time frequency domain identification of modal parameters in complex masonry structures under ambient vibrations

Abstract The dynamic identification of a large monumental structure is performed by using Time-Frequency Distributions. Acceleration signals are recorded on different points of the structure, allowing for the estimation of the building's parameters (i.e. frequency and instantaneous damping). The method uses auto- and cross-time-frequency transforms of the recorded signals to identify the vibration modes as a function of time and of the amplitude of the vibrations. The distributions considered have a quadratic structure, with convenient properties in the analysis of mechanical signals. In addition, quadratic distributions can use kernels in the ambiguity function domain that improve the reliability of the identification, reducing the cross terms of the distribution. The obtained results are compared with those afforded by Stochastic Subspace techniques. A model updating of the structure is also performed, starting from an indirect procedure, to provide model-based verifications

Results on stellar occultations by (307261) 2002 MS4

Transneptunian Objects (TNOs) are the remnants of our planetary system and can retain information about the early stages of the Solar System formation. Stellar occultation is a groundbased method used to study these distant bodies which have been presenting exciting results mainly about their physical properties. The big TNO called 2002 MS4 was discovered by Trujillo, C. A., & Brown, M. E., in 2002 using observations made at the Palomar Observatory (EUA). It is classified as a hot classical TNO, with orbital parameters a = 42 AU, e = 0.139, and i = 17.7º. Using thermal measurements with PACS (Herschel) and MIPS (Spitzer Space Telescope) instruments, Vilenius et al. 2012 obtained a radius of 467 +/- 23.5 km and an albedo of 0.051.Predictions of stellar occultations by this body in 2019 were obtained using the Gaia DR2 catalogue and NIMA ephemeris (Desmars et al. 2015) and made available in the Lucky Star web page (https://lesia.obspm.fr/lucky-star/). Four events were observed in South America and Canada. The first stellar occultation was detected on 09 July 2019, resulting in two positives and four negatives chords, including a close one which proven to be helpful to constrain the body’s size. This detection also allowed us to obtain a precise astrometric position that was used to update its ephemeris and improve the predictions of the following events. Two of them were detected on 26 July 2019, separated by eight hours. The first event was observed from South America and resulted in three positive detections, while the second, observed from Canada, resulted in a single chord. Another double chord event was observed on 19 August 2019 also from Canada.Facultad de Ciencias Astronómicas y Geofísica

Detailed Analysis of ITPR1 Missense Variants Guides Diagnostics and Therapeutic Design

BACKGROUND: The ITPR1 gene encodes the inositol 1,4,5-trisphosphate (IP3 ) receptor type 1 (IP3 R1), a critical player in cerebellar intracellular calcium signaling. Pathogenic missense variants in ITPR1 cause congenital spinocerebellar ataxia type 29 (SCA29), Gillespie syndrome (GLSP), and severe pontine/cerebellar hypoplasia. The pathophysiological basis of the different phenotypes is poorly understood. OBJECTIVES: We aimed to identify novel SCA29 and GLSP cases to define core phenotypes, describe the spectrum of missense variation across ITPR1, standardize the ITPR1 variant nomenclature, and investigate disease progression in relation to cerebellar atrophy. METHODS: Cases were identified using next-generation sequencing through the Deciphering Developmental Disorders study, the 100,000 Genomes project, and clinical collaborations. ITPR1 alternative splicing in the human cerebellum was investigated by quantitative polymerase chain reaction. RESULTS: We report the largest, multinational case series of 46 patients with 28 unique ITPR1 missense variants. Variants clustered in functional domains of the protein, especially in the N-terminal IP3 -binding domain, the carbonic anhydrase 8 (CA8)-binding region, and the C-terminal transmembrane channel domain. Variants outside these domains were of questionable clinical significance. Standardized transcript annotation, based on our ITPR1 transcript expression data, greatly facilitated analysis. Genotype-phenotype associations were highly variable. Importantly, while cerebellar atrophy was common, cerebellar volume loss did not correlate with symptom progression. CONCLUSIONS: This dataset represents the largest cohort of patients with ITPR1 missense variants, expanding the clinical spectrum of SCA29 and GLSP. Standardized transcript annotation is essential for future reporting. Our findings will aid in diagnostic interpretation in the clinic and guide selection of variants for preclinical studies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Neuroimaging biomarkers for clinical trials in atypical parkinsonian disorders: Proposal for a Neuroimaging Biomarker Utility System.

INTRODUCTION: Therapeutic strategies targeting protein aggregations are ready for clinical trials in atypical parkinsonian disorders. Therefore, there is an urgent need for neuroimaging biomarkers to help with the early detection of neurodegenerative processes, the early differentiation of the underlying pathology, and the objective assessment of disease progression. However, there currently is not yet a consensus in the field on how to describe utility of biomarkers for clinical trials in atypical parkinsonian disorders. METHODS: To promote standardized use of neuroimaging biomarkers for clinical trials, we aimed to develop a conceptual framework to characterize in more detail the kind of neuroimaging biomarkers needed in atypical parkinsonian disorders, identify the current challenges in ascribing utility of these biomarkers, and propose criteria for a system that may guide future studies. RESULTS: As a consensus outcome, we describe the main challenges in ascribing utility of neuroimaging biomarkers in atypical parkinsonian disorders, and we propose a conceptual framework that includes a graded system for the description of utility of a specific neuroimaging measure. We included separate categories for the ability to accurately identify an intention-to-treat patient population early in the disease (Early), to accurately detect a specific underlying pathology (Specific), and the ability to monitor disease progression (Progression). DISCUSSION: We suggest that the advancement of standardized neuroimaging in the field of atypical parkinsonian disorders will be furthered by a well-defined reference frame for the utility of biomarkers. The proposed utility system allows a detailed and graded description of the respective strengths of neuroimaging biomarkers in the currently most relevant areas of application in clinical trials

Neuroimaging biomarkers for clinical trials in atypical parkinsonian disorders: Proposal for a Neuroimaging Biomarker Utility System

IntroductionTherapeutic strategies targeting protein aggregations are ready for clinical trials in atypical parkinsonian disorders. Therefore, there is an urgent need for neuroimaging biomarkers to help with the early detection of neurodegenerative processes, the early differentiation of the underlying pathology, and the objective assessment of disease progression. However, there currently is not yet a consensus in the field on how to describe utility of biomarkers for clinical trials in atypical parkinsonian disorders.MethodsTo promote standardized use of neuroimaging biomarkers for clinical trials, we aimed to develop a conceptual framework to characterize in more detail the kind of neuroimaging biomarkers needed in atypical parkinsonian disorders, identify the current challenges in ascribing utility of these biomarkers, and propose criteria for a system that may guide future studies.ResultsAs a consensus outcome, we describe the main challenges in ascribing utility of neuroimaging biomarkers in atypical parkinsonian disorders, and we propose a conceptual framework that includes a graded system for the description of utility of a specific neuroimaging measure. We included separate categories for the ability to accurately identify an intention-to-treat patient population early in the disease (Early), to accurately detect a specific underlying pathology (Specific), and the ability to monitor disease progression (Progression).DiscussionWe suggest that the advancement of standardized neuroimaging in the field of atypical parkinsonian disorders will be furthered by a well-defined reference frame for the utility of biomarkers. The proposed utility system allows a detailed and graded description of the respective strengths of neuroimaging biomarkers in the currently most relevant areas of application in clinical trials.</p

A Qualitative Exploration of the Use of Contraband Cell Phones in Secured Facilities

Offenders accepting contraband cell phones in secured facilities violate state corrections law, and the possession of these cell phones is a form of risk taking behavior. When offenders continue this risky behavior, it affects their decision making in other domains where they are challenging authorities; and may impact the length of their incarceration. This qualitative phenomenological study examined the lived experience of ex-offenders who had contraband cell phones in secured correctional facilities in order to better understand their reasons for taking risks with contraband cell phones. The theoretical foundation for this study was Trimpop\u27s risk-homeostasis and risk-motivation theories that suggest an individual\u27s behaviors adapt to negotiate between perceived risk and desired risk in order to achieve satisfaction. The research question explored beliefs and perceptions of ex-offenders who chose to accept the risk of using contraband cell phones during their time in secured facilities. Data were collected anonymously through recorded telephone interviews with 8 male adult ex-offenders and analyzed using thematic content analysis. Findings indicated participants felt empowered by possession of cell phones in prison, and it was an acceptable risk to stay connected to family out of concern for loved ones. The study contributes to social change by providing those justice system administrators, and prison managers responsible for prison cell phone policies with more detailed information about the motivations and perspectives of offenders in respect to using contraband cell phones while imprisoned in secured facilities

Delayed recovery of movement-related cortical function in Parkinson's disease after striatal dopaminergic grafts

Intrastriatal transplantation of dopaminergic neurones aims to repair the selective loss of nigrostriatal projections and the consequent dysfunction of striatocortical circuitries in Parkinson's disease (PD). Here, we have studied the effects of bilateral human embryonic dopaminergic grafts on the movement-related activation of frontal cortical areas in 4 PD patients using H2 15O positron emission tomography and a joystick movement task. At 6.5 months after transplantation, mean striatal dopamine storage capacity as measured by 18F-dopa positron emission tomography was already significantly elevated in these patients. This was associated with a modest clinical improvement on the Unified Parkinson's Disease Rating Scale, whereas the impaired cortical activation was unchanged. At 18 months after surgery, there was further significant clinical improvement in the absence of any additional increase in striatal 18F-dopa uptake. Rostral supplementary motor and dorsal prefrontal cortical activation during performance of joystick movements had significantly improved, however. Our data suggest that the function of the graft goes beyond that of a simple dopamine delivery system and that functional integration of the grafted neurones within the host brain is necessary to produce substantial clinical recovery in PD

A molecular signature in blood identifies early Parkinson's disease

BACKGROUND: The search for biomarkers in Parkinson's disease (PD) is crucial to identify the disease early and monitor the effectiveness of neuroprotective therapies. We aim to assess whether a gene signature could be detected in blood from early/mild PD patients that could support the diagnosis of early PD, focusing on genes found particularly altered in the substantia nigra of sporadic PD. RESULTS: The transcriptional expression of seven selected genes was examined in blood samples from 62 early stage PD patients and 64 healthy age-matched controls. Stepwise multivariate logistic regression analysis identified five genes as optimal predictors of PD: p19 S-phase kinase-associated protein 1A (odds ratio [OR] 0.73; 95% confidence interval [CI] 0.60-0.90), huntingtin interacting protein-2 (OR 1.32; CI 1.08-1.61), aldehyde dehydrogenase family 1 subfamily A1 (OR 0.86; 95% CI 0.75-0.99), 19 S proteasomal protein PSMC4 (OR 0.73; 95% CI 0.60-0.89) and heat shock 70-kDa protein 8 (OR 1.39; 95% CI 1.14-1.70). At a 0.5 cut-off the gene panel yielded a sensitivity and specificity in detecting PD of 90.3 and 89.1 respectively and the area under the receiving operating curve (ROC AUC) was 0.96. The performance of the five-gene classifier on the de novo PD individuals alone composing the early PD cohort (n = 38), resulted in a similar ROC with an AUC of 0.95, indicating the stability of the model and also, that patient medication had no significant effect on the predictive probability (PP) of the classifier for PD risk. The predictive ability of the model was validated in an independent cohort of 30 patients at advanced stage of PD, classifying correctly all cases as PD (100% sensitivity). Notably, the nominal average value of the PP for PD (0.95 (SD = 0.09)) in this cohort was higher than that of the early PD group (0.83 (SD = 0.22)), suggesting a potential for the model to assess disease severity. Lastly, the gene panel fully discriminated between PD and Alzheimer's disease (n = 29). CONCLUSIONS: The findings provide evidence on the ability of a five-gene panel to diagnose early/mild PD, with a possible diagnostic value for detection of asymptomatic PD before overt expression of the disorder