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Respiratory practices to prevent or treat evolving bronchopulmonary dysplasia: a European survey
Get PDFObjective: To investigate respiratory practices to prevent or treat evolving BPD in neonatal intensive care units (NICUs) in Europe.Study design: Between March and July 2024, a web-based survey was sent to European NICUs caring for preterm infants with gestational age (GA) <28 weeks.Results: We received replies from 447/721 (62%) NICUs across 24 European countries. Almost 16% of NICUs routinely intubate at birth, especially if the GA is <24 weeks. During transition most NICUs use CPAP ≥5 cmH2O and start with an FiO2 0.3. Volume-targeted ventilation is the primary ventilation mode in 60% of the NICUs. Permissive hypercapnia is a common practice. Higher SpO2 target limits have been adopted, although alarm settings vary across NICUs. Caffeine is routinely started (96%). Surfactant is used in all NICUs, mostly rescue (74%) via less invasive administration (81%). Prophylactic inhaled nitric oxide (iNO) is not used. PDA treatment varies, half of NICUs pharmacologically treat PDA early, based on echocardiographic findings. Ureaplasma screening is done in 22% of NICUs. Most (97%) NICUs use postnatal corticosteroids, with dexamethasone being the preferred drug (65%) and starting 2-3 weeks after birth. Only 5% use corticosteroids prophylactically. After 2-3 weeks, diuretics are used frequently, inhaled corticosteroids/bronchodilators to a much lesser extent.Conclusion: This large survey shows considerable practice variation in preventing and treating evolving BPD across Europe, especially for interventions with limited evidence
The wisdom of Origen: sophia concepts in the work of Origen of Alexandria
Get PDFOrigen ranked wisdom as the highest achievement of Christian existence. This virtue characterised the initial prelapsarian condition and final bliss of human existence, and so significantly influenced how Origen understood the world and the soul’s place in it. However, while the Trinitarian and Christological significance of wisdom within his thought has received significant scholarly attention, Origen’s understand of the virtue of wisdom and its role in Christian life has been overlooked. This thesis argues that this concept provides a crucial lens through which to understand Origen’s theological project, one through which we will trace the connections between not only Trinitarian and Christological considerations, but also Origen’s anthropology, epistemology, apologetics, eschatology, pedagogy, and so on. Above all, the ideal of wisdom will be demonstrated to order Origen’s conception of Christian life, orienting Christianity in an intellectual and mystical direction while also conditioning the present and graduated nature of the Christian community and the incremental and progressive character of Christian revelation. By examining this topic which sits within a nexus of interrelated subjects, this thesis will contribute to a wider understanding of a number of interrelated aspects of Origen’s thought and will demonstrate that the inspired Christian sage is a crucial figure in his account of the God’s revelatory and redemptive economy
International clinical opinion on transparency, standardisation, and calibration alignment in the performance evaluation of systems for continuous glucose monitoring
Get PDFContinuous glucose monitoring (CGM) is now central to diabetes management, yet variation in how respective medical products are evaluated limits meaningful comparison between CGM systems. Three barriers currently constrain reliable interpretation of glucose‐derived measures. The first is limited transparency: in several regulatory settings, particularly those using Conformité Européenne marking, clinical‐study reports, reference‐method information and analytical documentation required for market authorisation are not publicly accessible. The second barrier is heterogeneity in study procedures. Existing evaluations use different reference‐glucose methods, sampling strategies, glucose‐manipulation protocols and participant characteristics, leading to accuracy estimates that cannot be interpreted consistently across systems. The third barrier is calibration alignment. Even with full transparency and aligned procedures, CGM systems may differ because their calibration algorithms are trained on distinct reference‐glucose datasets, influencing reported glucose ranges, automated insulin‐delivery behaviour and interpretation during device transitions. A modified Delphi process involving clinicians, laboratory scientists, and researchers identified these issues as the principal determinants of comparability. During this process, the International Federation of Clinical Chemistry and Laboratory Medicine released a validated framework for performance evaluation of CGM systems, providing a unified approach to reference‐method selection, dynamic in‐clinic testing, and structured reporting. Adoption would reduce procedural variability but does not resolve calibration‐alignment differences. This international clinical opinion proposes a pathway towards internationally interpretable CGM evaluation: immediate transparency of clinical evidence, routine declaration of calibration alignment, and progressive adoption of validated standardised procedures. These steps provide a foundation for reliable interpretation and globally comparable assessment of CGM technologies
Examining and addressing the structural and workforce challenges facing Burundi’s Emergency Obstetric and Neonatal Care (EmONC) Network
No full textIn 2015, Burundi committed to reducing maternal mortality by 60% (from 334 to 140 maternal deaths per 100,000 livebirths) and halving neonatal mortality (from 23 to 12 newborn deaths per 1,000 livebirths) by 2030. To achieve this, the country established in 2017 a “maternity network” comprising 112 emergency obstetric and neonatal care (EmONC) facilities distributed nationally, supported by development partners and policies to enhance their capacity. Despite these political and financial efforts, maternal and newborn death rates remained persistently high, compounded by the ongoing challenges in resource allocation. I used multiple-methods spanning document review, clinical EmONC vignettes, facility surveys, stakeholder engagement, and employed various statistical approaches to identify structural and workforce challenges and to develop efficient, equitable workforce investment proposals that could improve EmONC facility readiness.Initial explorations revealed that the classification of EmONC facilities into basic (BEmONC) and comprehensive (CEmONC) levels does not align with expected standards, as some BEmONC facilities perform CEmONC ‘signal functions’ and manage more deliveries and complications than hospitals. Using normative and expert resource thresholds, I identified deficits of approximately 162 doctors, 1,005 midwives and nurses, 132 delivery rooms, and 678 maternity beds, amongst others. Addressing these gaps would require United States dollar (USD) 32.9 million over five years, representing a 6% annual increase in health spending. A prioritisation framework identified 11 BEmONC and 13 CEmONC facilities, responsible for 30% of deliveries and 35% of complications but housing only 15% of available human resources, highlighting critical investment targets in the face of limited resources. Applying the Workload Indicator for Staffing Needs (WISN) methodology, I developed four workforce investment proposals, validated with stakeholders, and used a decision tree model to compare the costs and expected benefits. Results suggest that adding two midwives in each facility is more cost-effective, at approximately USD 2,381 per maternal life saved, nearly half the cost of full workforce packages. Using Burundi’s per capita gross domestic product (GDP) and the established cost-effectiveness thresholds (CETs) for maternal lives saved in low-income countries, the proposed investment falls within the CET for Burundi. Finally, a provider competence exam revealed generally poor EmONC skills among Burundian delivery care professionals, with doctors outperforming midwives and nurses. Most importantly, the current, routine EmONC training, costing nearly USD 8,131.99 per trainee, does not significantly improve competence of medical doctors. This underscores the need to redesign training modules and assessment tools tailored for doctors separately from midwives and nurses
Systematic review and data-driven insights into CHO cell engineering for next-generation antibody production
Get PDFChinese hamster ovary (CHO) cells remain the dominant platform for therapeutic antibody and biopharmaceutical production, yet productivity bottlenecks persist, particularly for complex molecules. To identify overarching trends in host cell optimization, a systematic review and quantitative cross-study analysis of 164 publications (2011-2024) reporting CHO cell engineering strategies with effects on titer or specific productivity was conducted. Data from 466 engineered targets were extracted and analyzed by strategy, pathway, and production context. The field - driven largely by antibody production - has evolved from simple overexpression toward CRISPR-mediated knockouts, while combinatorial approaches, and engineering of nuclear, epigenetic, and apoptotic/proliferative targets achieved the greatest gains. Despite technological advances, reported improvement folds remained stable, highlighting the need for pathway-informed, multi-target engineering. Future progress in predictive modeling of engineering strategies will depend on standardized models and structured datasets. This review provides a data-driven framework for rational CHO design to support next-generation biotherapeutic production
Assessing transporter‐mediated rifampin–linezolid interaction using physiologically‐based pharmacokinetic modelling
Get PDFAims: The study aims to develop a physiologically‐based pharmacokinetic (PBPK) model to quantitatively evaluate the role of ATP‐binding cassette sub‐family B member 1 (ABCB1) and ATP‐binding cassette super‐family G member 2 (ABCG2) in the drug–drug interaction (DDI) between rifampin and linezolid and to predict the impact of high‐dose rifampin on linezolid pharmacokinetics (PK). Methods: We developed a PBPK model of linezolid and verified this using published clinical PK data. The built‐in PK‐SIM PBPK model for rifampin was used as a perpetrator model, which incorporate ABCB1 and ABCG2 transporter activity, along with inhibition and induction kinetic parameters. Using the developed PBPK models, linezolid PK was predicted when co‐administered with rifampin and verified using published data. Based on the developed DDI model, linezolid exposure when co‐administered with high‐dose rifampin at steady state was predicted. Results: The developed linezolid PBPK model had acceptable predictive performance for 36 different PK arms from 13 individual clinical studies. The PBPK‐predicted DDI effect of standard dose rifampin on linezolid, with AUC and C max ratios of 0.77 and 0.87, respectively, aligned well with observed DDI ratio. PBPK simulations indicated that both ABCG2 and ABCB1 contributed to the DDI between linezolid and rifampin, with ABCB1 playing the major role in the interaction. Increasing the daily dose of rifampin from 10 mg/kg to 20–40 mg/kg resulted in a similar linezolid exposure. Conclusions: Our study suggested that ABCB1 is the primary transporter responsible for the interaction between rifampin and linezolid. The DDI effect of high‐dose rifampin on linezolid plasma exposure is similar to that of standard‐dose rifampin
Abundant Population of Broad H α Emitters in the GOODS-N Field Revealed by CONGRESS, FRESCO, and JADES
Get PDFWe present a spectroscopic search for broad Hα emitters at z ≈ 3.7–6.5 in the GOODS-N field, utilizing JWST/NIRCam slitless spectroscopy from FRESCO and CONGRESS, complemented by JADES imaging. We identify 19 broad Hα emitters with FWHM > 1000 km s−1 at z ≈ 4–5.5, including nine new sources. The broad Hα luminosity function derived from our sample is consistent with those of other JWST-selected broad-line active galactic nuclei (AGN) reported in the literature. The black hole masses and AGN bolometric luminosities inferred from the broad Hα components indicate that most sources are accreting at ∼10% of the Eddington limit. We derive their host stellar masses via spectral energy distribution (SED) fitting and find higher MBH/M* ratios relative to the local MBH–M* relations, consistent with previous studies. We find that 42% of the sample do not satisfy the widely used color selection criteria for little red dots (LRDs), with the majority of these sources lacking the characteristic steep rest-optical red slope, indicating that the LRD selection is highly incomplete when selecting AGN galaxies. A comparison of the average SEDs between our sample and LRDs selected in the same field reveals that the steep red slopes observed in some LRDs are likely due to line-boosting effects as previously suggested. Furthermore, we find that 68% of color-selected LRDs with Hα detections in the NIRCam/grism spectra do not exhibit broad-line features. While the limited sensitivity of the grism spectra may hinder the detection of broad-line components in faint sources, our findings still highlight the enigmatic nature of the LRD population
Audio-visual speech-in-noise tests for evaluating speech reception thresholds: A scoping review
Get PDFObjective: To evaluate the advancements in speech intelligibility testing over the recent decades, with a particular emphasis on the development of audiovisual speech in noise tests that incorporate both auditory and visual modalities for the measurement of speech recognition thresholds. Design: A scoping review was conducted systematically to examine the existing literature on speech intelligibility testing methods. Following comprehensive screening process, studies were selected for detailed analysis, focusing on audiovisual integration and potential for remote or automated administration within studies methodologies. Study Sample: The review encompassed 11 scholarly articles that investigated diverse approaches to speech intelligibility testing. Results: The analysis revealed variability in the accuracy and reliability of speech intelligibility testing methods. Although certain methods demonstrated efficacy in incorporating audiovisual cues, none of the reviewed studies included provisions for remote administration, thereby necessitating the presence of a clinician for test execution. This limitation underscores the imperative for further research development of remote testing methodologies that leverage audiovisual technologies to assess speech in noise. Conclusions: The findings of this review underscore the critical need for advancement in speech intelligibility testing methodologies particularly integrating audiovisual components and enabling remote administration. The development in this domain holds significant potential to enhance the assessment and implementation of assistive technologies for individuals with hearing impairments
Paper2Poster: towards multimodal poster automation from scientific papers
No full textAcademic poster generation is a crucial yet challenging task in scientific communication, requiring the compression of long-context interleaved documents into a single, visually coherent page. To address this challenge, we introduce the first benchmark and metric suite for poster generation, which pairs recent conference papers with author-designed posters and evaluates outputs on (i) Visual Quality—semantic alignment with human posters, (ii) Textual Coherence—language fluency, (iii) Holistic Assessment—six fine-grained aesthetic and informational criteria scored by a VLM-as-judge, and notably (iv) PaperQuiz—the poster’s ability to convey core paper content as measured by VLMs answering generated quizzes. Building on this benchmark, we propose PosterAgent, a top-down, visualin-the-loop multi-agent pipeline: the (a) Parser distills the paper into a structured asset library; the (b) Planner aligns text–visual pairs into a binary-tree layout that preserves reading order and spatial balance; and the (c) Painter–Commenter loop refines each panel by executing rendering code and using VLM feedback to eliminate overflow and ensure alignment. In our comprehensive evaluation, we find that GPT-4o outputs—though visually appealing at first glance—often exhibit noisy text and poor PaperQuiz scores, and we find that reader engagement is the primary aesthetic bottleneck, as human-designed posters rely largely on visual semantics to convey meaning. Our fully open-source variants (e.g., based on the Qwen-2.5 series) outperform existing 4o-driven multi-agent systems across nearly all metrics, while using 87% fewer tokens. It transforms a 22-page paper into a finalized yet editable ‘.pptx’ poster — all for just USD 0.005. These findings chart clear directions for the next generation of fully automated poster-generation models. The code and datasets are available at https://github.com/Paper2Poster/Paper2Poster