the baseline (no new vaccine) scenario and cumulative number needed to vaccinate (NNV) per case or death averted, 2025-50., Findings: By 2050, results suggest that 74·5% (uncertainty interval [UI] 70·2-78·6) of incident tuberculosis cases in China would occur in people aged 65 years or older, and 75·1% (66·8-80·7) of all cases would be due to reactivation, rather than new infection. All vaccine profiles delivered to older adults had higher population-level impact (reduction of incidence and mortality rates) and lower NNV per case and per death averted than if delivered to adolescents. For an intermediate vaccine scenario of 60% efficacy, 10-year protection, and 70% coverage, the reduction of tuberculosis incidence rates with older adult vaccination was 1·9 times (UI 1·5-2·6) to 157·5 times (119·3-225·6) greater than with adolescent vaccination, and the NNV was 0·011 times (0·008-0·014) to 0·796 times (0·632-0·970) lower. Furthermore, with older adult vaccination, post-infection vaccines provided substantially greater mortality and incidence rate reductions than pre-infection vaccines., Interpretation: Adolescent-targeted tuberculosis vaccines, the focus of many development plans, would have only a small impact in ageing, reactivation-driven epidemics such as those in China. Instead, an efficacious post-infection vaccine delivered to older adults will be crucial to maximise population-level impact in this setting and would provide an important contribution towards achieving WHO goals. Older adults should be included in tuberculosis vaccine clinical development and implementation planning., Funding: Aeras and UK MRC., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

South Africa has the highest tuberculosis (TB) disease incidence rate in the world, and TB is the leading infectious cause of death. Decisions on, and funding for, TB prevention and care policies are decentralised to the provincial governments and therefore, tools to inform policy need to operate at this level. We describe the use of a mathematical model planning tool at provincial level in a high HIV and TB burden country, to estimate the impact on TB burden of achieving the 90-(90)-90 targets of the Stop TB Partnership Global Plan to End TB. "TIME Impact" is a freely available, user-friendly TB modelling tool. In collaboration with provincial TB programme staff, and the South African National TB Programme, models for three (of nine) provinces were calibrated to TB notifications, incidence, and screening data. Reported levels of TB programme activities were used as baseline inputs into the models, which were used to estimate the impact of scale-up of interventions focusing on screening, linkage to care and treatment success. All baseline models predicted a trend of decreasing TB incidence and mortality, consistent with recent data from South Africa. The projected impacts of the interventions differed by province and were greatly influenced by assumed current coverage levels. The absence of provincial TB burden estimates and uncertainty in current activity coverage levels were key data gaps. A user-friendly modelling tool allows TB burden and intervention impact projection at the sub-national level. Key sub-national data gaps should be addressed to improve the quality of sub-national model predictions., Competing Interests: The authors have declared that no competing interests exist.

Root nodule symbiosis (RNS) is a feature confined to a single clade of plants, the Fabids. Among Fabids capable of RNS, legumes form root cortex-based nodules in symbioses with rhizobia, while actinorhizal species form lateral root-based nodules with actinomycetes. Cytokinin has previously been shown to be sufficient for "pseudonodule" initiation in model legumes. Here, we tested whether this response correlates with the ability to nodulate across a range of plant species. We analyzed the formation of pseudonodules in 17 nodulating and non-nodulating legume species, and 11 non-legumes, including nodulating actinorhizal species, using light and fluorescence microscopy. Cytokinin-induced pseudonodules arising from cortical cell divisions occurred in all nodulating legume species, but not in any of the other species, including non-nodulating legumes. Pseudonodule formation was dependent on the CRE1 cytokinin receptor in Medicago truncatula . Inhibition of root growth by cytokinin occurred across plant groups, indicating that pseudonodule development is the result of a specific cortical cytokinin response unique to nodulating legumes. Lack of a cortical cytokinin response from the Arabidopsis thaliana cytokinin reporter TCSn::GFP supported this hypothesis. Our results suggest that the ability to form cortical cell-derived nodules was gained in nodulating legumes, and likely lost in non-nodulating legumes, due to a specific root cortical response to cytokinin.

Background: Transmission patterns in high tuberculosis incidence areas in England are poorly understood but need elucidating to focus contact tracing. We study transmission within and between age, ethnic and immigrant groups using molecular data from the high incidence West Midlands region., Methods: Isolates from culture-confirmed tuberculosis cases during 2007-2011 were typed using 24-locus Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeats (MIRU-VNTR). We estimated the proportion of disease attributable to recent transmission, calculated the proportion of isolates matching those from the two preceding years ("retrospectively clustered"), and identified risk factors for retrospective clustering using multivariate analyses. We calculated the ratio (RCR) between the observed and expected proportion clustered retrospectively within or between age, ethnic and immigrant groups., Results: Of the 2159 available genotypes (79% of culture-confirmed cases), 34% were attributed to recent transmission. The percentage retrospectively clustered decreased from 50 to 24% for 0-14 and ≥ 65 year olds respectively (p = 0.01) and was significantly lower for immigrants than the UK-born. Higher than expected clustering occurred within 15-24 year olds (RCR: 1.4 (95% CI: 1.1-1.8)), several ethnic groups, and between UK-born or long-term immigrants with the UK-born (RCR: 1.8 (95% CI: 1.1-2.4) and 1.6 (95% CI: 1.2-1.9) respectively)., Conclusions: This study is the first to consider "who clusters with whom" in a high incidence area in England, laying the foundation for future whole-genome sequencing work. The higher than expected clustering seen here suggests that preferential mixing between some age, ethnic and immigrant groups occurs; prioritising contact tracing to groups with which cases are most likely to cluster retrospectively could improve TB control.

In order to increase therapeutic impact by enhancing awareness of clients' nonverbal communications, this article operationalizes the therapeutic alliance as a needs-satisfaction process. The client's competence as a needs seeker and the therapist assisting with the client's expression and satiation of basic social needs are proposed as being key mechanisms of change. Functional model of primary emotions derived from Panksepp's seven primary emotional systems (care seeking, caretaking, lust, fear and anxiety, anger, play, seeking, plus dominance and disgust) is integrated with Functional Analytic Psychotherapy's emphasis on in-session contingent natural reinforcement of clients' target behaviours. By identifying in-the-moment cues of underlying emotional-behavioural functions drawn from a categorization of clients' nonverbal communication can bridge the gap between client private events and therapist observables, in order to maximize therapist attunement and responsiveness to clients, and to increase the effectiveness of clinical interventions., (© 2018 John Wiley & Sons, Ltd.)

The original article [1] did not contain comprehensive information regarding two authors' affiliations that may be considered a potential competing interest.

Social capital (SC) is highlighted as an important factor for post-crisis mental health outcomes. However, the heterogeneous nature of the construct makes it difficult to get a clear picture of the evidence concerning the association between SC indices and mental health. This review examines how SC is conceptualized and measured, and the relationships with other variables in quantitative empirical studies investigating the associations between SC and mental health in post-disaster and post-conflict contexts. It includes primary data studies focusing on this association in civilian populations. Studies were identified by searching electronic databases, bibliographic mining, cited reference searching, and personal contact with experts. In total, 15 studies were included: 12 in post-natural disaster contexts and 3 in conflict-affected settings. Findings suggested that individual cognitive SC had an inverse association with post-traumatic stress disorder, anxiety, and depression, and that ecological cognitive SC was positively associated with mental well-being. Individual structural SC (in the form of community networks) may be psychologically protective. However, most of the evidence was cross-sectional, limiting conclusions about causal relationships. More clarity and consistency is needed in the conceptualization and measurement of SC in order to inform post-crisis mental health interventions. (Disaster Med Public Health Preparedness. 2018;12:791-802).

Globally, men have a higher epidemiologic burden of tuberculosis (incidence, prevalence, mortality) than women do, possibly due to differences in disease incidence, treatment initiation, self-cure, and/or untreated-tuberculosis mortality rates. Using a simple, sex-stratified compartmental model, we employed a Bayesian approach to explore which factors most likely explain men's higher burden. We applied the model to smear-positive pulmonary tuberculosis in Vietnam (2006-2007) and Malawi (2013-2014). Posterior estimates were consistent with sex-specific prevalence and notifications in both countries. Results supported higher incidence in men and showed that both sexes faced longer durations of untreated disease than estimated by self-reports. Prior untreated disease durations were revised upward 8- to 24-fold, to 2.2 (95% credible interval: 1.7, 2.9) years for men in Vietnam and 2.8 (1.8, 4.1) years for men in Malawi, approximately a year longer than for women in each country. Results imply that substantial sex differences in tuberculosis burden are almost solely attributable to men's disadvantages in disease incidence and untreated disease duration. The latter, for which self-reports provide a poor proxy, implies inadequate coverage of case-finding strategies. These results highlight an urgent need for better understanding of gender-related barriers faced by men and support the systematic targeting of men for screening.

Unlike drug dose optimisation, mathematical modelling has not been applied to vaccine dose finding. We applied a novel Immunostimulation/Immunodynamic mathematical modelling framework to translate multi-dose TB vaccine immune responses from mice, to predict most immunogenic dose in humans. Data were previously collected on IFN-γ secreting CD4+ T cells over time for novel TB vaccines H56 and H1 adjuvanted with IC31 in mice (1 dose groups (0.1-1.5 and 15 μg H56 + IC31), 45 mice) and humans (1 dose (50 μg H56/H1 + IC31), 18 humans). A two-compartment mathematical model, describing the dynamics of the post-vaccination IFN-γ T cell response, was fitted to mouse and human data, separately, using nonlinear mixed effects methods. We used these fitted models and a vaccine dose allometric scaling assumption, to predict the most immunogenic human dose. Based on the changes in model parameters by mouse H56 + IC31 dose and by varying the H56 dose allometric scaling factor between mouse and humans, we established that, at a late time point (224 days) doses of 0.8-8 μg H56 + IC31 in humans may be the most immunogenic. A 0.8-8 μg of H-series TB vaccines in humans, may be as, or more, immunogenic, as larger doses. The Immunostimulation/Immunodynamic mathematical modelling framework is a novel, and potentially revolutionary tool, to predict most immunogenic vaccine doses, and accelerate vaccine development., Competing Interests: The authors declare no competing interests.

Background: Exposure to armed conflict and forced displacement constitute significant risks for mental health. Existing evidence-based psychological interventions have limitations for scaling-up in low-resource humanitarian settings. The WHO has developed a guided self-help intervention, Self Help Plus (SH+), which is brief, implemented by non-specialists, and designed to be delivered to people with and without specific mental disorders. This paper outlines the study protocol for an evaluation of the SH+ intervention in northern Uganda, with South Sudanese refugee women., Methods: A two-arm, single-blind cluster-randomised controlled trial will be conducted in 14 villages in Rhino Camp refugee settlement, with at least 588 women experiencing psychological distress. Villages will be randomly assigned to receive either SH+ with enhanced usual care (EUC), or EUC alone. SH+ is a five-session guided self-help intervention delivered in workshops with audio-recorded materials and accompanying pictorial guide. The primary outcome is reduction in overall psychological distress over time, with 3 months post-treatment as the primary end-point. Secondary outcomes are self-defined psychosocial concerns, depression and post-traumatic stress disorder symptoms, hazardous alcohol use, feelings of anger, interethnic relations, psychological flexibility, functional impairment and subjective wellbeing. Psychological flexibility is a hypothesised mediator, and past trauma history and intervention attendance will be explored as potential moderators., Discussion: This trial will provide important information on the effectiveness of a scalable, guided self-help intervention for improving psychological health and wellbeing among people affected by adversity., Trial Registration: ISRCTN50148022; registered 13/03/2017.

Background: In this period of unprecedented levels of displacement, scalable interventions are needed to address mental health concerns of forced migrants in low-resource settings. This paper describes the adaptation and piloting of a guided, multi-media, self-help intervention, Self-Help Plus (SH+), which was developed to reduce psychological distress in large groups of people affected by adversity., Methods: Using a phased approach that included community consultations, cognitive interviewing, facilitator training, pilot implementation, and a qualitative process evaluation, we adapted SH+ for use among South Sudanese refugees in a refugee settlement in northern Uganda., Results: The SH+ materials, including audio-recorded sessions and an accompanying illustrated manual, were translated into Juba Arabic. Cognitive interviewing primarily resulted in adaptations to language with some minor adaptations to content. Facilitator training and supervision led to further suggested changes to delivery methods. An uncontrolled pilot study ( n = 65) identified changes in the expected direction on measures of psychological distress, functional impairment, depression, wellbeing, and psychological flexibility. The process evaluation resulted in further adaptations to intervention materials and the decision to focus future effectiveness evaluations of the intervention in its current form on South Sudanese female refugees., Conclusions: We found that this potentially scalable, guided self-help intervention could be adapted for and feasibly implemented among female South Sudanese refugees in northern Uganda. These findings lay the groundwork for a future rigorous evaluation of SH+ in this context.

Background: Increasing case notifications is one of the top programmatic priorities of National TB Control Programmes (NTPs). To find more cases, NTPs often need to consider expanding TB case-detection activities to populations with increasingly low prevalence of disease. Together with low-specificity diagnostic algorithms, these strategies can lead to an increasingly high number of false positive diagnoses, which has important adverse consequences., Methods: We apply TIME, a widely-used country-level model, to quantify the expected impact of different case-finding strategies under two scenarios. In the first scenario, we compare the impact of implementing two different diagnostic algorithms (higher sensitivity only versus higher sensitivity and specificity) to reach programmatic screening targets. In the second scenario, we examine the impact of expanding coverage to a population with a lower prevalence of disease. Finally, we explore the implications of modelling without taking into consideration the screening of healthy individuals. Outcomes considered were changes in notifications, the ratio of additional false positive to true positive diagnoses, the positive predictive value (PPV), and incidence., Results: In scenario 1, algorithm A of prolonged cough and GeneXpert yielded fewer additional notifications compared to algorithm B of any symptom and smear microscopy (n = 4.0 K vs 13.8 K), relative to baseline between 2017 and 2025. However, algorithm A resulted in an increase in PPV, averting 2.4 K false positive notifications thus resulting in a more efficient impact on incidence. Scenario 2 demonstrated an absolute decrease of 11% in the PPV as intensified case finding activities expanded into low-prevalence populations without improving diagnostic accuracy, yielding an additional 23 K false positive diagnoses for an additional 1.3 K true positive diagnoses between 2017 and 2025. Modelling the second scenario without taking into account screening amongst healthy individuals overestimated the impact on cases averted by a factor of 6., Conclusion: Our findings show that total notifications can be a misleading indicator for TB programme performance, and should be interpreted carefully. When evaluating potential case-finding strategies, NTPs should consider the specificity of diagnostic algorithms and the risk of increasing false-positive diagnoses. Similarly, modelling the impact of case-finding strategies without taking into account potential adverse consequences can overestimate impact and lead to poor strategic decision-making.