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Modeling Pharmaceutical Batch Cooling Crystallization Processes Using Computational Fluid Dynamics Coupled with a One-Dimensional Population Balance Model
Get PDFThe batch cooling crystallization of the α polymorphic form of l-glutamic acid from aqueous solution in a kilo-scale 20 L pharmaceutical batch crystallizer is simulated using a multiphase computational fluid dynamics (CFD) model coupled with a one-dimensional population balance equation (PBE). The predicted three-dimensional spatial and temporal distributions of turbulent kinetic energy, supersaturation, nucleation rate, and solid volume fraction provide a high fidelity and very detailed insights into the interplay between crystallizer hydrodynamics and crystallization process kinetics and their resultant impact upon the resulting crystal size distributions (CSDs). Comparison of the CFD-PBE modeling results with published experimental data (Liang, 2002) demonstrates the model’s predictive capability by reproducing the measured final CSDs with an acceptable degree of accuracy. An increase in impeller speed is found to increase both the measured and predicted CSD curves shift toward smaller particles sizes. In terms of the spatial variations of process parameters, the evolution of CSD during the crystallization process reveals significant variation of the evolving CSD at the early stages (between 45 and 40 °C) of the crystallization process, which is relatively invariant in the later stages (between 30 and 20 °C), consistent with the reduction of solution supersaturation within the batch process. The simulation results under different agitation rates reveal that at the higher rates, smaller crystals are produced due to a greater level of turbulence and higher supersaturation at an early stage of the process. Detailed sensitivity analysis on the effect of crystallization kinetics on the predicted CSD emphasizes the need for using reliable kinetic data relevant to the crystallization conditions being simulated
Chemical treatment-induced indirect-to-direct bandgap transition in MoS2:impact on excitonic emission
Get PDFEffective doping is crucial for overcoming performance limitations in two-dimensional (2D) transition metal dichalcogenide (TMD) devices. For light-emitting applications, however, doping must increase carrier injection without quenching excitonic emission. While chemical treatment with 1,2-dichloroethane (DCE) has been demonstrated as an effective post-growth n-doping method for 2D TMDs, its effects on optical properties, specifically the retention of optical characteristics and excitonic behaviour, remain unclear. Here, we investigate the layer- and time-dependent optical effects of DCE on molybdenum disulfide (MoS₂) using photoluminescence (PL) spectroscopy and Density Functional Theory (DFT). Our results show that DCE treatment rapidly reduces the indirect bandgap transition, while leaving the direct transition unaffected. DFT confirms that chlorine atoms bind to sulphur vacancies, creating in-gap states that facilitate non-radiative recombination and suppress the indirect PL. This work demonstrates DCE can selectively engineer the optical band structure in MoS₂, paving the way for more efficient 2D optoelectronic devices
Waveguide-integration and packaging of terahertz quantum-cascade lasers for Earth observation instrumentation
Get PDFWe demonstrate a range of schemes for the integration and packaging of terahertz quantum-cascade lasers (THz QCLs) for satellite applications. This includes embedding within precision-micromachined waveguide/diagonal feedhorn modules, enabling near-Gaussian far-field emission, and photonic integration with power modulators. We present an analysis of solder-mounting and packaging on device performance and show that modulation bandwidths exceeding 4 GHz can be obtained through integration with robust coplanar RF waveguides
The critical role of coefficients: updating allometric normalisation constants for modern ecology and modelling
Get PDFAllometry, the scaling of traits or biological rates with body mass, is central to a wide range of ecological research including dynamic food web modelling. There has been extensive focus on exponents (3/4 scaling laws), but little on the coefficients (normalisation constants). Coefficients that have been used since 2006 are derived from limited data and dated methodologies. Here, we compiled a data set of over 1000 genera with body mass spanning 10 orders of magnitude. We updated metabolism and production coefficients, deriving new genus and metabolic group levels estimates with phylogenetic hierarchical modelling providing robust inference. Our coefficients were mostly lower than those previously estimated, with increased uncertainty estimates. We used the Bioenergetic Food Web Model to evaluate their impact, finding increased biomass and species persistence but no change in stability. Our coefficients pave the way for future simulations that take advantage of subsets of genus and metabolic group data
Artificial intelligence-augmented small bowel capsule endoscopy for coeliac disease: a literature review on accuracy, workflow, and safety
Get PDFBackground and Objective: Coeliac disease (CeD) is a common, underdiagnosed enteropathy with rising incidence and diagnostic delay. This literature review synthesises advances in small bowel capsule endoscopy (SBCE) and artificial intelligence (AI) for SBCE, and outlines implications for clinical practice.
Methods: A comprehensive literature search in PubMed, Scopus, Embase, and Cochrane Library was conducted, where relevant articles published in English over the past ten years [2015–2025] were selected and analysed by two independent reviewers.
Key Content and Findings: Current evidence supports tissue transglutaminase immunoglobulin A (tTG-IgA) as the first-line test and endomysial antibody IgA (EMA-IgA) as a test to rule in disease. An adult no-biopsy pathway at ≥10 times the upper limit of normal (ULN) yields near-perfect specificity but modest sensitivity; therefore, histology remains the reference standard. Optimised biopsy protocols with ≥4 samples from the second part of the duodenum plus 1–2 samples from the bulb, which are well-oriented, increase diagnostic yield. SBCE complements oesophagogastroduodenoscopy (OGD) to map disease extent, detect complications, and guide care when biopsy is contraindicated. A positive baseline study may be prognostic. AI has progressed from per-frame villous atrophy (VA) detection (internal accuracy: 94–96%) to patient-level and severity curve methods showing high agreement with experts, enabling reproducible burden mapping. Across prospective studies and meta-analyses in mixed SBCE indications, AI assistance increases sensitivity without losing specificity and reduces review time approximately 10–12-fold. Gains are greatest for non-experts and for triage applications. Key limitations include small, single-centre datasets, inconsistent labelling, image frame analysis rather than full videos, data leakage risks, and uncertain generalisability across devices and populations. Priorities include multicentre, patient-wise external validation; harmonised International Capsule Endoscopy Research (I-CARE) lesion definitions; prevalence-aware calibration; equity-aware evaluation; and vendor-agnostic deployment.
Conclusions: AI-augmented SBCE can improve efficiency, consistency, and monitoring of CeD; however, adoption should remain human-in-the-loop and be anchored to safety protocols, including patency testing when retention risk is relevant. Equity considerations include serology-negative presentations in some populations and the need for calibrated thresholds aligned with real-world prevalence and costs
Doravirine versus dolutegravir-based regimen in antiretroviral treatment-naive people living with HIV-1 (ANRS0392s ELDORADO): protocol for an international, open-label, randomised, non-inferiority, phase III trial
Get PDFIntroduction
Increasing evidence suggests that dolutegravir (DTG), endorsed by the WHO since 2018 for first- line antiretroviral therapy (ART), is associated with significant weight gain and potentially also with cardiometabolic disorders. In an effort to expand therapeutic options for people living with HIV (PLHIV), the EvaLuating the non- inferiority of DORAvirine vs DOlutegravir trial aims to compare the virologic efficacy of doravirine (DOR) and DTG- based regimens and to assess their safety, including a focus on cardiometabolic effects.
Methods and analysis
This is an international, phase III, multicentre, open- label, non- inferiority, randomised trial that will enrol 610 ART- naïve PLHIV (HIV RNA≥1000 copies/ mL at screening) across six countries (Brazil, Cameroon, France, Côte d’Ivoire, Mozambique and Thailand) spanning four continents. Key inclusion criteria include age ≥18 years, confirmed HIV- 1 infection with plasma RNA levels ≥1000 copies/mL, indication for ART initiation and no prior ART exposure. Participants will be randomised in a 1:1 ratio to receive either DOR 100 mg once daily in combination with tenofovir disoproxil fumarate (TDF) (300 mg daily) plus lamivudine (3TC) (300 mg daily) or DTG (50 mg daily) in combination with TDF (300 mg once daily) plus either emtricitabine (FTC) (200 mg daily) or 3TC (300 mg daily). Randomisation will be stratified by screening HIV- 1 RNA load (≤100 000 or >100 000 copies/ mL) and by country. The primary outcome is virological efficacy, defined as the proportion of participants achieving HIV- 1 RNA <50 copies/mL at week 48 on the assigned treatment (FDA Snapshot algorithm). Secondary outcomes include cardiometabolic safety endpoints (ie, weight gain, insulin resistance, hypertension, diabetes, waist and hip circumferences, waist- to- hip ratio, fasting glycaemia, insulin and fasting serum lipids), along with mental health, quality of life, virological and immunological parameters. Final data collection is expected by July 2028.
Ethics and dissemination
Primary outcome results (week 48) are expected in early 2028. The project was submitted to and approved by national ethics committees and pharmaceutical regulatory authorities in all participating countries: Brazil (CEP INI FIOCRUZ (21.040- 900)/CEP HGNI (26.030- 380)); Cameroon (CNERSH (2024/09/1717/CE/CNERSH/SP)/Ministry of Public Health (D30- 1464/AAR/MINSANTE/SG/DROS/CRC); Côte d'Ivoire: (CNESVS (0018224/MSHPCMU/CNESVS- km)/AIRP (1329/AIRP/DISMP/Om/kbaag); France (CTIS CPP/ANSM (2023- 508626- 10- 00)); Mozambique (CNBS (20/ CNBS/25)/ANARME (4635/380/ANARME)); Thailand: (IHRP (08/1944)/Thai FDA: ongoing on 19 January 2026). The trial received authorisation from the French National Commission for Data Protection and Liberties (CNIL) under approval number 924 302. Written informed consent is obtained from all participants prior to any study- specific procedures and trial enrolment, in accordance with the Declaration of Helsinki and applicable national regulations. Study findings will be disseminated through publication in peer- reviewed journals and presentations at national and international scientific conferences. Results will also be communicated to policymakers, healthcare professionals, community stakeholders and study participants through appropriate dissemination activities, including policy briefs, stakeholder meetings and lay summaries on dedicated and easily accessible platforms.
Trial registration numbers NCT06203132; EU- CT, 2023- 508626- 10- 00
Interpretable Attention-Based Multi-Agent PPO for Latency Spike Resolution in 6G RAN Slicing
No full textSixth-generation (6G) radio access networks (RANs) must enforce strict service-level agreements (SLAs) for heterogeneous slices, yet sudden latency spikes remain difficult to diagnose and resolve with conventional deep reinforcement learning (DRL) or explainable RL (XRL). We propose \emph{Attention-Enhanced Multi-Agent Proximal Policy Optimization (AE-MAPPO)}, which integrates six specialized attention mechanisms into multi-agent slice control and surfaces them as zero-cost, faithful explanations. The framework operates across O-RAN timescales with a three-phase strategy: predictive, reactive, and inter-slice optimization. A URLLC case study shows AE-MAPPO resolves a latency spike in \,ms, restores latency to \,ms with reliability, and reduces troubleshooting time by while maintaining eMBB and mMTC continuity. These results confirm AE-MAPPO's ability to combine SLA compliance with inherent interpretability, enabling trustworthy and real-time automation for 6G RAN slicing
School readiness and the good level of development: policy constructions in English early childhood education
Get PDFThis paper critically analysed how school readiness has been historically and discursively constructed in Early Childhood Education (ECE) policy in England over the past four decades. Using Bacchi's ‘What's the Problem Represented to be?’ framework and Foucauldian concepts of governmentality, the paper explored how school readiness has shifted from a globally contested notion into a narrowly defined policy construct bound up with neoliberal economic goals and performativity pressures. Central to this shift is the Good Level of Development (GLD) assessment, undertaken at the end of the Reception year, which positions school readiness as both a vehicle for raising standards and a solution to economic inequality. Through historical‐discursive analysis, the paper highlighteds how school readiness in England has been constructed through neoliberal logics of data‐driven performativity and accountability mechanisms which have significant implications for teachers and children. The GLD functions as a measure of children's attainment but also as a technology of governance, influencing pedagogical decision‐making and narrowing the curriculum. The paper concluded by exploring alternative constructs of school readiness that reposition transition into school as a relational, bi‐directional process grounded in children's lived experiences and teachers' professional knowledge
Why current risk factor-based approaches fall short in predicting stillbirth: a national cohort study of nulliparous women in England
Get PDFBACKGROUND: Stillbirth is a profound and devastating outcome of pregnancy that has a long-lasting emotional and physiological impact on parents and families. Current risk assessment approaches largely rely on maternal characteristics and clinical history, yet their predictive accuracy remains poor, particularly among nulliparous women (women with no previous birth beyond 24 weeks of gestation). We evaluated the extent to which routinely collected pregnancy risk factors can predict stillbirth and assessed their contribution among singleton births in nulliparous women.
METHODS: We conducted a population-based retrospective cohort study of 876,279 nulliparous women receiving maternity care across 130 National Health Service (NHS) Trusts in England between 2015 and 2019. Thirty-one maternal and pregnancy factors routinely collected during antenatal care were analysed. We used modified Poisson regressions with generalised estimating equations to account for clustering of women within Trusts to compute risk ratios (RR) and 95% confidence intervals (CI). We calculated adjusted population attributable risks (PARs) for significant factors.
RESULTS: Among 876,279 nulliparous women receiving maternity care, 2568 stillbirths occurred. Modifiable maternal characteristics associated with increased risk included elevated body mass index (BMI) (RR 1.22, 95% CI 1.03-1.45 for BMI 35- < 40 kg/m2; RR 1.70, 95% CI 1.39-2.07 for BMI ≥ 40 kg/m2, both compared to BMI 18.5- < 25 kg/m2), smoking at booking (RR 1.34, 95% CI 1.19-1.51), current substance misuse (RR 1.52, 95% CI 1.16-1.98), lack of folic acid consumption before conception (RR 1.28, 95% CI 1.16-1.40) or during pregnancy (RR 1.38, 95% CI 1.18-1.61), and late antenatal booking after 12 weeks of gestation (RR 1.18, 95% CI 1.07-1.30). Fetal growth restriction accounted for the largest population attributable risk for stillbirth (RR 2.96, 95% CI 2.73-3.21).
CONCLUSIONS: Maternal and clinical risk factors explain only a fraction of stillbirths in nulliparous women and cannot underpin a clinically useful prediction model. These findings demonstrate the limitations of risk-based screening strategies and highlight the need for integrated approaches that combine maternal characteristics with biochemical, biophysical, and system-level factors to achieve meaningful advances in stillbirth prevention
A letter intervention to GPs practices to promoting prescription uptake in school-age children with asthma during summer holidays (TRAINS study): a pragmatic cluster randomised controlled trial
Get PDF>In school-aged children, asthma exacerbation rates peak following the return to school after the summer break. A cluster randomised controlled trial (PLEASANT) found that sending a reminder letter from a family doctor to parents of children with asthma during summer holiday led to a 30% increase in prescription collection in August and a decrease in unscheduled care visits after school return in the period September to December. This intervention also resulted in an estimated cost saving of £36.07 per patient per year. We aimed to assess whether informing general practitioner (GP) practices about the PLEASANT trial and its results could lead to its adoptation in routine practice. A pragmatic open label cluster randomised trial was conducted in England, involving GP practices contributing to the Clinical Practice Research Datalink (CPRD). All GP practices in CPRD were stratified by practice size (decile) and randomly allocated (1:1) to either the intervention or control group. In June 2021, the intervention group received a letter from CPRD via mail and email, informing them about the PLEASANT study findings and offering recommendations. The primary outcome was the proportion of children with asthma (aged 4–15) who collected a preventer prescription in August and September 2021. The trial received both University of Sheffield and Independent Scientific Advisory Committee (ISAC) Ethics approval and was registered with ClinicalTrials.gov (NCT05226091). This study included 1389 GP practices and total of 105,746 children with asthma. The practices were randomly assigned to either the intervention group (n = 693 practices, 52,166 individuals) or the control group (n = 695 practices, 53,580 individuals). Analysis showed that 15,716 children (35.3%) in the intervention group and 16,001 children (35.1%) in the control group collected a preventer prescription. No statistically significant difference was found between the two groups (OR 1.01, 95% CI 0.97–1.04), suggesting the intervention had no effect on prescription collection. The study results indicate that a passive intervention, consisting of providing a letter to GPs, did not yield the desired results. To effectively bridge the gap between evidence and practice, it may be worthwhile to consider exploring more proactive strategies to address the identified issues. The trial was registered under ClinicalTrials.gov ID: NCT05226091
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