A model for the motion of slender vortex filaments is extended to include the effect of gravity. The model, initially introduced by Callegari and Ting [“Motion of a curved vortex filament with decaying vortical core and axial velocity,” SIAM J. Appl. Math. 35, 148–175 (1978)], is based on a matched asymptotic expansion in which the outer solution, given by the Biot–Savart law, is matched with the inner solution derived from the Navier–Stokes equations. Building on recent work by Harikrishnan et al. [“On the motion of hairpin filaments in the atmospheric boundary layer,” Phys. Fluids 35, 076603 (2023)], the Boussinesq approximation is applied such that the density variations only enter in the gravity term. However, unlike Harikrishnan et al. [“On the motion of hairpin filaments in the atmospheric boundary layer,” Phys. Fluids 35, 076603 (2023)], the density variation enters at a lower order in the asymptotic expansion and, thus, has a more significant impact on the self-induced velocity of the vortex filament. In this regime, which corresponds to the regime studied by Chang and Smith [“The motion of a buoyant vortex filament,” J. Fluid Mech. 857, R1 (2018)], the effect of gravity is given by an alteration of the core constant, which couples the motion of the filament to the motion within the vortical core, in addition to a change in the compatibility conditions (evolution equations), which determine the leading order azimuthal and tangential velocity fields in the vortex core. The results are used to explain certain properties of buoyant vortex rings, as well as qualitatively explore the impact of gravity on tornado-type atmospheric vortices.
Weniger anzeigenPurpose: Six to 19% of critically ill COVID-19 patients display circulating auto-antibodies against type I interferons (IFN-AABs). Here, we establish a clinically applicable strategy for early identification of IFN-AAB-positive patients for potential subsequent clinical interventions.
Methods: We analyzed sera of 430 COVID-19 patients from four hospitals for presence of IFN-AABs by ELISA. Binding specificity and neutralizing activity were evaluated via competition assay and virus-infection-based neutralization assay. We defined clinical parameters associated with IFN-AAB positivity. In a subgroup of critically ill patients, we analyzed effects of therapeutic plasma exchange (TPE) on the levels of IFN-AABs, SARS-CoV-2 antibodies and clinical outcome.
Results: The prevalence of neutralizing AABs to IFN-alpha and IFN-omega in COVID-19 patients from all cohorts was 4.2% (18/430), while being undetectable in an uninfected control cohort. Neutralizing IFN-AABs were detectable exclusively in critically affected (max. WHO score 6-8), predominantly male (83%) patients (7.6%, 18/237 for IFN-alpha-AABs and 4.6%, 11/237 for IFN-omega-AABs in 237 patients with critical COVID-19). IFN-AABs were present early post-symptom onset and at the peak of disease. Fever and oxygen requirement at hospital admission co-presented with neutralizing IFN-AAB positivity. IFN-AABs were associated with lower probability of survival (7.7% versus 80.9% in patients without IFN-AABs). TPE reduced levels of IFN-AABs in three of five patients and may increase survival of IFN-AAB-positive patients compared to those not undergoing TPE.
Conclusion: IFN-AABs may serve as early biomarker for the development of severe COVID-19. We propose to implement routine screening of hospitalized COVID-19 patients for rapid identification of patients with IFN-AABs who most likely benefit from specific therapies.
Weniger anzeigenPurpose: Using the International Standard Classification of Education (ISCED), we examined the educational and vocational pathways of two comparable, parental cohorts: childhood cancer survivors (CCS) and their siblings. Both cohorts had previously entered parenthood. The aim of the study was to elucidate whether childhood cancer and treatment affect the educational pathways chosen by parents who are former patients.
Methods: We analysed data that was collected from childhood cancer survivors and their siblings regarding their offspring's health within the FeCt Multicentre Offspring Study (conducted 2013-2016). We evaluated and compared the professional pathways of (i) all participating survivors and all participating siblings and those of (ii) survivors and their biological siblings.
Results: Overall information on parental gender, age, and education were available from 1077 survivors and 246 siblings (group (i)). The majority of participants were female with a mean age of 35.2 (survivor) and 37.9 (sibling) years at time of survey. For subgroup (ii), analysis information was available on 191 survivors and 210 siblings. Fathers achieved university degrees significantly more often than mothers (p = 0.003 (i), p < 0.001 (ii)). The distribution of professional education was not significantly different between cancer survivors and siblings in either cohort (i) or (ii).
Conclusions: Regarding our research on the educational and vocational trajectory of CCS, patients can be reassured that family planning and vocational education are well compatible. Inequalities regarding gender-specific educational pathways remain to be addressed.
Implications for Cancer Survivors: CCS should monitor their fertility status regularly and, if necessary, cryopreserve germ cells or tissue in order to optimize their family planning. Educational opportunities should be pursued as desired and with confidence. Local as well as European aftercare programs can assist with family planning and education.
Weniger anzeigenIntroduction: The use of predictors of response to a specific treatment in patients with chronic spontaneous urticaria (CSU) can improve disease management, help prevent unnecessary healthcare costs, and save time. In this study, we aimed to identify predictors of complete response to standard-dosed and higher than standard-dosed antihistamine treatments in patients with CSU. Methods: Medical records of 475 CSU patients, 120 of them <18 years old, from 3 different centers were analyzed. We used 15 machine learning (ML) models as well as traditional statistical methods to predict complete response to standard-dosed and higher than standard-dosed antihistamine treatment based on 17 clinical parameters. Results: CSU disease activity, which was assessed by urticaria activity score (UAS), was the only clinical parameter that predicted complete response to standard-dosed and higher than standard-dosed antihistamine treatment, with ML models and traditional statistics, for all age groups. Based on ROC analyses, optimal cut-off values of disease activity to predict complete response were UAS <3 and UAS <4 for standard-dosed (area under the ROC curve [AUC] = 0.69; p = 0.001) and higher than standard-dosed (AUC = 0.79; p = 0.001) antihistamine treatments, respectively. Also, ML models identified lower total IgE (<150 IU/mL) as a predictor of complete response to a standard-dosed antihistamine and lower CRP (<3.4 mg/mL) as a predictor of complete response to higher than standard-dose antihistamine treatment. Discussion: In this study, we showed that patients with UAS <3 are highly likely to have complete response to standard-dosed AH and those with a UAS <4 are highly likely to have complete response to higher than standard-dosed AH treatment. Low CSU disease activity is the only universal predictor of complete response to AH treatment with both ML models and traditional statistics for all age groups.
Weniger anzeigenIntroduction: The objective of this retrospective study was to compare the predictive performance of the soluble fms-like tyrosine kinase 1 (sFlt-1) / placental growth factor (PlGF)-ratio alone or in a multi-marker regression model for preeclampsia-related maternal and/or fetal adverse outcomes in women >34 weeks of gestation. Methods: We analyzed the data collected from 655 women with suspected preeclampsia. Adverse outcomes were predicted by multivariable and univariable logistic regression models. The outcome of patients was evaluated within 14 days after presentation with signs and symptoms of preeclampsia or diagnosed preeclampsia.Results: The full model integrating available, standard clinical information and the sFlt-1/PlGF-ratio had the best predictive performance for adverse outcomes with an AUC of 72.6%, which corresponds to a sensitivity of 73.3% and specificity of 66.0%. The positive predictive value of the full model was 51.4% and the negative predictive value was 83.5%. 24.5% of patients, who did not experience adverse outcomes but were classified as high risk by sFlt-1/PlGF-ratio (>= 38), were correctly classified by the regression model. The sFlt-1/PlGF-ratio alone had a significantly lower AUC of 65.6%.Conclusions: Integrating angiogenic biomarkers in a regression model improved the prediction of preeclampsia-related adverse outcomes in women at risk after 34 weeks of gestation.
Weniger anzeigenBackground: The knowledge about the location and kinetics of tattoo pigments in human skin after application and during the recovery is restricted due to the limitation of in vivo methods for visualizing pigments. Here, the localization and distribution of tattoo ink pigments in freshly and old tattooed human skin during the regeneration of the epidermis and dermis were investigated in vivo.Methods: Two-photon excited fluorescence lifetime imaging (TPE-FLIM) was used to identify tattoo ink pigments in human skin in vivo down to the reticular dermis. One subject with a freshly applied tattoo and 10 subjects with tattoos applied over 3 years ago were investigated in the epidermal and dermal layers in vivo. One histological slide of tattooed skin was used to localize skin-resident tattoo pigment using light microscopy. Results: The carbon black particles deposited around the incision have still been visible 84 days after tattoo application, showing delayed recovery of the epidermis. The TPE-FLIM parameters of carbon black tattoo ink pigments were found to be different to all skin components except for melanin. Distinction from melanin in the skin was based on higher fluorescence intensity and agglomerate size. Using TPE-FLIM in vivo tattoo pigment was found in 75% of tattoos applied up to 9 years ago in the epidermis within keratinocytes, dendritic cells and basal cells and in the dermis within the macrophages, mast cells and fibroblasts. Loading of highly fluorescent carbon black particles enables in vivo imaging of dendritic cells in the epidermis and fibroblasts in the dermis, which cannot be visualized in native conditions. The collagen I structures showed a higher directionality similar to scar tissue resulting in a greater firmness and decreased elasticity of the tattooed skin. Conclusions: Here we show the kinetics and location of carbon black tattoo ink pigment immediately after application for the first time in vivo in human skin. Carbon black particles are located exclusively intracellularly in the skin of fresh and old tattoos. They are found within macrophages, mast cells and fibroblasts in the dermis and within keratinocytes, dendritic cells and basal cells in the continuously renewed epidermis even in 9-year-old tattoos in skin showing no inflammation.
Weniger anzeigenBackground: Complementary and integrative medicine (CIM) is increasingly provided at uni-versity outpatient departments (OPDs) in Germany, but its scientific evaluation is sparse. Therefore, we aimed to investigate and evaluate feasibility, patients' characteristics and com-plaints at a university's CIM-OPD.Methods: A prospective evaluation included new patients without age restriction. At baseline, and after six and 12 months, patients filled out paper questionnaires. Patients rated their mean subjectively perceived severity of the main complaint within the last seven days on a numeri-cal rating scale (NRS) from 0=no complaints to 10=maximum complaints, their perceived re-silience capacity in everyday life within the last seven days (0=not resilient to 10=very resili-ent), and their contentment with the treatment (0=not content to 10=very content). Diagnoses were provided by physicians and coded according to the International Statistical Classification of Diseases and Related Health Problems, 10th revision. All data were analyzed descriptively.Results: During two years, 536 new patients (72.6% response, age (mean +/- SD and range) 49.6 +/- 15.8 and 1 - 86 years, 75.7% female) chose to participate. The most frequent diagno-sis groups were neoplasms (C00-C97, n=143, 18.6%) and musculoskeletal diseases (M00-M99, n=137, 17.9%). In n=165 patients (30.8%) more than one diagnosis was provided. In a subgroup of 187 patients, who returned the questionnaire after 6 months, we compared base-line to 6-month values: severity of main complaint (mean +/- SD) 5.2 +/- 2.6 changed to 3.9 +/- 2.6; resilience capacity 5.1 +/- 2.6 to 5.6 +/- 2.4. After six months, respondents rated their content-ment with the treatment with (mean +/- SD) 7.7 +/- 2.6. Data after 12 months (n=113) are compa-rable to data after 6 months.Conclusion: Patients of our CIM-OPD had a broad age range, were predominantly female and suffered mostly from oncologic-related complaints and musculoskeletal diseases. In the responding subgroup after six months, patients were content with the treatment. These re-sults should be verified by further prospective evaluations.
Weniger anzeigenThis study addresses the gap in machine learning tools for positive results classification by evaluating the performance of SciBERT, a transformer model pretrained on scientific text, and random forest in clinical psychology abstracts. Over 1,900 abstracts were annotated into two categories: positive results only and mixed or negative results. Model performance was evaluated on three benchmarks. The best-performing model was utilized to analyze trends in over 20,000 psychotherapy study abstracts. SciBERT outperformed all benchmarks and random forest in in-domain and out-of-domain data. The trend analysis revealed nonsignificant effects of publication year on positive results for 1990–2005, but a significant decrease in positive results between 2005 and 2022. When examining the entire time span, significant positive linear and negative quadratic effects were observed. Machine learning could support future efforts to understand patterns of positive results in large data sets. The fine-tuned SciBERT model was deployed for public use.
Weniger anzeigenIntroduction: The aims of this study were to evaluate the relationship of clinical and imaging baseline factors and treatment on the occurrence of early neurological improvement (ENI) in the WAKE-UP trial of MRI-guided intravenous thrombolysis in unknown onset stroke and to examine the association of ENI with long-term favorable outcome in patients treated with intravenous thrombolysis. Methods: We analyzed data from all patients with at least moderate stroke severity, reflected by an initial National Institutes of Health Stroke Scale (NIHSS) score >= 4 randomized in the WAKE-UP trial. ENI was defined as a decrease in NIHSS of >= 8 or a decline to zero or 1 at 24 h after initial presentation to the hospital. Favorable outcome was defined as a modified Rankin Scale score of 0-1 at 90 days. We performed group comparison and multivariable analysis of baseline factors associated with ENI and performed mediation analysis to evaluate the effect of ENI on the relationship between intravenous thrombolysis and favorable outcome. Results: ENI occurred in 93 out of 384 patients (24.2%) and was more likely to occur in patients who received treatment with alteplase (62.4% vs. 46.0%, p = 0.009), had smaller acute diffusion-weighted imaging lesion volume (5.51 mL vs. 10.9 mL, p <= 0.001), and less often large-vessel occlusion on initial MRI (7/93 [12.1%] versus 40/291 [29.9%], p = 0.014). In multivariable analysis, treatment with alteplase (OR 1.97, 95% confidence interval [CI] 0.954-1.100), lower baseline stroke volume (OR 0.965, 95% CI: 0.932-0.994), and shorter time from symptom recognition to treatment (OR 0.994, 95% CI: 0.989-0.999) were independently associated with ENI. Patients with ENI had higher rates of favorable outcome at 90-day follow-up (80.6% vs. 31.3%, p <= 0.001). The occurrence of ENI significantly mediated the association of treatment with a good outcome, with ENI at 24 h explaining 39.4% (12.9-96%) of the treatment effect. Conclusion: Intravenous alteplase increases the odds of ENI in patients with at least moderate stroke severity, especially when given early. In patients with large-vessel occlusion, ENI is rarely observed without thrombectomy. ENI represents a good surrogate early marker of treatment effect as more than a third of good outcome at 90 days is explained by ENI at 24 h.
Weniger anzeigenIntroduction: Positively conditioned Pavlovian cues tend to promote approach and negative cues promote withdrawal in a Pavlovian-to-instrumental transfer (PIT) paradigm, and the strength of this PIT effect was associated with the subsequent relapse risk in alcohol-dependent (AD) patients. When investigating the effect of alcohol-related background cues, instrumental approach behavior was inhibited in subsequent abstainers but not relapsers. An automatic approach bias towards alcohol can be modified using a cognitive bias modification (CBM) intervention, which has previously been shown to reduce the relapse risk in AD patients. Here we examined the effects of such CBM training on PIT effects and explored its effect on the relapse risk in detoxified AD patients. Methods: N = 81 recently detoxified AD patients performed non-drug-related and drug-related PIT tasks before and after CBM versus placebo training. In addition, an alcohol approach/avoidance task (aAAT) was performed before and after the training to assess the alcohol approach bias. Patients were followed up for 6 months. Results: A stronger alcohol approach bias as well as a stronger non-drug-related PIT effect predicted relapse status in AD patients. No significant difference regarding relapse status or the number of heavy drinking days was found when comparing the CBM training group versus the placebo group. Moreover, there was no significant modulation effect of CBM training on any PIT effect or the aAAT. Conclusion: A higher alcohol approach bias in the aAAT and a stronger non-drug-related PIT effect both predicted relapse in AD patients, while treatment outcome was not associated with the drug-related PIT effect. Unlike expected, CBM training did not significantly interact with the non-drug-related or the drug-related PIT effects or the alcohol approach bias.
Weniger anzeigenAbandoning undesired newborn infants was a Roman form of family limitation. They were exposed or given to foster mothers. Christianization alleviated their lot when in 374 CE, Emperor Valentinian's law provided some protection. The Milan Foundling Hospital was established in 787 CE. When the Carolingian Empire fell apart during the 10th century, monastic networks (the Holy Spirit Order and Daughters of Charity) took over social support for the poor, the sick, and the insane. Foundling hospitals proliferated in Italy between the 13th and 15th centuries, in France during the 16th and 17th, and in Germany and Austria in the 18th century. Metropolitan hospices admitted thousands of infants each year. Most were not "found" exposed but were admitted anonymously via a revolving box or registered in an open office. Soon after admission, they were transported for foster care to wet nurses in villages. Sick infants, especially those suspected of suffering from syphilis, were denied the breast, and artificial feeding was tried with little success. Official death statistics were falsified by relating infant deaths not to admissions but to the total number of children cared for. Over 60% died during their first year of life, mostly from pre-admission problems such as malformation, hypothermia, and disease; from poor hygiene in overcrowded wards; and from artificial feeding. Although not intended for that purpose, the hospices became medical research institutions when in late 18th century, physicians and surgeons were employed by maternity and foundling hospitals.
Weniger anzeigenThe Quinisext Council, assembled in Constantinople shortly after 690 to issue a series of more than 100 canons on practical issues and on clerical discipline, was designed as an Ecumenical council, but failed to gain ‘universal’ acceptance in the West. Moving beyond traditional interpretations which saw the conflict over the Quinisext Council largely as one between Emperor Justinian II in Constantinople and the papacy in Rome, the article asks how issues related to the Quinisext Council were received in the churches of the Exarchate of Ravenna and the Lombard, Visigothic, Frankish and Anglo-Saxon kingdoms. Drawing on accounts in Paulus Diaconus’ ‘History of the Lombards’, the ‘Chronicle of Alfons III’ ( of Asturia ) and Agnellus’ ‘Book of Pontiffs of the Church of Ravenna’, it is argued that there must have been a much wider debate about the Quinisext canons on celibacy and on chastity of clerics. As is shown by the analysis of these sources, some of the Quinisext canons on these topics were accepted in the exarchate of Ravenna, the Lombard kingdom of Italy and the Visigothic kingdom in Spain and Southern Gaul around 700; only when attitudes changed profoundly after the mid-eighth century, the acceptance of the council’s decisions by rulers and bishops became subject to polemical narratives in later historiography. By contrast, a case can be made on the basis of synodal decisions, canon law, hagiographical texts, theological treatises and chronicles that in the Frankish and Anglo-Saxon kingdoms, the Quinisext canons on clerical marriage were refuted by bishops, who confirmed older positions on the debated issues as transmitted through canon law tradition. Asking what may have caused both the acceptance and rejection of the Council’s decisions and revisiting the development of the papacy’s attitude to the Quinisext canons, it is argued here that juxtapositions and a priori-statements on religious culture in ‘East’ and ‘West’ are not helpful to understand the wide-ranging connectivity and communication that becomes visible from this debate. A Mediterranean perspective that fully embraces the world of the post-Roman ‘West’ including Britain does more justice to the openness of historical processes around 700.
Weniger anzeigenWelchen Ort hat Literatur in flüchtiger Zeit? Worin liegt die Aufgabe des gedruckten Buchstabens, heute wie einst Medium beständiger Fixierung und Hort dauerhafter Aufbewahrung, verglichen mit den digitalisierten Zeichenwelten einer elektronischen Schreibkultur? Gibt es auf dem gemeinsamen Grund des analogen und des digitalen Worts, von allen Unterschieden abgesehen, möglicherweise so etwas wie ein nomadisches Schreiben? Wie begegnen literarische Werke allgemeiner den universalen Bewegungen ihrer globalisierten Gegenwart? Bilden sie Stätten der Ruhe und der Kontemplation oder werden sie selbst zu Räumen der Unrast und des Aufruhrs? Auf solche und ähnliche Fragen antwortet dieses Buch anhand der ersten groß angelegten Untersuchung zum Nomadischen in der deutschsprachigen Gegenwartsliteratur. Es komplementiert die "Theorie des Nomadischen" (2024) durch eine Analyse zum Werk von Christoph Ransmayr, in dessen Schaffen das nomadische Argument eine konzentrierte Grundlage und Gestalt gewinnt. In der gezielt gegenstandsnahen Auseinandersetzung mit ihm werden theoretische Positionen erweitert und vertieft, in der Medialität des Materials interpretative Horizonte über das Literarische hinausgeführt. „Signaturen“ sind epochale „Kennzeichen“ ebenso wie mediale „Zeichenzusammenhänge“, die auch multiple Bild- und Klangereignisse einschließen. Die Spannweite reicht von der intermedialen Konfiguration aus Text, Bild, Ton über den Roman bis zum episodischen Erzählen zwischen poetischem und publizistischem Arbeiten. An den geisterhaften Übergängen von Heim und Heimsuchung, Ökologie und Ökonomie, sprachlicher und kolonialer Gewalt werden geschichtliche Größen von der antiken Literatur bis zu Film und Serialität zum Leben erweckt. In der Konzentration auf kanonische Schlüsselwerke des Autors samt deren textuellen und medialen Variationen aus vier Jahrzehnten liefert das Buch zugleich die bislang umfassendste Studie zu Ransmayrs Œuvre überhaupt. Sie erscheint im Jahr seines 70. Geburtstags.
Weniger anzeigenCrystalline materials such as monazite have been considered for the storage of radionuclides due to their favorable radiation stability. Understanding their structural chemical response to radiation damage as solid solutions is a key component of determining their suitability for radionuclide immobilization. Herein, high-resolution structural studies were performed on ceramics of the monazite solid solution La1–xCexPO4 (x = 0.25, 0.5, 0.75, 1) in order to understand the role of structural chemistry on irradiation stability. Ceramic samples were irradiated with 14 MeV Au ions with 1014 ions/cm2 and 1015 ions/cm2 to simulate the recoil of daughter nuclei from the alpha decay of actinide radionuclides. The extent of radiation damage was analyzed in detail using scanning electron microscopy (SEM), Raman spectroscopy, grazing incidence X-ray diffraction (GI-XRD), and high-energy-resolution fluorescence detection extended X-ray absorption fine structure (HERFD-EXAFS) spectroscopy. SEM and Raman spectroscopy revealed extensive structural damage as well as the importance of grain boundary regions, which appear to impede the propagation of defects. Both radiation-induced amorphization and recrystallization were studied by GI-XRD, highlighting the ability of monazite to remain crystalline at high fluences throughout the solid solution. Both, diffraction and HERFD-EXAFS experiments show that while atomic disorder is increased in irradiated samples compared to pristine ceramics, the short-range order was found to be largely preserved, facilitating recrystallization. However, the extent of recrystallization was found to be dependent on the solid solution composition. Particularly, the samples with uneven ratios of solute cations, La0.75Ce0.25PO4 and La0.25Ce0.75PO4 were observed to exhibit the least apparent radiation damage resistance. The findings of this work are discussed in the context of the monazite solid solution chemistry and their appropriateness for radionuclide immobilization.
Weniger anzeigenThe neuronal endoplasmic reticulum (ER) consists of a dynamic, tubular network that extends all the way from the soma into dendrites, axons, and synapses. This morphology gives rise to an enormous membrane surface area that, through the presence of tethering proteins, lipid transfer proteins, and ion channels, plays critical roles in local calcium regulation, membrane dynamics, and the supply of ions and lipids to other organelles. Here, we summarize recent advances that highlight the various roles of the neuronal ER in axonal growth, repair, and presynaptic function. We review the variety of contact sites between the ER and other axonal organelles and describe their influence on neurodevelopment and neurotransmission.
Weniger anzeigenBackground: Hypophosphatasia (HPP) is a rare congenital disease caused by a mutation affecting tissue non-specific alkaline phosphatase, an enzyme involved in phosphate metabolism. The clinical manifestation usually includes bone-mineralization disorders, neurological symptoms, and persistent muscle pain.Case report: This case involves a woman in her sixties of Central European descent who suffers from life-long chronic pain and muscle weakness due to hypophosphatasia and concomitant degenerative changes of the lumbar spine. The patient is physically impaired and limited in her ability to walk as a result. HPP-specific and guideline-based multimodal pain management including enzyme replacement therapy with asfotase alfa, opioids, invasive orthopedic and neurosurgical procedures, long-term physiotherapy, and psychotherapy did not yield sufficient treatment results. The average pain was given as 8.5 on a numerical rating scale (NRS, 0-10) for the last 3 years. Treatment with a cannabidiol-predominant, full-spectrum, prescription cannabis extract led to a clinically meaningful pain reduction to 2.5/10 NRS, a discontinuation of opioids, and a recent resumption of employment as a physician.Conclusion: A more widespread consideration of medical cannabinoids in the treatment of complex chronic pain is proposed. Cannabinoids may pose a particularly potent treatment option for HPP-related symptoms and inflammation due to their known anti-inflammatory properties.
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