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Niemann-Pick Type C (NPC) is a genetic neurodegenerative lysosomal storage disorder commonly associated with psychiatric symptoms and delays to accurate diagnosis and treatment. This study investigated biomarker levels and diagnostic utility of plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in NPC compared to healthy controls. Patients with NPC were recruited from a specialist assessment and management service. Data was available from an age and sex-matched healthy control group. NfL and GFAP were measured on Quanterix Simoa HD-X analysers and groups compared using generalised linear models. NfL levels were compared to, and percentiles derived from, recently developed NfL reference ranges. Plasma NfL was significantly elevated in 11 patients with NPC compared to 25 controls (mean 17.1 vs. 7.4 pg/ml, < 0.001), and reference ranges (all >98 percentile). NfL distinguished NPC from controls with high accuracy. GFAP levels were not elevated in NPC (66.6 vs. 75.1 pg/ml). The study adds important evidence on the potential diagnostic utility of plasma NfL in NPC, extends the literature of NfL as a diagnostic tool to differentiate neurodegenerative from primary psychiatric disorders, and adds support to the pathology in NPC primarily involving neuronal, particularly axonal, degeneration.

ABSTRACTObjectivesCarer burden is common in younger-onset dementia (YOD), often due to the difficulty of navigating services often designed for older people with dementia. Compared to Alzheimer’s disease (AD), the burden is reported to be higher in behavioral variant frontotemporal dementia (bvFTD). However, there is little literature comparing carer burden specifically in YOD. This study hypothesized that carer burden in bvFTD would be higher than in AD. DesignRetrospective cross-sectional study. SettingTertiary neuropsychiatry service in Victoria, Australia. ParticipantsPatient-carer dyads with YOD. MeasurementsWe collected patient data, including behaviors using the Cambridge Behavioral Inventory-Revised (CBI-R). Carer burden was rated using the Zarit Burden Inventory-short version (ZBI-12). Descriptive statistics and Mann-Whitney U tests were used to analyze the data. ResultsCarers reported high burden (ZBI-12 mean score = 17.2, SD = 10.5), with no significant difference in burden between younger-onset AD and bvFTD. CBI-R stereotypic and motor behaviors, CBI-R everyday skills, and total NUCOG scores differed between the two groups. There was no significant difference in the rest of the CBI-R subcategories, including the behavior-related domains. ConclusionCarers of YOD face high burden and are managing significant challenging behaviors. We found no difference in carer burden between younger-onset AD and bvFTD. This could be due to similarities in the two subtypes in terms of abnormal behavior, motivation, and self-care as measured on CBI-R, contrary to previous literature. Clinicians should screen for carer burden and associated factors including behavioral symptoms in YOD syndromes, as they may contribute to carer burden regardless of the type.

Most people with dementia experience neuropsychiatric symptoms (NPS), including anxiety, depression or disinhibition. There is growing interest in the relationship between NPS and cognitive impairment, but data is still limited. This study aimed to investigate the specific associations between NPS and cognition in people with dementia. MEDLINE, EMBASE and PsycINFO were searched for published, peer-reviewed studies of associations between at least one NPS and one cognitive ability in people with dementia. The quality of the studies was assessed with the NIH National Heart, Lung and Blood Institute’s quality assessment tools. A meta-analysis was conducted using Robumeta package for R. Ninety studies were included. We found significant associations between NPS, global cognition and cognitive domains, e.g. apathy was associated with global cognitive and memory impairment; dysphoria was associated with worse attention; delusions with executive dysfunction. Increased NPS in people with dementia are associated with worse cognitive performance. There were few studies looking at associations between some neuropsychiatric clusters and cognitive abilities, and there was little research on causal relationships. Our review was limited by the inclusion of studies that reported associations in specific formats, and most included people with a diagnosis of Alzheimer’s disease (AD). However, given the large number of studies, this is unlikely to have biased results. More research is needed that includes diverse people with different dementia syndromes. Registration: PROSPERO 2020 CRD42020165565.

During exploration using electromagnetic methods, secondary electro magnetic (EM) fields due to induced currents from conductors, together with the primary EM field, are re corded with a suit able receiver at various points in space. In general, the secondary EM field at the receiver, which contains all the in for mation regarding under ground conductors, may be several orders of magnitude smaller than the primary field. Under these conditions the separation of the measured total EM field into its primary and secondary parts is difficult. For the purpose of measuring the secondary fields in the absence of the primary field, time-do main electromagnetic measurements, often referred to as transient electromagnetic (TEM) techniques are employed. Comparative numerical modeling using a single component (measuring the vertical component of the field, Hz) TEM receiver and a three-component (measuring Hx, Hy, and Hz) TEM receiver was under taken. A for ward modeling approach was used to compute the voltage response of half-space containing one or more conductive bodies ex cited by a bi-polar square wave form. Al though this method utilizes conductor scattering, it is particularly useful as a practical use for unexploded dordnance (UXO) detection. Un like single component data, results from the three-component data are unambiguous as to the location and orientation of conductors. Measurements with the addition of horizontal- component data for secondary magnetic fields lead a better indication of tar get location, and tar get size determination, orientation, and characteristics, especially for the tar gets in the horizontal plan. A three-component TEM field experiment at a well-documented well site (NCU cam pus) was con sis tent with the effects predicted by our the oretical modeling. As a result, the three-component TEM survey is an essential element for high-resolution EM engineering survey.

The Taiwan orogeny is young and presently very active. To improve understanding of the tectonics of Taiwan, especially the present of fluid of interconnected fluids such as water and partial melts in the Earth¢XPs crust, transect across the central island of Taiwan by using broadband magneto-telluric (MT) soundings was made from 1995 - 2006. More than 80 MT stations were surveyed around this transect and a profile almost perpendicular to the regional strike of Taiwan was obtained. A 2-D constrained inversion was implemented and included static shift, topography and the ocean effect. This resistivity model is characterized by three main conductive anomalies located beneath the Coastal Plains, Central Range and Longitudinal Valley. Correlation of the conductors to the seismicity, the heat flow and surface geology of Taiwan suggest that the Coastal Plain conductor represents fluids, the Central Range conductor reflects both fluids and the effect of enhanced temperature, and the Longitudinal Valley conductor depicts the suture zone of the plates¢XP boundary, respectively. These lo resistivity zones could represent zones of reduced viscosity that may control the deformation of this active orogen. The GPS observations of a general motion in Taiwan area support this tectonic implication.

Background It is clinically a challenging task to accurately differentiate complex young‐onset neurodegenerative disorders from psychiatric disorders which often present with similar neuropsychiatric symptoms (NPS) in their early stages. The aim of this study is to provide a more nuanced understanding of the interplay between NPS, cognition and multiple pathologies that may drive these disorders. Method This study was conducted at the Neuropsychiatry Centre, the Royal Melbourne Hospital, Melbourne, Australia, as part of a large, multi‐site research study, the Markers in Neuropsychiatric Disorders Study. Sixty participants, including people with Alzheimer’s disease, Huntington’s disease, frontotemporal dementia, major depressive disorder and generalised anxiety disorder and together with healthy controls, were recruited and assessed for plasma biomarkers, NPS and cognition. Their plasma levels of amyloid‐beta, total‐tau (t‐tau), phosphorylated‐tau (p‐tau), neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAP) were measured. The severity of multiple common NPS such as depression, anxiety and apathy were also measured. Cognitive functions were measured by a combination of cognitive screening tool and standardised neuropsychological assessments. General linear regressions were used to investigate the associations between biomarkers, NPS and cognition in these disorders and the differences between the two clinical groups. Result The analysis of the collected data is ongoing. However, results from a pilot study suggest that memory recall was related to an interplay between AT(N) pathologies, and executive function was related to a neuronal pathology. The severity of NPS may moderate these relationships. Conclusion Young‐onset neuropsychiatric disorders, presenting with overlapping symptoms, pose a diagnostic dilemma. The results of this study provide a more nuanced understanding of the intricate interplay between NPS, cognition and biomarkers that may shed light into the differentiation between young‐onset neurodegenerative disorders and psychiatric disorders.

Background Young‐onset dementia (YOD) refers to the occurrence of dementia symptoms in people under the age of 65. Neuropsychiatric symptoms (NPS) are increasingly considered as the preclinical manifestations of YOD, posing a challenge to differentiate from psychiatric conditions with overlapping symptoms. The aim of this study is to investigate the AT(N), neuronal and glial pathologies underlying NPS and cognition in YOD. Method This study used clinical data from the Neuropsychiatry Centre, the Royal Melbourne Hospital, Melbourne, Australia. Sixty‐nine people with YOD were identified and assessed for biomarkers, NPS and cognition (mean age [SD] = 57.6 [7.3], female N = 23 [33%]). Their cerebrospinal fluid and plasma levels of amyloid‐beta, total‐tau (t‐tau), phosphorylated‐tau (p‐tau), neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAP) were measured. Common NPS such as depressive and behavioural symptoms were also measured. Cognitive functions were measured by a comprehensive battery of neuropsychological assessments. General linear regressions were used to investigate the associations between biomarkers, NPS and cognition. Result Memory recall was correlated with levels of amyloid‐beta (r = .52, 95% conference interval [CI] = [.32, .75]), t‐tau (r = ‐.4, 95% CI = [‐.65, ‐.16]) and p‐tau (r = ‐.34, 95% CI = [‐.58, ‐.11]). Executive function was correlated with levels of NfL (r = ‐.4, 95% CI = [‐.78, ‐.03]). Levels of NfL were further correlated with the severity of stress (r = ‐.41, 95% CI = [‐.73, ‐.11]). No evidence of associations between levels of GFAP and NPS or cognition was observed. Visuoconstruction was correlated with levels of amyloid‐beta (r = .45, 95% CI = [.24, .67]), in which this relationship was moderated by the severity of self‐care problems (F [6, 28] = 5.48, p < .05). Conclusion The results suggest that the changes in memory recall are associated with an intricate interplay between AT(N) pathologies in people with YOD. Executive function in YOD may be related to neuronal alterations rather than glial alternations in the brain. Combining biomarker results, the real challenge of self‐care problems in people with YOD observed by their caregivers may serve as a surrogate estimate to predict outcomes in visuoconstruction.

α-Phase hematite photoelectrodes can split water. This material is nontoxic, inexpensive, and chemically stable; its low energy gap of 2.3 eV absorbs light with wavelengths lower than 550 nm, accounting for approximately 30% of solar energy. Previously, we reported polyhedral pseudocubic α-Fe2O3 nanocrystals using a facile hydrothermal route to increase spatial charge separation, enhancing the photocurrent of photocatalytic activity in the water-splitting process. Here, we propose a p-n junction structure in the photoanode of pseudocubic α-Fe2O3 to improve short carrier diffusion length, which limits its photocatalytic efficiency. We dope Zn on top of an Fe2O3 photoanode to form a layer of p-type semiconductor material; Sn is doped from the FTO substrate to form a layer of n-type semiconductor material. The p-n junction, n-type Fe2O3:Sn and p-type Fe2O3:Zn, increase light absorption and charge separation caused by the internal electric field in the p-n junction.

This study examines the relationships among perceived price, quality, and value and their impact on the intent to participate in marathon events. An online questionnaire survey was administered to individuals who had participated in a marathon within the past ten years. Participants were selected using purposive sampling. A total of 609 valid responses were collected. The results showed that both perceptions of price and quality of marathon events are significant predictors of intention to participate in marathon events. Moreover, participants’ perceived value mediated the impacts of perceived price and quality on behavioral intention. The findings offer key implications, including ways to promote active participation in marathon events. In addition, the findings emphasize the need to account for and fully understand perceived price and quality when designing marketing strategies aimed at attracting marathon participants.

Xanthelasma palpebrarum (XP) is a sign of hyperlipidemia and is closely linked to atherosclerosis. Since fatty liver shares similar risk factors with atherosclerosis, we hypothesized that patients with XP are also at risk of non-alcoholic fatty liver disease (NAFLD). In this retrospective cohort study, 37 patients with XP were compared with sex- and age-matched controls undergoing general health examination. Moreover, demographic information and lipid profiles were compared. The risk of NAFLD was evaluated using the hepatic steatosis and ZJU indices. In addition, we analyzed publicly available RNA sequencing data from the GSE48452 and GSE61260 datasets in the Gene Expression Omnibus database. Patients with XP had higher scores of hepatic steatosis index (37 ± 1.13 vs 32 ± 0.82, p=0.0006) and ZJU index (38.77 ± 1.0 vs 33.88 ± 0.74, p=0.0002). In addition, they had higher levels of lipid parameters, including total cholesterol, low-density lipoprotein (LDL), and fasting glucose. Among patients with fatty liver, individuals presenting with XP showed higher serum levels of total cholesterol (216 ± 10.4 vs 188.9 ± 7.6, p=0.04), fasting glucose (117.1 ± 6.4 vs 98.3 ± 2.4, p=0.002), and low-density lipoprotein (145.1 ± 8.7 vs 115.6 ± 6.4, p=0.009) than those without XP. In gene expression analysis, individuals presenting with non-alcoholic steatohepatitis showed higher scores of xanthelasma than those without non-alcoholic steatohepatitis. Our results suggest that individuals with XP have a higher risk of progression to NAFLD and develop a more severe dyslipidemia.