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Objective:Behavioral weightmanagement programs (BWMPs) for adults lead to greater weight loss at 12 months than minimal-intervention control treatments. However, there is considerable heterogeneity in the content of BWMPs and outcomes of treatment. This study assessed the contribution of individual components of BWMPs, using Bayesian component network meta-analysis. Methods:Randomized controlled trials of BWMPs in adults were identified (latest search: December 2019) and arms coded for presence or absence of 29 intervention components grouped by type, content, provider, mode of delivery, and intensity. Results:A total of 169 studies (41 judged at high risk of bias) were included in the main analysis. Six components had effect estimates indicating clinically significant benefit and credible intervals (CrIs) excluding no difference: change in diet (mean difference [MD] =−1.84 kg, 95% CrI: −2.91 to −0.80); offering partial (MD=−2.12 kg, 95% CrI: −3.39 to −0.89) or total meal replacements (MD = −2.63 kg, 95% CrI: −4.58 to −0.73); delivery by a psychologist/counselor (MD=−1.45 kg, 95% CrI: −2.81 to −0.06) or dietitian (MD=−1.31 kg, 95% CrI: −2.40 to −0.24); and home setting (MD=−1.05 kg, 95% CrI: −2.02 to −0.09). Conclusions:Future program development should consider including these components; other approaches continue to warrant evaluation of effectiveness.

Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere in a changing climate – the “global carbon budget” – is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe and synthesize data sets and methodology to quantify the five major components of the global carbon budget and their uncertainties. Fossil CO2 emissions (EFOS) are based on energy statistics and cement production data, while emissions from land-use change (ELUC), mainly deforestation, are based on land use and land-use change data and bookkeeping models. Atmospheric CO2 concentration is measured directly and its growth rate (GATM) is computed from the annual changes in concentration. The ocean CO2 sink (SOCEAN) and terrestrial CO2 sink (SLAND) are estimated with global process models constrained by observations. The resulting carbon budget imbalance (BIM), the difference between the estimated total emissions and the estimated changes in the atmosphere, ocean, and terrestrial biosphere, is a measure of imperfect data and understanding of the contemporary carbon cycle. All uncertainties are reported as ±1σ. For the last decade available (2010–2019), EFOS was 9.6 ± 0.5 GtC yr−1 excluding the cement carbonation sink (9.4 ± 0.5 GtC yr−1 when the cement carbonation sink is included), and ELUC was 1.6 ± 0.7 GtC yr−1. For the same decade, GATM was 5.1 ± 0.02 GtC yr−1 (2.4 ± 0.01 ppm yr−1), SOCEAN 2.5 ± 0.6 GtC yr−1, and SLAND 3.4 ± 0.9 GtC yr−1, with a budget imbalance BIM of −0.1 GtC yr−1 indicating a near balance between estimated sources and sinks over the last decade. For the year 2019 alone, the growth in EFOS was only about 0.1 % with fossil emissions increasing to 9.9 ± 0.5 GtC yr−1 excluding the cement carbonation sink (9.7 ± 0.5 GtC yr−1 when cement carbonation sink is included), and ELUC was 1.8 ± 0.7 GtC yr−1, for total anthropogenic CO2 emissions of 11.5 ± 0.9 GtC yr−1 (42.2 ± 3.3 GtCO2). Also for 2019, GATM was 5.4 ± 0.2 GtC yr−1 (2.5 ± 0.1 ppm yr−1), SOCEAN was 2.6 ± 0.6 GtC yr−1, and SLAND was 3.1 ± 1.2 GtC yr−1, with a BIM of 0.3 GtC. The global atmospheric CO2 concentration reached 409.85 ± 0.1 ppm averaged over 2019. Preliminary data for 2020, accounting for the COVID-19-induced changes in emissions, suggest a decrease in EFOS relative to 2019 of about −7 % (median estimate) based on individual estimates from four studies of −6 %, −7 %, −7 % (−3 % to −11 %), and −13 %. Overall, the mean and trend in the components of the global carbon budget are consistently estimated over the period 1959–2019, but discrepancies of up to 1 GtC yr−1 persist for the representation of semi-decadal variability in CO2 fluxes. Comparison of estimates from diverse approaches and observations shows (1) no consensus in the mean and trend in land-use change emissions over the last decade, (2) a persistent low agreement between the different methods on the magnitude of the land CO2 flux in the northern extra-tropics, and (3) an apparent discrepancy between the different methods for the ocean sink outside the tropics, particularly in the Southern Ocean. This living data update documents changes in the methods and data sets used in this new global carbon budget and the progress in understanding of the global carbon cycle compared with previous publications of this data set (Friedlingstein et al., 2019; Le Quéré et al., 2018b, a, 2016, 2015b, a, 2014, 2013). The data presented in this work are available at https://doi.org/10.18160/gcp-2020 (Friedlingstein et al., 2020).

Objective: To undertake a randomized comparison of the Biodesign Surgisis anal fistula plug against surgeon's preference in treating cryptoglandular transsphincteric fistula-in-ano. Summary Background Data: The efficacy of the Biodesign Surgisis anal fistula plug in healing anal fistulae is uncertain. Methods: Participants were randomized to the fistula plug with surgeon's preference (advancement flap, cutting seton, fistulotomy, Ligation of the Intersphincteric Fistula Tract procedure). The primary outcome was faecal incontinence quality of life (FIQoL) at 12-months. Secondary outcomes were fistula healing, incontinence rates, and complication and reintervention rates. Results: Between May 2011 and March 2016, 304 participants were randomized to fistula plug or surgeon's preference. No differences were seen in FIQoL between the 2 groups at 12 months. Clinical fistula healing was reported in 66/122 (54%) of the fistula plug and 66/119 (55%) of the surgeon's preference groups at 12 months. Fecal incontinence rates improved marginally in both the groups. Complications and reinterventions were frequent, with significantly more complications in the fistula plug group at 6-weeks (49/142, 35% vs 25/137, 18%; P=0.002). The mean total costs were £2738 (s.d. £1151) for the fistula plug and £2308 (s.d. £1228) for the surgeon's preference group (mean difference +£430, P=0.0174). The average total quality adjusted life years (QALYs) gained was marginally higher in the fistula plug group. The fistula plug was 35% to 45% likely to be cost-effective across a willingness to pay threshold of £20,000 to £30,000 / QALY. Conclusions: The Biodesign Surgisis anal fistula plug is associated with similar FIQoL and healing rates to surgeon's preference at 12 months. Higher costs and highly uncertain gains in QALYs mean that the fistula plug may not be considered as a cost-effective treatment in the UK NHS.

Objectives:\ud To investigate whether elevated urinary HAI-1, EpCAM and EGFR are independent prognostic biomarkers within non-muscle-invasive bladder cancer (NMIBC) patients, and have utility for risk stratification to facilitate treatment decisions.\ud \ud Results:\ud After accounting for EAU risk group in NMIBC patients, the risk of BC-specific death was 2.14 times higher (95% CI: 1.08 to 4.24) if HAI-1 was elevated and 2.04 times higher (95% CI: 1.02 to 4.07) if EpCAM was elevated. The majority of events occurred in the high-risk NMIBC group and this is where the biggest difference is seen in the survival curves when plotted for EAU risk groups separately. In MIBC patients, being elevated for any of the three biomarkers was significantly associated with BC-specific mortality after accounting for other risk factors, HR = 4.30 (95% CI: 1.85 to 10.03).\ud \ud Patients and Methods:\ud Urinary levels of HAI-1, EpCAM and EGFR were measured by ELISA in 683 and 175 patients with newly-diagnosed NMIBC and MIBC, respectively, recruited to the Bladder Cancer Prognosis Programme. Associations between biomarkers and progression, BC-specific mortality and all-cause mortality were evaluated using univariable and multivariable Cox regression models, adjusted for European Association of Urology (EAU) NMIBC risk groups. The upper 25% of values for each biomarker within NMIBC patients were considered as elevated. Exploratory analyses in urine from MIBC patients were also undertaken.\ud \ud Conclusion:\ud Urinary HAI-1 and EpCAM are prognostic biomarkers for NMIBC patients. These biomarkers have potential to guide treatment decisions for high-risk NMIBC patients. Further analyses are required to define the roles of HAI-1, EpCAM and EGFR in MIBC patients.

Objectives: To investigate whether elevated urinary HAI-1, EpCAM and EGFR are independent prognostic biomarkers within non-muscle-invasive bladder cancer (NMIBC) patients, and have utility for risk stratification to facilitate treatment decisions. Results: After accounting for EAU risk group in NMIBC patients, the risk of BCspecific death was 2.14 times higher (95% CI: 1.08 to 4.24) if HAI-1 was elevated and 2.04 times higher (95% CI: 1.02 to 4.07) if EpCAM was elevated. The majority of events occurred in the high-risk NMIBC group and this is where the biggest difference is seen in the survival curves when plotted for EAU risk groups separately. In MIBC patients, being elevated for any of the three biomarkers was significantly associated with BC-specific mortality after accounting for other risk factors, HR = 4.30 (95% CI: 1.85 to 10.03). Patients and Methods: Urinary levels of HAI-1, EpCAM and EGFR were measured by ELISA in 683 and 175 patients with newly-diagnosed NMIBC and MIBC, respectively, recruited to the Bladder Cancer Prognosis Programme. Associations between biomarkers and progression, BC-specific mortality and all-cause mortality were evaluated using univariable and multivariable Cox regression models, adjusted for European Association of Urology (EAU) NMIBC risk groups. The upper 25% of values for each biomarker within NMIBC patients were considered as elevated. Exploratory analyses in urine from MIBC patients were also undertaken. Conclusion: Urinary HAI-1 and EpCAM are prognostic biomarkers for NMIBC patients. These biomarkers have potential to guide treatment decisions for high-risk NMIBC patients. Further analyses are required to define the roles of HAI-1, EpCAM and EGFR in MIBC patients.

There is increasing concern about Mycoplasma genitalium as a cause of urethritis, cervicitis, pelvic inflammatory disease (PID), infertility and ectopic pregnancy. Commercial nucleic acid amplification tests (NAATs) are becoming available, and their use in screening for M. genitalium has been advocated, but M. genitalium’s natural history is poorly-understood, making screening’s effectiveness unclear. We used a transmission-dynamic compartmental model to synthesise evidence from surveillance data and epidemiological and behavioural studies to better understand M. genitalium’s natural history, and then examined the effects of implementing NAAT testing. Introducing NAAT testing initially increases diagnoses, by finding a larger proportion of infections; subsequently the diagnosis rate falls, due to reduced incidence. Testing only symptomatic patients finds relatively little infection in women, as a large proportion is asymptomatic. Testing both symptomatic and asymptomatic patients has a much larger impact and reduces cumulative PID incidence in women due to M. genitalium by 31.1% (95% range:13.0%-52.0%) over 20 years. However, there is important uncertainty in M. genitalium’s natural history parameters, leading to uncertainty in the absolute reduction in PID and sequelae. Empirical work is required to improve understanding of key aspects of M. genitalium’s natural history before it will be possible to determine the effectiveness of screening.

Background: Sexually transmitted infection (STI) diagnoses are increasing and efforts to reduce transmission have failed. There are major uncertainties in the evidence base surrounding the delivery of STI care for men. Aim: To improve the sexual health of young men in the UK by determining optimal strategies for STI testing and care. Objectives: To develop an evidence-based clinical algorithm for STI testing in asymptomatic men; model mathematically the epidemiological and economic impact of removing microscopy from routine STI testing in asymptomatic men; conduct a pilot randomised controlled trial (RCT) of accelerated partner therapy (APT; new models of partner notification to rapidly treat male sex partners of people with STIs) in primary care; explore the acceptability of diverse venues for STI screening in men; and determine optimal models for the delivery of screening. Design: Systematic review of the clinical consequences of asymptomatic non-chlamydial, non-gonococcal urethritis (NCNGU); case–control study of factors associated with NCNGU; mathematical modelling of the epidemiological and economic impact of removing microscopy from asymptomatic screening and cost-effectiveness analysis; pilot RCT of APT for male sex partners of women diagnosed with Chlamydia trachomatis infection in primary care; stratified random probability sample survey of UK young men; qualitative study of men’s views on accessing STI testing; SPORTSMART pilot cluster RCT of two STI screening interventions in amateur football clubs; and anonymous questionnaire survey of STI risk and previous testing behaviour in men in football clubs. Settings: General population, genitourinary medicine clinic attenders, general practice and community contraception and sexual health clinic attenders and amateur football clubs. Participants: Men and women. Interventions: Partner notification interventions: APTHotline [telephone assessment of partner(s)] and APTPharmacy [community pharmacist assessment of partner(s)]. SPORTSMART interventions: football captain-led and health adviser-led promotion of urine-based STI screening. Main outcome measures: For the APT pilot RCT, the primary outcome, determined for each contactable partner, was whether or not they were considered to have been treated within 6 weeks of index diagnosis. For the SPORTSMART pilot RCT, the primary outcome was the proportion of eligible men accepting screening. Results: Non-chlamydial, non-gonococcal urethritis is not associated with significant clinical consequences for men or their sexual partners but study quality is poor (systematic review). Men with symptomatic and asymptomatic NCNGU and healthy men share similar demographic, behavioural and clinical variables (case–control study). Removal of urethral microscopy from routine asymptomatic screening is likely to lead to a small rise in pelvic inflammatory disease (PID) but could save > £5M over 20 years (mathematical modelling and health economics analysis). In the APT pilot RCT the proportion of partners treated by the APTHotline [39/111 (35%)], APTPharmacy [46/100 (46%)] and standard patient referral [46/102 (45%)] did not meet national standards but exceeded previously reported outcomes in community settings. Men’s reported willingness to access self-sampling kits for STIs and human immunodeficiency virus infection was high. Traditional health-care settings were preferred but sports venues were acceptable to half of men who played sport (random probability sample survey). Men appear to prefer a ‘straightforward’ approach to STI screening, accessible as part of their daily activities (qualitative study). Uptake of STI screening in the SPORTSMART RCT was high, irrespective of arm [captain led 28/56 (50%); health-care professional led 31/46 (67%); poster only 31/51 (61%)], and costs were similar. Men were at risk of STIs but previous testing was common. Conclusions: Men find traditional health-care settings the most acceptable places to access STI screening. Self-sampling kits in football clubs could widen access to screening and offer a public health impact for men with limited local sexual health services. Available evidence does not support an association between asymptomatic NCNGU and significant adverse clinical outcomes for men or their sexual partners but the literature is of poor quality. Similarities in characteristics of men with and without NCNGU precluded development of a meaningful clinical algorithm to guide STI testing in asymptomatic men. The mathematical modelling and cost-effectiveness analysis of removing all asymptomatic urethral microscopy screening suggests that this would result in a small rise in adverse outcomes such as PID but that it would be highly cost-effective. APT appears to improve outcomes of partner notification in community settings but outcomes still fail to meet national standards. Priorities for future work include improving understanding of men’s collective behaviours and how these can be harnessed to improve health outcomes; exploring barriers to and facilitators of opportunistic STI screening for men attending general practice, with development of evidence-based interventions to increase the offer and uptake of screening; further development of APT for community settings; and studies to improve knowledge of factors specific to screening men who have sex with men (MSM) and, in particular, how, with the different epidemiology of STIs in MSM and the current narrow focus on chlamydia, this could negatively impact MSM’s sexual health. Funding: The National Institute for Health Research Programme Grants for Applied Research programme.

Background: Results of previous research have identified the need for further investigation into the compliance with good practice guidelines for current decision-analytic modeling (DAM). Objective: To identify the extent to which recent model-based economic evaluations of interventions focused on lowering the blood pressure (BP) of patients with hypertension conform to published guidelines for DAM in health care using a five-dimension framework developed to assess compliance to DAM guidelines. Methods: A systematic review of English language articles was undertaken to identify published model-based economic evaluations that examined interventions aimed at lowering BP. The review covered the period January 2000 to March 2015 and included the following electronic bibliographic databases: EMBASE and Medline via Ovid interface and the Centre for Reviews and Dissemination’s (CRD) NHS-EED. Data were extracted based on different components of good practice across five dimensions utilizing a framework to assess compliance to DAM guidelines. Results: Thirteen articles were included in this review. The review found limited compliance to good practice DAM guidelines, which was most frequently justified by the lack of data. Conclusions: The assessment of structural uncertainty cannot yet be considered common practice in primary prevention and management of hypertension, and researchers seem to face difficulties with identifying sources of structural uncertainty and then handling them correctly. Additional guidelines are needed to aid researchers in identifying and managing sources of potential structural uncertainty. Adherence to guidelines is not always possible and it does pose challenges, in particular when there are limitations due to data availability that restrict, for example, a validation process.

Background: Returning to and staying at work following illness is associated with better physical and psychological functioning. Not working has been shown to be associated with reduced self-esteem, lowered self-efficacy, and decreased belief in one's ability to return to the workplace. Although there is a growing body of research looking at what predicts return to work following cancer treatment, there are fewer studies examining interventions targeting return to work.\ud \ud Objective: The primary objective is to assess the feasibility and acceptability of a theoretically led workbook intervention designed to support cancer patients in returning to work to inform a fully powered randomized controlled trial (RCT).\ud \ud Methods: This is a multicenter feasibility RCT where the main analysis uses a qualitative approach. Sixty participants (aged 18-65 years) who have received a diagnosis of cancer and who intend to return to work will be randomized to either the WorkPlan intervention group or a usual care group (ratio 1:1). Participants in the intervention group will receive a guided workbook intervention (which contains activities aimed at eliciting thoughts and beliefs, identifying targets and actions, and concrete steps to achieve goals) and will receive telephone support over a 4-week period. The primary outcome measure is time taken to return to work (in days), and secondary outcome measures include mood, quality of life, illness perceptions, and job satisfaction. Data will be collected through postal questionnaires administered immediately postintervention and at 6- and 12-month follow-ups. In addition, interviews will be undertaken immediately postintervention (to explore acceptability of the intervention and materials) and at 12-month follow-up (to explore perceptions of participation in the trial and experiences of returning to work).\ud \ud Results: Enrollment for the study will be completed in May 2016. Data analysis will commence in April 2017, and the first results are expected to be submitted for publication in late 2017.\ud \ud Conclusions: Currently no standardized return-to-work intervention based on targeting cancer patient beliefs is in existence. If the intervention is shown to be feasible and acceptable, the results of this study will inform a future full RCT with the potential to provide a valuable and cost-efficient tool in supporting cancer survivors in the return-to-work process.

Background: The prevalence of chronic kidney disease (CKD) is high in general populations around the world. Targeted testing and screening for CKD are often conducted to help identify individuals that may benefit from treatment to ameliorate or prevent their disease progression. Aims: This systematic review examines the methods used in economic evaluations of testing and screening in CKD, with a particular focus on whether test accuracy has been considered, and how analysis has incorporated issues that may be important to the patient, such as the impact of testing on quality of life and the costs they incur. Methods: Articles that described model-based economic evaluations of patient testing interventions focused on CKD were identified through the searching of electronic databases and the hand searching of the bibliographies of the included studies. Results: The initial electronic searches identified 2,671 papers of which 21 were included in the final review. Eighteen studies focused on proteinuria, three evaluated glomerular filtration rate testing and one included both tests. The full impact of inaccurate test results was frequently not considered in economic evaluations in this setting as a societal perspective was rarely adopted. The impact of false positive tests on patients in terms of the costs incurred in re-attending for repeat testing, and the anxiety associated with a positive test was almost always overlooked. In one study where the impact of a false positive test on patient quality of life was examined in sensitivity analysis, it had a significant impact on the conclusions drawn from the model. Conclusion: Future economic evaluations of kidney function testing should examine testing and monitoring pathways from the perspective of patients, to ensure that issues that are important to patients, such as the possibility of inaccurate test results, are properly considered in the analysis.

Since the 19 March 2008 explosion within Halema‘uma‘u that formed the new vent at Kilauea’s summit, degassing rates have been greatly elevated above the levels typical of previous years. The location and subsequent dispersion of this new degassing presents its own specific problems compared to that in the east rift zone. For example, throughout 2008 the Halema’uma’u plume was generally blown through the Kau desert, directly affecting downwind communities. In this study we present measurements made in July and halogens (HF, HCl, HBr and HI) in the new 2008. We characterize the gas chemistry in terms of SO 2 plume from Halema’uma’u in order to compare them with other plumes worldwide, including those from subduction zone settings and other emissions from Kilauea itself. Further to this we characterize the plume’s chemistry in terms of emissions of environmentally important metallic species both in the size- segregated aerosol (important for determining atmospheric lifetime and potential speciation) and in the case of Hg in the gas phase (both in the elemental form and reactive forms). To complement this plume characterization we also looked at preliminary environmental samples of grasses, rainwater and fog in order to investigate potential future avenues for research into the environmental consequences of Kilauea’s volcanic emissions.

Gas bubbles form as magmas ascend in the crust and exsolve volatiles. These bubbles evolve chemically and physically as magma decompression and crystallization proceed. It is generally assumed that the gas remains in thermal equilibrium with the melt but the relationship between gas and melt redox state is debated. Here, using absorption spectroscopy, we report the composition of gases emitted from the lava lake of Kīlauea Volcano, Hawaii, and calculate equilibrium conditions for the gas emissions. Our observations span a transition between more and less vigorous-degassing regimes. They reveal a temperature range of up to 250 °C, and progressive oxidation of the gas, relative to solid rock buffers, with decreasing gas temperature. We suggest that these phenomena are the result of changing gas bubble size. We find that even for more viscous magmas, fast-rising bubbles can cool adiabatically, and lose the redox signature of their associated melts. This process can result in rapid changes in the abundances of redox-sensitive gas species. Gas composition is monitored at many volcanoes in support of hazard assessment but time averaging of observations can mask such variability arising from the dynamics of degassing. In addition, the observed redox decoupling between gas and melt calls for caution in using lava chemistry to infer the composition of associated volcanic gases.

The Observing Air–Sea Interactions Strategy (OASIS) is a new United Nations Decade of Ocean Science for Sustainable Development programme working to develop a practical, integrated approach for observing air–sea interactions globally for improved Earth system (including ecosystem) forecasts, CO2 uptake assessments called for by the Paris Agreement, and invaluable surface ocean information for decision makers. Our “Theory of Change” relies upon leveraged multi-disciplinary activities, partnerships, and capacity strengthening. Recommendations from >40 OceanObs’19 community papers and a series of workshops have been consolidated into three interlinked Grand Ideas for creating #1: a globally distributed network of mobile air–sea observing platforms built around an expanded array of long-term time-series stations; #2: a satellite network, with high spatial and temporal resolution, optimized for measuring air–sea fluxes; and #3: improved representation of air–sea coupling in a hierarchy of Earth system models. OASIS activities are organized across five Theme Teams: (1) Observing Network Design & Model Improvement; (2) Partnership & Capacity Strengthening; (3) UN Decade OASIS Actions; (4) Best Practices & Interoperability Experiments; and (5) Findable–Accessible–Interoperable–Reusable (FAIR) models, data, and OASIS products. Stakeholders, including researchers, are actively recruited to participate in Theme Teams to help promote a predicted, safe, clean, healthy, resilient, and productive ocean.