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System-size dependence of strangeness production in nucleus-nucleus collisions at √sNN = 17.3 GeV
(2005)
Emission of pi, K, phi and Lambda was measured in near-central C+C and Si+Si collisions at 158 AGeV beam energy. Together with earlier data for p+p, S+S and Pb+Pb, the system-size dependence of relative strangeness production in nucleus-nucleus collisions is obtained. Its fast rise and the saturation observed at about 60 participating nucleons can be understood as onset of the formation of coherent partonic subsystems of increasing size. PACS numbers: 25.75.-q
Production of Lambda and Antilambda hyperons was measured in central Pb-Pb collisions at 40, 80, and 158 A GeV beam energy on a fixed target. Transverse mass spectra and rapidity distributions are given for all three energies. The Lambda/pi ratio at mid-rapidity and in full phase space shows a pronounced maximum between the highest AGS and 40 A GeV SPS energies, whereas the anti-Lambda}/pi ratio exhibits a monotonic increase. PACS numbers: 25.75.-q
Results are presented on Omega production in central Pb+Pb collisions at 40 and 158 AGeV beam energy. Given are transverse-mass spectra, rapidity distributions, and total yields for the sum Omega+Antiomega at 40 AGeV and for Omega and Antiomega separately at 158 AGeV. The yields are strongly under-predicted by the string-hadronic UrQMD model and are in better agreement with predictions from a hadron gas models. PACS numbers: 25.75.Dw
Particle production in central Pb+Pb collisions was studied with the NA49 large acceptance spectrometer at the CERN SPS at beam energies of 20, 30, 40, 80, and 158 GeV per nucleon. A change of the energy dependence is observed around 30A GeV for the yields of pions and strange particles as well as for the shapes of the transverse mass spectra. At present only a reaction scenario with onset of deconfinement is able to reproduce the measurements.
The hadronic final state of central Pb+Pb collisions at 20, 30, 40, 80, and 158 AGeV has been measured by the CERN NA49 collaboration. The mean transverse mass of pions and kaons at midrapidity stays nearly constant in this energy range, whereas at lower energies, at the AGS, a steep increase with beam energy was measured. Compared to p+p collisions as well as to model calculations, anomalies in the energy dependence of pion and kaon production at lower SPS energies are observed. These findings can be explained, assuming that the energy density reached in central A+A collisions at lower SPS energies is sufficient to transform the hot and dense nuclear matter into a deconfined phase.
The hadronic final state of central Pb+Pb collisions at 20, 30, 40, 80, and 158 AGeV has been measured by the CERN NA49 collaboration. The mean transverse mass of pions and kaons at midrapidity stays nearly constant in this energy range, whereas at lower energies, at the AGS, a steep increase with beam energy was measured. Compared to p+p collisions as well as to model calculations, anomalies in the energy dependence of pion and kaon production at lower SPS energies are observed. These findings can be explained, assuming that the energy density reached in central A+A collisions at lower SPS energies is sufficient to force the hot and dense nuclear matter into a deconfined phase.
Introduction: Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) occurs approximately 1 in 3.500 live births representing the most common malformation of the upper digestive tract. Only half a century ago, EA/TEF was fatal among affected newborns suggesting that the steady birth prevalence might in parts be due to mutational de novo events in genes involved in foregut development.
Methods: To identify mutational de novo events in EA/TEF patients, we surveyed the exome of 30 case-parent trios. Identified and confirmed de novo variants were prioritized using in silico prediction tools. To investigate the embryonic role of genes harboring prioritized de novo variants we performed targeted analysis of mouse transcriptome data of esophageal tissue obtained at the embryonic day (E) E8.5, E12.5, and postnatal.
Results: In total we prioritized 14 novel de novo variants in 14 different genes (APOL2, EEF1D, CHD7, FANCB, GGT6, KIAA0556, NFX1, NPR2, PIGC, SLC5A2, TANC2, TRPS1, UBA3, and ZFHX3) and eight rare de novo variants in eight additional genes (CELSR1, CLP1, GPR133, HPS3, MTA3, PLEC, STAB1, and PPIP5K2). Through personal communication during the project, we identified an additional EA/TEF case-parent trio with a rare de novo variant in ZFHX3. In silico prediction analysis of the identified variants and comparative analysis of mouse transcriptome data of esophageal tissue obtained at E8.5, E12.5, and postnatal prioritized CHD7, TRPS1, and ZFHX3 as EA/TEF candidate genes. Re-sequencing of ZFHX3 in additional 192 EA/TEF patients did not identify further putative EA/TEF-associated variants.
Conclusion: Our study suggests that rare mutational de novo events in genes involved in foregut development contribute to the development of EA/TEF.
Dual-energy CT (DECT) has emerged into clinical routine as an imaging technique with unique postprocessing utilities that improve the evaluation of different body areas. The virtual non-calcium (VNCa) reconstruction algorithm has shown beneficial effects on the depiction of bone marrow pathologies such as bone marrow edema. Its main advantage is the ability to substantially increase the image contrast of structures that are usually covered with calcium mineral, such as calcified vessels or bone marrow, and to depict a large number of traumatic, inflammatory, infiltrative, and degenerative disorders affecting either the spine or the appendicular skeleton. Therefore, VNCa imaging represents another step forward for DECT to image conditions and disorders that usually require the use of more expensive and time-consuming techniques such as magnetic resonance imaging, positron emission tomography/CT, or bone scintigraphy. The aim of this review article is to explain the technical background of VNCa imaging, showcase its applicability in the different body regions, and provide an updated outlook on the clinical impact of this technique, which goes beyond the sole improvement in image quality.
Highlights
• MRI and ultrasound provided significant correlations between findings suggestive of vasculitis and the final diagnosis.
• Careful selection of available imaging techniques is warranted considering the time course, location, and clinical history.
• Considering its moderate diagnostic power to distinguish tracer uptake, a holistic view of PET/CT findings is essential.
Abstract
Purpose: To assess the diagnostic value of different imaging modalities in distinguishing systemic vasculitis from other internal and immunological diseases.
Methods: This retrospective study included 134 patients with suspected vasculitis who underwent ultrasound, magnetic resonance imaging (MRI), or 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) between 01/2010 and 01/2019, finally consisting of 70 individuals with vasculitis. The main study parameter was the confirmation of the diagnosis using one of the three different imaging modalities, with the adjudicated clinical and histopathological diagnosis as the gold standard. A secondary parameter was the morphological appearance of the vessel affected by vasculitis.
Results: Patients with systemic vasculitis had myriad clinical manifestations with joint pain as the most common symptom. We found significant correlations between different imaging findings suggestive of vasculitis and the final adjudicated clinical diagnosis. In this context, on MRI, vessel wall thickening, edema, and diameter differed significantly between vasculitis and non-vasculitis groups (p < 0.05). Ultrasound revealed different findings that may serve as red flags in identifying patients with vasculitis, such as vascular occlusion or halo sign (p = 0.02 vs. non-vasculitis group). Interestingly, comparing maximal standardized uptake values from PET/CT examinations with vessel wall thickening or vessel diameter did not result in significant differences (p > 0.05).
Conclusions: We observed significant correlations between different imaging findings suggestive of vasculitis on ultrasound or MRI and the final adjudicated diagnosis. While ultrasound and MRI were considered suitable imaging methods for detecting and discriminating typical vascular changes, 18F-FDG PET/CT requires careful timing and patient selection given its moderate diagnostic accuracy.
Objectives: To determine the diagnostic accuracy of dual-energy CT (DECT) virtual noncalcium (VNCa) reconstructions for assessing thoracic disk herniation compared to standard grayscale CT. Methods: In this retrospective study, 87 patients (1131 intervertebral disks; mean age, 66 years; 47 women) who underwent third-generation dual-source DECT and 3.0-T MRI within 3 weeks between November 2016 and April 2020 were included. Five blinded radiologists analyzed standard DECT and color-coded VNCa images after a time interval of 8 weeks for the presence and degree of thoracic disk herniation and spinal nerve root impingement. Consensus reading of independently evaluated MRI series served as the reference standard, assessed by two separate experienced readers. Additionally, image ratings were carried out by using 5-point Likert scales. Results: MRI revealed a total of 133 herniated thoracic disks. Color-coded VNCa images yielded higher overall sensitivity (624/665 [94%; 95% CI, 0.89–0.96] vs 485/665 [73%; 95% CI, 0.67–0.80]), specificity (4775/4990 [96%; 95% CI, 0.90–0.98] vs 4066/4990 [82%; 95% CI, 0.79–0.84]), and accuracy (5399/5655 [96%; 95% CI, 0.93–0.98] vs 4551/5655 [81%; 95% CI, 0.74–0.86]) for the assessment of thoracic disk herniation compared to standard CT (all p < .001). Interrater agreement was excellent for VNCa and fair for standard CT (ϰ = 0.82 vs 0.37; p < .001). In addition, VNCa imaging achieved higher scores regarding diagnostic confidence, image quality, and noise compared to standard CT (all p < .001). Conclusions: Color-coded VNCa imaging yielded substantially higher diagnostic accuracy and confidence for assessing thoracic disk herniation compared to standard CT.
This prospective study sought to evaluate potential savings of radiation dose to medical staff using real-time dosimetry coupled with visual radiation dose feedback during angiographic interventions. For this purpose, we analyzed a total of 214 angiographic examinations that consisted of chemoembolizations and several other types of therapeutic interventions. The Unfors RaySafe i2 dosimeter was worn by the interventionalist at chest height over the lead protection. A total of 110 interventions were performed with real-time radiation dosimetry allowing the interventionalist to react upon higher x-ray exposure and 104 examinations served as the comparative group without real-time radiation monitoring. By using the real-time display during interventions, the overall mean operator radiation dose decreased from 3.67 (IQR, 0.95–23.01) to 2.36 μSv (IQR, 0.52–12.66) (−36%; p = 0.032) at simultaneously reduced operator exposure time by 4.5 min (p = 0.071). Dividing interventions into chemoembolizations and other types of therapeutic interventions, radiation dose decreased from 1.31 (IQR, 0.46-3.62) to 0.95 μSv (IQR, 0.53-3.11) and from 24.39 (IQR, 12.14-63.0) to 10.37 μSv (IQR, 0.85-36.84), respectively, using live-screen dosimetry (p ≤ 0.005). Radiation dose reductions were also observed for the participating assistants, indicating that they could also benefit from real-time visual feedback dosimetry during interventions (−30%; p = 0.039). Integration of real-time dosimetry into clinical processes might be useful in reducing occupational radiation exposure time during angiographic interventions. The real-time visual feedback raised the awareness of interventionalists and their assistants to the potential danger of prolonged radiation exposure leading to the adoption of radiation-sparing practices. Therefore, it might create a safer environment for the medical staff by keeping the applied radiation exposure as low as possible.
Explosive volcanism affects weather and climate. Primary volcanic ash particles which act as ice nuclei (IN) can modify the phase and properties of cold tropospheric clouds. During the Eyjafjallajökull volcanic eruption we have measured the highest ice nucleus number concentrations (>600 L) in our record of 2 years of daily IN measurements in central Germany. Even in Israel, located about 5000 km away from Iceland, IN were as high as otherwise only during desert dust storms. These measurements are the only ones available on the properties of IN in the Eyjafjallajökull plume. The measured high concentrations and high activation temperature (−8 °C) point to an important impact of volcanic ash on microphysical and radiative properties of clouds through enhanced glaciation.
This paper presents results from the "INUIT-JFJ/CLACE 2013" field campaign at the high alpine research station Jungfraujoch in January/February 2013. The chemical composition of ice particle residuals (IPR) in a size diameter range of 200–900 nm was measured in orographic, convective and non-convective clouds with a single particle mass spectrometer (ALABAMA) under ambient conditions characterized by temperatures between −28 and −4 °C and wind speed from 0.1 to 21 km h−1. Additionally, background aerosol particles in cloud free air were investigated. The IPR were sampled from mixed-phase clouds with two inlets which selectively extract small ice crystals in-cloud, namely the Counterflow Virtual Impactor (Ice-CVI) and the Ice Selective Inlet (ISI). The IPR as well as the aerosol particles were classified into seven different particle types: (1) black carbon, (2) organic carbon, (3) black carbon internally mixed with organic carbon, (4) minerals, (5) one particle group (termed "BioMinSal") that may contain biological particles, minerals, or salts, (6) industrial metals, and (7) lead containing particles. For any sampled particle population it was determined by means of single particle mass spectrometer how many of the analyzed particles belonged to each of these categories. Accordingly, between 20 and 30% of the IPR and roughly 42% of the background particles contained organic carbon. The measured fractions of minerals in the IPR composition varied from 6 to 33%, while the values for the "BioMinSal" group were between 15 and 29%. Four percent to 31% of the IPR contained organic carbon mixed with black carbon. Both inlets delivered similar results of the chemical composition and of the particle size distribution, although lead was found only in the IPR sampled by the Ice-CVI. The results show that the ice particle residual composition varies substantially between different cloud events, which indicates the influence of different meteorological conditions, such as origin of the air masses, temperature and wind speed.
In the present work, three different techniques are used to separate ice-nucleating particles (INP) and ice particle residuals (IPR) from non-ice-active particles: the Ice Selective Inlet (ISI) and the Ice Counterflow Virtual Impactor (Ice-CVI), which sample ice particles from mixed phase clouds and allow for the analysis of the residuals, as well as the combination of the Fast Ice Nucleus Chamber (FINCH) and the Ice Nuclei Pumped Virtual Impactor (IN-PCVI), which provides ice-activating conditions to aerosol particles and extracts the activated ones for analysis. The collected particles were analyzed by scanning electron microscopy and energy-dispersive X-ray microanalysis to determine their size, chemical composition and mixing state. Samples were taken during January/February 2013 at the High Alpine Research Station Jungfraujoch. All INP/IPR-separating techniques had considerable abundances (median 20–70%) of contamination artifacts (ISI: Si-O spheres, probably calibration aerosol; Ice-CVI: Al-O particles; FINCH + IN-PCVI: steel particles). Also, potential measurement artifacts (soluble material) occurred (median abundance < 20%). After removal of the contamination particles, silicates and Ca-rich particles, carbonaceous material and metal oxides were the major INP/IPR particle types separated by all three techniques. Minor types include soot and Pb-bearing particles. Sea-salt and sulfates were identified by all three methods as INP/IPR. Lead was identified in less than 10% of the INP/IPR. It was mainly present as an internal mixture with other particle types, but also external lead-rich particles were found. Most samples showed a maximum of the INP/IPR size distribution at 400 nm geometric diameter. In a few cases, a second super-micron maximum was identified. Soot/carbonaceous material and metal oxides were present mainly in the submicron range. ISI and FINCH yielded silicates and Ca-rich particles mainly with diameters above 1 μm, while the Ice-CVI also sampled many submicron particles. Probably owing to the different meteorological conditions, the INP/IPR composition was highly variable on a sample to sample basis. Thus, some part of the discrepancies between the different techniques may result from the (unavoidable) non-parallel sampling. The observed differences of the particles group abundances as well as the mixing state of INP/IPR point to the need of further studies to better understand the influence of the separating techniques on the INP/IPR chemical composition.
We have sampled atmospheric ice nuclei (IN) and aerosol in Germany and in Israel during spring 2010. IN were analyzed by the static vapor diffusion chamber FRIDGE, as well as by electron microscopy. During the Eyjafjallajökull volcanic eruption of April 2010 we have measured the highest ice nucleus number concentrations (>600 l−1) in our record of 2 yr of daily IN measurements in central Germany. Even in Israel, located about 5000 km away from Iceland, IN were as high as otherwise only during desert dust storms. The fraction of aerosol activated as ice nuclei at −18 °C and 119% rhice and the corresponding area density of ice-active sites per aerosol surface were considerably higher than what we observed during an intense outbreak of Saharan dust over Europe in May 2008.
Pure volcanic ash accounts for at least 53–68% of the 239 individual ice nucleating particles that we collected in aerosol samples from the event and analyzed by electron microscopy. Volcanic ash samples that had been collected close to the eruption site were aerosolized in the laboratory and measured by FRIDGE. Our analysis confirms the relatively poor ice nucleating efficiency (at −18 °C and 119% ice-saturation) of such "fresh" volcanic ash, as it had recently been found by other workers. We find that both the fraction of the aerosol that is active as ice nuclei as well as the density of ice-active sites on the aerosol surface are three orders of magnitude larger in the samples collected from ambient air during the volcanic peaks than in the aerosolized samples from the ash collected close to the eruption site. From this we conclude that the ice-nucleating properties of volcanic ash may be altered substantially by aging and processing during long-range transport in the atmosphere, and that global volcanism deserves further attention as a potential source of atmospheric ice nuclei.
Background: Dual-source dual-energy computed tomography (DECT) offers the potential for opportunistic osteoporosis screening by enabling phantomless bone mineral density (BMD) quantification. This study sought to assess the accuracy and precision of volumetric BMD measurement using dual-source DECT in comparison to quantitative CT (QCT). Methods: A validated spine phantom consisting of three lumbar vertebra equivalents with 50 (L1), 100 (L2), and 200 mg/cm3 (L3) calcium hydroxyapatite (HA) concentrations was scanned employing third-generation dual-source DECT and QCT. While BMD assessment based on QCT required an additional standardised bone density calibration phantom, the DECT technique operated by using a dedicated postprocessing software based on material decomposition without requiring calibration phantoms. Accuracy and precision of both modalities were compared by calculating measurement errors. In addition, correlation and agreement analyses were performed using Pearson correlation, linear regression, and Bland-Altman plots. Results: DECT-derived BMD values differed significantly from those obtained by QCT (p < 0.001) and were found to be closer to true HA concentrations. Relative measurement errors were significantly smaller for DECT in comparison to QCT (L1, 0.94% versus 9.68%; L2, 0.28% versus 5.74%; L3, 0.24% versus 3.67%, respectively). DECT demonstrated better BMD measurement repeatability compared to QCT (coefficient of variance < 4.29% for DECT, < 6.74% for QCT). Both methods correlated well to each other (r = 0.9993; 95% confidence interval 0.9984–0.9997; p < 0.001) and revealed substantial agreement in Bland-Altman plots. Conclusions: Phantomless dual-source DECT-based BMD assessment of lumbar vertebra equivalents using material decomposition showed higher diagnostic accuracy compared to QCT.
Objectives: To compare dual-energy CT (DECT) and MRI for assessing presence and extent of traumatic bone marrow edema (BME) and fracture line depiction in acute vertebral fractures. Methods: Eighty-eight consecutive patients who underwent dual-source DECT and 3-T MRI of the spine were retrospectively analyzed. Five radiologists assessed all vertebrae for presence and extent of BME and for identification of acute fracture lines on MRI and, after 12 weeks, on DECT series. Additionally, image quality, image noise, and diagnostic confidence for overall diagnosis of acute vertebral fracture were assessed. Quantitative analysis of CT numbers was performed by a sixth radiologist. Two radiologists analyzed MRI and grayscale DECT series to define the reference standard. Results: For assessing BME presence and extent, DECT showed high sensitivity (89% and 84%, respectively) and specificity (98% in both), and similarly high diagnostic confidence compared to MRI (2.30 vs. 2.32; range 0–3) for the detection of BME (p = .72). For evaluating acute fracture lines, MRI achieved high specificity (95%), moderate sensitivity (76%), and a significantly lower diagnostic confidence compared to DECT (2.42 vs. 2.62, range 0–3) (p < .001). A cutoff value of − 0.43 HU provided a sensitivity of 89% and a specificity of 90% for diagnosing BME, with an overall AUC of 0.96. Conclusions: DECT and MRI provide high diagnostic confidence and image quality for assessing acute vertebral fractures. While DECT achieved high overall diagnostic accuracy in the analysis of BME presence and extent, MRI provided moderate sensitivity and lower confidence for evaluating fracture lines.
During January/February 2013, at the High Alpine Research Station Jungfraujoch a measurement campaign was carried out, which was centered on atmospheric ice-nucleating particles (INP) and ice particle residuals (IPR). Three different techniques for separation of INP and IPR from the non-ice-active particles are compared. The Ice Selective Inlet (ISI) and the Ice Counterflow Virtual Impactor (Ice-CVI) sample ice particles from mixed phase clouds and allow for the analysis of the residuals. The combination of the Fast Ice Nucleus Chamber (FINCH) and the Ice Nuclei Pumped Counterflow Virtual Impactor (IN-PCVI) provides ice-activating conditions to aerosol particles and extracts the activated INP for analysis.Collected particles were analyzed by scanning electron microscopy and energy-dispersive X-ray microanalysis to determine size, chemical composition and mixing state. All INP/IPR-separating techniques had considerable abundances (median 20 – 70 %) of instrumental contamination artifacts (ISI: Si-O spheres, probably calibration aerosol; Ice-CVI: Al-O particles; FINCH+IN-PCVI: steel particles). Also, potential sampling artifacts (e.g., pure soluble material) occurred with a median abundance of < 20 %. While these could be explained as IPR by ice break-up, for INP their IN-ability pathway is less clear. After removal of the contamination artifacts, silicates and Ca-rich particles, carbonaceous material and metal oxides were the major INP/IPR particle types separated by all three techniques. Soot was a minor contributor. Lead was detected in less than 10 % of the particles, of which the majority were internal mixtures with other particle types. Sea-salt and sulfates were identified by all three methods as INP/IPR. Most samples showed a maximum of the INP/IPR size distribution at 400 nm geometric diameter. In a few cases, a second super-micron maximum was identified. Soot/carbonaceous material and metal oxides were present mainly in the submicron range. ISI and FINCH yielded silicates and Ca-rich particles mainly with diameters above 1 μm, while the Ice-CVI also separated many submicron IPR. As strictly parallel sampling could not be performed, a part of the discrepancies between the different techniques may result from variations in meteorological conditions and subsequent INP/IPR composition. The observed differences in the particle group abundances as well as in the mixing state of INP/IPR express the need for further studies to better understand the influence of the separating techniques on the INP/IPR chemical
composition.
A subgroup of pediatric acute T-lymphoblastic leukemia (T-ALL) was characterized by a gene expression profile comparable to that of early T-cell precursors (ETPs) with a highly unfavorable outcome. We have investigated clinical and molecular characteristics of the ETP-ALL subgroup in adult T-ALL. As ETP-ALL represents a subgroup of early T-ALL we particularly focused on this cohort and identified 178 adult patients enrolled in the German Acute Lymphoblastic Leukemia Multicenter studies (05/93–07/03). Of these, 32% (57/178) were classified as ETP-ALL based on their characteristic immunophenotype. The outcome of adults with ETP-ALL was poor with an overall survival of only 35% at 10 years, comparable to the inferior outcome of early T-ALL with 38%. The molecular characterization of adult ETP-ALL revealed distinct alterations with overexpression of stem cell-related genes (BAALC, IGFBP7, MN1, WT1). Interestingly, we found a low rate of NOTCH1 mutations and no FBXW7 mutations in adult ETP-ALL. In contrast, FLT3 mutations, rare in the overall cohort of T-ALL, were very frequent and nearly exclusively found in ETP-ALL characterized by a specific immunophenotype. These molecular characteristics provide biologic insights and implications with respect to innovative treatment strategies (for example, tyrosine kinase inhibitors) for this high-risk subgroup of adult ETP-ALL.
Purpose: To evaluate intermediate and long-term visual outcomes and safety of a phakic intraocular posterior chamber lens with a central hole (ICL V4c) for myopic eyes.
Methods: Retrospective, consecutive case study of patients that uneventfully received a ICL V4c for myopia correction, with a 5-year postoperative follow-up. Department of Ophthalmology, Goethe University Frankfurt, Germany.
Results: From 241 eyes that underwent ICL implantation, we included 45 eyes with a mean age at surgery of 33 years ± 6 (18–48 years), with a 5 years follow-up. CDVA improved from 0.05logMAR ± 0.15 CDVA preoperatively to − 0.00 ± 0,07 at 5 years and did not change significantly from 3 to 5 years’ time (p = 0.266). The mean spherical equivalent (SE) improved from -10.13D ± 3.39 to − 0.45D ± 0.69. The change in endothelial cell count showed a mean decrease of 1.9% per year throughout the follow-up. Safety and efficacy index were 1.16 and 0.78, respectively. Cataract formation was seen in 2 of 241 eyes (0.8%), but in none of the 45 eyes that finished the 5-year follow-up.
Conclusions: Our data show a good intermediate and long-term stability, efficiency, and safety of ICL V4c phakic lenses in myopic eyes comparable to other known literature.
Purpose: To assess the diagnostic precision of three different workstations for measuring thoracic aortic aneurysms (TAAs) in vivo and ex vivo using either pre-interventional computed tomography angiography scans (CTA) or a specifically designed phantom model.
Methods: This retrospective study included 23 patients with confirmed TAA on routinely performed CTAs. In addition to phantom tube diameters, one experienced blinded radiologist evaluated the dimensions of TAAs on three different workstations in two separate rounds. Precision was assessed by calculating measurement errors. In addition, correlation analysis was performed using Pearson correlation.
Results: Measurements acquired at the Siemens workstation deviated by 3.54% (range, 2.78–4.03%; p = 0.14) from the true size, those at General Electric by 4.05% (range, 1.46–7.09%; p < 0.0001), and at TeraRecon by 4.86% (range, 3.22–6.45%; p < 0.0001). Accordingly, Siemens provided the most precise workstation at simultaneously most fluctuating values (scattering of 4.46%). TeraRecon had the smallest fluctuation (scattering of 2.83%), but the largest deviation from the true size of the phantom. The workstation from General Electric showed a scattering of 2.94%. The highest overall correlation between the 1st and 2nd rounds was observed with measurements from Siemens (r = 0.898), followed by TeraRecon (r = 0.799), and General Electric (r = 0.703). Repetition of measurements reduced processing times by 40% when using General Electric, by 20% with Siemens, and by 18% with TeraRecon.
Conclusions: In conclusion, all three workstations facilitated precise assessment of dimensions in the majority of cases at simultaneously high reproducibility, ensuring accurate pre-interventional planning of thoracic endovascular aortic repair.
Purpose: To compare the effective lens position (ELP), anterior chamber depth (ACD) changes, and visual outcomes in patients with and without pseudoexfoliation syndrome (PEX) after cataract surgery.
Design: Prospective, randomized, fellow-eye controlled clinical case series.
Methods: This prospective comparative case series enrolled 56 eyes of 56 consecutive patients with (n = 28) or without PEX (n = 28) and clinically significant cataract who underwent standard phacoemulsification and were implanted with single-piece acrylic posterior chamber intraocular lenses (IOLs). The primary outcome parameters were the ACD referring to the distance between the corneal anterior surface and the lens anterior surface, which is an indicator of the postoperative axial position of the IOL (the so-called ELP) and distance corrected visual acuity (DCVA).
Results: Before surgery, the ACD was 2.54 ± 0.42 mm in the PEX group and 2.53 ± 0.38 mm in the control group (p = 0.941). Postoperatively, the ACD was 4.29 ± 0.71 mm in the PEX group and 4.33 ± 0.72 mm in the normal group, respectively (p = 0.533). There was no significant difference in ACD changes between groups (PEX group: 1.75 ± 0.74 mm, control group: 1.81 ± 0.61 mm, p = 0.806) and DCVA pre- (p = 0.469) and postoperatively (PEX group: 0.11 ± 0.13 logMAR, control group: 0.09 ± 0.17 logMAR, p = 0.245) between groups.
Conclusion: Preoperative and postoperative ACD, as an indicator of ELP, between PEX eyes and healthy eyes after cataract surgery showed no significant difference. Phacoemulsification induced similar changes in eyes with PEX compared to healthy eyes.
Background: Pulmonary nocardiosis (PN) is an uncommon but potentially life-threatening infection. Most of our knowledge is derived from case reports or smaller case series. Recently, increasing PN incidence rates have been reported. We aim to describe the clinical course of and risk factors for PN in four Western European countries and to estimate population-based annual hospitalization rates.
Methods: Retrospective evaluation (1995 to 2011) of the clinical course of and risk factors for PN in patients from 11 hospitals in four European countries (Germany, Austria, Switzerland and The Netherlands). Calculation of population-based estimates of hospitalization rates of PN in Germany (2005 to 2011) using official German nationwide diagnosis-related groups (DRG) hospital statistics.
Results: Forty-three patients fulfilled stringent criteria for proven (n = 8) and probable (n = 35) PN; seven with extrapulmonary dissemination. Within the 43 patients, major PN risk factors were immunocompromising (83.7%) and/or pulmonary (58.1%; in 27.9% as only comorbidity) comorbidities. Median duration of PN targeted therapy was 12 weeks. Distinguished patterns of resistance were observed (imipenem susceptibility: N. farcinica 33.3%; N. asteroides 66.7%). Overall mortality rate was 18.9%; in disseminated PN 50%. Over time, annual PN hospitalization rates remained unchanged at around 0.04/100′000 with the highest rate among men aged 75–84 years (0.24/100′000).
Conclusion: PN is rare, but potentially life-threatening, and mainly affects immunocompromised elder males. Overall annual hospitalization rates remained stable between 2005 and 2011.
Background: High-dose chemotherapy (HDC) with autologous stem-cell rescue (ASCR) is a treatment option for pediatric patients with relapsed nephroblastoma. We present long term results of 9 patients treated between 1993 and 2013 at our center.
Procedure: Reinduction therapy was carried out according to GPOH and SIOP recommendations. The conditioning regimen consisted of carboplatin (1 200 mg/m²), etoposide (800 mg/m² or 40 mg/kg) and melphalan (180 mg/m²). Purging of the grafts with immunomagnetic CD34 positive selection was performed in 5 patients.
Results: 8 of 9 Patients (90%) are alive without evidence of disease after a median follow-up of 8.5 years. Leukocyte engraftment occurred after a median of 10 days (range 8-12). Median numbers of 667/µl CD3+, 329/µl CD4+, 369/µl CD8+T cells and 949/µl B cells were reached after 180 days. No negative impact of CD34 selection was observed. No transplantation-related death occurred. Acute toxicity comprised mucositis III°-IV° in all and veno-occlusive disease in one patient. Long term effects probably related to treatment occurred in 3/7 evaluable patients and comprised hearing impairment, reduced renal phosphate reabsorption, mild creatinine elevation and hypothyroidism (n=1, each).
Conclusion: Thus, in our experience HDC with ASCR is an effective treatment of recurrent or refractory nephroblastoma with acceptable side effects. However, a randomized trial proving its efficiency with a high level of evidence is needed.
As new generations of targeted therapies emerge and tumor genome sequencing discovers increasingly comprehensive mutation repertoires, the functional relationships of mutations to tumor phenotypes remain largely unknown. Here, we measured ex vivo sensitivity of 246 blood cancers to 63 drugs alongside genome, transcriptome, and DNA methylome analysis to understand determinants of drug response. We assembled a primary blood cancer cell encyclopedia data set that revealed disease-specific sensitivities for each cancer. Within chronic lymphocytic leukemia (CLL), responses to 62% of drugs were associated with 2 or more mutations, and linked the B cell receptor (BCR) pathway to trisomy 12, an important driver of CLL. Based on drug responses, the disease could be organized into phenotypic subgroups characterized by exploitable dependencies on BCR, mTOR, or MEK signaling and associated with mutations, gene expression, and DNA methylation. Fourteen percent of CLLs were driven by mTOR signaling in a non–BCR-dependent manner. Multivariate modeling revealed immunoglobulin heavy chain variable gene (IGHV) mutation status and trisomy 12 as the most important modulators of response to kinase inhibitors in CLL. Ex vivo drug responses were associated with outcome. This study overcomes the perception that most mutations do not influence drug response of cancer, and points to an updated approach to understanding tumor biology, with implications for biomarker discovery and cancer care.
Background: Depression is a disorder with high prevalence in primary health care and a significant burden of illness. The delivery of health care for depression, as well as other chronic illnesses, has been criticized for several reasons and new strategies to address the needs of these illnesses have been advocated. Case management is a patient-centered approach which has shown efficacy in the treatment of depression in highly organized Health Maintenance Organization (HMO) settings and which might also be effective in other, less structured settings. Methods/Design: PRoMPT (PRimary care Monitoring for depressive Patients Trial) is a cluster randomised controlled trial with General Practice (GP) as the unit of randomisation. The aim of the study is to evaluate a GP applied case-management for patients with major depressive disorder. 70 GPs were randomised either to intervention group or to control group with the control group delivering usual care. Each GP will include 10 patients suffering from major depressive disorder according to the DSM-IV criteria. The intervention group will receive treatment based on standardized guidelines and monthly telephone monitoring from a trained practice nurse. The nurse investigates the patient's status concerning the MDD criteria, his adherence to GPs prescriptions, possible side effects of medication, and treatment goal attainment. The control group receives usual care – including recommended guidelines. Main outcome measure is the cumulative score of the section depressive disorders (PHQ-9) from the German version of the Prime MD Patient Health Questionnaire (PHQ-D). Secondary outcome measures are the Beck-Depression-Inventory, self-reported adherence (adapted from Moriskey) and the SF-36. In addition, data are collected about patients' satisfaction (EUROPEP-tool), medication, health care utilization, comorbidity, suicide attempts and days out of work. The study comprises three assessment times: baseline (T0) , follow-up after 6 months (T1) and follow-up after 12 months (T2). Discussion: Depression is now recognized as a disorder with a high prevalence in primary care but with insufficient treatment response. Case management seems to be a promising intervention which has the potential to bridge the gap of the usually time-limited and fragmented provision of care. Case management has been proven to be effective in several studies but its application in the private general medical practice setting remains unclear.
Purpose: To stratify differences in visual semantic and quantitative imaging features in intensive care patients with nonspecific mastoid effusions versus patients with acute mastoiditis (AM) requiring surgical treatment. Methods: We included 48 patients (male, 28; female, 20; mean age, 59.5 ± 18.1 years) with mastoid opacification (AM, n = 24; control, n = 24) who underwent clinically indicated cerebral CT between 12/2007 and 07/2018 in this retrospective study. Semantic features described the extend and asymmetry of mastoid and middle-ear cavity opacification and complications like erosive changes. Minimum, maximum and mean Hounsfield unit (HU) values were obtained as quantitative features. We analyzed the features employing univariate testing. Results: Compared to intensive care patients, AM patients revealed asymmetric mastoid or middle-ear cavity opacification (likelihood-ratio (LR) < 0.001). Applying a dedicated threshold of the extent of opacification, AM patients reached significance levels of LR = 0.042 and 0.002 for mastoid and middle-ear cavity opacification. AM cases showed higher maximum and mean HU values (p = 0.009, p = 0.024). Conclusions: We revealed that the extent and asymmetry of mastoid and middle-ear cavity opacification differs significantly between AM patients and intensive care patients. Multicenter research is needed to expand our cohort and possibly pave the way to build a non-invasive predictive model for AM in the future.
Background: To assess the potential of radiomic features to quantify components of blood in intraaortic vessels to non-invasively predict moderate-to-severe anemia in non-contrast enhanced CT scans. Methods: One hundred patients (median age, 69 years; range, 19–94 years) who received CT scans of the thoracolumbar spine and blood-testing for hemoglobin and hematocrit levels ± 24 h between 08/2018 and 11/2019 were retrospectively included. Intraaortic blood was segmented using a spherical volume of interest of 1 cm diameter with consecutive radiomic analysis applying PyRadiomics software. Feature selection was performed applying analysis of correlation and collinearity. The final feature set was obtained to differentiate moderate-to-severe anemia. Random forest machine learning was applied and predictive performance was assessed. A decision-tree was obtained to propose a cut-off value of CT Hounsfield units (HU). Results: High correlation with hemoglobin and hematocrit levels was shown for first-order radiomic features (p < 0.001 to p = 0.032). The top 3 features showed high correlation to hemoglobin values (p) and minimal collinearity (r) to the top ranked feature Median (p < 0.001), Energy (p = 0.002, r = 0.387), Minimum (p = 0.032, r = 0.437). Median (p < 0.001) and Minimum (p = 0.003) differed in moderate-to-severe anemia compared to non-anemic state. Median yielded superiority to the combination of Median and Minimum (p(AUC) = 0.015, p(precision) = 0.017, p(accuracy) = 0.612) in the predictive performance employing random forest analysis. A Median HU value ≤ 36.5 indicated moderate-to-severe anemia (accuracy = 0.90, precision = 0.80). Conclusions: First-order radiomic features correlate with hemoglobin levels and may be feasible for the prediction of moderate-to-severe anemia. High dimensional radiomic features did not aid augmenting the data in our exemplary use case of intraluminal blood component assessment.
Purpose: To identify transjugular intrahepatic portosystemic shunt (TIPS) thrombosis in abdominal CT scans applying quantitative image analysis.
Materials and methods: We retrospectively screened 184 patients to include 20 patients (male, 8; female, 12; mean age, 60.7 ± 8.87 years) with (case, n = 10) and without (control, n = 10) in-TIPS thrombosis who underwent clinically indicated contrast-enhanced and unenhanced abdominal CT followed by conventional TIPS-angiography between 08/2014 and 06/2020. First, images were scored visually. Second, region of interest (ROI) based quantitative measurements of CT attenuation were performed in the inferior vena cava (IVC), portal vein and in four TIPS locations. Minimum, maximum and average Hounsfield unit (HU) values were used as absolute and relative quantitative features. We analyzed the features with univariate testing.
Results: Subjective scores identified in-TIPS thrombosis in contrast-enhanced scans with an accuracy of 0.667 – 0.833. Patients with in-TIPS thrombosis had significantly lower average (p < 0.001), minimum (p < 0.001) and maximum HU (p = 0.043) in contrast-enhanced images. The in-TIPS / IVC ratio in contrast-enhanced images was significantly lower in patients with in-TIPS thrombosis (p < 0.001). No significant differences were found for unenhanced images. Analyzing the visually most suspicious ROI with consecutive calculation of its ratio to the IVC, all patients with a ratio < 1 suffered from in-TIPS thrombosis (p < 0.001, sensitivity and specificity = 100%).
Conclusion: Quantitative analysis of abdominal CT scans facilitates the stratification of in-TIPS thrombosis. In contrast-enhanced scans, an in-TIPS / IVC ratio < 1 could non-invasively stratify all patients with in-TIPS thrombosis.
Introduction: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. Methods: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. Results: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. Conclusion: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.
Purpose: A study of real-time adaptive radiotherapy systems was performed to test the hypothesis that, across delivery systems and institutions, the dosimetric accuracy is improved with adaptive treatments over non-adaptive radiotherapy in the presence of patient-measured tumor motion.
Methods and materials: Ten institutions with robotic(2), gimbaled(2), MLC(4) or couch tracking(2) used common materials including CT and structure sets, motion traces and planning protocols to create a lung and a prostate plan. For each motion trace, the plan was delivered twice to a moving dosimeter; with and without real-time adaptation. Each measurement was compared to a static measurement and the percentage of failed points for γ-tests recorded.
Results: For all lung traces all measurement sets show improved dose accuracy with a mean 2%/2 mm γ-fail rate of 1.6% with adaptation and 15.2% without adaptation (p < 0.001). For all prostate the mean 2%/2 mm γ-fail rate was 1.4% with adaptation and 17.3% without adaptation (p < 0.001). The difference between the four systems was small with an average 2%/2 mm γ-fail rate of <3% for all systems with adaptation for lung and prostate.
Conclusions: The investigated systems all accounted for realistic tumor motion accurately and performed to a similar high standard, with real-time adaptation significantly outperforming non-adaptive delivery methods.
Simple Summary: Penile cancer is a rare but aggressive malignancy characterized by rapid tumor growth as well as prompt metastasis in groin lymphatics. While localized diseases can be successfully cured by surgery in most cases, no truly effective treatment options have been established for metastatic diseases as of yet. In the current investigation, we assessed the value of selected members of the PI3K/mTOR/AKT pathway to serve as tumor markers or therapeutic targets for this disease. Higher expression of AKT was significantly more prevalent in high-grade tumors and independently predictive of the worse survival parameters, while increased expression of pmTOR was associated with an inferior prognosis as well. Treatment with the pan-AKT inhibitor capivasertib in PeCa cell lines induced significant reduction of cell viability and movement capacity. These findings might aid in the understanding of the molecular tumor background as well as development of novel treatment options for advanced penile cancer.
Abstract: The PI3K/mTOR/AKT pathway might represent an intriguing option for treatment of penile cancer (PeCa). We aimed to assess whether members of this pathway might serve as biomarkers and targets for systemic therapy. Tissue of primary cancer from treatment-naïve PeCa patients was used for tissue microarray analysis. Immunohistochemical staining was performed with antibodies against AKT, pAKT, mTOR, pmTOR, pS6, pPRAS, p4EBP1, S6K1 and pp70S6K. Protein expression was correlated with clinicopathological characteristics as well as overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS) and metastasis-free survival (MFS). AKT inhibition was tested in two primarily established, treatment-naïve PeCa cell lines by treatment with capivasertib and analysis of cell viability and chemotaxis. A total of 76 patients surgically treated for invasive PeCa were included. Higher expression of AKT was significantly more prevalent in high-grade tumors and predictive of DSS and OS in the Kaplan–Meier analysis, and an independent predictor of worse OS and DSS in the multivariate regression analysis. Treatment with pan-AKT inhibitor capivasertib in PeCa cell lines induced a significant downregulation of both total AKT and pAKT as well as decreased cell viability and chemotaxis. Selected protein candidates of the mTOR/AKT signaling pathway demonstrate association with histological and survival parameters of PeCa patients, whereas AKT appears to be the most promising one.
The bromodomain and PHD-finger containing transcription factor (BPTF) is part of the nucleosome remodeling factor (NURF) complex and has been implicated in multiple cancer types. Here, we report the discovery of a potent and selective chemical probe targeting the bromodomain of BPTF with an attractive pharmacokinetic profile enabling cellular and in vivo experiments in mice. Microarray-based transcriptomics in presence of the probe in two lung cancer cell lines revealed only minor effects on the transcriptome. Profiling against a panel of cancer cell lines revealed that the antiproliferative effect does not correlate with BPTF dependency score in depletion screens. Both observations and the multi-domain architecture of BPTF suggest that depleting the protein by proteolysis targeting chimeras (PROTACs) could be a promising strategy to target cancer cell proliferation. We envision that the presented chemical probe and the related negative control will enable the research community to further explore scientific hypotheses with respect to BPTF bromodomain inhibition.
Vampire bats are the only mammals that feed exclusively on blood. To uncover genomic changes associated with this dietary adaptation, we generated a haplotype-resolved genome of the common vampire bat and screened 27 bat species for genes that were specifically lost in the vampire bat lineage. We found previously unknown gene losses that relate to reduced insulin secretion (FFAR1 and SLC30A8), limited glycogen stores (PPP1R3E), and a unique gastric physiology (CTSE). Other gene losses likely reflect the biased nutrient composition (ERN2 and CTRL) and distinct pathogen diversity of blood (RNASE7) and predict the complete lack of cone-based vision in these strictly nocturnal bats (PDE6H and PDE6C). Notably, REP15 loss likely helped vampire bats adapt to high dietary iron levels by enhancing iron excretion, and the loss of CYP39A1 could have contributed to their exceptional cognitive abilities. These findings enhance our understanding of vampire bat biology and the genomic underpinnings of adaptations to blood feeding.
Investigators in the cognitive neurosciences have turned to Big Data to address persistent replication and reliability issues by increasing sample sizes, statistical power, and representativeness of data. While there is tremendous potential to advance science through open data sharing, these efforts unveil a host of new questions about how to integrate data arising from distinct sources and instruments. We focus on the most frequently assessed area of cognition - memory testing - and demonstrate a process for reliable data harmonization across three common measures. We aggregated raw data from 53 studies from around the world which measured at least one of three distinct verbal learning tasks, totaling N = 10,505 healthy and brain-injured individuals. A mega analysis was conducted using empirical bayes harmonization to isolate and remove site effects, followed by linear models which adjusted for common covariates. After corrections, a continuous item response theory (IRT) model estimated each individual subject’s latent verbal learning ability while accounting for item difficulties. Harmonization significantly reduced inter-site variance by 37% while preserving covariate effects. The effects of age, sex, and education on scores were found to be highly consistent across memory tests. IRT methods for equating scores across AVLTs agreed with held-out data of dually-administered tests, and these tools are made available for free online. This work demonstrates that large-scale data sharing and harmonization initiatives can offer opportunities to address reproducibility and integration challenges across the behavioral sciences.
Chemical pollution caused by synthetic organic chemicals at low concentrations in the environment poses a growing threat to the ecological status of aquatic ecosystems. These chemicals are regularly released into surface waters through both treated and untreated effluents from wastewater treatment plants (WWTPs), agricultural runoff, and industrial discharges. Consequently, they accumulate in surface waters, distribute amongst environmental compartments according to their physicochemical properties, and cause adverse effects on aquatic organisms. Unfortunately, there is a lack of data regarding the occurrence of synthetic organic chemicals, henceforth micropollutants, in South American freshwater ecosystems, especially in Chile.
To address this research gap, we present a comprehensive dataset comprising concentrations of 153 emerging chemicals, including pesticides, pharmaceutical and personal care products (PPCPs), surfactants, and industrial chemicals. These chemicals were found to co-occur in surface waters within Central Chile, specifically in the River Aconcagua Basin. Our sampling strategy involved collecting surface water samples from streams and rivers with diverse land uses, such as agriculture, urban areas, and natural reserves. For sample extraction, we employed an on-site large-volume solid phase extraction (LVSPE) device. The resulting environmental extracts were then subjected to wide-scope chemical target screening using gas chromatography and liquid chromatography high-resolution mass spectrometry (GC- and LCsingle bondHRMS).
The dataset we present holds significant value in assessing the chemical status of water bodies. It enables comparative analysis of pollution fingerprints associated with emerging chemicals across different freshwater systems. Moreover, the data can be reused for environmental risk assessment studies. Its utilisation will contribute to a better understanding of the impact and extent of chemical pollution in aquatic ecosystems, facilitating the development of effective mitigation strategies.
SARS-CoV-2 and stroke characteristics: a report from the Multinational COVID-19 Stroke Study Group
(2020)
Background: Stroke is reported as a consequence of SARS-CoV-2 infection. However, there is a lack of regarding comprehensive stroke phenotype and characteristics
Methods: We conducted a multinational observational study on features of consecutive acute ischemic stroke (AIS), intracranial hemorrhage (ICH), and cerebral venous or sinus thrombosis (CVST) among SARS-CoV-2 infected patients. We further investigated the association of demographics, clinical data, geographical regions, and countries’ health expenditure among AIS patients with the risk of large vessel occlusion (LVO), stroke severity as measured by National Institute of Health stroke scale (NIHSS), and stroke subtype as measured by the TOAST criteria. Additionally, we applied unsupervised machine learning algorithms to uncover possible similarities among stroke patients.
Results: Among the 136 tertiary centers of 32 countries who participated in this study, 71 centers from 17 countries had at least one eligible stroke patient. Out of 432 patients included, 323(74.8%) had AIS, 91(21.1%) ICH, and 18(4.2%) CVST. Among 23 patients with subarachnoid hemorrhage, 16(69.5%) had no evidence of aneurysm. A total of 183(42.4%) patients were women, 104(24.1%) patients were younger than 55 years, and 105(24.4%) patients had no identifiable vascular risk factors. Among 380 patients who had known interval onset of the SARS-CoV-2 and stroke, 144(37.8%) presented to the hospital with chief complaints of stroke-related symptoms, with asymptomatic or undiagnosed SARS-CoV-2 infection. Among AIS patients 44.5% had LVO; 10% had small artery occlusion according to the TOAST criteria. We observed a lower median NIHSS (8[3-17], versus 11 [5-17]; p=0.02) and higher rate of mechanical thrombectomy (12.4% versus 2%; p<0.001) in countries with middle to high-health expenditure when compared to countries with lower health expenditure. The unsupervised machine learning identified 4 subgroups, with a relatively large group with no or limited comorbidities.
Conclusions: We observed a relatively high number of young, and asymptomatic SARS-CoV-2 infections among stroke patients. Traditional vascular risk factors were absent among a relatively large cohort of patients. Among hospitalized patients, the stroke severity was lower and rate of mechanical thrombectomy was higher among countries with middle to high-health expenditure.
Tumor cells frequently overexpress heat shock protein 70 (Hsp70) and present it on their cell surface, where it can be recognized by pre‐activated NK cells. In our retrospective study the expression of Hsp70 was determined in relation to tumor‐infiltrating CD56+ NK cells in formalin‐fixed paraffin embedded (FFPE) tumor specimens of patients with SCCHN (N = 145) as potential indicators for survival and disease recurrence. All patients received radical surgery and postoperative cisplatin‐based radiochemotherapy (RCT). In general, Hsp70 expression was stronger, but with variable intensities, in tumor compared to normal tissues. Patients with high Hsp70 expressing tumors (scores 3–4) showed significantly decreased overall survival (OS; p = 0.008), local progression‐free survival (LPFS; p = 0.034) and distant metastases‐free survival (DMFS; p = 0.044), compared to those with low Hsp70 expression (scores 0–2), which remained significant after adjustment for relevant prognostic variables. The adverse prognostic value of a high Hsp70 expression for OS was also observed in patient cohorts with p16‐ (p = 0.001), p53‐ (p = 0.0003) and HPV16 DNA‐negative (p = 0.001) tumors. The absence or low numbers of tumor‐infiltrating CD56+ NK cells also correlated with significantly decreased OS (p = 0.0001), LPFS (p = 0.0009) and DMFS (p = 0.0001). A high Hsp70 expression and low numbers of tumor‐infiltrating NK cells have the highest negative predictive value (p = 0.00004). In summary, a strong Hsp70 expression and low numbers of tumor‐infiltrating NK cells correlate with unfavorable outcome following surgery and RCT in patients with SCCHN, and thus serve as negative prognostic markers.
Low serum concentrations of the amino acid homoarginine (HA) are associated with increased cardiovascular mortality by incompletely understood mechanisms. This study sought to assess the influence of HA on cardiac remodeling in rats undergoing either transaortic banding or inhibition of nitric oxide synthesis by Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME). Male Wistar rats (n = 136) underwent sham operation (SH) or aortic banding (AB). Both groups were equally divided into 14 subgroups, receiving different doses of HA alone or in combination with lisinopril, spironolactone, or L-NAME for 4 weeks. HA treatment in AB animals resulted in a dose-dependent improvement of cardiac function up to a concentration of 800 mg·kg−1·day−1. Combining 800 mg·kg−1·day−1 HA with spironolactone or lisinopril yielded additional effects, showing a positive correlation with LV ejection fraction (+33%, p = 0.0002) and fractional shortening (+41%, p = 0.0014). An inverse association was observed with collagen area fraction (−41%, p < 0.0001), myocyte cross-sectional area (−22%, p < 0.0001) and the molecular markers atrial natriuretic factor (−74%, p = 0.0091), brain natriuretic peptide (−42%, p = 0.0298), beta-myosin heavy chain (−46%, p = 0.0411), and collagen type V alpha 1 chain (−73%, p = 0.0257) compared to placebo-treated AB animals. Co-administration of HA and L-NAME was found to attenuate cardiac remodeling and prevent NO-deficient hypertension following AB. HA treatment has led to a dose-dependent improvement of myocardial function and marked histological and molecular changes in cardiac remodeling following AB. Combining HA with standard heart failure medication resulted in additional beneficial effects boosting its direct impact on heart failure pathophysiology.
Highlights
• 153 chemicals of emerging concern detected in complex multi-component mixtures.
• 108 possible mixture risk assessment scenarios were investigated.
• Non-detects, QSARs, and experimental ecotoxicological data were integrated for risk assessment.
• 8 chemicals were the main risk drivers in at least one site across the River Aconcagua basin.
Abstract
Environmental risk assessments strategies that account for the complexity of exposures are needed in order to evaluate the toxic pressure of emerging chemicals, which also provide suggestions for risk mitigation and management, if necessary. Currently, most studies on the co-occurrence and environmental impacts of chemicals of emerging concern (CECs) are conducted in countries of the Global North, leaving massive knowledge gaps in countries of the Global South.
In this study, we implement a multi-scenario risk assessment strategy to improve the assessment of both the exposure and hazard components in the chemical risk assessment process. Our strategy incorporates a systematic consideration and weighting of CECs that were not detected, as well as an evaluation of the uncertainties associated with Quantitative Structure-Activity Relationships (QSARs) predictions for chronic ecotoxicity. Furthermore, we present a novel approach to identifying mixture risk drivers. To expand our knowledge beyond well-studied aquatic ecosystems, we applied this multi-scenario strategy to the River Aconcagua basin of Central Chile. The analysis revealed that the concentrations of CECs exceeded acceptable risk thresholds for selected organism groups and the most vulnerable taxonomic groups. Streams flowing through agricultural areas and sites near the river mouth exhibited the highest risks. Notably, the eight risk drivers among the 153 co-occurring chemicals accounted for 66–92 % of the observed risks in the river basin. Six of them are pesticides and pharmaceuticals, chemical classes known for their high biological activity in specific target organisms.
n this paper we report on the investigation of baryonic resonance production in proton-proton collisions at the kinetic energies of 1.25 GeV and 3.5 GeV, based on data measured with HADES. Exclusive channels npπ+ and ppπ0 as well as ppe+e− were studied simultaneously in the framework of a one-boson exchange model. The resonance cross sections were determined from the one-pion channels for Δ(1232) and N(1440) (1.25 GeV) as well as further Δ and N* resonances up to 2 GeV/c2 for the 3.5 GeV data. The data at 1.25 GeV energy were also analysed within the framework of the partial wave analysis together with the set of several other measurements at lower energies. The obtained solutions provided the evolution of resonance production with the beam energy, showing a sizeable non-resonant contribution but with still dominating contribution of Δ(1232)P33. In the case of 3.5 GeV data, the study of the ppe+e− channel gave the insight on the Dalitz decays of the baryon resonances and, in particular, on the electromagnetic transition form-factors in the time-like region. We show that the assumption of a constant electromagnetic transition form-factors leads to underestimation of the yield in the dielectron invariant mass spectrum below the vector mesons pole. On the other hand, a comparison with various transport models shows the important role of intermediate ρ production, though with a large model dependency. The exclusive channels analysis done by the HADES collaboration provides new stringent restrictions on the parameterizations used in the models.
his contribution aims to give a basic overview of the latest results regarding the production of resonances in different collision systems. The results were extracted from experimental data collected with HADES that is a multipurpose detector located at the GSI Helmholtzzentrum, Darmstadt. The main points discussed here are: the properties of the strange resonances Λ(1405) and Σ(1385), the role of Δ’s as a source of pions in the final state, the production dynamics reflected in form of differential cross sections, and the role of the ϕ meson as a source for K− particles.
The introduction of robotically assisted surgery was a milestone for minimally invasive surgery in the 21st century. Currently, there are two CE-approved robotically assisted surgery systems for use and development in pediatrics. Specifically, tremor filtration and optimal visualization are approaches which can have enormous benefits for procedures in small bodies. Robotically assisted surgery in children might have advantages compared to laparoscopic or open approaches. This review focuses on the research literature regarding robotically assisted surgery that has been published within the past decade. A literature search was conducted to identify studies comparing robotically assisted surgery with laparoscopic and open approaches. While reported applications in urology were the most cited, three other fields (gynecology, general surgery, and “others”) were also identified. In total, 36 of the publications reviewed suggested that robotically assisted surgery was a good alternative for pediatric procedures. After several years of experience of this surgery, a strong learning curve was evident in the literature. However, some authors have highlighted limitations, such as high cost and a limited spectrum of small-sized instruments. The recent introduction of reusable 3 mm instruments to the market might help to overcome these limitations. In the future, it can be anticipated that there will be a broader range of applications for robotically assisted surgery in selected pediatric surgeries, especially as surgical skills continue to improve and further system innovations emerge.
Grasping the meaning of everyday visual events is a fundamental feat of human intelligence that hinges on diverse neural processes ranging from vision to higher-level cognition. Deciphering the neural basis of visual event understanding requires rich, extensive, and appropriately designed experimental data. However, this type of data is hitherto missing. To fill this gap, we introduce the BOLD Moments Dataset (BMD), a large dataset of whole-brain fMRI responses to over 1,000 short (3s) naturalistic video clips and accompanying metadata. We show visual events interface with an array of processes, extending even to memory, and we reveal a match in hierarchical processing between brains and video-computable deep neural networks. Furthermore, we showcase that BMD successfully captures temporal dynamics of visual events at second resolution. BMD thus establishes a critical groundwork for investigations of the neural basis of visual event understanding.
The thrombopoietin receptor agonist eltrombopag was successfully used against human cytomegalovirus (HCMV)-associated thrombocytopenia refractory to immunomodulatory and antiviral drugs. These effects were ascribed to effects of eltrombopag on megakaryocytes. Here, we tested whether eltrombopag may also exert direct antiviral effects. Therapeutic eltrombopag concentrations inhibited HCMV replication in human fibroblasts and adult mesenchymal stem cells infected with six different virus strains and drug-resistant clinical isolates. Eltrombopag also synergistically increased the anti-HCMV activity of the mainstay drug ganciclovir. Time-of-addition experiments suggested that eltrombopag interferes with HCMV replication after virus entry. Eltrombopag was effective in thrombopoietin receptor-negative cells, and addition of Fe3+ prevented the anti-HCMV effects, indicating that it inhibits HCMV replication via iron chelation. This may be of particular interest for the treatment of cytopenias after haematopoietic stem cell transplantation, as HCMV reactivation is a major reason for transplantation failure. Since therapeutic eltrombopag concentrations are effective against drug-resistant viruses and synergistically increase the effects of ganciclovir, eltrombopag is also a drug repurposing candidate for the treatment of therapy-refractory HCMV disease.
The nucleoside analogue nelarabine, the prodrug of arabinosylguanine (AraG), has been known for decades to be effective against acute lymphoblastic leukaemias of T-cell (T-ALL), but not of B-cell (B-ALL) origin. The mechanisms underlying this lineage-specific drug sensitivity have remained elusive. Data from pharmacogenomics studies and from a panel of ALL cell lines revealed an inverse correlation of SAMHD1 expression and nelarabine sensitivity. SAMHD1 can hydrolyse and thus inactivate triphosphorylated nucleoside analogues. Transcriptomic and protein expression profiling of cell lines and patient-derived leukaemic blasts revealed lower SAMHD1 abundance in T-ALL than in B-ALL. Mechanistically, SAMHD1 promoter methylation strongly correlated with suppressed SAMHD1 expression, while T-ALL cells did not display increased global DNA methylation. Targeted SAMHD1 degradation using virus-like particles containing Vpx sensitised B-ALL cells to AraG, while ectopic SAMHD1 expression in SAMHD1-null T-ALL cells induced AraG resistance. SAMHD1 had a larger impact on cytarabine activity than on nelarabine/ AraG activity in acute myeloid leukaemia (AML) cells, but more strongly affected nelarabine/ AraG activity in ALL cells. This indicates a critical role of the cancer entity. In conclusion, lineage-specific differences in SAMHD1 promoter methylation and, in turn, SAMHD1 expression levels determine ALL cell response to nelarabine. SAMHD1 is a potential biomarker for the identification of ALL patients likely to benefit from nelarabine therapy and a therapeutic target to overcome nelarabine resistance.
Die Fundmeldungen in Band 34 von Botanik und Naturschutz in Hessen stammen von: Dirk Bönsel, Martin De Jong, Klaus Dühr, Uta Engel, Benjamin Feller, Christian Feuring, Thomas Gregor, Arthur Händler, Karsten Horn, Diemut Klärner, Julia Kruse, Eric Martiné, Hasko Friedrich Nesemann, Kai Uwe Nierbauer, Uwe Raabe, Susanne Raehse, Felix Reischmann, Bernd Sauerwein, Petra Schmidt, Fabian Schrauth, Christof Nikolaus Schröder, Helmut Siebert, Michael Thieme, Otto Wacker und Rüdiger Wittig.
Dendritic spines are crucial for excitatory synaptic transmission as the size of a spine head correlates with the strength of its synapse. The distribution of spine head sizes follows a lognormal-like distribution with more small spines than large ones. We analysed the impact of synaptic activity and plasticity on the spine size distribution in adult-born hippocampal granule cells from rats with induced homo- and heterosynaptic long-term plasticity in vivo and CA1 pyramidal cells from Munc-13-1-Munc13-2 knockout mice with completely blocked synaptic transmission. Neither induction of extrinsic synaptic plasticity nor the blockage of presynaptic activity degrades the lognormal-like distribution but changes its mean, variance and skewness. The skewed distribution develops early in the life of the neuron. Our findings and their computational modelling support the idea that intrinsic synaptic plasticity is sufficient for the generation, while a combination of intrinsic and extrinsic synaptic plasticity maintains lognormal like distribution of spines.
Feeding exclusively on blood, vampire bats represent the only obligate sanguivorous lineage among mammals. To uncover genomic changes associated with adaptations to this unique dietary specialization, we generated a new haplotype-resolved reference-quality genome of the common vampire bat (Desmodus rotundus) and screened 26 bat species for genes that were specifically lost in the vampire bat lineage. We discovered previously-unknown gene losses that relate to metabolic and physiological changes, such as reduced insulin secretion (FFAR1, SLC30A8), limited glycogen stores (PPP1R3E), and a distinct gastric physiology (CTSE). Other gene losses likely reflect the biased nutrient composition (ERN2, CTRL) and distinct pathogen diversity of blood (RNASE7). Interestingly, the loss of REP15 likely helped vampire bats to adapt to high dietary iron levels by enhancing iron excretion and the loss of the 24S-hydroxycholesterol metabolizing enzyme CYP39A1 could contribute to their exceptional cognitive abilities. Finally, losses of key cone phototransduction genes (PDE6H, PDE6C) suggest that these strictly-nocturnal bats completely lack cone-based vision. These findings enhance our understanding of vampire bat biology and the genomic underpinnings of adaptations to sanguivory.