Research Funding Research Articles

An international multidisciplinary consensus on pediatric metabolic dysfunction-associated fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in children and adolescents, particularly those with obesity. NAFLD is considered a hepatic manifestation of the metabolic syndrome due to its close associations with abdominal obesity, insulin resistance, and atherogenic dyslipidemia. Experts have proposed an alternative terminology, metabolic dysfunction-associated fatty liver disease (MAFLD), to better reflect its pathophysiology. This study aimed to develop consensus statements and recommendations for pediatric MAFLD through collaboration among international experts. A group of 65 experts from 35 countries and six continents, including pediatricians, hepatologists, and endocrinologists, participated in a consensus development process. The process encompassed various aspects of pediatric MAFLD, including epidemiology, mechanisms, screening, and management. In round 1, we received 65 surveys from 35 countries and analyzed these results, which informed us that 73.3% of respondents agreed with 20 draft statements while 23.8% agreed somewhat. The mean percentage of agreement or somewhat agreement increased to 80.85% and 15.75%, respectively, in round 2. The final statements covered a wide range of topics related to epidemiology, pathophysiology, and strategies for screening and managing pediatric MAFLD. The consensus statements and recommendations developed by an international expert panel serve to optimize clinical outcomes and improve the quality of life for children and adolescents with MAFLD. These findings emphasize the need for standardized approaches in diagnosing and treating pediatric MAFLD. This work was funded by the National Natural Science Foundation of China (82070588, 82370577), the National Key R&D Program of China (2023YFA1800801), National High Level Hospital Clinical Research Funding (2022-PUMCH-C-014), the Wuxi Taihu Talent Plan (DJTD202106), and the Medical Key Discipline Program of Wuxi Health Commission (ZDXK2021007).

A Review of Lawson Criterion for Nuclear Fusion

In the pursuit for abundant clean energy from nuclear fusion, the Lawson Criterion is cited by fusion researchers and experimentalists as the condition to exceed for fusion of atomic nuclei to occur. In his 1955 paper J.D. Lawson analyzed a fusion plasma conforming to thermodynamic principles at steadystate but with stated omissions and simplifications. Modern fusion researchers developed many incantations of the Lawson Criterion urging their brand leads to fusion ignition, necessarily to sell a rational fusion hypothesis and attract research funding. Others have shown how confined fusion in the laboratory cannot satisfy a positive energy balance due to energy losses from the system. A literature search for "fusion energy balance" shows a suspicious absence of this sanity-check to verify the energy condition was met. This paper applies conservation of energy from classical thermodynamics to a fusion plasma and summarizes eleven modern Lawson-like interpretations in a uniform way, doing so shows the requirements for fusion ignition are not met. Indeed despite billions of speculative dollars spent, sustained laboratory fusion has not been demonstrated in any experimental apparatus built and tested to date worldwide. Heed the warning, in 1955 John D. Lawson wrote: “To conclude we emphasize that these conditions, though necessary are far from sufficient. The working cycle that has been assumed is very optimistic.”

Adaptation of the technology readiness levels for impact assessment in implementation sciences: The TRL-IS checklist

BackgroundIntervention development is a critical process in implementation research. There are key stages involved in the process to design, pilot, demonstrate and release a technology or an intervention. The Technology Readiness Level (TRL) is a globally accepted instrument for assessing the maturity of research development. However, the original levels do not fit all, and some adjustments are required for its applicability in implementation sciences. AimsThis study aimed to gather the prior knowledge base on TRL in public and population health research; to develop a standard definition of readiness, and to adapt and validate the TRL to an implementation science context (TRL-IS). Materials and methodsA Mixed methods approach has been followed in this study. A scoping review using the PRISMA extension (PRISMA-ScR) informed a nominal expert panel for developing a standard definition of readiness and to modify the TRL following an ontoterminology approach. Then the maturity of six practical case study examples were rated by ten researchers using the modified TRL to estimate inter-rater reliability, and a group of experts provided final content and face validity and feasibility.This mixed methods study included 1) a scoping review to examine the current literature and develop a knowledge base, identify knowledge gaps and to clarify concepts; 2) the development of a standard definition of ‘Readiness’ and related terms; and 3) adaptation of the TRL to implementation science and development of a checklist to rate the maturity of applications.A standard definition of readiness and related terms was produced by the core team, and an international nominal group (n = 30) was conducted to discuss and validate the definition and terms, and the location of ‘Readiness’ in the initiation and early development phases of implementation.Following feedback from the nominal group, the development of the TRL-IS was finalised and a TRL-IS rating checklist was developed to rate the maturity of applications. The TRL-IS checklist was tested using six cases based on real world studies on implementation research.The inter-rater reliability of the TRL-IS was evaluated by ten raters and finally six raters evaluated the content and face validity, and feasibility, of the TRL-IS checklist using the System Usability Scale (SUS). ResultsFew papers (n = 11) utilised the TRL to evaluate the readiness of readiness of health and social science implementation research. The main changes in the adaption of the TRL-IS included the removal of laboratory testing, limiting the use of “operational” environment and a clearer distinction between level 6 (pilot in a relevant environment) and 7 (demonstration in the real world prior to release). The adapted version was considered relevant by the expert panel. The TRL-IS checklist showed evidence of good inter-rater reliability (ICC = 0.90 with 95 % confident interval = 0.74–0.98, p < .001) and provides a consistent metric. ConclusionsIn spite of recommendations made by national and international research funding agencies, few health and social science implementation studies include the TRL as part of their evaluation protocol. The TRL-IS offers a high degree of conceptual clarity between scientific maturity phases or readiness levels, and good reliability among raters of varying experience. This study highlights that adoption of the TRL-IS framework in implementation sciences will bolster the scientific robustness and comparability of research maturity in this domain.

Harnessing the potential of African youth for transforming health research in Africa

Africa faces a significant burden of infectious diseases, including Malaria and HIV/AIDS, along with an increasing prevalence of non-infectious diseases such as diabetes and cancer. This dual health challenge is amplified by socioeconomic difficulties, restricted access to healthcare, and lifestyle changes, thus present unique scientific needs. Effectively addressing these issues requires a skilled scientific workforce adept in comprehensive healthcare strategies. This analysis explores the critical landscape of health research in Africa, emphasizing the unique opportunity presented by the continent’s youthful population, projected to reach almost 1 billion by 2050. The youth’s innovative potential and fresh perspectives offer a chance to overcome development barriers in health research. Nevertheless, challenges such as under-resourced education, limited research training, inadequate mentorship, and funding difficulties persist. This paper urgently calls upon African leaders, international partners, and stakeholders to prioritize health research, mobilize funding, forge strategic partnerships, and empower the youth as essential steps to capitalize on the continent’s dynamic youth for breakthrough health outcomes. Such investments are vital not just for health but for the overall economic, social, and strategic growth of the continent. Through shared responsibility and a united effort, the potential of African youth can be harnessed, leading to transformative research, improved health outcomes, and a prosperous future. This perspective represents the collective voice of passionate young researchers and advocates across Africa, calling for a new era of health research on the continent.

The Bullwhip Effect in Servitized Manufacturers

The shift to a service-oriented economy has driven traditional product-oriented manufacturing firms to integrate various services into their businesses. This study aims to provide empirical evidence on how manufacturers’ service offerings impact demand variability and intrafirm bullwhip effects. Through “bag-of-words” text mining on 10-K filings of U.S.-listed manufacturing firms, we propose a novel measurement to identify annual services offered. We validate the measurement’s statistical and economic significance and verify its consistency with the results obtained using the large language model (i.e., GPT-4). Services are categorized as complementing product sales (e.g., maintenance and repair) or substituting product sales entirely (e.g., machine hours). Utilizing difference-in-difference techniques, we find robust evidence that manufacturers’ service offerings reduce the bullwhip effect in two steps: basic complementing services decrease demand variability, whereas advanced substituting services mitigate intrafirm bullwhip. Moreover, servitization mainly minimizes demand variability through information channels, whereas increased production efficiency decreases intrafirm bullwhip. Our findings contribute to understanding manufacturers’ business model innovations by demonstrating that servitization can smooth demand and mitigate intrafirm bullwhip. This paper was accepted by Karan Girotra, operations management. Funding: This work was supported by the National Natural Science Foundation of China [Grants 71931007, 72091214] and General Research Fund by Hong Kong Research Grants Council [Grant 14505320]. Supplemental Material: The data and the online appendix are available at https://doi.org/10.1287/mnsc.2023.01026 .

Transport research implementation: current issues and lessons learned from Europe and China

The implementation of the research results is seen as a crucial step in the development of innovation in the transport sector. Moving to such an implementation is not always easy or straightforward. It requires a suitable organizational framework both inside as well as outside research producing entities and a number of other facilitating factors that are usually found within an innovation ecosystem. The paper examines systematically the conditions and prevailing practices for transport research implementation in Europe (the European Union) and China and draws useful insights as to the factors that influence such implementation, the incentives, and other facilitating provisions that the research funding organizations can take. It also analyses the current practice and lessons learned for research implementation on the road to innovation production in four major areas of transport research namely: Automated Mobility, Intelligent Railways, Shared and Micromobility applications, and Electromobility.

Observational signatures of rotating black holes in the semiclassical gravity with trace anomaly* *Partly Supported by the National Natural Science Foundation of China (12275004, 12205013, 11873044). MG is also endorsed by ”the Fundamental Research Funds for the Central Universities” (2021NTST13)

In a recent work by Fernandes [Phys. Rev. D 108(6), L061502 (2023)], an exact stationary and axisymmetric solution was discovered in semiclassical gravity with type-A trace anomaly. This was identified as a quantum-corrected version of the Kerr black hole. In this study, we explore the observational signatures of this black hole solution. Our investigation reveals that prograde and retrograde light rings exist, whose radii increase monotonically with the coupling parameter α. When α is negative, the shadow area for the quantum-corrected black hole is smaller than that of the Kerr black hole, whereas when α is positive, the area is larger. For a near-extremal black hole, its high-spin feature (the NHEKline) is found to be highly susceptible to disruption by α. Furthermore, we discuss the images of the quantum-corrected black hole in the presence of a thin accretion disk and compare them to those of the Kerr black hole. Our study highlights the importance of near-horizon emission sources in detecting the effects of quantum corrections by black hole images.

Hybrid simulation of a steel frame with Dissipative Replaceable Link Frames

In the last decades, high priority has been given to enhancing the seismic resilience of structures by reducing the damage of structural and non-structural elements after a disaster. In this context, the European Research Fund for Coal and Steel (RFCS) project DISSIPABLE was funded to perform large demonstration tests of steel frames equipped with easily repairable seismic dissipative devices. The paper extensively describes the experimental campaign carried out at the University of Trento on a steel frame equipped with innovative Dissipative Replaceable Link Frame (DRLF) systems, composed of two rigid columns connected by weakened beams at their ends. Hybrid Simulation was employed, enabling to physically test the first floor of the building yet allowing for considering the response of the remaining five floors, which were numerically simulated. A bidimensional frame was tested under increasing seismic intensity levels: Damage Limitation, Significant Damage and Near Collapse limit states. The experimental results proved that the DRLF system was able to dissipate energy and protect the primary elements of the structure from plasticisation. Moreover, the structure's re-centring capability was verified to ensure the components' replaceability. Finally, the calibration of the nonlinear model was performed following the tests, which allowed to develop a high-fidelity model suitable for further numerical investigation.

E061 Attitudes and barriers to pulmonary arterial hypertension screening in systemic sclerosis patients: a survey of UK-based rheumatologists

Abstract Background/Aims Pulmonary arterial hypertension (PAH) affects approximately 10% of patients with SSc and is a major cause of morbidity and mortality. PAH is often asymptomatic, and therefore, proactive screening is crucial for early detection and improved survival, including through early treatment intervention. Although there are various proposed international guidelines for screening, there is currently no dedicated UK-based guidance. Our aim is to explore current UK screening practices for SSc-PAH patients, including identifying barriers and potential solutions. Methods A survey of 31 questions was developed and included six sections: clinician demographics, the importance of screening, screening practices, barriers to screening, treatment, and patient education. The survey was disseminated among rheumatologists working in the UK. Results Forty-four rheumatologists working in the UK participated in the study, and the majority completed all the questions. Around one-third (37.0%) worked in specialised SSc units (university or general hospitals [54.5% and 45.4%, respectively]). The majority recognised that SSc-PAH is a major cause of morbidity and mortality. Over half (60.0%) reported using the DETECT algorithm to screen for SSc-PAH, although other algorithms were also sometimes used. All of the respondents utilised transthoracic echocardiogram, and almost all (95.0%) performed pulmonary function tests for screening purposes. Various challenges and barriers were identified relating to SSc-PAH screening (Figure 1A), with the difficulty in interpreting results from other hospitals and extended wait times for diagnostic tests being the most reported (76.0% and 74.0%, respectively). Most respondents agreed that access to key investigations (87.0%), ongoing clinician education (82.0%), multidisciplinary meetings (79.5%) and a better understanding of proposed screening algorithms (79.5%) could be potential solutions (Figure 1B). Conclusion Rheumatologists recognise that SSc-PAH screening is crucial to improve outcomes including survival; however, variable practices exist. There are various barriers to SSc-PAH screening and we have identified a number of practical potential solutions. Disclosure M.P. Álvarez Hernández: None. Y. Allanore: Honoraria; Speaking fees from Janssen outside the submitted work. I. Andrade: Other; Honoraria (speaker) fees, scientific board member for EchoRight™and advisory board participant for ‘Pulmonary hypertension in the primary care setting’ for Janssen, outside the submitted work. M.H. Buch: Other; Speaker fees from Boehringer Ingelheim, outside the submitted work. G. Coghlan: Other; Consultancy and working groups fees from Janssen and MSD; honoraria from Inari and Janssen; grants from Janssen. F. Del Galdo: Other; Consulting fees and research support from Janssen, outside the submitted work. C. Denton: Honoraria; Consulting fees and research support from Janssen, outside the submitted work. D. Khanna: Honoraria; Consultant: Amgen, Abbvie, BI, AZ, Merck, Horizon, Prometheus, Janssen, GSK. Grants- Pfizer, BI, Horizon. D.G. Kiely: Honoraria; Participation in advisory boards, steering committees, speaker fees and support to attend educational meetings from Acceleron, Gossamer, GSK, Janssen, Ferrer, MSD and United Therapeutics. Other; grant funding from GSK and Janssen. His work is supported by a grant from the NIHR Biomedical research Centre Sheffield. J. Pauling: Honoraria; Consultancy work for AstraZeneca, Boehringer Ingelheim, IsomAb, Janssen, Permeatus and Sojournix; speaker honoraria and educational support from Janssen. S. Ramjug: Consultancies; Consulting fees from Janssen, outside the submitted work. M. Hughes: Other; Speaking fees from Actelion, Eli Lilly, Janssen and Pfizer, outside the submitted work; research funding from Janssen; member of a data and safety monitoring board for Certa Therapeutics.

P112 The Impact of Filgotinib on Disease Activity Outcomes With Concomitant Pain Control in the Phase 3 FINCH Studies

Abstract Background/Aims Patients with rheumatoid arthritis (RA) often experience substantial pain despite treatment, and consider pain control an important treatment outcome. This post-hoc analysis of the FINCH studies assessed specific effects of filgotinib (FIL) on pain and its relationship with efficacy in patients with RA. Methods FINCH 1-3 (NCT02889796, NCT02873936, NCT02886728) were Phase 3, randomized, double-blind trials of FIL 100 mg and 200 mg (FIL100/200). For each treatment group, patients reported pain on a 100-mm visual analog scale (VAS). VAS pain ≤20 mm indicated health status was not negatively affected by pain; ≤10 mm reflected limited to no pain. Time to first VAS pain ≤10 mm was assessed. The duration of the study period during which VAS pain was ≤20 mm or ≤ 10 mm and the proportion of patients who achieved remission at Week 24 was evaluated. Of patients who achieved DAS28-CRP or CDAI remission, the proportion who also reported VAS pain ≤20 mm or ≤ 10 mm was determined. Results In FINCH 1, there was a higher probability of achieving VAS pain ≤10 mm with FIL200, vs ADA + MTX or PBO + MTX; responses were better or comparable with FIL100 vs other treatments. Similar findings were seen in FINCH 2 and 3. In FINCH 1, the time during which VAS pain score was ≤20 mm or ≤ 10 mm was greatest in the FIL200 group (Table). The duration of time under each pain threshold was greater in each FIL group vs PBO in FINCH 2 (Table) and in each FIL group vs MTX in FINCH 3. The proportion of patients who achieved VAS pain ≤20 mm and ≤10 mm in addition to DAS28-CRP remission was 35.8% and 26.3%, respectively, in the FIL200 + MTX group, vs 24.6% and 17.2% in the ADA + MTX group. Findings were similar when CDAI remission was assessed for FINCH 1 and 2. Conclusion Across the studies, duration of threshold pain responses achieved over the observation periods was greater with FIL vs comparators. These findings suggest that JAK1 inhibition may offer potential added value with respect to patient-reported pain as well as treat-to-target goals. Disclosure P.C. Taylor: Consultancies; AbbVie, Biogen, Eli Lilly, Fersenius Kabi, Galapagos, Gilead, GSK, Janssen, Nordic Pharma, Sanofi, UCB. Grants/research support; P.T. has received funding for research from Galapagos. A. Kavanaugh: Consultancies; AbbVie, Amgen, BMS, Janssen, Novartis, Pfizer, UCB. P. Nash: Honoraria; AbbVie, BMS, Celgene, Eli Lilly, Galapagos, GSK, Janssen, Novartis, Pfizer. Grants/research support; AbbVie, BMS, Celgene, Eli Lilly, Galapagos, GSK, Janssen, Novartis, Pfizer. J. Pope: Consultancies; AbbVie. G. Pongratz: Consultancies; AbbVie, Boehringer Ingelheim, Galapagos, Eli Lilly, Pfizer, Roche. Honoraria; AbbVie, Boehringer Ingelheim, Eli Lilly, Pfizer, Roche, Sanofi. B. Fautrel: Consultancies; AbbVie, BMS, Chugai, Fersenius Kabi, Galapagos, Eli Lilly, Medac, Nordic Pharma, Novartis, Pfizer, Sobi, UCB. Grants/research support; AbbVie, Eli Lilly, Pfizer. R. Alten: Consultancies; AbbVie, Amgen, Biogen, BMS, Celltrion, Gilead, Janssen, Eli Lilly, Medac, MSD, Mylan, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Viatris. Honoraria; AbbVie, Amgen, Biogen, BMS, Celltrion, Gilead, Janssen, Eli Lilly, Medac, MSD, Mylan, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Viatris. K. Hasegawa: Shareholder/stock ownership; Gilead. Other; Employee of Gilead. S. Rao: Other; Employee of Gilead. D. De Vries: Shareholder/stock ownership; Galapagos. Other; Employee of Galapagos. P. Stiers: Shareholder/stock ownership; Galapagos. Other; Employee of Galapagos. C. Watson: Shareholder/stock ownership; Galapagos. Other; Employee of Galapagos. R. Westhovens: Consultancies; Celltrion, Galapagos, Gilead. Honoraria; Celltrion, Galapagos, Gilead.

P179 CD19hi B cells express T-bet and display activated metabolism and function in rheumatoid arthritis and systemic lupus erythematosus patient samples

Abstract Background/Aims CD19, a co-receptor of the B cell receptor, fine-tunes the threshold for B-cell activation with implications for cell metabolism and function. Activating receptors such as CD40, IFNγR and TLRs also influence B cell activation. B cell subpopulation, double negative (DN, IgD-CD27-) T-bet+ B cells, is considered pathogenic in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Here, we explored whether CD19hi B cells differed from CD19lo B cells with regards to proliferation, metabolism, and function. Methods Peripheral blood samples from nine healthy participants, 16 RA and 20 SLE patients were analysed. Subgroup analysis of rituximab-treated (RTX-T), n = 6 versus rituximab naïve (RTX-N), n = 6, was performed. B cells or peripheral blood mononuclear cells were stimulated with anti-IgG, anti-IgM and anti-human CD40 antibodies and a TLR9 agonist for 20 hours prior to flow cytometric analysis of B cell expression of phosphorylated AMPK (pAMPK, the master regulator of metabolism), intracellular expression of Ki67 (proliferation marker), and cytokines IL-6 and IL-10. Statistical analysis was performed using GraphPad Prism v10.0.1. Results Compared to CD19+CD20+ B cells, CD19+CD20- B cells: 1) were predominantly composed of DN (55% versus 19%, p &amp;lt; 0.01) and IgD-CD27+ memory subpopulations (37% versus 25%, p = 0.1094); 2) were detectable at a hierarchical frequency, RTX-T&amp;gt;RTX-N&amp;gt;HC cohorts; 3) had a greater frequency of Ki67+ cells (38% versus 5%, p &amp;lt; 0.01); 4) displayed higher CD38 MFI (41478.0 versus 10589.0, p &amp;lt; 0.01). Approximately 50% of CD19hi B cells were T-bet+, compared to 28% of CD19lo B cells (n = 33, p &amp;lt; 0.0001). Compared to CD19lo, CD19hi B cells 1) expressed (MFI) significantly greater TLR7, TLR9, IFNγR and pAMPK (n = 7 for all except pAMPK, n = 4), and 2) had greater frequency of IL6+ and IL10+ B cells (n = 7, p &amp;lt; 0.05) (Table). Conclusion CD20- B cell subpopulations with potent proliferative capacity express CD19. Further, CD19hi B cells: 1) upregulate the TLR-IFNγ-T-bet pathway; 2) have significantly greater expression of pAMPK; 3) have higher cytokine expression compared to CD19lo B cells. These data suggest the activation pathway, metabolic activity, and functional profile of CD19hi cells. Therefore, the potential of CD19hi cells to promote inflammation provides strong rationale for targeting CD19 in autoimmune disease with emerging therapies such as CAR-T cells and T cell engagers. Disclosure K. Shah: Grants/research support; KS has received funding for research from Roche. M.J. Leandro: Consultancies; MJL acted as a consultant for Roche and Genentech. Other; MJL received funds less than $10000 and support to attend educational conferences. M.S. Cragg: Consultancies; Consultant for BioInvent International, Boehringer Ingelheim, GSK, Radiant, iteos, Surrozen, Hanall and Mestag. Honoraria; He has received honoraria/speakers fees from Boehringer Ingelheim, Amgen, Roche and Symphogen. Grants/research support; BioInvent International, GSK and UCB. F. Kollert: Corporate appointments; FK is employed by Roche. Shareholder/stock ownership; FK has stock ownership at Roche. F. Schuler: Corporate appointments; FS is employed by Roche. Shareholder/stock ownership; FS has patents and stock ownership at Roche. D.A. Isenberg: None. A. Akbar: None. C. Klein: Corporate appointments; CK is employed by Roche. Shareholder/stock ownership; CK has patents and stock ownership at Roche. V. Reddy: Grants/research support; VR has received a research grant from Roche.

Harnessing fluorescence resonance energy transfer for improved solar still performance with zinc oxide nanoparticles and activated carbon

The Single Slope Corrugated Wick type Solar Distillers (SWS) have attracted significant research funding owing to their simple preparation process and excellent durability against heat and moisture. However, there is a recognized need to enhance their solar energy conversion efficiency. The utilization of ZnO nanoparticles (Z) in SWS is limited by their light absorption capacity, resulting in suboptimal thermal energy conversion and solar energy absorption. In this investigation, we propose an innovative method known as Fluorescence Resonance Energy Transfer (FRET), combining crystallized Z with activated carbon (AC) derived from areca nut shells. This novel approach substantially boosts the thermal efficiency of solar energy utilization in SWS by facilitating efficient energy transfer from ZAC to water.The FRET technique enables the effective transfer of energy from ZAC to water and is comprehensively analyzed. By utilizing Z as donors and AC as acceptors, the photoluminescence emitted by ZAC can be absorbed by both components, thereby increasing the carrier population as of Corrugated Wick-type towards the condenser face within SWS. The evaporation rate from water to the condensing surface is significantly higher in SWS with ZAC compared to conventional wick-type solar stills (CWS), attributed to the efficient heat transfer facilitated through multi-dimensional heterojunctions within ZAC. The energy and charge transfer processes are optimized for both summer and winter operating conditions. The ZAC-based SWS exhibits exceptional resilience in various ambient conditions, resulting in a substantial 33.989 % enhancement in distillation efficiency during summer and a notable 31.199 % improvement in winter. The incorporation of ZAC elevates the production of distillate water to 6.325 liters/m2 per day in summer and 5.840 liters/m2 per day in winter (24 h). The energy distribution among particle components is extensively scrutinized using the FRET mechanism.

Online Advertisement Allocation Under Customer Choices and Algorithmic Fairness

Advertising is a crucial revenue source for e-commerce platforms and a vital online marketing tool for their sellers. In this paper, we explore dynamic ad allocation with limited slots upon each customer’s arrival for an e-commerce platform, where customers follow a choice model when clicking the ads. Motivated by the recent advocacy for the algorithmic fairness of online ad delivery, we adjust the value from advertising by a general fairness metric evaluated with the click-throughs of different ads and customer types. The original online ad-allocation problem is intractable, so we propose a novel stochastic program framework (called two-stage target-debt) that first decides the click-through targets and then devises an ad-allocation policy to satisfy these targets in the second stage. We show the asymptotic equivalence between the original problem, the relaxed click-through target optimization, and the fluid-approximation ( Fluid ) convex program. We also design a debt-weighted offer-set algorithm and demonstrate that, as long as the problem size scales to infinity, this algorithm is (asymptotically) optimal under the optimal first-stage click-through target. Compared with the Fluid heuristic and its resolving variants, our approach has better scalability and can deplete the ad budgets more smoothly throughout the horizon, which is highly desirable for the online advertising business in practice. Finally, our proposed model and algorithm help substantially improve the fairness of ad allocation for an online e-commerce platform without significantly compromising efficiency. This paper was accepted by Jeannette Song, operations management. Funding: Y. Rong is supported by the National Natural Science Foundation of China [Grants 72025201, 72331006, and 72221001]. R. Zhang is grateful for the financial support from the Hong Kong Research Grants Council General Research Fund [Grants 14502722 and 14504123] and the National Natural Science Foundation of China [Grants 72293560 and 72293565]. H. Zheng is supported by the National Natural Science Foundation of China [Grants 72231003, 72325003, and 72221001]. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2021.04091 .

E070 Sustained and consistent efficacy of bimekizumab in patients with active psoriatic arthritis regardless of prior TNF-inhibitor status: results from the phase 3 BE OPTIMAL and BE COMPLETE trials

Abstract Background/Aims Bimekizumab (BKZ), a humanised monoclonal IgG1 antibody that inhibits IL-17A and IL-17F, has demonstrated rapid efficacy in joint and skin outcomes for patients with active psoriatic arthritis (PsA) who are bDMARD-naïve (BE OPTIMAL; NCT03895203) and TNFi-inadequate responders (TNFi-IR) (BE COMPLETE; NCT03896581). Here we report longer-term PsA response criteria (PsARC) response, along with health-related quality of life (HRQoL) outcomes in BE OPTIMAL and BE COMPLETE. Methods BE OPTIMAL and BE COMPLETE were randomised multicentre, double-blind, placebo (PBO)-controlled, parallel-group, phase 3 trials. BE OPTIMAL included a 16-week (Wk) double-blind, PBO-controlled period and a 36-Wk active-treatment period. Patients were randomised (3:2) to receive BKZ 160mg Q4W, or PBO. At Wk16, PBO patients switched to BKZ. In BE COMPLETE, patients with inadequate response or intolerance to TNFis were randomised (2:1) to receive either BKZ 160mg Q4W or PBO for 16Wks after which they were eligible for entry into BE VITAL (NCT04009499; open-label extension). We report PsARC response rates at Wk52 (BE OPTIMAL) and Wk40 (BE COMPLETE). Additionally, the association of PsARC responders with HRQoL-related outcomes (HAQ-DI, FACIT-Fatigue and SF-36) for the randomised set are also reported. Data are reported as non-responder imputation (NRI) and observed cases (OC). Results In BE OPTIMAL, 821/852 (96.4%) patients completed Wk16 and 761 (89.3%) completed Wk52. In BE COMPLETE, 388/400 (97%) patients completed Wk16, 377 (94.3%) entered BE VITAL and 360 (90.0%) completed Wk40. Baseline characteristics were comparable between groups within both trials. In BE OPTIMAL, PsARC response (NRI) was achieved by 80.3% BKZ and 40.2% PBO patients at Wk16 and was sustained or increased at Wk52 to 79.1% BKZ and 79.7% PBO/BKZ patients. In BE COMPLETE, PsARC response (NRI) was achieved by 85.4% BKZ and 30.8% PBO at Wk16 and was sustained or increased at Wk40 to 77.9% BKZ and 75.2% PBO/BKZ patients. Clinically meaningful improvements in HAQ-DI and SF 36-PCS scores, and FACIT-Fatigue were achieved from baseline among PsARC responders compared to non-responders (Table). Conclusion Improvements in PsARC were sustained up to 1 year in BKZ-treated patients and associated with improvement in HRQoL and fatigue, regardless of whether patients were bDMARD-naïve (BE OPTIMAL) or TNFi-IR (BE COMPLETE). Disclosure W.R. Tillett: Other; WRT has received Research funding, consulting and or speaker fees from: Abbvie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma. B. Ink: Shareholder/stock ownership; BI is a shareholder of AbbVie, GlaxoSmithKline and UCB Pharma. R. Bajracharya: Other; RB is an employee and shareholder of UCB Pharma. V. Taieb: Other; VT is an employee of UCB Pharma. P. Sharma: Other; PS has done Advisory Board for UCB Pharma. D. McGonagle: Grants/research support; DM has received research grants/research support from AbbVie, Celgene, Janssen, Merck, and, Pfizer. Other; DM has received honoraria or consultation fees and has been paid as a speaker for AbbVie, Celgene, Janssen, Merck, Novartis, Pfizer, and UCB Pharma. L.C. Coates: Consultancies; LCC has worked as a paid consultant for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Moonlake, Novartis, Pfizer and UCB Pharma. Grants/research support; LCC has received grants/research support from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma. Other; LCC has been paid as a speaker for AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Medac, Novartis, Pfizer and UCB Pharma. I.B. McInnes: Grants/research support; IM has received grants/research support from Astra Zeneca, Abbvie, BMS, Compugen, Cabaletta, EveloBio, Eli Lilly, GSK, Janssen, Novartis, Moonlake, Novartis, Sanofi, UCB Pharma, XinThera.

P146 A phase II, randomised, double-blind, placebo-controlled trial exploring pharmacokinetics, safety and efficacy of intravenous factor XIII treatment in adults with systemic sclerosis

Abstract Background/Aims Systemic sclerosis (SSc) is a multi-system autoimmune disease with significant morbidity and mortality, and an unmet therapeutic need. The pathogenesis of SSc involves dysfunctional immune signalling, fibroblast behaviour and vascular development. Factor XIII (FXIII) is an enzyme involved in coagulation, and in wound healing where it promotes angiogenesis via inhibition of thrombospondin-1 (TSP-1). Therapeutic administration of FXIII in SSc is proposed to increase angiogenesis via suppression of TSP-1, which is known to be dysregulated in SSc. Previous preclinical and clinical studies suggest that therapeutic administration of factor XIII could improve vascular function in SSc. Methods Two interlinked clinical trials were conducted at a single centre. First, a single-dose open-label study was performed to assess the safety and pharmacokinetics of FXIII treatment in SSc. Eight adult patients with limited or diffuse SSc received a single dose of intravenous purified human FXIII, followed by a 6-week monitoring period. Second, a phase II, double-blind, randomised, placebo-controlled study was performed to investigate the safety and efficacy of factor XIII treatment in SSc. 18 adult patients with limited or diffuse SSc were randomised 2:1 to receive study intervention (intravenous purified human FXIII) or placebo (intravenous 0.9% sodium chloride solution). Safety endpoints were assessment of the safety and tolerability of FXIII treatment via review of adverse events, physical examination and monitoring of physiological function. Efficacy was explored as change in skin severity by modified Rodnan skin score (mRSS) at week 24 compared to baseline, and change in severity of Raynaud’s phenomenon, assessed by review of the Raynaud’s Condition Score (RCS) at week 24, compared to baseline. The study is registered with ClinicalTrials.gov (number NCT02551042). Results The main objective of the clinical trial was met by demonstrating that FXIII is safe and well tolerated in SSc. Pharmacokinetic analysis showed a predictable rise and fall in FXIII level following therapeutic administration, with the mean time taken for the FXIII level to return to within 10 IU/dL of the endogenous level being 16.6 days (SD 8.7). Adverse event and safety monitoring did not reveal any concerning pattern. Study intervention-related adverse events were self-resolving and tolerable. There was no statistically significant change in mRSS or RCS during the trial, but there was a trend towards improvement in RCS in the FXIII group (mean change in RCS of -1.2 (95% CI -2.26 to -0.14) in the FXIII group versus -0.83 (95% CI -3.44 to 1.77) in the placebo group). Conclusion Our results suggest that therapeutic strategies to modulate links between coagulation and tissue repair using FXIII are safe and feasible. Further studies with different patient populations and FXIII doses could investigate the role of FXIII in SSc further. Disclosure A. Leslie: Other; A.L. is an employee of GSK. S. Vigneswaran: None. K. Khan: None. V. Ong: None. C.P. Denton: Consultancies; C. D. has received consulting fees from Roche, Janssen, GlaxoSmithKline, Sanofi, Galapagos, Boehringer Ingelheim, and CSL Behring, and Acceleron. Grants/research support; C. D. has received research funding from CSL Behring, Horizon, Abbvie, and GlaxoSmithKline.

Decolonising global health research: Shifting power for transformative change.

Recent debates on decolonizing global health have spurred interest in addressing the power asymmetries and knowledge hierarchies that sustain colonial ideas and relationships in global health research. This paper applies three intersecting dimensions of colonialism (colonialism within global health; colonisation of global health; and colonialism through global health) to develop a broader and more structural understanding of the policies and actions needed to decolonise global health research. It argues that existing guidelines and checklists designed to make global health research more equitable do not adequately address the underlying power asymmetries and biases that prevail across the global health research ecosystem. Beyond encouraging fairer partnerships within individual research projects, this paper calls for more emphasis on shifting the balance of decision-making power, redistributing resources, and holding research funders and other power-holders accountable to the places and peoples involved in and impacted by global health research.

Mobilizing knowledge about urban change for equity and sustainability: developing 'Change Stories', a multi-country transdisciplinary study.

Health-focused research funders increasingly support multi-country research partnerships that study health, urban development and equity in global settings. To develop new knowledge that benefits society, these grants require researchers to integrate diverse knowledges and data, and to manage research-related aspects of coloniality, such as power imbalances and epistemic injustices. We conducted research to develop a transdisciplinary study proposal with partners in multiple middle and high income countries, aiming to embed equity into the methodology and funding model. Parallel to literature review, we used participatory and social research methods to identify case study cities for our primary study and to inform our study design. We conducted semi-structured interviews with informed and consented sustainable urban development experts in the USA (n=23). We co-developed our research approach with our global advisory group (n=14) and conducted a participatory workshop (n=30) to identify case study sites, also informed by conversations with international academic experts in sustainable development (n=27). Through literature review we found that there is a need to study the contextual pre-conditions of urban transformation, the influence of coloniality on understandings of how cities can change and the failure of standard development practices to meet the needs of all residents and the planet. Through expert input and literature we found that decolonial and storytelling methods may help us show the complexities behind stories of urban transformation, particularly the role of marginalized populations in creating long-term change. There are multiple benefits of conducting research to develop an equitably designed multi-country research collaboration. We built new partnerships and co-developed our research approach, creating new understanding of diverse collaborators' disciplinary perspectives and institutional requirements. By investigating the informational needs of U.S. sustainable development actors and designing our study to meet these needs, we have increased the likelihood that our research will create impact.

Exploring virtual funding committee practices in the allocation of National Institute for Health and Care Research funding: A netnographic study.

Funding committees, comprising members with a range of knowledge, skills, and experience, are considered integral to the decision-making process of funding organisations for recommending or allocating research funding. However, there is limited research investigating the decision-making processes, the role of members and their social interactions during funding committee meetings conducted both virtually and face-to-face. Using a mixed-methods design and following netnography principles, the study observed nine National Institute for Health and Care Research programmes funding committee meetings conducted virtually during October 2020 to December 2021; complemented by interviews with committee chairs and members (18 interviews) and NIHR staff (12 interviews); an online survey (50 responses); and documentary analysis. Personal reflections through immersive journals also formed part of the analysis. Three main themes were identified from the observations, interviews, and online survey: efficiency of virtual committee meetings (importance of preparation, and the role of formality, process, and structure); understanding the effect of virtual committee meetings on well-being (effects of fatigue and apprehension, and the importance of work life balance); understanding social interactions and engagement (levels of engagement, contribution and inclusivity, awareness of unconscious bias and the value of social networking). Examining the decision-making practices of one funding organisation across several research programmes, across multiple committee meetings over one year has generated new insights around funding committee practices that previous studies have not been able to explore or investigate. Overall, it was observed that fair and transparent funding recommendations and outcomes can be achieved through virtual funding committees. However, whilst virtual funding committees have many benefits and opportunities, such as the potential to increase membership diversity and inclusivity, and be more environmentally sustainable, more evidence is needed to evaluate their effectiveness, with particular focus on issues of fatigue, engagement, and committee cohesion, especially when new committee members join.

A scoping review on what constitutes a good research culture.

The crisis in research culture is well documented, covering issues such as a tendency for quantity over quality, unhealthy competitive environments, and assessment based on publications, journal prestige and funding. In response, research institutions need to assess their own practices to promote and advocate for change in the current research ecosystem. The purpose of the scoping review was to explore ' What does the evidence say about the 'problem' with 'poor' research culture, what are the benefits of 'good' research culture, and what does 'good' look like?' A scoping review was undertaken. Six databases were searched along with grey literature. Eligible literature had relevance to academic research institutions, addressed research culture, and were published between January 2017 to May 2022. Evidence was mapped and themed to specific categories. The search strategy, screening and analysis took place between April-May 2022. 1666 titles and abstracts, and 924 full text articles were assessed for eligibility. Of these, 253 articles met the eligibility criteria for inclusion. A purposive sampling of relevant websites was drawn from to complement the review, resulting in 102 records included in the review. Key areas for consideration were identified across the four themes of job security, wellbeing and equality of opportunity, teamwork and interdisciplinary, and research quality and accountability. There are opportunities for research institutions to improve their own practice, however institutional solutions cannot act in isolation. Research institutions and research funders need to work together to build a more sustainable and inclusive research culture that is diverse in nature and supports individuals' well-being, career progression and performance.

Research on the mechanism of government subsidy on enterprise innovation based on industry-university-research collaboration

This paper provides a theoretical and empirical examination of the relationship between government subsidies, enterprise innovation, and Industry-University-Research (IUR) collaboration. The study begins with a theoretical analysis of the impact of government subsidies on IUR collaboration and enterprise innovation, employing a dynamic game model. Secondly, the research sample comprises A-share listed enterprises in China, and the theoretical findings are validated through empirical methods. Moreover, this study investigates the mediating influence of IUR collaboration and the heterogenous impacts of government subsidies. Research has shown that government subsidies can facilitate enterprises in establishing IUR collaboration, enhancing the extent of IUR collaboration, and effectively stimulating enterprises to participate in innovation. Government subsidies have a more pronounced impact on non-state-owned enterprises, high-tech enterprises, and enterprises in eastern regions in terms of incentivization. By enhancing IUR upgrade, government subsidies can offset the shortcomings in limited Research and Experimental Development (R&D) funding and inadequate technical reserves of non-high-technology enterprises. This could result in an improvement in the quality of innovation and the performance of the subsidized enterprises.