High SUVs have more robust repeatability in patients with metastatic prostate cancer: results from a prospective test-retest cohort imaged with 18F-DCFPyL

OBJECTIVES: In patients with prostate cancer (PC) receiving prostate-specific membrane antigen- (PSMA-) targeted radioligand therapy (RLT), higher baseline standardized uptake values (SUVs) are linked to improved outcome. Thus, readers deciding on RLT must have certainty on the repeatability of PSMA uptake metrics. As such, we aimed to evaluate the test-retest repeatability of lesion uptake in a large cohort of patients imaged with (18)F-DCFPyL. METHODS: In this prospective, IRB-approved trial (NCT03793543), 21 patients with history of histologically proven PC underwent two (18)F-DCFPyL PET/CTs within 7 days (mean 3.7, range 1 to 7 days). Lesions in the bone, lymph nodes (LN), and other organs were manually segmented on both scans, and uptake parameters were assessed (maximum (SUV(max)) and mean (SUV(mean)) SUVs), PSMA-tumor volume (PSMA-TV), and total lesion PSMA (TL-PSMA, defined as PSMA − TV × SUV(mean))). Repeatability was determined using Pearson's correlations, within-subject coefficient of variation (wCOV), and Bland-Altman analysis. RESULTS: In total, 230 pairs of lesions (177 bone, 38 LN, and 15 other) were delineated, demonstrating a wide range of SUV(max) (1.5–80.5) and SUV(mean) (1.4–24.8). Including all sites of suspected disease, SUVs had a strong interscan correlation (R(2) ≥ 0.99), with high repeatability for SUV(mean) and SUV(max) (wCOV, 7.3% and 12.1%, respectively). High SUVs showed significantly improved wCOV relative to lower SUVs (P < 0.0001), indicating that high SUVs are more repeatable, relative to the magnitude of the underlying SUV. Repeatability for PSMA-TV and TL-PSMA, however, was low (wCOV ≥ 23.5%). Across all metrics for LN and bone lesions, interscan correlation was again strong (R(2) ≥ 0.98). Moreover, LN-based SUV(mean) also achieved the best wCOV (3.8%), which was significantly reduced when compared to osseous lesions (7.8%, P < 0.0001). This was also noted for SUV(max) (wCOV, LN 8.8% vs. bone 12.0%, P < 0.03). On a compartment-based level, wCOVs for volumetric features were ≥22.8%, demonstrating no significant differences between LN and bone lesions (PSMA-TV, P =0.63; TL-PSMA, P =0.9). Findings on an entire tumor burden level were also corroborated in a hottest lesion analysis investigating the SUV(max) of the most intense lesion per patient (R(2), 0.99; wCOV, 11.2%). CONCLUSION: In this prospective test-retest setting, SUV parameters demonstrated high repeatability, in particular in LNs, while volumetric parameters demonstrated low repeatability. Further, the large number of lesions and wide distribution of SUVs included in this analysis allowed for the demonstration of a dependence of repeatability on SUV, with higher SUVs having more robust repeatability

DynamicEarthNet: Daily Multi-Spectral Satellite Dataset for Semantic Change Segmentation

Earth observation is a fundamental tool for monitoring the evolution of land use in specific areas of interest. Observing and precisely defining change, in this context, requires both time-series data and pixel-wise segmentations. To that end, we propose the DynamicEarthNet dataset that consists of daily, multi-spectral satellite observations of 75 selected areas of interest distributed over the globe with imagery from Planet Labs. These observations are paired with pixel-wise monthly semantic segmentation labels of 7 land use and land cover (LULC) classes. DynamicEarthNet is the first dataset that provides this unique combination of daily measurements and high-quality labels. In our experiments, we compare several established baselines that either utilize the daily observations as additional training data (semi-supervised learning) or multiple observations at once (spatio-temporal learning) as a point of reference for future research. Finally, we propose a new evaluation metric SCS that addresses the specific challenges associated with time-series semantic change segmentation. The data is available at: https://mediatum.ub.tum.de/1650201

Preserved emotional awareness of pain in a patient with extensive bilateral damage to the insula, anterior cingulate, and amygdala

Functional neuroimaging investigations of pain have discovered a reliable pattern of activation within limbic regions of a putative "pain matrix" that has been theorized to reflect the affective dimension of pain. To test this theory, we evaluated the experience of pain in a rare neurological patient with extensive bilateral lesions encompassing core limbic structures of the pain matrix, including the insula, anterior cingulate, and amygdala. Despite widespread damage to these regions, the patient's expression and experience of pain was intact, and at times excessive in nature. This finding was consistent across multiple pain measures including self-report, facial expression, vocalization, withdrawal reaction, and autonomic response. These results challenge the notion of a "pain matrix" and provide direct evidence that the insula, anterior cingulate, and amygdala are not necessary for feeling the suffering inherent to pain. The patient's heightened degree of pain affect further suggests that these regions may be more important for the regulation of pain rather than providing the decisive substrate for pain's conscious experience

Physiological Correlates of Volunteering

We review research on physiological correlates of volunteering, a neglected but promising research field. Some of these correlates seem to be causal factors influencing volunteering. Volunteers tend to have better physical health, both self-reported and expert-assessed, better mental health, and perform better on cognitive tasks. Research thus far has rarely examined neurological, neurochemical, hormonal, and genetic correlates of volunteering to any significant extent, especially controlling for other factors as potential confounds. Evolutionary theory and behavioral genetic research suggest the importance of such physiological factors in humans. Basically, many aspects of social relationships and social activities have effects on health (e.g., Newman and Roberts 2013; Uchino 2004), as the widely used biopsychosocial (BPS) model suggests (Institute of Medicine 2001). Studies of formal volunteering (FV), charitable giving, and altruistic behavior suggest that physiological characteristics are related to volunteering, including specific genes (such as oxytocin receptor [OXTR] genes, Arginine vasopressin receptor [AVPR] genes, dopamine D4 receptor [DRD4] genes, and 5-HTTLPR). We recommend that future research on physiological factors be extended to non-Western populations, focusing specifically on volunteering, and differentiating between different forms and types of volunteering and civic participation

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease

Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in $\textit{CHM}$ in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.This work was supported by The National Institute for Health Research England (NIHR) for the NIHR BioResource – Rare Diseases project (grant number RG65966). The Moorfields Eye Hospital cohort of patients and clinical and imaging data were ascertained and collected with the support of grants from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, National Health Service Foundation Trust, and UCL Institute of Ophthalmology, Moorfields Eye Hospital Special Trustees, Moorfields Eye Charity, the Foundation Fighting Blindness (USA), and Retinitis Pigmentosa Fighting Blindness. M.M. is a recipient of an FFB Career Development Award. E.M. is supported by UCLH/UCL NIHR Biomedical Research Centre. F.L.R. and D.G. are supported by Cambridge NIHR Biomedical Research Centre

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A Unified Framework for Implicit Sinkhorn Differentiation

The Sinkhorn operator has recently experienced a surge of popularity in computer vision and related fields. One major reason is its ease of integration into deep learning frameworks. To allow for an efficient training of respective neural networks, we propose an algorithm that obtains analytical gradients of a Sinkhorn layer via implicit differentiation. In comparison to prior work, our framework is based on the most general formulation of the Sinkhorn operator. It allows for any type of loss function, while both the target capacities and cost matrices are differentiated jointly. We further construct error bounds of the resulting algorithm for approximate inputs. Finally, we demonstrate that for a number of applications, simply replacing automatic differentiation with our algorithm directly improves the stability and accuracy of the obtained gradients. Moreover, we show that it is computationally more efficient, particularly when resources like GPU memory are scarce.Comment: To appear at CVPR 202

Exact buckling and vibration solutions for stepped rectangular plates

10.1006/jsvi.2001.3922Journal of Sound and Vibration2503503-517JSVI