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Ireland has > 50% of the EU’s ocean-raised bogs; however, degradation through land-use activities has transformed them from carbon (C) sinks to sources. Given their significant role in climate mitigation, it is essential to quantify the emissions resulting from land use degradation of these ecosystems. A seven-class land-use classification system for Irish peatlands (LUCIP) was developed and mapped using Sentinel-2 imagery, random forest machine learning and Google Earth Engine. The results revealed that agricultural grassland comprised 43% of the land use on raised bogs, followed by, forestry (21%), cutover (11%), cutaway (10%) remnant peatlands (13%), waterbodies and built-up ~ 1% each. The overall accuracy of the map was 89%. The map was used to estimate CO 2 emissions for four classes constituting 85% of raised bogs: cutover, cutaway, grassland, and forestry using the IPCC wetlands supplement and literature-based emission factors, we estimated emissions at ~ 1.92 (± 1.58–2.27 Mt CO 2 -C-yr −1 ) and ~ 0.68 Mt CO 2 -C-yr −1 (± 0.44–0.91 Mt CO 2 -C-yr −1 ) respectively. This is the first study to spatially quantify land use and related emissions from raised bogs. The results have revealed widespread degradation of these globally rare habitats, making them net emitters of CO 2 . The map is vital for the conservation of these ecosystems through restoration efforts, and the methodology can also be applied to other regions with similar peatland land use issues.

MicroRNAs (miRNAs) function as endogenous translational repressors of protein-coding genes in animals by binding to target sites in the 3' UTRs of mRNAs. Because a single nucleotide change in the sequence of a target site can affect miRNA regulation, naturally occurring SNPs in target sites are candidates for functional variation that may be of interest for biomedical applications and evolutionary studies. However, little is known to date about variation among humans at miRNAs and their target sites. In this study, we analyzed publicly available SNP data in context with miRNAs and their target sites throughout the human genome, and we found a relatively low level of variation in functional regions of miRNAs, but an appreciable level of variation at target sites. Approximately 400 SNPs were found at experimentally verified target sites or predicted target sites that are otherwise evolutionarily conserved across mammals. Moreover, [almost equal to]250 SNPs potentially create novel target sites for miRNAs in humans. If some variants have functional effects, they might confer phenotypic differences among humans. Although the majority of these SNPs appear to be evolving under neutrality, interestingly, some of these SNPs are found at relatively high population frequencies even in experimentally verified targets, and a few variants are associated with atypically long-range haplotypes that may have been subject to recent positive selection.

Rising prevalence of bedaquiline resistance undermines benefits from this life-saving drug for rifampicin-resistant tuberculosis (RR tuberculosis). Despite increasing awareness, patient-level outcomes for bedaquiline-resistant tuberculosis have not been well characterised and case management has been poorly defined. We did a retrospective cohort study of bedaquiline-resistant tuberculosis with matched RR tuberculosis controls at a tuberculosis referral hospital in East London, South Africa. Cases included patients aged 13 years or older with a phenotypic bedaquiline-resistant Mycobacterium tuberculosis isolate identified between Jan 1, 2018 and June 30, 2023. Controls with confirmed bedaquiline-susceptible tuberculosis, matched 1:1 by baseline culture status, age, and HIV status, were selected from a prospective observational study conducted during an overlapping period at the same facility. Primary outcomes included time to sputum culture conversion (SCC), a modified WHO-defined unfavourable outcome, and tuberculosis-free survival (alive, with SCC, and in care or treatment completed) up until 18 months. Adjusted analyses used Cox proportional hazards and logistic regression models. 82 patients with bedaquiline-resistant tuberculosis were included, 57 (70%) of whom were HIV positive. Bedaquiline was prescribed for 72 (88%) of 82 patients and meropenem (plus amoxicillin–clavulanate) for 32 (39%) of 82. Together with bedaquiline, the most frequently prescribed drugs included clofazimine, linezolid, and terizidone. Median time to SCC after treatment initiation was 175 days (IQR 100–254) in the bedaquiline-resistant cohort and 32 days (30–42) in matched controls. In the analysis of the combined cohorts, bedaquiline resistance (adjusted hazard ratio 0·03, 95% CI 0·0023–0·29, p=0·003) was associated with longer time to SCC when adjusted for baseline microscopy grade and baseline fluoroquinolone resistance. WHO treatment outcomes in those with bedaquiline-resistant tuberculosis were unfavourable in 54 (67%) of 81 patients, driven by treatment failure in 35 (43%) of 81. At 18 months, 43 (52%) of 82 patients had reached tuberculosis-free survival, 19 (23%) of 82 had died, and 50 (79%) of 63 survivors were still on treatment. Current treatment options for bedaquiline-resistant tuberculosis result in prolonged therapy, delayed microbiological responses, and poor clinical outcomes. Implementation of more rapid resistance testing, including targeted next-generation sequencing, and access to novel treatment options within randomised controlled trials for bedaquiline-resistant tuberculosis, are priorities for tuberculosis programmes. The South African Medical Research Council.

The majority of mammalian proteins are glycosylated, with the glycans serving to modulate a wide range of biological activities. Variations in protein glycosylation can have dramatic effects on protein stability, immunogenicity, antibody effector function, pharmacological safety and potency, as well as serum half-life. The glycosylation of therapeutic biologicals is a critical quality attribute (CQA) that must be carefully monitored to ensure batch-to-batch consistency. Notably, many factors can affect the composition of the glycans during glycoprotein production, and variations in glycosylation are among the leading causes of pharmaceutical batch rejection. Currently, the characterization of protein glycosylation relies heavily on methods that employ chromatography and/or mass spectrometry, which require a high level of expertise, are time-consuming and costly and, because they are challenging to implement during in-process biologics production or during in vitro glycan modification, are generally performed only post-production. Here we report a simplified approach to assist in monitoring glycosylation features during glycoprotein engineering, that employs flow cytometry using fluorescent microspheres chemically coupled to high-specificity glycan binding reagents. In our GlycoSense method, a range of carbohydrate-sensing microspheres with distinct optical properties may be combined into a multiplex suspension array capable of detecting multiple orthogonal glycosylation features simultaneously, using commonplace instrumentation, without the need for glycan release. The GlycoSense method is not intended to replace more detailed post-production glycan profiling, but instead, to complement them by potentially providing a cost-effective, rapid, yet robust method for use at-line as a process analytic technology (PAT) in a biopharmaceutical workflow or at the research bench. The growing interest in using in vitro glycoengineering to generate glycoproteins with well-defined glycosylation, provides motivation to demonstrate the capabilities of the GlycoSense method, which we apply here to monitor changes in the protein glycosylation pattern (GlycoPrint) during the in vitro enzymatic modification of the glycans in model glycoproteins.

To evaluate the impact of socioeconomic support on tuberculosis preventive therapy initiation in household contacts of tuberculosis patients and on treatment success in patients. A non-blinded, household-randomized, controlled study was performed between February 2014 and June 2015 in 32 shanty towns in Peru. It included patients being treated for tuberculosis and their household contacts. Households were randomly assigned to either the standard of care provided by Peru's national tuberculosis programme (control arm) or the same standard of care plus socioeconomic support (intervention arm). Socioeconomic support comprised conditional cash transfers up to 230 United States dollars per household, community meetings and household visits. Rates of tuberculosis preventive therapy initiation and treatment success (i.e. cure or treatment completion) were compared in intervention and control arms. Overall, 282 of 312 (90%) households agreed to participate: 135 in the intervention arm and 147 in the control arm. There were 410 contacts younger than 20 years: 43% in the intervention arm initiated tuberculosis preventive therapy versus 25% in the control arm (adjusted odds ratio, aOR: 2.2; 95% confidence interval, CI: 1.1-4.1). An intention-to-treat analysis showed that treatment was successful in 64% (87/135) of patients in the intervention arm versus 53% (78/147) in the control arm (unadjusted OR: 1.6; 95% CI: 1.0-2.6). These improvements were equitable, being independent of household poverty. A tuberculosis-specific, socioeconomic support intervention increased uptake of tuberculosis preventive therapy and tuberculosis treatment success and is being evaluated in the Community Randomized Evaluation of a Socioeconomic Intervention to Prevent TB (CRESIPT) project.

Contacts of tuberculosis index cases are at increased risk of developing tuberculosis. Screening, preventive therapy, and surveillance for tuberculosis are underused interventions in contacts, particularly adults. We developed a score to predict risk of tuberculosis in adult contacts of tuberculosis index cases. In 2002–06, we recruited contacts aged 15 years or older of index cases with pulmonary tuberculosis who lived in desert shanty towns in Ventanilla, Peru. We followed up contacts for tuberculosis until February, 2016. We used a Cox proportional hazards model to identify index case, contact, and household risk factors for tuberculosis from which to derive a score and classify contacts as low, medium, or high risk. We validated the score in an urban community recruited in Callao, Peru, in 2014–15. In the derivation cohort, we identified 2017 contacts of 715 index cases, and median follow-up was 10·7 years (IQR 9·5–11·8). 178 (9%) of 2017 contacts developed tuberculosis during 19 147 person-years of follow-up (incidence 0·93 per 100 person-years, 95% CI 0·80–1·08). Risk factors for tuberculosis were body-mass index, previous tuberculosis, age, sustained exposure to the index case, the index case being in a male patient, lower community household socioeconomic position, indoor air pollution, previous tuberculosis among household members, and living in a household with a low number of windows per room. The 10-year risks of tuberculosis in the low-risk, medium-risk, and high-risk groups were, respectively, 2·8% (95% CI 1·7–4·4), 6·2% (4·8–8·1), and 20·6% (17·3–24·4). The 535 (27%) contacts classified as high risk accounted for 60% of the tuberculosis identified during follow-up. The score predicted tuberculosis independently of tuberculin skin test and index-case drug sensitivity results. In the external validation cohort, 65 (3%) of 1910 contacts developed tuberculosis during 3771 person-years of follow-up (incidence 1·7 per 100 person-years, 95% CI 1·4–2·2). The 2·5-year risks of tuberculosis in the low-risk, medium-risk, and high-risk groups were, respectively, 1·4% (95% CI 0·7–2·8), 3·9% (2·5–5·9), and 8·6%· (5·9–12·6). Our externally validated risk score could predict and stratify 10-year risk of developing tuberculosis in adult contacts, and could be used to prioritise tuberculosis control interventions for people most likely to benefit. Wellcome Trust, Department for International Development Civil Society Challenge Fund, Joint Global Health Trials consortium, Bill & Melinda Gates Foundation, Imperial College National Institutes of Health Research Biomedical Research Centre, Foundation for Innovative New Diagnostics, Sir Halley Stewart Trust, WHO, TB REACH, and Innovation for Health and Development.

Active case-finding among contacts of patients with tuberculosis is a global health priority, but the effects of active versus passive case-finding are poorly characterised. We assessed the contribution of active versus passive case-finding to tuberculosis detection among contacts and compared sex and disease characteristics between contacts diagnosed through these strategies. In shanty towns in Callao, Peru, we identified index patients with tuberculosis and followed up contacts aged 15 years or older for tuberculosis. All patients and contacts were offered free programmatic active case-finding entailing sputum smear microscopy and clinical assessment. Additionally, all contacts were offered intensified active case-finding with sputum smear and culture testing monthly for 6 months and then once every 4 years. Passive case-finding at local health facilities was ongoing throughout follow-up. Between Oct 23, 2002, and May 26, 2006, we identified 2666 contacts, who were followed up until March 1, 2016. Median follow-up was 10·0 years (IQR 7·5–11·0). 232 (9%) of 2666 contacts were diagnosed with tuberculosis. The 2-year cumulative risk of tuberculosis was 4·6% (95% CI 3·5–5·5), and overall incidence was 0·98 cases (95% CI 0·86–1·10) per 100 person-years. 53 (23%) of 232 contacts with tuberculosis were diagnosed through active case-finding and 179 (77%) were identified through passive case-finding. During the first 6 months of the study, 23 (45%) of 51 contacts were diagnosed through active case-finding and 28 (55%) were identified through passive case-finding. Contacts diagnosed through active versus passive case-finding were more frequently female (36 [68%] of 53 vs 85 [47%] of 179; p=0·009), had a symptom duration of less than 15 days (nine [25%] of 36 vs ten [8%] of 127; p=0·03), and were more likely to be sputum smear-negative (33 [62%] of 53 vs 62 [35%] of 179; p=0·0003). Although active case-finding made an important contribution to tuberculosis detection among contacts, passive case-finding detected most of the tuberculosis burden. Compared with passive case-finding, active case-finding was equitable, helped to diagnose tuberculosis earlier and usually before a positive result on sputum smear microscopy, and showed a high burden of undetected tuberculosis among women. Wellcome Trust, Department for International Development Civil Society Challenge Fund, Joint Global Health Trials consortium, Bill & Melinda Gates Foundation, Imperial College National Institutes of Health Research Biomedical Research Centre, Foundation for Innovative New Diagnostics, Sir Halley Stewart Trust, WHO, TB REACH, and IFHAD: Innovation for Health and Development.

Wetlands are one of the major contributors of methane (CH 4 ) emissions to the atmosphere and the intensity of emissions is driven by local environmental variables and spatial heterogeneity. Peatlands are a major wetland class and there are numerous studies that provide estimates of methane emissions at chamber or eddy covariance scales, but these are not often aggregated to the site/ecosystem scale. This study provides a robust approach to map dominant vegetation communities and to use these areas to upscale methane fluxes from chamber to site scale using a simple weighted-area approach. The proposed methodology was tested at three peatlands in Ireland over a duration of 2 years. The annual vegetation maps showed an accuracy ranging from 83 to 99% for near-natural to degraded sites respectively. The upscaled fluxes were highest (2.25 and 3.80 gC m −2 y −1 ) at the near-natural site and the rehabilitation (0.17 and 0.31 gC m −2 y −1 ), degraded (0.15 and 0.27 gC m −2 y −1 ) site emissions were close to net-zero throughout the study duration. Overall, the easy to implement methodology proposed in this study can be applied across various landuse types to assess the impact of peatland rehabilitation on methane emissions by mapping ecological change.

[...]current global policies focus on providing tuberculosis-affected households with economic support to prevent catastrophic costs associated with treatment, travel to receive care, and time off work. [...]cost-opportunity and cost-effectiveness of socioeconomic support for tuberculosis-affected households are likely to depend on targeted strategies that focus on specific tuberculosis-affected beneficiaries, but relevant analyses are lacking. Tuberculosis-sensitive approaches involve strengthening national social protection strategies and adapting them to be more inclusive to people at risk of tuberculosis infection and disease, such as Brazil's Bolsa Família social welfare programme, which has been associated with improved tuberculosis treatment outcomes and reduced incidence.18,19 Although initially expensive,20 tuberculosis-sensitive interventions could lead to improved long-term population outcomes in health (including tuberculosis), food security, and poverty alleviation. [...]a combination of tuberculosis-sensitive and tuberculosis-specific support is likely to be the most impactful approach to comprehensively address the social determinants of tuberculosis. [...]consideration should be given to how socioeconomic support would be funded (eg, governmental, charitable, crowd-sourcing), by whom it will be delivered (eg, national tuberculosis programmes, the third sector, civil society), how it might be improved by streamlined service delivery (eg, ambulatory care, decentralisation, out-of-hours services), and the timeframes, indicators, and outcome measures used to judge its success (eg, tuberculosis-related, broader health outcomes, psychosocial and economic impact).

Concordant with increasing interest in the social determinants of health in general, and of tuberculosis in particular, the Sustainable Development Goals and WHO's new End TB Strategy place emphasis on social protection and poverty-alleviation programmes.8 This new strategy aligns tuberculosis-control policies with global attempts to address HIV and AIDS, maternal and child health, and other public health priorities, which already integrate social protection with biomedical interventions.3 In the context of tuberculosis, social protection interventions can be tuberculosis-specific, designed exclusively for people living with active tuberculosis disease;9,10 tuberculosis-inclusive, for which broader interventions include tuberculosis disease in their eligibility criteria; or tuberculosis-sensitive, for which interventions include activities aimed at reducing tuberculosis risk.11 These complementary approaches might incentivise and enable patients with tuberculosis, and people at risk of developing tuberculosis, to equitably access biomedical care while preventing so-called catastrophic costs,7 reducing impoverishment, and addressing risk factors for tuberculosis disease.10 So how can we tackle the social determinants of tuberculosis sufficiently to support its elimination?