Amprion (United States)

The energy transition poses significant challenges for the electrical distribution grid. This paper examines curative system operation in the 110 kV distribution grid that aims to tackle some of these challenges. Unlike preventive system operation, which avoids potential violations of operating thresholds during normal operation before they occur, curative system operation aims to maintain the grid within permissible thresholds only after a critical event through prepared, targeted measures. This paper analyses the complex requirements and challenges in implementing curative measures, particularly in comparison to existing approaches and concerning the high node density and the multitude of possible measures involving renewable generation plants and other customer facilities in the high-voltage distribution grid. By defining relevant thresholds and considering influencing factors, a unified understanding of curative system operation in the distribution grid is established. The paper demonstrates how curative system operation approaches can contribute to ensuring system security and describes the advantages of their utilization. Finally, perspectives for future research in the area of curative system operation in the 110 kV distribution grid are outlined.

Generate preliminary data in support of the notion that self-replicating proteins are the etiologic basis for Sporadic ALS.

ObjectiveRemote identification of individuals with severe hyposmia may enable scalable recruitment of participants with underlying alpha‐synuclein aggregation. We evaluated the performance of a staged screening paradigm using remote smell testing to enrich for abnormal dopamine transporter single‐photon emission computed tomography imaging (DAT‐SPECT) and alpha‐synuclein aggregation.MethodsThe Parkinson's Progression Markers Initiative (PPMI) recruited participants for the prodromal cohort who were 60‐years and older without a Parkinson's disease diagnosis. Participants were invited to complete a University of Pennsylvania Smell Identification Test (UPSIT) independently through an online portal. Hyposmic participants were invited to complete DAT‐SPECT, which determined eligibility for enrollment in longitudinal assessments and further biomarker evaluation including cerebrospinal fluid alpha‐synuclein seed amplification assay (aSynSAA).ResultsAs of January 29, 2024, 49,843 participants were sent an UPSIT and 31,293 (63%) completed it. Of UPSIT completers, 8,301 (27%) scored <15th percentile. Of 1,546 who completed DAT‐SPECT, 1,060 (69%) had DAT‐SPECT binding <100% expected for age and sex. Participants with an UPSIT <10th percentile (n = 1,221) had greater likelihood of low DAT‐SPECT binding compared to participants with an UPSIT in the 10th to 15th percentile (odds ratio, 3.01; 95% confidence interval, 1.85–4.91). Overall, 55% (198/363) of cases with UPSIT <15th percentile and DAT‐SPECT <100% had positive aSynSAA, which increased to 70% (182/260) when selecting for more severe hyposmia (UPSIT <10th percentile).InterpretationRemote screening for hyposmia and reduced DAT‐SPECT binding identifies participants with a high proportion positive aSynSAA. Longitudinal data will be essential to define progression patterns in these individuals to ultimately inform recruitment into disease modification clinical trials. ANN NEUROL 2025;97:730–740

Load frequency control is a well-established concept in AC-operated power systems. Balancing services are used to continuously keep the equilibrium between feed-in and withdrawal of electrical energy. In recent years, significant harmonization efforts took place in Europe to create a common domestic market for balancing energy. Beside alignment of market rules and product definitions, the establishment of European balancing platforms has been one cornerstone in this development. In 2022, the last two platforms went live enabling all connected countries to commonly activate balancing energy. This paper introduces the general concept of balancing platforms as well as the relevant elements of economic surplus resulting from the exchange of balancing energy. Based on the actual submitted bids, the economic surplus generated at the European balancing platforms for Frequency Restoration Reserves during the first year of operation is assessed. Without additional surplus due to unsatisfied demand, the economic surplus resulting from the exchange of balancing energy sums up to 81.5 m. € in the considered period. The experience from setting up and operating European balancing results in an outlook on further opportunities to foster competition by extending the European balancing platforms into balancing capacity cooperations.

CSF α-synuclein seed amplification assay (SAA) is a sensitive and specific tool for detecting Lewy body (LB) co-pathology in AD. 1637 cross-sectional and 407 longitudinal CSF samples from ADNI were tested with SAA. We examined longitudinal dynamics of Aβ, α-synuclein seeds, and p-tau181, along with global and domain-specific cognition in stable SAA+, stable SAA-, and those who converted to SAA+ from SAA-. SAA+ individuals had faster cognitive decline than SAA-, notably in MCI, and presented with earlier symptom onset. SAA+ conversion was associated with CSF Aβ42-positivity but did not impact progression of either Aβ42 or p-tau181 status. Aβ42, p-tau181, and α-syn SAA were all strong predictors of clinical progression, particularly Aβ42. In vitro α-syn SAA kinetic parameters were associated with participant demographics, clinical profiles, and cognitive decline. These results highlight the interplay between Aβ and α-synuclein and their association with disease progression.

Lewy body disease (LBD) is a common primary or co-pathology in neurodegenerative syndromes. An alpha-synuclein seed amplification assay (αSyn-SAA) is clinically available, but clinical performance, especially lower sensitivity in amygdala-predominant cases, is not well understood. Antemortem CSF from neuropathology-confirmed LBD cases was tested with αSyn-SAA (N=56). Diagnostic performance and clinicopathological correlations were examined. Similar to prior reports, sensitivity was 100% for diffuse and transitional LBD (9/9), and overall specificity was 96.3% (26/27). Sensitivity was lower in amygdala-predominant (6/14, 42.8%) and brainstem-predominant LBD (1/6, 16.7%), but early spread outside these regions (without meeting criteria for higher stage) was more common in αSyn-SAA-positive cases (6/7, 85.7%) than negative (2/13, 15.4%). In this behavioral neurology cohort, αSyn-SAA had excellent diagnostic performance for cortical LBD. In amygdala- and brainstem-predominant cases, sensitivity was lower, but positivity was associated with anatomical spread, suggesting αSyn-SAA detects early LBD progression in these cohorts. A cerebrospinal fluid alpha-synuclein assay detects cortical LBD with high sensitivity/specificity. Positivity in prodromal stages of LBD was associated with early cortical spread. The assay provides precision diagnosis of LBD that could support clinical trials. The assay can also identify LBD co-pathology, which may impact treatment responses.

IntroductionSynucleinopathies such as Parkinson's disease (PD) and multiple system atrophy (MSA) can be challenging to diagnose due to the symptom overlap with, for example, atypical parkinsonisms like progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Seed amplification assays (SAA), developed for the detection of α-synuclein (αSyn) aggregates in CSF, have been successful when used as a biomarker evaluation for synucleinopathies. In this study, we investigated the potential of this assay to not only detect αSyn seeds in CSF, but also discriminate between movement disorders. MethodsThe αSyn-SAA was tested in a Scandinavian cohort composed of 129 CSF samples from patients with PD (n = 55), MSA (n = 27), CBD (n = 7), and PSP (n = 16), as well as healthy controls (HC, n = 24). ResultsThe αSyn seed amplification assay (αSyn-SAA) was able to correctly identify all PD samples as positive (sensitivity of 100%) while also discriminating the PD group from HC (70.8% specificity, p < 0.0001) and tauopathies [CBD (71% specificity) and PSP (75% specificity), p < 0.0001)]. The αSyn-SAA was also able to identify almost all MSA samples as positive for αSyn aggregation (sensitivity of 92.6%). In general, this assay is able to discriminate between the synucleinopathies and tauopathies analyzed herein (p < 0.0001) despite the overlapping symptoms in these diseases. ConclusionThese findings suggest the αSyn-SAA is a useful diagnostic tool for differentiating between different parkinsonian disorders, although further optimization may be needed.

Misfolded alpha-synuclein (αSyn) aggregates are a hallmark event in Parkinson's disease (PD) and other synucleinopathies. Recently, αSyn seed amplification assays (αSyn-SAAs) have shown promise as a test for biochemical diagnosis of synucleinopathies. αSyn-SAAs use the intrinsic self-replicative nature of misfolded αSyn aggregates (seeds) to multiply them in vitro. In these assays, αSyn seeds circulating in biological fluids are amplified by a cyclical process that includes aggregate fragmentation into smaller self-propagating seeds, followed by elongation at the expense of recombinant αSyn (rec-αSyn). Amplification of the seeds allows detection by fluorescent dyes specific for amyloids, such as thioflavin T. Several αSyn-SAA reports have been published in the past under the names 'protein misfolding cyclic amplification' (αSyn-PMCA) and 'real-time quaking-induced conversion'. Here, we describe a protocol for αSyn-SAA, originally reported as αSyn-PMCA, which allows detection of αSyn aggregates in cerebrospinal fluid samples from patients affected by PD, dementia with Lewy bodies or multiple-system atrophy (MSA). Moreover, this αSyn-SAA can differentiate αSyn aggregates from patients with PD versus those from patients with MSA, even in retrospective samples from patients with pure autonomic failure who later developed PD or MSA. We also describe modifications to the original protocol introduced to develop an optimized version of the assay. The optimized version shortens the assay length, decreases the amount of rec-αSyn required and reduces the number of inconclusive results. The protocol has a hands-on time of ~2 h per 96-well plate and can be performed by personnel trained to perform basic experiments with specimens of human origin.

The Lewy Body Dementia Association (LBDA) held a virtual event, the LBDA Biofluid/Tissue Biomarker Symposium, on January 25, 2021, to present advances in biomarkers for Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLBs) and Parkinson's disease dementia (PDD). The meeting featured eight internationally known scientists from Europe and the United States and attracted over 200 scientists and physicians from academic centers, the National Institutes of Health, and the pharmaceutical industry. Methods for confirming and quantifying the presence of Lewy body and Alzheimer's pathology and novel biomarkers were discussed.