Interaction between multiple bubbles in microchannel flow boiling and the effects on heat transfer

Flow boiling in microchannels have widely been studied in order to design more efficient cooling systems with numerical simulations forming a crucial part to deal with the areas that cannot be investigated experimentally. Previously published research largely focussed on the behaviour of a single bubble. Here, we focus on the behaviour of multiple bubbles. In this study, the influence of the distance between the bubbles (liquid slug length) is investigated in both an axisymmetric and a planar domain for two and three bubbles present. In this regard, an interface-tracking adaptive mesh refinement model was implemented to improve simulation time. Results show that the heat transfer was improved with sequential bubbles, and a 50% increase in heat transfer coefficient was observed for the cases investigated with three bubbles present. The heat transfer also improved the closer the bubbles were together.ThermaSMART Project of the European Commission, the Edinburgh Compute & Data Facility (ECDF) and Centre for High Performance Computing (CHPC), South Africa.https://www.elsevier.com/locate/ichmt2023-10-22hj2022Mechanical and Aeronautical Engineerin

Autologous whole blood clot and negative-pressure wound therapy in South Africa: A comparison of the cost and social considerations

Background. Advanced wound treatment modalities enhance healing of hard-to-heal wounds, decrease the risk of amputations, and improve the quality of life of patients. Modalities have different rates of efficacy and incur different social and financial costs to the individual and the healthcare system. Two such modalities, the autologous whole blood clot (WBC) and negative-pressure wound therapy (NPWT), were compared in the South African (SA) context. The comparison was conducted on hard-to-heal wounds, with a specific focus on diabetic foot ulcers (DFUs). Objectives. To compare the social considerations and financial costs of using autologous WBC v. NPWT in the treatment of DFUs in SA. Methods. Data were obtained based on current supply costs from SA suppliers for the two modalities, the standard of care for both modalities, the number of applications required for each, and social considerations provided by SA wound management clinicians. Wound healing rates were obtained from the published literature. This information was used to calculate costs of two scenarios (scenario 1: low exudate v. scenario 2: high exudate), which were compared over two treatment durations (4 and 12 weeks) for each treatment modality. Calculations included weekly cost of supplies, total cost saved by a patient with a DFU managed with either of the wound therapies, and the difference in total cost saved between the two modalities. Key social considerations were assessed qualitatively from discussions with SA clinicians experienced in both autologous WBC and NPWT, and from published research. Results. The cost of supplies per week was ZAR3 250 for autologous WBC and ZAR4 804 for NPWT in scenario 1, and ZAR3 332 and ZAR6 612 in scenario 2. With healing rates over 4 weeks’ treatment duration of 19% for autologous WBC and 10% for NPWT, autologous WBC saved ZAR17 719.93, or 9% more than using NPWT, in scenario 1 and ZAR18 381.47, or 10% more, in scenario 2. At 12 weeks’ treatment duration, healing rates for autologous WBC and NPWT were 75% and 43%, respectively. In scenario 1, results indicated a 43% cost difference between the two modalities. Autologous WBC had a total cost saving of ZAR61 874.40 compared with NPWT over a period of 12 weeks. In scenario 2, results indicated a 46% cost difference between the two modalities. Autologous WBC had a total cost saving of ZAR70 454.68 compared with NPWT over a period of 12 weeks. One of the identified social considerations is that NPWT needs a reliable supply of electricity to recharge the pump, while autologous WBC does not. Conclusion. Both modalities are safe and effective in treating hard-to-heal wounds of the lower extremities. Autologous WBC consistently demonstrated better outcomes than NPWT in terms of both healing rate and cost-effectiveness, as well as having some advantages in terms of social considerations in SA

Adaptive mesh refinement method for the reduction of computational costs while simulating slug flow

Microchannel flow boiling has been the focus of many experimental and numerical investigations due to the high heat transfer coefficients that it can induce. However, experimental research has been limited due to the small scales involved, leading researchers to employ computational fluid dynamics (CFD) simulations to resolve the dearth of research on microchannel flow boiling. Conventional CFD methods use a fine uniform mesh to capture the small scales and gradients, such as the liquid-vapour interface. This method has a large computational cost, and as a result, most research reported in the literature has been limited to two-dimensional axisymmetric domains. An interface-tracking adaptive mesh refinement model was created in this study to overcome the limitation of high computational costs without losing accuracy. This model dynamically refined the mesh only in the regions of interest and allowed a coarser mesh in the rest of the domain. This novel approach was able to recreate previously published results with a maximum error of 6.7%, while using less than 1.6% of the mesh elements. Several simulations were conducted in ANSYS Fluent 19.1 to determine the optimal settings for this new method to maintain accuracy and reduce cell count. These settings were determined as three levels of refinement (δL = 3), four refined cells on either side of the interface (δM = 4), and was implemented every five time steps (δT = 5). Finally, a case study was conducted to illustrate the possibility of simulating two-phase flow in microchannels in three dimensions with this method.ThermaSMART project of the European Commission, the Edinburgh Compute & Data Facility (ECDF) and the Centre for High Performance Computing (CHPC), South Africa.https://www.elsevier.com/locate/ichmt2023-10-23hj2022Mechanical and Aeronautical Engineerin

Patient-Reported Outcomes in ATLAS and FLAIR Participants on Long-Acting Regimens of Cabotegravir and Rilpivirine Over 48 Weeks

The phase 3 ATLAS and FLAIR studies demonstrated that maintenance with Long-Acting (LA) intramuscular cabotegravir and rilpivirine is non-inferior in efficacy to current antiretroviral (CAR) oral therapy. Both studies utilized Patient-Reported Outcome instruments to measure treatment satisfaction (HIVTSQ) and acceptance (ACCEPT general domain), health status (SF-12), injection tolerability/acceptance (PIN), and treatment preference. In pooled analyses, LA-treated patients (n = 591) demonstrated greater mean improvements from baseline than the CAR group (n = 591) in treatment satisfaction (Week 44, + 3.9 vs. +0.5 HIVTSQs-points; p /= 97% of LA group participants with recorded data preferred LA treatment compared with prior oral therapy. These results further support the potential of a monthly injectable option for people living with HIV seeking an alternative to daily oral treatment

FEM-PrEP: Adherence Patterns and Factors Associated With Adherence to a Daily Oral Study Product for Pre-exposure Prophylaxis

Background:Several clinical trials have demonstrated the safety and effectiveness of oral tenofovir disoproxil fumarate (TDF), with or without emtricitabine (FTC), as pre-exposure prophylaxis (PrEP) for reducing the risk of HIV acquisition. Adherence to the study product was insufficient to demonstrate the effectiveness of FTC/TDF in 2 PrEP clinical trials conducted among women (FEM-PrEP and the Vaginal and Oral Interventions to Control the Epidemic study), but further analyses of adherence in these studies may inform PrEP demonstration projects and future HIV prevention clinical trials.Methods:We randomly selected a subcohort of 150 participants randomized to FTC/TDF in 3 FEM-PrEP sites (Bondo, Kenya; Bloemfontein, South Africa; and Pretoria, South Africa) to examine adherence levels over time and to assess factors associated with adherence, based on plasma tenofovir and intracellular tenofovir diphosphate drug concentrations in specimens collected at 4-week visit intervals.Results:We observed drug concentrations consistent with good adherence in 28.5% of all visit intervals when drug was available to use, but only 12% of participants achieved good adherence throughout their study participation. In multivariate analysis, the Bloemfontein site [odds ratio (OR): 2.43; 95% confidence interval (CI): 1.32 to 4.48] and liking the pill color (OR: 2.93; 95% CI: 1.18 to 7.27) were positively associated with good adherence, whereas using oral contraceptive pills at enrollment was negatively associated with good adherence (OR: 0.37; 95% CI: 0.18 to 0.74).Conclusions:Most participants did not regularly adhere to the study product throughout their trial participation, although a small minority did. Few factors associated with good adherence to the study product were identified in FEM-PrEP

Accuracy of Self-Report and Pill-Count Measures of Adherence in the FEM-PrEP Clinical Trial: Implications for Future HIV-Prevention Trials

Oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) has been evaluated as pre-exposure prophylaxis (PrEP). We describe the accuracy of self-reported adherence to FTC/TDF and pill counts when compared to drug concentrations in the FEM-PrEP trial. Using drug concentrations of plasma tenofovir (TFV) and intracellular tenofovir diphosphate (TFVdp) among a random sub-sample of 150 participants assigned to FTC/TDF, we estimated the positive predictive value (PPV) of four adherence measures. We also assessed factors associated with misreporting of adherence using multiple drug-concentration thresholds and explored pill use and misreporting using semi-structured interviews (SSIs). Reporting use of ≥1 pill in the previous 7days had the highest PPV, while pill-count data consistent with missing ≤1day had the lowest PPV. However, all four measures demonstrated poor PPV. Reported use of oral contraceptives (OR 2.26; p=0.014) and weeks of time in the study (OR 1.02; p<0.001) were significantly associated with misreporting adherence. Although most SSI participants said they did not misreport adherence, participant-dependent adherence measures were clearly unreliable in the FEM-PrEP trial. Pharmacokinetic monitoring remains the measure of choice until more reliable participant-dependent measures are developed

Study design for development of novel safety biomarkers of drug-induced liver injury by the translational safety biomarker pipeline (TransBioLine) consortium: a study protocol for a nested case–control study

A lack of biomarkers that detect drug-induced liver injury (DILI) accurately continues to hinder early- and late-stage drug development and remains a challenge in clinical practice. The Innovative Medicines Initiative’s TransBioLine consortium comprising academic and industry partners is developing a prospective repository of deeply phenotyped cases and controls with biological samples during liver injury progression to facilitate biomarker discovery, evaluation, validation and qualification.In a nested case–control design, patients who meet one of these criteria, alanine transaminase (ALT) ≥ 5 × the upper limit of normal (ULN), alkaline phosphatase ≥ 2 × ULN or ALT ≥ 3 ULN with total bilirubin > 2 × ULN, are enrolled. After completed clinical investigations, Roussel Uclaf Causality Assessment and expert panel review are used to adjudicate episodes as DILI or alternative liver diseases (acute non-DILI controls). Two blood samples are taken: at recruitment and follow-up. Sample size is as follows: 300 cases of DILI and 130 acute non-DILI controls. Additional cross-sectional cohorts (1 visit) are as follows: Healthy volunteers (n = 120), controls with chronic alcohol-related or non-alcoholic fatty liver disease (n = 100 each) and patients with psoriasis or rheumatoid arthritis (n = 100, 50 treated with methotrexate) are enrolled. Candidate biomarkers prioritised for evaluation include osteopontin, glutamate dehydrogenase, cytokeratin-18 (full length and caspase cleaved), macrophage-colony-stimulating factor 1 receptor and high mobility group protein B1 as well as bile acids, sphingolipids and microRNAs. The TransBioLine project is enabling biomarker discovery and validation that could improve detection, diagnostic accuracy and prognostication of DILI in premarketing clinical trials and for clinical healthcare application

Study design for development of novel safety biomarkers of drug-induced liver injury by the translational safety biomarker pipeline (TransBioLine) consortium: a study protocol for a nested case–control study

A lack of biomarkers that detect drug-induced liver injury (DILI) accurately continues to hinder early- and late-stage drug development and remains a challenge in clinical practice. The Innovative Medicines Initiative’s TransBioLine consortium comprising academic and industry partners is developing a prospective repository of deeply phenotyped cases and controls with biological samples during liver injury progression to facilitate biomarker discovery, evaluation, validation and qualification. In a nested case–control design, patients who meet one of these criteria, alanine transaminase (ALT) ≥ 5 × the upper limit of normal (ULN), alkaline phosphatase ≥ 2 × ULN or ALT ≥ 3 ULN with total bilirubin > 2 × ULN, are enrolled. After completed clinical investigations, Roussel Uclaf Causality Assessment and expert panel review are used to adjudicate episodes as DILI or alternative liver diseases (acute non-DILI controls). Two blood samples are taken: at recruitment and follow-up. Sample size is as follows: 300 cases of DILI and 130 acute non-DILI controls. Additional cross-sectional cohorts (1 visit) are as follows: Healthy volunteers (n = 120), controls with chronic alcohol-related or non-alcoholic fatty liver disease (n = 100 each) and patients with psoriasis or rheumatoid arthritis (n = 100, 50 treated with methotrexate) are enrolled. Candidate biomarkers prioritised for evaluation include osteopontin, glutamate dehydrogenase, cytokeratin-18 (full length and caspase cleaved), macrophage-colony-stimulating factor 1 receptor and high mobility group protein B1 as well as bile acids, sphingolipids and microRNAs. The TransBioLine project is enabling biomarker discovery and validation that could improve detection, diagnostic accuracy and prognostication of DILI in premarketing clinical trials and for clinical healthcare application