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Background and purpose: Two novel enzyme replacement therapies (ERTs), studied in phase 3 trials in late‐onset Pompe patients, reached marketing authorization by the European Medicines Agency in 2022 and 2023. The European Pompe Consortium (EPOC) updates and extends the scope of the 2017 recommendations for starting, switching and stopping ERT. Methods: The European Pompe Consortium consists of 25 neuromuscular and metabolic experts from eight European countries. This update was performed after an in‐person meeting, three rounds of discussion and voting to provide a consensus recommendation. Results: The patient should be symptomatic, that is, should have skeletal muscle weakness or respiratory muscle involvement. Muscle magnetic resonance imaging findings showing substantial fat replacement can support the decision to start in a patient‐by‐patient scenario. Limited evidence supports switching ERT if there is no indication that skeletal muscle and/or respiratory function have stabilized or improved during standard ERT of 12 months or after severe infusion‐associated reactions. Switching of ERT should be discussed on a patient‐by‐patient shared‐decision basis. If there are severe, unmanageable infusion‐associated reactions and no stabilization in skeletal muscle function during the first 2 years after starting or switching treatment, stopping ERT should be considered. After stopping ERT for inefficacy, restarting ERT can be considered. Six‐monthly European Pompe Consortium muscle function assessments are recommended. Conclusions: The triple‐S criteria on ERT start, switch and stop include muscle magnetic resonance imaging as a supportive finding and the potential option of home infusion therapy. Six‐monthly long‐term monitoring of muscle function is highly recommended to cover insights into the patient's trajectory under ERT. [ABSTRACT FROM AUTHOR]

Subsurface drainage plays a crucial role in excess water removal through perforated pipes buried in the soil. The Red River Valley of eastern North Dakota and west central Minnesota often requires pumped drainage outlets due to its flat topography, with many modern systems incorporating variable frequency drives (VFD) for improved efficiency. VFDs adjust pump speeds to match drainage needs, but this dynamic operation complicates accurate flow rate estimation for edge-of-field monitoring. This project aimed to devise an automated method for calculating flow rate estimates from VFD pumping systems involving tank geometry, operational water levels, and pump duty cycling. Linear regressions with calibration data from a transit-time ultrasonic flowmeter produced mixed outcomes. Some linear regressions revealed errors in calculated versus measured flow rate of =14%, while other regressions showed errors nearing 40%. To address this, future efforts should explore methods incorporating the pump's electrical characteristics. This approach would provide a more accurate representation of the unstable and intricate pumping operations during transient conditions. [ABSTRACT FROM AUTHOR]

Deuterium metabolic imaging (DMI) is an emerging magnetic resonance technique, for non‐invasive mapping of human brain glucose metabolism following oral or intravenous administration of deuterium‐labeled glucose. Regional differences in glucose metabolism can be observed in various brain pathologies, such as Alzheimer's disease, cancer, epilepsy or schizophrenia, but the achievable spatial resolution of conventional phase‐encoded DMI methods is limited due to prolonged acquisition times rendering submilliliter isotropic spatial resolution for dynamic whole brain DMI not feasible. The purpose of this study was to implement non‐Cartesian spatial‐spectral sampling schemes for whole‐brain 2H FID‐MR Spectroscopic Imaging to assess time‐resolved metabolic maps with sufficient spatial resolution to reliably detect metabolic differences between healthy gray and white matter regions. Results were compared with lower‐resolution DMI maps, conventionally acquired within the same session. Six healthy volunteers (4 m/2 f) were scanned for ~90 min after administration of 0.8 g/kg oral [6,6′]‐2H glucose. Time‐resolved whole brain 2H FID‐DMI maps of glucose (Glc) and glutamate + glutamine (Glx) were acquired with 0.75 and 2 mL isotropic spatial resolution using density‐weighted concentric ring trajectory (CRT) and conventional phase encoding (PE) readout, respectively, at 7 T. To minimize the effect of decreased signal‐to‐noise ratios associated with smaller voxels, low‐rank denoising of the spatiotemporal data was performed during reconstruction. Sixty‐three minutes after oral tracer uptake three‐dimensional (3D) CRT‐DMI maps featured 19% higher (p =.006) deuterium‐labeled Glc concentrations in GM (1.98 ± 0.43 mM) compared with WM (1.66 ± 0.36 mM) dominated regions, across all volunteers. Similarly, 48% higher (p =.01) 2H‐Glx concentrations were observed in GM (2.21 ± 0.44 mM) compared with WM (1.49 ± 0.20 mM). Low‐resolution PE‐DMI maps acquired 70 min after tracer uptake featured smaller regional differences between GM‐ and WM‐dominated areas for 2H‐Glc concentrations with 2.00 ± 0.35 mM and 1.71 ± 0.31 mM, respectively (+16%; p =.045), while no regional differences were observed for 2H‐Glx concentrations. In this study, we successfully implemented 3D FID‐MRSI with fast CRT encoding for dynamic whole‐brain DMI at 7 T with 2.5‐fold increased spatial resolution compared with conventional whole‐brain phase encoded (PE) DMI to visualize regional metabolic differences. The faster metabolic activity represented by 48% higher Glx concentrations was observed in GM‐ compared with WM‐dominated regions, which could not be reproduced using whole‐brain DMI with the low spatial resolution protocol. Improved assessment of regional pathologic alterations using a fully non‐invasive imaging method is of high clinical relevance and could push DMI one step toward clinical applications. [ABSTRACT FROM AUTHOR]

Objective: To assess the oncological and functional outcomes of focal high‐intensity focused ultrasound (HIFU) in treating localised prostate cancer (PCa), a 3‐year prospective study was undertaken using periodic post‐ablation saturation biopsies. Patients and Methods: Men with two or fewer lesions of grade group (GG) ≤3 PCa were eligible for participation. Additional criteria included a prostate‐specific antigen (PSA) level of ≤15 ng/mL, clinical T1c‐T2, and a life expectancy of ≥10 years. The primary endpoint was failure‐free survival (FFS), defined as absence of clinically significant PCa (csPCa) in‐ or out‐of‐field on protocol‐mandated saturation biopsy, no whole‐gland or systemic salvage treatment, PCa metastasis, or PCa‐related death. Results are reported using two distinct definitions of csPCa: (i) the presence of any GG ≥2 and (ii) any GG ≥3 or core involvement of ≥6 mm. Secondary endpoints were functional patient‐reported outcome measures addressing urinary, sexual, and bowel function. Results: A total of 91 patients were included: six (7%) with GG1 and 85 (93%) with GG ≥2. In all, 83 (91%) underwent at least one follow‐up biopsy. Biopsy attendance at 6, 12, and 36 months was 84%, 67%, and 51%, respectively. The FFS at these time points for any GG ≥2 PCa was 79% (95% confidence interval [CI] 80–88%), 57% (95% CI 48–69%) and 44% (95% CI 34–56%), respectively. Using the second definition, FFS were 88% (95% CI 81–95%), 70% (95% CI 61–81%) and 65% (95% CI 55–77%), respectively. The 3‐year cancer‐specific survival was 100%, and freedom from metastasis was 99%. Magnetic resonance imaging (MRI) (negative predictive value of up to 89%, 95% CI 84–93%) and relative decrease of PSA values (P = 0.4) performed poorly in detecting residual disease. Urinary and bowel assessment returned to baseline questionnaire scores within 3 months. In all, 17 (21%) patients reported meaningful worsening in erectile function. A significant decrease of PCa related anxiety was observed. Conclusions: Focal HIFU treatment for localised PCa shows excellent functional outcomes with half of the patients remaining cancer‐free after 3 years. Whole‐gland treatment was avoided in 81%. Early follow‐up biopsies are crucial to change or continue the treatment modality at the right time, while the use of MRI and PSA in detecting PCa recurrence is uncertain. [ABSTRACT FROM AUTHOR]

Based on the question of the representability of economy and economics in audiovisual media, developments on the financial markets have often been discussed as a depiction problem. The abstractness and complexity of economic interrelations seem to defy classical modes of storytelling and dramatization. Nevertheless, public opinion about economic changes and dependencies crucially relies on audiovisual media. But how can the public communicate in images, sounds, and words about forces that are out of sight and out of reach, and can supposedly only be adequately grasped by experts? In a case study on audiovisual images of the global financial crisis (2007–), this paper tracks and analyzes a recurring motif: the staging of expert knowledge as close‐ups of expressive faces vis‐à‐vis computer screens in television news, documentaries, as well as feature films. It draws on the use of digital tools for corpus exploration (reverse image search) and the visualization of video annotations. By relating and comparing different staging strategies by which these "broker faces" become embodiments of turbulent market dynamics, the paper proposes to not regard them as repeated instantiations of the same metaphor, but as a developing web of cinematic metaphors. Different perspectives (news of market developments or historical accounts of crisis developments) and affective stances toward the global financial crisis are expressed in these variations of the face‐screen constellation. The paper thus presents a selection of different appearances of "broker faces" as a medium for an audiovisual discourse of the global financial crisis. A concluding analysis of a scene from Margin Call focuses on its specific intertwining of expert and screen as an ambivalent movement figuration of staging insight. Between the feeling of discovery (of a potential future threat) and the sense of being haunted (by a menacing force), the film stages the emergence of a "broker face" in an atmospheric tension between suspense and melancholy. We argue that the film thereby reframes the motif and poses questions of agency, temporality, and expert knowledge. [ABSTRACT FROM AUTHOR]

Context: Non-alcoholic fatty liver disease (NAFLD) is a leading causes of liver-related morbidity and mortality. While data on acromegaly, a state of chronic growth hormone (GH)/insulin-like growth factor I (IGF-I) excess, suggest an inverse relationship with intrahepatic lipid (IHL) content, less is known about the impact of the GH/IGF-I axis on IHL, lipid composition, and phosphor metabolites in individuals without disorders of GH secretion. Objective: The aim was to investigate the relation between activity of the GH/IGF-I axis and IHL content and phosphor metabolism. Methods: We performed a cross-sectional study in 59 otherwise metabolically healthy individuals (30 females), of which 16 met the criteria of NAFLD with IHL of ≥5.6%. The GH/IGF-I axis was evaluated in a fasting state and during an oral glucose tolerance test (OGTT). Insulin sensitivity was estimated by validated indices. IHL, lipid composition (unsaturation index), and phosphate metabolites were analyzed by using 1 H/31P magnetic resonance spectroscopy. Results: In the overall cohort (40.6 ± 15 years; body mass index: 24.5 ± 3 kg/m2 ; IGF-I: 68.0 ± 17% upper limit of normal), fasting GH (R = −0.31; P = .02), GH during oral glucose tolerance test (R = −0.51; P < .01), and IGF-I (R = −0.28; P = .03) inversely correlated with IHL. GH levels during OGTT were significantly lower in NAFLD than in controls (47.7 [22; 143] ng/mL/min vs 16.8 [7; 32] ng/mL/min; P = .003). GH/IGF-I axis activity correlated with lipid composition and with phosphor metabolites. In multiple regression analysis, the GH/IGF-I axis activity was a strong predictor for IHL and lipid composition independent from insulin sensitivity. Conclusion: GH/IGF-I axis activity impacts hepatic lipid and phosphate metabolism in individuals without disorders in GH secretion. Lower GH axis activity is associated with higher IHL and an unfavorable lipid composition, probably mediated by changes in hepatic energy metabolism. [ABSTRACT FROM AUTHOR]

A 24-year-old man with diabetes mellitus presented with advanced kidney disease and severe proteinuria. Genetic testing revealed ABCC8-MODY12 (OMIM 600509), and a kidney biopsy showed nodular glomerulosclerosis. He commenced dialysis shortly thereafter, and glycemic control improved on treatment with a sulfonylurea. Diabetic end-stage kidney disease in patients with ABCC8-MODY12 has not been reported until now. Thus, our case highlights the risk for early-onset and severe diabetic kidney disease in patients with ABCC8-MODY12 and the importance of timely genetic diagnosis in unusual cases of diabetes to allow for proper treatment and prevention of late sequelae of diabetes. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with non-muscle invasive (NMI) urothelial bladder cancer (BC) are more likely to have a second cancer in the upper urinary tract (UTUC). During bladder cancer follow-up, UTUC can be detected early by regular imaging of the upper urinary tract. However, there is little evidence that this strategy is useful. We performed a retrospective analysis of patients with NMIBC treated at our center between 2003 and 2016. Our results show that regular imaging has a low detection rate and that UTUCs were only found in individuals who already had a high-risk disease, suggesting that only these individuals may require upper-tract surveillance. In the future, risk-adjusted follow-up strategies should be explored. Patients with non-muscle invasive (NMI) urothelial bladder cancer (BC) are at increased risk for the development of a secondary upper-urinary-tract urothelial carcinoma (UTUC). We aimed to assess the usefulness of routine upper-tract imaging surveillance during NMIBC follow-up in a patient cohort of a tertiary academic center. All routine upper-tract-imaging scans using computerized tomography urography (CTU) between 2003 and 2016 were assessed for UTUC detection. A total of 315 patients were analyzed. Initial tumor stage was Ta in 207 patients (65.7%), T1 in 98 patients (31.1%) and pure CIS in 10 patients (3.2%). A total of 149 (47.3%) presented with low-grade (LG), and 166 (52.7%) with high-grade (HG) disease. Median follow-up was 48 months (IQR: 55). Four patients (1.2%) were diagnosed with UTUC during follow-up. All four patients presented with initial Ta HG BC. Two of the patients (50%) were diagnosed by routine upper tract imaging. The other two patients were diagnosed after development of symptoms. The 5- and 10-year UTUC-free survival was 98.5% (standard error (SE) 0.9) and 97.6% (SE 1.3), respectively. UTUCs were detected exclusively in patients with initial HG disease, indicating that upper-tract surveillance might only be necessary in these patients. [ABSTRACT FROM AUTHOR]

A study was conducted at three sites in North Dakota to strengthen understanding of the usefulness of different proximal geophysical data types in agricultural contexts of varying pedology. This study hypothesizes that electromagnetic induction (EMI), gamma‐ray sensor (GRS), cosmic‐ray neutron sensor (CRNS), and elevation data layers are all useful in multiple linear regression (MLR) predictions of soil properties that meet expert criteria at three agricultural sites. In addition to geophysical data collection with vehicle‐mounted sensors, 15 soil samples were collected at each site and analyzed for nine soil properties of interest. A set of model training data was compiled by pairing the sampled soil property measurements with the nearest geophysical data. Eleven models passed expert‐defined uncertainty criteria at Site 1, 16 passed at Site 2, and 14 passed at Site 3. Electrical conductivity (EC), organic matter (OM), available water holding capacity, silt, and clay were predicted at Site 1 with an R‐squared of prediction (Rpred2)$(R_{pred}^2)$ >.50 and acceptable root mean square error of prediction (RMSEP). Bulk density (BD), OM, available water capacity, silt, and clay were predicted with Rpred2$R_{pred}^2$ >.50 and acceptable RMSEP at Site 2. At Site 3, no soil properties were predicted with acceptable RMSEP and an Rpred2$R_{pred}^2$ >.50. These results confirm feasibility of our method, and the authors recommend the prioritization of EMI data collection if geophysical data collection is limited to a single mapping effort and calibration soil samples are few. Core Ideas: Framework given to assess relationships between proximal sensing and soil properties.Correlations between sensing data and soil properties varied among three study sites.Electromagnetic induction was most consistently useful in soil property prediction. [ABSTRACT FROM AUTHOR]

Leptin (encoded by Lep) controls body weight by regulating food intake and fuel partitioning. Obesity is characterized by leptin resistance and increased endocannabinoid tone. Here we show that leptin infused into the mediobasal hypothalamus (MBH) of rats inhibits white adipose tissue (WAT) lipogenesis, which occurs independently of signal transducer and activator of transcription-3 (STAT3) signaling. Correspondingly, transgenic inactivation of STAT3 signaling by mutation of the leptin receptor (s/s mice) leads to reduced adipose mass compared to db/db mice (complete abrogation of leptin receptor signaling). Conversely, the ability of hypothalamic leptin to suppress WAT lipogenesis in rats is lost when hypothalamic phosphoinositide 3-kinase signaling is prevented or when sympathetic denervation of adipose tissue is performed. MBH leptin suppresses the endocannabinoid anandamide in WAT, and, when this suppression of endocannabinoid tone is prevented by systemic CB1 receptor activation, MBH leptin fails to suppress WAT lipogenesis. These data suggest that the increased endocannabinoid tone observed in obesity is linked to a failure of central leptin signaling to restrain peripheral endocannabinoids., The increased prevalence of obesity worldwide is associated with an epidemic of type 2 diabetes mellitus. It is well established that a tight correlation exists between body adiposity and glucose [...]

Background: Biliary phosphatidylcholine (PtdC) concentration plays a role in the pathogenesis of bile duct diseases. In vivo phosphorus‐31 magnetic resonance spectroscopy (31P‐MRS) at 7 T offers the possibility to assess this concentration noninvasively with high spectral resolution and signal intensity. Purpose Comparison of PtdC levels of cholangiopathic patient groups to a control group using a measured T1 relaxation time of PtdC in healthy subjects. Study Type: Case control. Subjects: Two patient groups with primary sclerosing cholangitis (PSC, 2f/3 m; age: 43 ± 7 years) and primary biliary cholangitis (PBC, 4f/2 m; age: 57 ± 6 years), and a healthy control group (CON, 2f/3 m; age: 38 ± 7 years). Ten healthy subjects for the assessment of the T1 relaxation time of PtdC. Field Strength/Sequence: A 3D phase‐encoded pulse‐acquire 31P‐MRSI sequence for PtdC quantification and a 1D image‐selected in vivo 31P spectroscopy for T1 estimation at 7 T, and a T2‐weighted half‐Fourier single‐shot turbo spin echo MRI sequence for volumetry at 3 T. Assessment Calculation of gallbladder volumes and PtdC concentration in groups using hepatic gamma‐adenosine triphosphate signal as an internal reference and correction for insufficient relaxation of PtdC with a T1 value assessed in healthy subjects. Statistical Tests: Group comparison of PtdC content and gallbladder volumes of the PSC/PBC and CON group using Student's t‐tests with a significance level of 5%. Results: PtdC T1 value of 357 ± 85 msec in the gallbladder. Significant lower PtdC content for the PSC group, and for the female subgroup of the PBC group compared to the CON group (PSC/CON: 5.74 ± 0.73 mM vs. 9.64 ± 0.97 mM, PBC(f)/CON: 5.77 ± 1.44 mM vs. 9.64 ± 0.97 mM). Significant higher gallbladder volumes of the patient groups compared to the CON group (PSC/CON: 66.3 ± 15.8 mL vs. 20.9 ± 2.2 mL, PBC/CON: 49.8 ± 18.2 mL vs. 20.9 ± 2.2 mL). Data Conclusion: This study demonstrated the application of a 31P‐MRSI protocol for the quantification of PtdC in the human gallbladder at 7 T. Observed differences in PtdC concentration suggest that this metabolite could serve as a biomarker for specific hepatobiliary disorders. Level of Evidence: 2 Technical Efficacy Stage: 3 [ABSTRACT FROM AUTHOR]

This paper describes a case study of cold bent insulating glass units (IGUs) for use in facades or roofs using the example of a demonstrator called the "Twisted Tower". Modern designs often try to combine a curved shape with transparency. Cold bending IGUs is a cost efficient method to achieve both. In such applications the bending angles are often limited by the allowable deformations of the primary seal which ensures the gas tightness of the IGU. This investigation shows IGUs with much more acute bending angles than in standard applications were achieved using a flexible yet durable thermoplastic spacer ensuring superior gas tightness. This work investigates the geometry, the deformations and fixing options for the bent IGU form. The results demonstrate the advantages of using such spacer systems for these applications. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate whether the lack of signal transducer and activator of transcription 5 (STAT5) in mature adipocytes of obese mice (Stat5Adipoq mice) improves glucose and lipid metabolism as previously observed in lean mice. Male Stat5Adipoq mice and their wild type (WT) littermates were fed high-fat diet (HFD). Effects of adipocyte STAT5 deficiency on adiposity as well as on glucose and lipid metabolism were determined under ad libitum feeding and after weight loss induced by calorie restriction. Compared to WT mice, obese Stat5Adipoq mice showed modestly accelerated weight gain and blunted depletion of fat stores under calorie restriction (reduction in % body fat after 3 weeks: WT, -9.3±1.1, vs Stat5Adipoq, -5.9±0.8, p = 0.04). No differences were observed between Stat5Adipoq and WT mice with regard to parameters of glucose and lipid metabolism including basal glycaemia, glucose tolerance, and plasma triglycerides. In conclusion, STAT5 deficiency in the adipocyte of HFD-fed obese mice was associated with increased fat accumulation. In contrast to previous findings in lean mice, however, lipid accumulation was not associated with any improvement in glucose and lipid metabolism. Our results do not support adipocyte STAT5 as a promising target for the treatment of obesity-associated metabolic derangements. [ABSTRACT FROM AUTHOR]