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Mechanism of Diabetes Remission or Improvement in Glucose Control Following Roux-en-Y Gastric Bypass Versus Sleeve Gastrectomy: A Systematic Review and Meta-Analysis
Get PDFBackground: The mechanisms of diabetes remission following bariatric surgery independent of calorie restriction and weight loss remain unclear. Objectives: To undertake a systematic review and meta-analysis to investigate mechanisms underpinning diabetes remission. Methods: We included individuals with type 2 diabetes who have undergone RYGB, SG, and a very low-calorie diet (VLCD). In total, 234 studies were identified (N = 52 for qualitative; N = 40 for quantitative synthesis). Review Manager v5.4 and IBM SPSS for Windows (v28.0.1.1) were used for analysis. Results: Crude annualised diabetes relapse rates for RYGB and SG are as follows: −6.98 ± 16.19 (p = 0.046) and −2.75 ± 4.94 (p = 0.08); crude remission rates for RYGB and SG, respectively, are as follows: 39.59 ± 45.93 (p = 0.000) and 33.36 ± 33.87 SG (p = 0.006). Differences in other metabolic outcomes (standardised mean difference and 95% confidence intervals (CIs)) are BMI: ([RYGB: −2.73, 95%CI: −3.14 to −2.32, p < 0.000001) (SG: −2.82, 95%CI: −5.04 to −0.60, p = 0.01)]; HbA1c: [(RYGB: −1.58, 95%CI: −2.16 to −1.00, p < 0.00001) (SG: −1.42, 95%CI: −1.69 to −1.15, p < 0.00001)]; insulin: [(RYGB: 0.16, 95%CI: −0.19 to −0.50, p = 0.37) (SG: −3.00, 95%CI: −3.17 to −2.82, p = 0.75)]; and fat mass [(RYGB: −2.56, 95%CI: −4.49 to −0.64, p = 0.009) (SG: −1.69, 95%CI: −4.58 to 1.21, p = 0.25)]. RYGB and SG produced a significant improvement in HOMA-B measurements. Adiponectin and the Matsuda index were significantly increased with RYGB. No difference was observed for other metabolic markers (RYGB: GLP-1, GIP, leptin, ghrelin, PYY) (SG: GLP-1 and FGF19) (VLCD: leptin, GLP-1, GIP, and ghrelin). Conclusions: Diabetes remission following RYGB and SG was primarily driven by improvement in beta-cell function, with improvement in insulin resistance markers also observed for RYGB, driven by reductions in fat mass. No other metabolic mechanism explaining diabetes remission was observed based on clinical studies
Do oil price forecast disagreement of survey of professional forecasters predict crude oil return volatility?
Get PDFThis paper explores whether the dispersion in forecasted crude oil prices from the European Central Bank Survey of Professional Forecasters can provide insights for predicting crude oil return volatility. It is well-documented that higher disagreement among forecasters of asset price implies greater uncertainty and higher return volatility. Using several Generalized Autoregressive Conditional Heteroskedasticity with Mixed Data Sampling (GARCH-MIDAS) models, we find, based on the in-sample estimation results, the oil market experiences greater volatility when the forecasters’ disagreements increase. The model that integrates both historical realized variance and forward-looking forecaster disagreement into the conditional variance, along with the model focusing solely on pure forward-looking forecaster disagreement, exhibits a much superior fit to the data compared to the model relying solely on realized variance and the models considering forward-looking forecasted mean return. The out-of-sample forecasting results unequivocally illustrate that incorporating forecaster disagreement offers valuable insights, markedly enhancing the predictive accuracy of crude oil return volatility within the GARCH-MIDAS model. Moreover, we illustrate the economic benefit of considering forecasters’ disagreement when forecasting volatility, demonstrating its significance for VaR risk management
Illiquidity, R&D Investment, and Stock Returns
Get PDFWe propose a dynamic model of research and development (R&D) venture, which predicts that the positive relation between the firm's R&D investment and the expected stock returns strengthens with illiquidity. Consistent with the model's prediction, empirical evidence based on cross-sectional regressions and double-sorted portfolios largely suggests a stronger and positive R&D–return relation among illiquid stocks. A further analysis shows that the important role of illiquidity in the R&D–return relation cannot be explained by factors, such as financial constraints, innovation ability, and product market competition. Collectively, our results suggest that stock illiquidity is an independent driver of the R&D premium
Optimization of grid-connected solar PV systems with Hybrid Energy Storage System: A case study of the Sri Lankan power system
Get PDFGreenhouse gas emissions from fossil fuel-based electricity generation significantly contribute to climate change. This research aims to mitigate these emissions by reducing reliance on fossil fuels and maximizing solar photovoltaic (PV) energy generation. It is supported by a grid-connected Hybrid Energy Storage System (HESS) integrating lithium-ion Battery Storage (BS) and Pumped Hydro Storage (PHS). An optimization algorithm is employed to minimize total expenditures, including capital, operational, replacement costs, as well as costs associated with solar curtailment and supplemental thermal energy over the lifetime of the system. The Non-dominated Sorting Genetic Algorithm (NSGA-II) is used to solve the multi-objective optimization problem through the open-source Python framework Pymoo (multi-objective optimization in Python). Optimal capacities for solar PV and BS are determined for short-term intervals, while PHS capacities are evaluated based on regional geological feasibility. A novel energy management strategy ensures an effective balance between energy generation and storage. Optimization results are visualized through Pareto optimal charts and supplemented by economic and environmental analyses to identify sustainable scenarios. Sensitivity analysis further refines the optimal capacities for solar PV, BS, and PHS. The proposed methodology is validated using the Sri Lankan power system. A detailed roadmap is developed to guide the incremental additions of solar PV, BS, and PHS capacities. Final results indicate minimal total cost variations, ranging from −14.05% to 56.69%, and an increase in solar PV generation between 2.19% and 5.13%, due to fluctuations in the interest rate of the country
Parameter inference for stochastic reaction models of ion channel gating from whole-cell voltage-clamp data
Get PDFMathematical models of ion channel gating describe the changes in ion channel configurations due to the electrical activity of the cell membrane. Experimental findings suggest that ion channels behave randomly, and therefore stochastic models of ion channel gating should be more realistic than deterministic counterparts. Whole-cell voltage-clamp data allow us to calibrate the parameters of ion channel models. However, standard methods for deterministic models do not distinguish between stochastic channel gating and measurement error noise, resulting in biased estimates, whereas conventional approaches for stochastic models are computationally demanding. We propose a state-space model of ion channel gating based on stochastic reaction networks, and a maximum likelihood inference procedure to estimate the unknown parameters. Simulation studies show that: (i) our proposed method infers the unknown parameters with low uncertainty and outperforms standard approaches whilst being computationally efficient, and (ii) considering stochastic mechanisms of flickering between conducting and non-conducting open states improves the estimates in the total number of ion channels. Finally, the application of our method to experimental data correctly distinguished the 50-Hz measurement error from noise due to stochastic gating. This method improves data-driven models of ion channel dynamics, by accounting for stochastic gating and measurement errors during inference. This article is part of the theme issue 'Uncertainty quantification for healthcare and biological systems (Part 1)'
Benefits of Calibrating a Global Hydrological Model for Regional Analyses of Flood and Drought Projections: A Case Study of the Yangtze River Basin
Get PDFUncalibrated global hydrological models are primarily used to inform projections of flood and drought changes under global warming and their impacts, but it remains unclear how model calibration might benefit these projections. Using the Yangtze River Basin as a case study, we compare projected changes in flood and drought frequencies and their impacts—area, population, and gross domestic product affected—at various warming levels, from uncalibrated and calibrated simulations with the Community Water Model. These projections are driven by 10 General Circulation Models (GCMs) from Coupled Model Intercomparison Project Phase 6, within the Inter-Sectoral Impact Model Intercomparison Project framework. Calibration significantly improves simulated discharge, yet the impact of calibration under climate change on projected increases in flood frequency and their associated impacts is minor, in contrast to its notable role in drought projections. We further quantify the relative contribution of GCMs, emission scenarios, and calibration approaches to the projected impacts, finding that GCMs primarily drive projected flood changes, while emission scenarios and calibration contribute more significantly to the variance in drought projections after 2050. The differing sensitivities to calibration are attributed to the dominance of extreme precipitation in flood generation and the influence of long-term evapotranspiration trends on drought occurrence. The findings imply that future projections of relative changes in flood frequency and risks based on uncalibrated hydrological models are likely still quite reliable for warm and humid regions. However, careful calibration and model improvement is crucial for enhancing the reliability of future drought impact assessments
Reframing internationalism and patriotism: The Labour Party and the Ukraine–Russia war
Get PDFThe Labour Party’s response to the Ukraine-Russia war offers some important insights into its internationalism and patriotism. Both aspects experienced considerable strain during Corbyn’s leadership, with the Party perceived as weak on international affairs and unpatriotic. The Starmer leadership, first in opposition and now in government, has drawn on earlier notions and previous leaders and luminaries, emphasising a more traditional view of British patriotism and Britain’s world role. In the speeches, briefings and outputs of leading Party figures such Starmer, Lammy and Healey, the Party has emphasised its ‘ironclad’ support for Ukrainian sovereignty, territorial integrity and resisting Russian aggression. As such, the conflict has opened up possibilities to return to earlier understandings of internationalism and patriotism, stressing that Britain will be secure at home and comfortable playing a leading role in Europe and, more widely, on the global stage
Proactive clinical review of patients taking opioid medicines long term for persistent pain led by clinical pharmacists in primary care teams (PROMPPT): a non-randomised mixed methods feasibility study
Get PDFBackgroundGiven the poor long-term effectiveness of opioids for persistent non-cancer pain, and their potential for harm, evidence-based interventions to address opioid overprescribing for persistent pain are needed. This study aimed to explore the acceptability and feasibility of a primary care practice pharmacist-led intervention (PROMPPT review) for patients prescribed opioids for persistent pain and the feasibility of evaluating PROMPPT in a definitive trial.MethodsA single-arm study, with mixed methods process evaluation, was conducted in four English primary care practices. Adults prescribed opioids for ≥ 6 months were invited to participate in the Management of Opioids and Persistent Pain (MOPP) study by completing baseline and 3-month follow-up questionnaires. Practices invited a representative sample of MOPP participants to schedule a PROMPPT review, eight of which were audio-recorded. Following the review, pharmacists completed intervention delivery templates, and participants were sent an Acceptability Questionnaire and invited to consent to an interview.ResultsBetween November 2020 and May 2021, 148 participants were recruited to the MOPP study. Of these, 123 (83%) completed 3-month follow-up. Of 88 MOPP participants invited for a PROMPPT review, 80 (91%) attended. The review was rated completely acceptable or acceptable in 90% (45/50) of acceptability questionnaires returned. Overall, participants interviewed (n = 15) perceived the review as a good idea and recommended it to others; they preferred face-to-face consultations. Prior to the review, they reported mixed feelings, including feeling ‘pleased’ to be invited and ‘grateful’ someone was taking an interest, alongside concerns about what would happen during the review, including opioids being stopped and changes being detrimental. Following the review, those with a clear plan for follow-up/access to the pharmacist felt reassured about making changes to their pain medicines, whilst those advised to arrange follow-up as needed were less satisfied and more likely to report confusion about the plan.ConclusionsPROMPPT reviews appeared acceptable to patients, review uptake was high, and the study demonstrated the feasibility of a large definitive trial to evaluate PROMPPT. The review invitation, patient information, and pharmacist training were refined based on the findings ahead of a large cluster randomised controlled trial.Trial registrationISRCTN, ISRCTN87628403, registered 31 July 202
Atomic-Scale Imaging of Transformation of Nickel Nanocrystals to Nickel Carbides in Real Time
Get PDFTransition of metal-to-metal carbide plays a key role in heterogeneous catalysis. We confined nickel nanocrystals in single-walled carbon nanotubes, stimulated delivery of carbon atoms by the 80 keV electron beam, and imaged the entire carbonization process by time-resolved aberration-corrected transmission electron microscopy at the atomic scale. Metal nanocrystal Ni40 progressively capturing carbon atoms evolved from pure metal to Ni40C20 and then to Ni40C40. The carbonization is accompanied by changes in the structure of the crystal, including a two-dimensionalization process, at the Ni40C40 stage. This work provides valuable insights into the atomic mechanism of metal carbide formation, which may help to develop stable catalysts and provide a reliable route for synthesizing metal-based two-dimensional materials
A proximity labelling-based approach to directly detect mRNA delivery to specific subcellular locations
No full textMessenger RNA (mRNA) therapeutics show considerable promise but face delivery challenges, as effective cytosolic entry and subsequent translation are normally limited by endosomal entrapment. While various approaches have been used to investigate determinants of effective RNA delivery, these methods tend to be indirect, qualitative, or rely on labeled RNA. There is a need for quantitative approaches that can directly measure mRNA delivery to its functional sites within the cell. Here, we adapted the APEXseq approach for proximity biotinylation and isolation of mRNA at specific subcellular locations. We combined APEX2 labeling with reverse-transcription quantitative PCR to investigate mRNA delivery to the cytoplasm and endoplasmic reticulum, the two major sites of translation, and found it was most effective in the endoplasmic reticulum. We incorporated a biotinylated spike-in RNA to improve existing methodology by allowing normalization of data and optimization of mRNA pull-down conditions. Finally, we combined this method with protein assays to investigate the role of different signal peptides in mRNA delivery to, and translation at, the endoplasmic reticulum. This new approach shows promise as a tool for future investigation of productive delivery of therapeutic mRNA
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