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Antenatal risk estimation for exchange transfusions in neonates with hemolytic disease of the fetus and newborn in a changing treatment landscape:A multicenter, retrospective cohort study
No full textBackground: Neonates with hemolytic disease of the fetus and newborn (HDFN) may require exchange transfusions (ET) for severe hyperbilirubinemia. We evaluated if ET in neonates with HDFN was associated with the maximum maternal titer and antibody-dependent cellular cytotoxicity (ADCC) and we determined the change in the number of hospitals performing ET in the Netherlands.Study Design and Methods: National, multicenter analysis of neonates for whom an ET product (c.q. reconstituted whole blood) was ordered between Jan 1, 2011 and Dec 31, 2021 in the Netherlands. To quantify the ET risk, we retrieved maternal serological test results for cases with an ET for non-ABO HDFN (numerator) and from all alloimmunized pregnancies (denominator). Current and past ET practices were assessed with a questionnaire.Results: Twenty-four participating centers ordered 1564 of the total 1824 (84%) ET products in the 11-year study period. We identified 627 patients for whom a product was ordered, among these 111 (17.7%) received ET for HDFN. We found increasing ET rates in D-mediated HDFN from 0.9% (5/558) when maximum titers were ≤ 1:32 to 19.6% (18/92) if titers were 1:512. Rates of ET increased from 1.1% (9/823) if the maximum ADCC was <50% to 18.7% (72/386) if the ADCC was ≥50%. The number of hospitals practicing ET nowadays was 36.7% (18/49), a 56.1% decline compared to before 2010 (41/49).Discussion: Antenatal serological tests may aid caregivers to anticipate the need for ET in neonates with non-ABO HDFN. We found a substantially altered treatment landscape with considerably fewer Dutch hospitals performing ET.</p
Moving Signature of Frailty:From Physical Activity Patterns as Behavioral Biomarkers to Digital-Assisted Intervention
No full textAs our society ages, supporting older adults in maintaining their vitality and preventing functional decline has become an important public health priority. Frailty, a condition that makes people more vulnerable to loss of independence, can often be slowed or even reversed if caught early. Current assessment tools often lack sensitivity to provide specific insights needed for personalized prevention.To address this gap, our research monitored older adults' daily movements (from walking to turning in bed) using wearable sensors. We combined this continuous digital tracking data with traditional health measures to gain a fuller picture of both physical behavior and how people perceive their own health.Our study revealed that early signs of frailty may include a "fragmented" pattern of daily physical activity, alongside slight declines in physical function. More importantly, we found that how older adults feel about their health is a strong driver of their ability to stay active. After all, even those who appear active may still be frail if they perceive their health as poor.We also developed a personalized activity program that adapts to each individual's physical capacity and personal preferences assisted by digital technology. Early results indicate this tailored approach is both feasible and promising.Inspired by the ancient wisdom of "treating disease before it arises" (上工治未病), our work demonstrates that digital-assisted monitoring and intervention offer a practical approach for frailty management and promoting healthy aging
Effect of Endobronchial Valve Treatment on Skeletal Muscles, Fatigue, and Sleep in Severe Emphysema Patients
No full textIntroduction: Skeletal muscle dysfunction, fatigue, and poor sleep quality are common in severe emphysema patients. Endobronchial valve (EBV) treatment is a bronchoscopic procedure which improves pulmonary function, quality of life, and exercise capacity in these patients. However, its potential beneficial effects on skeletal muscle function, fatigue, and sleep are unclear. Our aim was to investigate the effects of EBV treatment on these outcomes. Methods: We conducted a prospective cohort study assessing the second parasternal intercostal muscle thickening fraction, and quadriceps muscle thickness and rectus femoris cross-sectional area (RFCSA), both using ultrasound, limb muscle function using the 30-s sit-to-stand test, fatigue with the Checklist Individual Strength (CIS) fatigue subscale (score ≥36 indicating severe fatigue), and sleep quality with the Pittsburgh Sleep Quality Index (PSQI) at baseline and 6 months following EBV treatment. Results: A total of 20 patients were included. At the 6-month follow-up, significant improvements were observed in pulmonary function, quadriceps thickness, and RFCSA in the nondominant leg, as well as in limb muscle function. Intercostal thickening fraction did not change following treatment. Fatigue decreased significantly, reducing severe fatigue prevalence from 70% to 25%. Sleep quality was generally poor and remained unchanged. Conclusion: Our results show that quadriceps muscle size and function, as well as fatigue, significantly improve following EBV treatment in severe emphysema patients. However, BLVR seems to have no impact on intercostal thickening fraction and patient-reported sleep quality. This study highlights the beneficial extrapulmonary effects of EBV treatment in patients with severe emphysema, further supporting its clinical use.</p
Viewing Ethnocentrism and Ethnorelativism Through a Two-Factor Lens:A Dual-Spectrum Model for Intercultural Development
No full textIntercultural literature often treats ethnocentrism and ethnorelativism as opposite ends of a single continuum. This paper challenges that assumption by adapting Herzberg’s two-factor theory to propose a dual-spectrum model: (1) a “hygiene” axis (ethnocentrism ↔ absence of ethnocentrism) that prevents harm, and (2) a “motivator” axis (absence of ethnorelativism ↔ ethnorelativism) that enables growth. This paper argues that reducing ethnocentrism does not automatically produce ethnorelativism, and that gains in ethnorelativism can coexist with stress-activated in-group bias which is the key concept of ethnocentrism. This dual-spectrum model can explain why bias reduction does not automatically yield adaptive collaboration and why sophisticated perspective-taking can still buckle under stress. This paper translates the model into testable propositions, a two-dimensional (2×2) typology, a portfolio of instruments for measurements, and intervention strategies. It also specifies implications for research, education, and organisational practice, especially under boundary conditions in cultural and organisational contexts, to clarify further when the axes move together, lag, or diverge. This paper also provides examples of educational program design that deliberately pair “anti-deficit” (hygiene) interventions with “growth-positive” (motivator) interventions. Hygiene secures the floor, and motivators raise the ceiling
Sustaining Knowledge Infrastructures:Asking the Right Questions and Listening for Answers
No full textSustaining knowledge infrastructures (KIs) remains a persistent issue that requires continued engagement from diverse stakeholders as new questions and values arise in relation to KI maintenance. We draw on existing academic literature, practical experience with KI projects, and our discussions at a 2024 workshop for researchers and practitioners exploring KI evaluation to pose five questions for KI project managers to consider when thinking about how to make their KIs evolve sustainably over time. These questions include reflecting on sustainability throughout the life cycle of KIs, communicating evolving visions and values, engaging communities, “right sizing” a KI, and developing an iterative process for decision-making. Reflecting on these themes, we suggest, can support KI stakeholders to evolve (not necessarily “grow”) to meet the needs and values of their communities. How these themes are discussed will necessarily vary by funding sources, discipline(s), governance, communities, and other contextual factors. However, adopting a deliberate and strategic approach to KI sustainability and aligning the invisible infrastructural work of KI maintenance with the outward-facing institutional work is, we argue, relevant to all KIs
Iron and nitrogen stress controls summertime biogeochemistry in the high-latitude North Atlantic
No full textHigh-latitude North Atlantic currents (60°–70°N) exhibit contrasting nutrient stoichiometries, but the spatial extent of post-spring bloom iron (Fe) and nitrogen (N) stress on phytoplankton around Iceland remains poorly constrained. Here we pair in situ biogeochemical characteristics with 72 h Fe and N addition experiments in the East Greenland Current (EGC), Irminger Current (IC), Atlantic Current (AC), and East Icelandic Current (EIC) regions. Dissolved iron (dFe) was elevated in the EGC region and depleted in Atlantic surface waters. Unlike dFe, surface nitrate in the EGC region was depleted and elevated in Atlantic waters. Chlorophyll a (Chl a) and particulate organic carbon standing stocks in the diatom and chlorophyte enriched EGC were ~ 40% lower than in the haptophyte dominated Atlantic waters. Changes in photophysiology during the incubation experiments revealed widespread Fe stress in the IC and in most of the AC stations. Notably, 80% of the experiments with nutrient stoichiometry suggesting Fe limitation (dFe < 0.2 nmol L−1, N > 0.6 μmol L−1) revealed Fe stress. In contrast, 30% of the experiments with nutrient stoichiometry suggesting N limitation (N < 0.6 μmol L−1, dFe > 0.2 nmol L−1) showed N stress, mainly in the EGC region. The EIC showed depleted concentrations of nitrate and dFe at the surface. Here, one incubation experiment revealed responses of combined N and Fe stress. The strong summertime density differences between the EGC and Atlantic water masses most likely limits the ability of advected dFe from Greenland and the Arctic to fertilize the Fe-depleted Atlantic waters.</p
LightGBM-Based Seizure Detection Method in Pilocarpine Mouse Model of Epilepsy
No full textElectroencephalogram (EEG) has been the gold standard for measuring epileptic activity in rodent models of epilepsy. Manual scoring of seizures in EEG recordings lasting from days to months is laborious and prone to human error. The existing literature on automatic seizure detection in rodent models of epilepsy is limited, and the electrographic characteristics of induced epilepsy significantly differ from those of other epilepsy types. This study employed a Light Gradient Boosting Machine (LightGBM), with the dataset carefully partitioned into separate training and testing sets to ensure no data overlap. The model was trained using five-fold cross-validation to enhance robustness and generalisability. The training, validation, and independent test sets comprised 29,722 h of EEG recordings from 102 mice with pilocarpine-induced temporal lobe epilepsy. Following feature selection, model training, and post-processing, the lightGBM-based model exhibited a sensitivity of 80%, a specificity of 99%, and an F1-score of 0.71 on the independent test set. Multiple pairwise and non-parametric statistical tests indicated that envelope, skewness, and kurtosis, identified as the three most significant features in the feature importance ranking, exhibit statistically significant differences in their distributions (p-value < 0.05). The statistical analysis revealed significant differences across the three features and between seizure and non-seizure events for each feature, highlighting their relevance for discriminating epileptic activity. This study highlights the potential to support the automation of seizure event detection in preclinical rodent models of epileps
Programming Penicillium rubens:Epigenetic and Genetic Strategies for Discovery and Synthesis of Natural Products
No full textFilamentous fungi such as Penicillium rubens are prolific sources of bioactive secondary metabolites, yet most biosynthetic gene clusters (BGCs) remain transcriptionally silent under laboratory conditions. This thesis aims to unlock this cryptic potential in P. rubens through integrated genetic and metabolic engineering.First, we systematically dissected epigenetic control of secondary metabolism by targeting histone deacetylases (HDACs). CRISPR/Cas9-mediated deletion of nine HDAC genes revealed strong class specificity. Class I/II HDACs (HosA, HdaA, HosB) emerged as major regulators, causing pronounced transcriptomic reprogramming and selective changes in production of native metabolites, including roquefortine, chrysogine, and fungisporin. In contrast, class III sirtuins showed limited effects under the tested conditions.Second, we characterized the Zn₂Cys₆ transcription factor McrA as a global metabolic regulator. Loss of McrA impaired development and increased stress sensitivity, but induced a major metabolic shift. Integrated transcriptomics and metabolomics showed that McrA coordinates primary and secondary metabolism and controls multiple BGCs, leading to overproduction of roquefortine and activation of otherwise silent pathways that yielded novel brasiliamide- and ochratoxin-like analogs.Finally, we engineered a secondary metabolite-deficient P. rubens 4xKO strain into a chassis for heterologous flavonoid production. Introduction of plant 4cl and chs, combined with process optimization, enabled high-level naringenin production from p-coumaric acid with an 88% molar yield. We further uncovered a native naringenin degradation route, identifying an actionable target for improving product stability and titers.Together, this work elucidates epigenetic and transcriptional control layers of fungal metabolism and establishes P. rubens as a versatile platform for natural product discovery and bioproduction
Impact on Hospital Resource Utilization of Endoluminal Bypass Using the Viabahn Endoprosthesis with Heparin Bioactive Surface Compared With Surgical Femoropopliteal Bypass
Get PDFObjective: To assess the impact of heparin-bonded endoprosthesis compared with femoropopliteal bypass on key hospital resources and revenues up to 1-year follow-up. Design: A 2-arm scenario resource consumption data analysis was modeled based on a multicentre prospective randomized controlled trial. Setting: Six centers in the Netherlands. Participants: A total of 100 patients were assigned to 2 arms (50 each arm). The first arm evaluated endovascular treatment using the heparin-bonded Viabahn endoprosthesis and the second the femoropopliteal bypass. Resource consumption rates were compared between arms. Primary and secondary outcomes measures: Resource consumption rates, including hospital stay for bypass procedure, operating room time, type of anesthesia, number of used (endo)grafts, use of different types of bed locations (vascular ward, medium or intensive care), readmission for wound infections, and reinterventions over a period of 12 months. Results: Endovascular repair used fewer hospital resources, with an overall difference of €149.983. Hospital stay was 118 days less (261 vs 379), including 21 fewer days in medium/intensive care (5 vs 26) and 50 fewer operating room hours (100 vs 150). Fewer patients required general anesthesia (31 vs 39), and there were less surgical site infections (3 vs 12). In the surgical bypass group, there were 18 fewer days of hospital stay related to reinterventions (80 vs 62), and the cost of the devices was €309.996, cheaper. The total monetary difference was € 160.013, in favor of the femoropopliteal bypass (€3.200, per patient). Conclusions: Endovascular repair of the superficial femoral artery reduces the use of valuable hospital resources. Its major limitation is the cost of the devices, which should be balanced against the reduction in peri-procedural morbidity and faster recovery. In the context of shortage of hospital beds, it offers capacity benefits, allowing for the treatment of more patients overall. These benefits may outweigh the fewer reinterventions in the surgical bypass group. Registration: The SuperB Trial was registered in clinicaltrials.gov; NCT-ID: NCT01220245. Clinical Impact: Modeling is a useful technique to predict the impact of treatment modalities on hospital resources and revenue. This study uses real-world data from the SuperB Trial to compare two treatment strategies of superficial femoral artery disease, reflecting actual clinical practice and patient outcomes. The analysis focused on direct costs associated with hospital resources and device usage without considering indirect costs or long-term cost-effectiveness. The analysis showed that endovascular repair reduces the use of valuable hospital resources. Its major limitation is device costs, which should be balanced against the reduction in peri-procedural morbidity and faster recovery. In the context of shortage of hospital beds, it offers capacity benefits, allowing for the treatment of more patients overall.</p