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Neuroimaging and Pathology Biomarkers in Parkinson's Disease and Parkinsonism
Get PDFThe "Neuroimaging and Pathology Biomarkers in Parkinson's Disease" course held on 12-13 September 2025 in Milan, Italy, convened an international faculty to review state-of-the-art biomarkers spanning neurotransmitter dysfunction, protein pathology and clinical translation. Here, we synthesize the four themed sessions and highlights convergent messages for diagnosis, stratification and trial design. The first session focused on neuroimaging markers of neurotransmitter dysfunction, highlighting how positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI) provided complementary insights into dopaminergic, noradrenergic, cholinergic and serotonergic dysfunction. The second session addressed in vivo imaging of protein pathology, presenting recent advances in PET ligands targeting α-synuclein, progress in four-repeat tau imaging for progressive supranuclear palsy and corticobasal syndromes, and the prognostic relevance of amyloid imaging in the context of mixed pathologies. Imaging of neuroinflammation captures inflammatory processes in vivo and helps study pathophysiological effects. The third session bridged pathology and disease mechanisms, covering the biology of α-synuclein and emerging therapeutic strategies, the clinical potential of seed amplification assays and skin biopsy, the impact of co-pathologies on disease expression, and the "brain-first" versus "body-first" model of pathological spread. Finally, the fourth session addressed disease progression and clinical translation, focusing on imaging predictors of phenoconversion from prodromal to clinically overt stages of synucleinopathies, concepts of neural reserve and compensation, imaging correlates of cognitive impairment, and MRI approaches for atypical parkinsonism. Biomarker-informed pharmacological, infusion-based, and surgical strategies, including network-guided and adaptive deep brain stimulation, were discussed as examples of how multimodal biomarkers may inform personalized management. Across all sessions, the need for harmonization, longitudinal validation, and pathology-confirmed outcome measures was consistently emphasized as essential for advancing biomarker qualification in multicentre research and clinical practice
Using Patient Feedback to Improve Treatment Outcomes for Patients with Congenital Dyserythropoietic Anaemia Type I Receiving Interferon Therapy
Get PDFCongenital dyserythropoietic anaemia type-I (CDA-I) is a rare autosomal recessive disease characterised by ineffective erythropoiesis, haemolysis and non-haematological developmental abnormalities. Its treatment is multifactorial, including the management of anaemia, iron overload and prevention of osteoporosis. The only treatment specific to CDA-I is subcutaneous interferon alpha (IFNα) 2A. This study presents the first summary of all published cases of CDA-I patients (n = 33) treated with IFNα and categorises their outcome. We also present new unpublished cases (n = 7). Overall, we find that IFNα administration causes a statistically significant mean increase in haemoglobin of 30.7 g/L (p < 0.001). However, we note that previous studies do not assess the impact of IFNα therapy on providing symptomatic benefit to patients with CDA-I, or the weight of side effects on their quality of life. We collaborate directly with patients through the organisation Congenital Anaemia Network to establish patient preferences regarding IFNα treatment. We propose a classification framework for the use of IFNα in CDA-I that includes patient-reported outcome measures in addition to grading response according to changes in Hb levels. We believe that the use of this framework will aid standardisation in measuring response to therapy, improve clinical practice and assist in future research
Sub-Lethal Toxicity of Bifenthrin and Acetamiprid Through Dietary Trophic Route: Effects on the Foraging Activity, Social Interactions, and Longevity of Apis mellifera L
Get PDFApis mellifera L. is an important pollinator of both wild and domesticated crop plants, thus greatly contributing to plant biodiversity and commercial agriculture. However, in field conditions, honey bees remain exposed to different pesticides which ultimately affect colony health parameters and their associated ecological services. In the current study, the individual toxicities of sub-lethal doses of two distinct insecticides (bifenthrin and acetamiprid) belonging to different groups (pyrethroid and neonicotinoid) were assessed against the foraging activity, social interactions, and longevity of A. mellifera. The bees were exposed to individual doses of both insecticides via the dietary trophic route through contaminated pollen and nectar under natural field conditions. Sunflower crop (Hysun-33) was sown at nine different sites with an isolation distance of 3 km, and was treated with different doses (1/2, 1/4, 1/10, and 1/20 of the recommended field doses) of both insecticides. However, the untreated control crop plots were not subjected to any chemical treatments (bee colonies received no insecticide, and served as the baseline for making comparison). Twenty-seven bee colonies were introduced in these sites after seven days of treatment applications. Significant differences were observed in the foraging activity of A. mellifera (including bees going out from the hive, returning foragers, and those carrying pollens). The fecundity, adult longevity, and social behaviors like trophallaxis and antennation were significantly lower in bees exposed to higher individual insecticidal concentrations. However, the hatching duration, larval duration, and pupal duration were not affected by the tested insecticidal treatments. Overall, these findings demonstrate that the dietary trophic exposure of sub-lethal doses of insecticides compromised colony activities, which is indeed a matter of concern regarding the existing pesticide application methods in different agro-ecosystems. Such impacts may ultimately impair the survival of colonies, particularly when bees remain exposed to these chemicals over an extended period of time. Therefore, future studies must consider the pesticide application techniques and their application timing to mitigate the direct and indirect negative impacts of pesticides on pollinators
Respiratory Syncytial Virus Positivity Rate and Clinical Characteristics Amongst Children Under 5 Years of Age at the Emergency and Outpatient Settings in Jordan: A Cross-Sectional Study
Get PDFBackgroundAcute viral respiratory infections are a major cause of morbidity among young children, with respiratory syncytial virus (RSV) being the leading pathogen. In Jordan and globally, most RSV research has focused on hospitalized patients, while data from emergency departments (EDs) and outpatient settings remain limited.MethodsThis cross-sectional study was conducted at two major Jordanian hospitals between November 2022 and March 2023. Children under five years of age presenting to EDs or outpatient clinics with symptoms of acute respiratory infection were enrolled. Nasopharyngeal specimens were tested for RSV, and subtypes (RSV-A and RSV-B) were identified using multiplex RT-PCR.ResultsOf 229 enrolled children, 92 (40.2%) tested positive for RSV, with RSV-B accounting for 81.5% of positive cases. RSV positivity was higher in ED presentations than in outpatient clinics (46% vs. 35%). Wheezing (72.8% vs. 39.4%, p < 0.001) and dyspnea (33.7% vs. 14.6%, p = 0.001) were significantly more frequent among RSV-positive patients. Independent predictors of RSV positivity included non-referred outpatient visits (OR = 15.26), non-referred ED visits (OR = 42.93), younger age, and prior systemic steroid use.ConclusionsRSV poses a substantial burden in outpatient and ED settings. Identified demographic and clinical predictors may help target high-risk groups for future preventive interventions
Silent Witness as Civic Theology: Zurab Kiknadze and the Ethics of Public Religion in Post-Soviet Georgia
Get PDFIn post-Soviet Georgia, the renewed visibility of religion in the public sphere has generated ambivalent effects, fostering both social cohesion and identity-based exclusion. This article focuses on the work I Am the Way by Georgian Orthodox thinker Zurab Kiknadze to explore how a non-instrumental, ethics-based conception of public religion can be sociologically conceptualized. Drawing on a qualitative, hermeneutic-narrative method, the analysis identifies two core motifs in Kiknadze’s thought—“spiritual journey” and “silent witness”—and interprets them through the lenses of public religion theory (Casanova), lived religion paradigms (McGuire, Ammerman), and post-secular debates (Habermas). The findings indicate that Kiknadze understands faith not as a marker of dogmatic or ethno-political belonging but as a practice contributing to ethical continuity and the reconstruction of social trust. Within this framework, “silent witness” is defined as a form of faith grounded in consistency, humility, and action-oriented conviction; it is proposed as a transferable sociological mechanism that supports trust, reconciliation, and inclusive citizenship in transitional societies. Centering on the Georgian case, this article offers a conceptual contribution to rethinking the public role of religion in post-authoritarian contexts within an ethical framework
Humans are more prosocial in poor foraging environments
Get PDFProsocial behaviours are essential for solving global challenges. Often, these behaviours have been measured using economic games or tasks where people decide between helping or not. However, in everyday life current behaviours are interrupted with alternative opportunities. Across three independent samples (two preregistered, total n = 510), people watched a movie whilst encountering opportunities that benefitted another person or themselves. Crucially, participants decided in different poor and rich foraging environments where the average reward values of opportunities changed. We demonstrate a stronger environmental influence on decisions that benefit others: people were more willing to interrupt their behaviour to help others in poor environments, where the average reward value was lower, compared to richer environments where average reward value was higher. Computational modelling revealed that the opportunity costs of the different foraging environments were valued distinctly for others. Factors of utilitarianism, and empathy/emotional motivation, captured variability in opportunity costs for others. We show that when humans decide to engage in prosocial behaviours depends on the quality of opportunities in one’s environment, which is critical as environments change
Activity outcomes from past patients after total knee arthroplasty: regression tree analysis to generate insights for new patients
No full textTriangle splatting for real-time radiance field rendering
Get PDFThe field of computer graphics was revolutionized by models such as NeRF and 3D Gaussian Splatting, displacing triangles as the dominant representation for photogrammetry. In this paper, we argue for a triangle comeback. We develop a differentiable renderer that directly optimizes triangles via end-to-end gradients. We achieve this by rendering each triangle as differentiable splats, combining the efficiency of triangles with the adaptive density of representations based on independent primitives. Compared to popular 2D and 3D Gaussian Splatting methods, our approach achieves competitive rendering and convergence speed, and demonstrates high visual quality. On the MipNeRF360 dataset, our method outperforms concurrent nonvolumetric primitives in visual fidelity and achieves higher perceptual quality than the state-of-the-art Zip-NeRF on indoor scenes. Triangles are simple, compatible with standard graphics stacks and GPU hardware, and highly efficient. Our results highlight the efficiency and effectiveness of triangle-based representations for high-quality novel view synthesis. Triangles bring us closer to mesh-based optimization by combining classical computer graphics with modern differentiable rendering frameworks. The project page is https://trianglesplatting.github.io
Yb2-Tb upconversion in a hetero-trimetallic molecular lanthanide complex
Get PDFPhoton Upconversion in molecular hetero-metallic lanthanide systems is challenged by the lack of chemical diversity displayed by the lanthanide ions. Here, we report the multi-photon photophysical properties of a series of molecular hetero-trimetallic lanthanide complexes Yb2Ln (Ln = Eu3+, Gd3+, Tb3+) assembled from kinetically inert building blocks providing site-specific chemical control regarding introduction of doddering lanthanide ions. The hetero-trimetallic complex Yb2Tb shows efficient Yb2 → Tb photon upconversion via cooperative sensitisation in both D2O and H2O. By contrast, Yb2Eu does not show Yb2 → Eu upconversion, while Yb2Gd has been used as a spectroscopic blank. We find that the Yb2 → Tb energy transfer appears to be independent of OH quenching from the solvent. Additionally, we report the intermetallic distances in the complex using density functional theory and molecular dynamics simulations. We find that the Yb2 → Tb cooperative sensitisation upconversion energy transfer remains effective despite relatively long intermetallic distances between donor pairs (13.5-25 Å) and between the Yb2 donor and the Tb acceptor (11.5-13.5 Å)
Investigating neurovascular coupling as an early, reliable biomarker of cerebral endothelial function
No full textCerebral small vessel disease (SVD) is a leading cause of stroke and vascular dementia, yet effective early biomarkers for detection and prevention remain limited. While SVD has traditionally been characterised by structural MRI markers, emerging evidence from functional MRI suggests that endothelial dysfunction is central in its pathogenesis. Neurovascular coupling (NVC), which reflects the dynamic relationship between neuronal activity and cerebral blood flow, offers a scalable, non-invasive marker of cerebral endothelial function and early cerebrovascular impairment. This thesis investigates the potential of NVC as an early functional biomarker of SVD, examining its associations with vascular risk factors, structural brain changes, and cognitive outcomes. The work began with a systematic review synthesizing current evidence on NVC changes in SVD, and demonstrated consistent NVC reductions with increased burdens of SVD neuroimaging markers. In the prospective UK Biobank cohort, which provided extensive clinical and multi-modal neuroimaging data from over 35,000 participants, I showed that impaired NVC was associated with higher cardiovascular risk profiles, including an elevated 10-year risk of heart disease or stroke, even in individuals without manifest cerebrovascular disease or detectable white matter hyperintensities (WMH) on MRI. Next, I then found that NVC was impaired with greater volumes of both macrostructural (WMH) and microstructural white matter injuries, and these associations being amplified by ageing and biological sex. I found that NVC in the females UK Biobank participants consistently exhibited higher NVC than males independent of age and vascular risk factors. This led to a hypothesis-driven analysis focused on hormonal influences, where I found that postmenopausal status was associated with lower NVC. However, this decline appeared primarily driven by ageing rather than menopause alone, though NVC fluctuations were observed during the perimenopausal stage, suggesting potential oestrogen effects on endothelial function. The cardiovascular system is known to exhibit diurnal variations, most notably in blood pressure. I explored whether similar patterns exist for NVC, demonstrating a distinct midday ‘dip’ in NVC between 8 a.m. and 8 p.m. This diurnal variation was influenced by ischaemic stroke, SVD, and sleep-related risk factors, further supporting the ability of NVC to reflect vascular function. Finally, I investigated the association between NVC and cognitive performances. Cross-sectional analyses revealed that higher NVC was associated with better cognitive function, particularly in domains of processing speed and executive function. However, NVC showed limited ability to predict cognitive decline over a two-year follow-up, suggesting that while it may reflect current cognitive status, its predictive value for future decline may be restricted.Collectively, these findings support the use of NVC as a functional biomarker of cerebral endothelial dysfunction in early SVD, with potential applications in population screening, risk stratification, and monitoring treatment response