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Breast cancer screening using clinical breast examination:A cost-effectiveness analysis for South Africa
Get PDFIntroduction: WHO emphasises screening and early diagnosis to reduce advanced cancer incidence and mortality. In low- to middle-income countries, breast cancer (BC) survival rates are low because of late detection. South Africa's policy recommends twice-yearly clinical breast examinations (CBEs) for asymptomatic women aged 40-69. We assessed the impact of scaling up CBE screening on mortality and cost-effectiveness. Methods: Using trial data on downstaging, we compared the current baseline (5% coverage) with Scenario 1 (25% coverage by year 5, i.e. 5% increase annually) and Scenario 2 (75% coverage by year 5, i.e. 17.5% increase annually). A cohort model tracked women from screening to diagnosis, estimating downstaging’s impact on BC cases over their lifetime. Costs from the healthcare payer’s perspective are presented in 2022 US dollars. Results: Five-year screen detection rates were 2.39 and 2.08 per 1,000 women screened for Scenarios 1 and 2, respectively. Scenario 1 reduced BC mortality by 0.7% and Scenario 2 by 2.3%. Compared to no screening, the current baseline screening program averts 1,645 DALYs at 17,776/DALY averted, whereas Scenario 2 averted 12,165 DALYs at 3,015/DALY averted. However, decisions on the best screening policy are not solely based on cost-effectiveness. They involve careful consideration of budgetary constraints and competing healthcare priorities. Scale-up should consider system capacity, minimum care standards and cost-effective early detection strategies
Enhancing Oil Recovery with Shape-Modified Silica Nanoparticles: Efficiency in Oil-Wet Sandstone Reservoirs via Imbibition and Micromodel Approaches
Get PDFThis study investigates the use of shape-modified silica nanoparticles functionalized with sodium (C14–16) olefin sulfonate (SOS) for enhancing oil recovery in oil-wet sandstone reservoirs. Characterization techniques, including scanning electron microscopy (SEM), Brunauer–Emmett–Teller (BET), Thermogravimetric analysis (TGA), and Fourier transform infrared spectroscopy (FTIR), verified successful surface modification. Functionalization reduced the mean particle size from 188 ± 15 to 98 ± 14 nm and enhanced stability, with zeta potential increasing from −11 to −46 mV. Nanoemulsion tests showed that SOS-functionalized nanoparticles achieved the lowest creaming degree and produced smaller oil droplets. The interfacial tension between crude oil and SOS-functionalized nanoparticles decreased from 24 to 1 mN/m, with further reductions observed upon the addition of alkali. Wettability alteration was also achieved, with contact angles shifting from 20° (oil-wet) to 173° (strongly water-wet) in the presence of SOS-functionalized nanoparticles. Spontaneous imbibition tests demonstrated oil recoveries of 77% with SOS-functionalized nanoparticles, outperforming SOS alone (42%) and unmodified nanoparticles (35%). Micro-CT scanning of the samples after imbibition test showed lower pore connectivity reduction with SOS-functionalized nanoparticles (31%) compared to unmodified nanoparticles (59%). Micromodel flooding tests confirmed enhanced oil recovery, with SOS-functionalized nanoparticles achieving 86% recovery compared to SOS (38%) and unmodified nanoparticles (18%). This study highlights the potential of SOS-functionalized silica nanoparticles to improve oil recovery in oil-wet sandstone reservoirs through wettability alteration, interfacial tension reduction, and stabilized emulsions
Oral Microbiome Dysbiosis and Citrullination in Rheumatoid Arthritis
No full textRheumatoid arthritis and periodontal diseases, both characterized by chronic inflammation, share many common risk factors, sparking interest in understanding their established association. Emerging research has shed light on the link between these two diseases potentially occurring through the intricate interactions within the oral microbiome. The enrichment of pathogenic strains and species in this microbial community disrupts the delicate balance of both ecological and immunological homeostasis with the host. Particular attention has been paid to the role of key pathogens, such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, known for their immunomodulatory abilities. The generation of an autoimmune response against proteins modified by citrullination is known to be a key step in the pathogenesis of RA. Importantly, the bidirectional citrullination mediated by both host innate immune cells and oral bacteria generates citrullinated peptide neoepitopes, which may serve as potential triggers for the loss of tolerance and subsequent autoimmunity in susceptible individuals. This review highlights the importance of understanding the mechanisms through which oral microbiome dysbiosis and citrullination contribute to the onset and progression of RA. Insights into these mechanisms not only advance pathobiological understanding but also offer potential therapeutic targets. Furthermore, we discuss the potential impact of nonsurgical periodontal treatment in modifying disease progression or mitigating RA, underscoring the critical role of periodontal health in managing systemic inflammatory conditions
Comparative Effectiveness of Abatacept Versus Adalimumab in Shared Epitope Positive and Negative Patients With Rheumatoid Arthritis
Get PDFObjective
The effect of the shared epitope (SE) and valine at position 11 (Val11) of HLA–DRB1 on the activation of CD4+ T cells is expected to be diminished by abatacept, a costimulation blocker. However, published evidence on the value of genetic stratification for abatacept treatment is conflicting. We aimed to compare the difference in effectiveness of abatacept and adalimumab in patients carrying the SE (or Val11).
Methods
The Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate is a nationwide observational cohort study recruiting patients from 53 centers across the United Kingdom before the initiation of biologic treatment and following them up prospectively for 12 months. Three hundred forty-two patients starting either abatacept or adalimumab were eligible for this analysis. Serum drug levels for abatacept, adalimumab, and methotrexate were determined at multiple time points. Multivariate modeling integrating demographic, clinical, and pharmacological variables was used to test for associations between the number of copies of the SE or Val11 and response to treatment (EULAR response; Disease Activity Score in 28 joints [DAS28] remission; change in DAS28). Differential effectiveness between drugs and genetic markers was assessed by the significance of their interaction term.
Results
There was no difference in the efficacy of abatacept versus adalimumab. We found weak evidence for an independent association of genetic markers with response to treatment (Val11 with EULAR response: P = 0.02), but there was no significant difference in this effect between drugs.
Conclusion
We found no evidence that HLA typing is clinically useful to support prescription decisions for these two drugs
Distributed train timetable synchronization in metro network: An ADMM-based decomposition framework
Get PDFThe increasing spatial or temporal scales of metro networks generate an important research challenge in developing fast and efficient optimization methods for handling the train timetable synchronization problem (TTSP). This paper develops a distributed optimization algorithm for the TTSP of complex metro networks, with the objective of minimizing both the waiting time of inbound and transferring passengers in the whole network. We construct explicit dynamic equations of train passenger loads throughout the network and quantify the transferring passengers at transfer stations. These equations encapsulate the dynamic passenger transfer behavior within the metro system. To deal with the computationally expensive large-scale MINP problem, an alternating direction method of multipliers (ADMM) based decomposition approach is proposed to split the original TTSP into a set of single-line timetabling subproblems that can be solved in a decentralized manner. Furthermore, a novel heuristic two-level ADMM-based approach, where the upper level decides the connections among trains of different lines and the lower level applies standard ADMM with fixed binary variables to optimize the timetable, is designed to deal with the nonconvexity issue. We demonstrate its ability to conveniently obtain a high-quality solution to the network timetable synchronization problem numerically
Quantifying association of early proteinuria and estimated glomerular filtration rate changes with long-term kidney failure in C3 glomerulopathy and immune-complex membranoproliferative glomerulonephritis using the United Kingdom RaDaR Registry
Get PDFIntroduction
C3 glomerulopathy (C3G) and immune-complex membranoproliferative glomerulonephritis (IC-MPGN) are rare disorders that frequently result in kidney failure over the long-term. Presently, there are no disease-specific treatments approved for these disorders, although there is much interest in the therapeutic potential of complement inhibition. However, the limited duration and necessarily small size of controlled trials means there is a need to quantify how well short-term changes in estimated glomerular filtration rate (eGFR) and proteinuria predict the clinically important outcome of kidney failure.
Methods
We address this using longitudinal data from the UK Registry of Rare Kidney Diseases (RaDaR) involving retrospective and prospective data collection with linkage to hospital laboratories via automated feeds of 371 patients. Analyses of kidney survival were conducted using Kaplan–Meier and Cox regression with eGFR slope estimated using linear mixed models.
Results
In a median of 11.0 (inter quartile range 7.4-15.1) years follow-up, 148 patients (40%) reached kidney failure. There was no significant difference in progression to kidney failure between C3G and IC-MPGN groups. Baseline urine protein-creatinine ratio (UPCR), although high, was not associated with kidney failure in either group. Two-year eGFR slope had a modest association with kidney failure. In contrast, both 20%‒50% and 50 mg/mmol reductions in UPCR between 0-12 months were associated with lower kidney failure risk in both groups. Notably, those with a UPCR under 100 mg/mmol at 12 months had a substantially lower risk of kidney failure (hazard ratio 0.10 (95% confidence interval 0.03-0.30).
Conclusions
Overall, proteinuria a short time after diagnosis is strongly associated with long-term outcomes and a UPCR under 100 mg/mmol at one year is associated with a substantially lower kidney failure risk
The role of surface-active macromolecules in the ice-nucleating ability of lignin, Snomax, and agricultural soil extracts
Get PDFOrganic matter in agricultural soil dust can enhance dust's ice-nucleating ability relative to mineral dust and thus impact local cloud formation. But how is this organic matter able to nucleate ice? We hypothesised that hydrophobic interfaces, such as the air–water interface, influence how organic matter nucleates ice, which can be quantified by measuring surface tension. Here, we investigated correlations between surfactant properties and ice-nucleating activities of amphiphilic macromolecules common in agricultural soils and known ice nucleators, namely lignin and macromolecules from Snomax. Lignin and Snomax solutions were analysed using our droplet freezing technique, FINC, and an optical contact angle tensiometer. Results showed that lignin and Snomax solutions of increasing concentrations had increasing ice-nucleating activity and decreasing surface tension. In addition, high-speed cryo-microscopy of the same solutions revealed a preference for freezing at the air–water interface, consistent with these proxies being ice-active surfactants preferentially residing at the air–water interface, and thus hydrophobic surfaces. We then tested this relationship in field-collected agricultural soil extracts from the UK and Canada. Despite the trend observed for lignin and Snomax, there was no clear correlation between surface tension and freezing temperature of the soil extracts. This discrepancy may arise from the high complexity of the soil solutions, where hydrophobic interfaces in the bulk potentially compete with the air–water interface. Overall, we present further evidence of the role of hydrophobic interfaces in the heterogeneous ice nucleation of organic aerosols with implications for aerosol–cloud interactions
Organic carbon, sea level and carbonate weathering controls on marine carbon isotope perturbations across the Hirnantian glaciation
No full textThe Hirnantian isotopic carbon excursion (HICE) records a dramatic perturbation to the global carbon cycle across the Late Ordovician Hirnantian glaciation. The HICE is characterized by variable duration and amplitude in global records, but its ultimate driver, and controls on the observed variability, are poorly understood. Here, we present a comprehensive compilation of geochemical data and paired carbon and calcium isotope records for two continuous Hirnantian sections at Wanhe and Shuanghe on the Yangtze Shelf (South China). Our results reveal a lateral gradient of up to 4 ‰ in organic carbon isotope (δ13Corg) values across the shelf, decreasing from nearshore to offshore. Carbonate carbon isotope (δ13Ccarb) data from the Wanhe and Shuanghe sections also show pronounced variability, which cannot be fully explained by primary mineralogical changes or early marine diagenesis. We therefore interpret the spatial δ13Corg patterns as reflecting, at least in part, shelf-scale heterogeneity in seawater dissolved inorganic carbon isotope (δ13CDIC) values. Our compilation further suggests that substantial organic carbon burial likely triggered the HICE, while sea-level change subsequently drove the asynchronous, spatially heterogeneous changes in seawater δ13CDIC values. Additionally, enhanced carbonate weathering, linked to falling syn-glacial sea-level, amplified the spatial heterogeneity in regional marine δ13CDIC values. Moderate δ13Corg changes (<+2 ‰) are observed in central shelf areas across the Hirnantian glaciation, suggesting that the global carbon cycle perturbations during this ice age were of more modest amplitude than often suggested
The attitudes of individuals with or at risk of adult‐onset genetic conditions on reproductive genetic testing: a systematic review
Get PDFIndividuals who carry a genetic variant for a genetic disease can access reproductive genetic testing in order to prevent the transmission of the gene variant to their children. This systematic review aimed to synthesize the findings from both qualitative and quantitative literature to understand these individuals' attitudes toward pre-implantation genetic testing (PGT) and prenatal testing (PNT) and how they make decisions around them. A systematic search was undertaken following PRISMA guidelines, with 37 articles meeting the inclusion criteria for evaluating experiences and attitudes of individuals with or at risk of adult-onset genetic conditions on reproductive genetic testing. Relevant findings from each study were included in a thematic synthesis. Five analytical themes were generated to elucidate the attitudes toward reproductive genetic testing and the factors that impact decision-making in individuals with or at risk of late-onset genetic diseases: (1) Preventing gene transmission; (2) finding the threshold: evaluating the necessity of reproductive genetic testing; (3) ethical/acceptability considerations; (4) external influences in decision-making; and (5) psychological and practical concerns of reproductive genetic testing. This review highlights several factors that influence attitudes toward reproductive genetic testing. Complex decision-making was a cross-cutting experience that characterizes and defines reproductive genetic testing for late-onset conditions. There was a general consensus of support for reproductive genetic testing and a belief that it should be available to all. The need for awareness and education on reproductive genetic testing is evident. Future work should look at how to address these knowledge deficits, while exploring individuals' preferences for when and by whom information is delivered. Acknowledging the complexity of decision-making can encourage meaningful discussions and address potential issues
Comparison of Isoprene-Derived Secondary Organic Aerosol Formation Pathways at an Urban and a Forest Site
Get PDFAtmospheric oxidation of nonmethane hydrocarbons (NMHCs) under low nitrogen oxide conditions plays a critical role in the formation of oxygenated volatile organic compounds (OVOCs), yet measurements reflecting an accurate representation of these processes remain challenging. This study investigates the oxidation products of nbutane and 1-butene (C4 oxidation) under both low and high NOx regimes and of isoprene in a low NOx regime using the NSF NCAR atmospheric simulation chamber. Measurements were obtained using the Trace Organic Gas Analyzer (TOGA) and a proton-transfer reaction mass spectrometer (PTR-MS) and compared with predictions from a box model using the Master Chemical Mechanism (MCMv3.3.1). Our results show that under low NOx conditions, C4 hydroperoxides convert on the PTR-MS instrument surfaces to carbonyl artifacts, precluding an accurate picture of atmospheric composition. The PTR-MS conversion efficiencies for n-butane hydroperoxides, 1-butene hydroxy hydroperoxides, and ISOPOOH to carbonyl products were found to be 35 ± 1%, 67 ± 5%, and 24 ± 2%, respectively. TOGA exhibited minimal bias due to its inert internal surfaces. To further investigate surface effects, this study assessed the relative conversion of hydroperoxides to carbonyl products during analyte transmission through both stainless steel (SS) tubing and tubing treated to improve inertness (Restek Sulfinert) at different temperatures. We found that the conversion efficiency increases with temperature for hydroperoxides formed from both isoprene and C4 oxidation and that the treated surface tubing is far superior to that of untreated SS in preventing these conversion reactions. These findings highlight the potential for significant error from the reported low NOx oxidation products of the many other hydrocarbons in historical VOC data sets, apart from the previously studied isoprene. Accurate quantification of OVOCs in these environments is essential for refining atmospheric models and understanding chemical cycling in the changing NOx landscape
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