Dynamic modelling of metals in topsoils of UK and Chinese catchments

Strongly particle–reactive contaminants such as metals may exhibit highly accumulative behaviour when input to soils. This may cause exceedence of threshold concentrations for risk, for example for ecological effects or for crop metal content, if accumulation continues for a sufficiently long period. Since remediation of soils contaminated beyond threshold metal concentrations is likely to be costly and technically difficult, there is a need for tools to predict present and future accumulation of metals given future projections of inputs. The Intermediate Dynamic Model for Metals (IDMM) is an intermediate complexity model for describing and predicting metal accumulation and loss in topsoils over timescales of decades to centuries. The model combines mechanistic and empirical submodels for metal speciation, partitioning and aging in soils to predict solid phase and porewater metal speciation, leaching losses and plant uptake in response to time–varying inputs. The model has been applied both to a set of upland UK catchments, and to the Guanting reservoir catchment of northern China. The latter scenario presents a strongly contrasting environment, in terms of precipitation and soil chemistry, to the UK catchments. The model is driven by time series inputs of metals, starting from a pristine ‘steady state’ where input and output metal fluxes are in balance. Following estimation of historic metal inputs, particularly from atmospheric deposition, the model is able to make robust predictions of present day topsoil metal pools (within a factor of three of observations). The model thus provides a useful tool for predicting future trajectories of metal concentrations in topsoil, allowing assessment of potential risks due to varying scenarios of metal inputs

Atypical antipsychotic therapy in Parkinson's disease psychosis: A retrospective study.

ObjectiveParkinson's disease psychosis (PDP) is a frequent complication of idiopathic Parkinson's disease (iPD) with significant impact on quality of life and association with poorer outcomes. Atypical antipsychotic drugs (APDs) are often used for the treatment of PDP; however, their use is often complicated by adverse drug reactions (ADRs). In this study, we present patients with PDP who were treated with the most commonly used atypical antipsychotic agents and review their respective ADRs.MethodsA retrospective study was carried out to include a total of 45 patients with iPD who visited a movement disorders clinic between 2006 and 2015. All PDP patients treated with atypical APDs were included in the analysis for their specific ADRs.ResultsForty-five iPD patients (mean age of onset: 62.67 ± 9.86 years) were included, of those 10 patients had psychosis (mean age of onset: 76.80 ± 4.61 years). Of the 45 patients, 22.2% were found to have psychotic symptoms, of whom 70% had hallucinations, 20% had delusions, and 10% illusions. Seventy percent of psychotic symptoms occurred after ten or more years from diagnosis of iPD. PDP patients were treated with quetiapine, olanzapine, and risperidone separately or in combination, all of which were found to have certain ADRs.LimitationsThis study was limited by its retrospective study design and small sample size and with likely selection bias.ConclusionsThe prevalence of PDP is relatively high in older patients with iPD. The uses of the currently available atypical APDs in this patient population are often complicated by ADRs. The selective 5-HT 2A inverse agonist, pimavanserin, could be a better alternative in the treatment of PDP

Molecular imaging of dopamine synthesis and release

Positron emission tomography (PET) can be used to measure striatal dopamine synthesis and release, both of which have been shown to be elevated in schizophrenia. One study has demonstrated that first degree relatives of schizophrenia patients exhibit increased dopamine synthesis capacity, suggesting this could be an endophenotype or susceptibility marker. However, the specific relation to schizophrenia was not tested, as the index cases were not studied. In this thesis, I directly tested the hypothesis that both members of twin pairs discordant for schizophrenia show similar increases in dopamine synthesis capacity. I found that striatal dopamine synthesis capacity is not elevated in individuals at genetic risk of schizophrenia or in stable patients with chronic schizophrenia, suggesting that it is not a vulnerability marker for schizophrenia, and is associated with active psychosis only. I also tested whether dopamine synthesis capacity is elevated in otherwise healthy people who report hallucinations. No elevation was found, suggesting that the underlying neurobiology is distinct from schizophrenia. I then considered whether it would be possible to examine similar relationships with measurements of dopamine release. Methodologies for this measurement were still limited: antagonist radioligands such as [11C] raclopride have been used, but the dynamic range for the measure is small, confounding precision. I hypothesised that agonist radioligands could provide a more sensitive measure. [11C]-(+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol ([11C]-(+)-PHNO) is a D2/D3 agonist PET radioligand. I directly compared the sensitivity of [11C]-(+)-PHNO to amphetamine challenge with that of the antagonist ligand [11C] raclopride. Mass carry-over and cerebellar binding were potential problems with [11C]-(+)-PHNO. I therefore designed a study to quantify these factors. I found that [11C]-(+)-PHNO is superior to [11C]raclopride for studying acute fluctuations in dopamine in the striatum. Use of [11C]-(+)-PHNO will allow quantification of smaller changes in dopamine release, although mass effects and displaceable cerebellar binding are potential confounding factors

Cognitive correlates of psychopathology in functional/dissociative seizures and non-lesional epilepsy:An exploratory study

Objective: To explore the relationship between cognitive functioning and psychopathological features in Functional/Dissociative Seizures (FDS), and test whether this differs from that observed in epilepsy. Methods: We recruited a cross-sectional sample of adults (age &gt; 18) with a diagnosis of non-lesional epilepsy or FDS between January 2021 and July 2022 (n = 73). Participants completed a series of psychiatric questionnaires and neuropsychological measures. Spearman's Correlation Coefficient was computed between each of the psychiatric and cognitive measures in each group. Fisher's Z test of significance for independent correlation coefficients then tested the significance of the difference between correlation coefficients for the two groups. Results: There were no group differences in neuropsychological test scores. However, people with FDS reported higher seizure severity, depression levels, number of medically unexplained somatic symptoms, and exposure to traumatic events compared to epilepsy. Results of the Fisher's Z-test revealed significant differences in correlation coefficients between groups in two instances. First, in the association between the number of traumatic experiences and cognitive switching (z = 2.77, p = 0.006); the number of traumatic experiences were positively associated with cognitive switching in epilepsy but showed a non-significant negative trend in FDS. Secondly, in the association between vocabulary abilities and the number of medically unexplained symptoms (z = −2.71; p = 0.007); higher vocabulary ability was associated with fewer somatic symptoms in epilepsy, while no such correlation was observed in FDS. Significance: This study provides preliminary evidence for the complex interplay between cognitive functioning and psychopathology in FDS and epilepsy. Neurocognitive functioning such as vocabulary abilities or attentional switching may play a role in the expression or maintenance of pathological features of FDS.</p

Resting-state EEG for the diagnosis of idiopathic epilepsy and psychogenic nonepileptic seizures: A systematic review

Quantitative markers extracted from resting-state electroencephalogram (EEG) reveal subtle neurophysiological dynamics which may provide useful information to support the diagnosis of seizure disorders. We performed a systematic review to summarize evidence on markers extracted from interictal, visually normal resting-state EEG in adults with idiopathic epilepsy or psychogenic nonepileptic seizures (PNES). Studies were selected from 5 databases and evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2. 26 studies were identified, 19 focusing on people with epilepsy, 6 on people with PNES, and one comparing epilepsy and PNES directly. Results suggest that oscillations along the theta frequency (4–8 Hz) may have a relevant role in idiopathic epilepsy, whereas in PNES there was no evident trend. However, studies were subject to a number of methodological limitations potentially introducing bias. There was often a lack of appropriate reporting and high heterogeneity. Results were not appropriate for quantitative synthesis. We identify and discuss the challenges that must be addressed for valid resting-state EEG markers of epilepsy and PNES to be developed

Resting-state EEG for the diagnosis of idiopathic epilepsy and psychogenic nonepileptic seizures: A systematic review

Quantitative markers extracted from resting-state electroencephalogram (EEG) reveal subtle neurophysiological dynamics which may provide useful information to support the diagnosis of seizure disorders. We performed a systematic review to summarize evidence on markers extracted from interictal, visually normal resting-state EEG in adults with idiopathic epilepsy or psychogenic nonepileptic seizures (PNES). Studies were selected from 5 databases and evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2. 26 studies were identified, 19 focusing on people with epilepsy, 6 on people with PNES, and one comparing epilepsy and PNES directly. Results suggest that oscillations along the theta frequency (4–8 Hz) may have a relevant role in idiopathic epilepsy, whereas in PNES there was no evident trend. However, studies were subject to a number of methodological limitations potentially introducing bias. There was often a lack of appropriate reporting and high heterogeneity. Results were not appropriate for quantitative synthesis. We identify and discuss the challenges that must be addressed for valid resting-state EEG markers of epilepsy and PNES to be developed

Combined dynamics of mercury and terrigenous organic matter following impoundment of Churchill Falls Hydroelectric Reservoir, Labrador

Sediments from two recently (40 years) flooded lakes (Gabbro lake and Sandgirt lake) and an unflooded lake (Atikonak lake) were sampled to investigate the effects of reservoir impoundment on mercury (Hg) and terrigenous organic matter (TOM) loading in the Churchill Falls Hydroelectric complex in Labrador, Canada. Lignin biomarkers in TOM, which exclusively derive from terrestrial vegetation, were used as biomarkers for the presence and source origin of TOM—and for Hg due to their close associations—in sediments. In the two flooded Gabbro and Sandgirt lakes, we observed drastic increases in total mercury concentrations, T-[Hg], in sediments, which temporally coincided with the time of reservoir impoundment as assessed by 210Pb age dating. In the natural Atikonak lake sediments, on the other hand, T-[Hg] showed no such step-increase but gradually and slowly increased until present. T-[Hg] increases in lake sediments after flooding were also associated with a change in the nature of TOM: biomarker signatures changed to typical signatures of TOM from vegetated terrestrial landscape surrounding the lakes, and indicate a change to TOM that was much less degraded and typical of forest soil organic horizons. We conclude that T-[Hg] increase in the sediments of the two flooded reservoirs was the result of flooding of surrounding forests, whereby mainly surface organic horizons and upper soil horizons were prone to erosion and subsequent re-sedimentation in the reservoirs. The fact that T-[Hg] was still enriched 40 years after reservoir impoundment indicates prolonged response time of lake Hg and sediment loadings after reservoir impoundments

Does human presynaptic striatal dopamine function predict social conformity?

Socially desirable responding (SDR) is a personality trait which reflects either a tendency to present oneself in an overly positive manner to others, consistent with social conformity (impression management (IM)), or the tendency to view one's own behaviour in an overly positive light (self-deceptive enhancement (SDE)). Neurochemical imaging studies report an inverse relationship between SDR and dorsal striatal dopamine D2/3 receptor availability. This may reflect an association between SDR and D2/3 receptor expression, synaptic dopamine levels or a combination of the two. In this study, we used a [(18)F]-DOPA positron emission tomography (PET) image database to investigate whether SDR is associated with presynaptic dopamine function. Striatal [(18)F]-DOPA uptake, ( kicer, min-1), was determined in two independent healthy participant cohorts (n=27 and 19), by Patlak analysis using a cerebellar reference region. SDR was assessed using the revised Eysenck Personality Questionnaire (EPQ-R) Lie scale, and IM and SDE were measured using the Paulhus Deception Scales. No significant associations were detected between Lie, SDE or IM scores and striatal [(18)F]-DOPA kicer . These results indicate that presynaptic striatal dopamine function is not associated with social conformity and suggests that social conformity may be associated with striatal D2/3 receptor expression rather than with synaptic dopamine levels.</p

Nature or nurture? Determining the heritability of human striatal dopamine function:an [18F]-DOPA PET study

Striatal dopamine function is important for normal personality, cognitive processes and behavior, and abnormalities are linked to a number of neuropsychiatric disorders. However, no studies have examined the relative influence of genetic inheritance and environmental factors in determining striatal dopamine function. Using [18F]-DOPA positron emission tomography (PET), we sought to determine the heritability of presynaptic striatal dopamine function by comparing variability in uptake values in same sex monozygotic (MZ) twins to dizygotic (DZ) twins. Nine MZ and 10 DZ twin pairs underwent high-resolution [18F]-DOPA PET to assess presynaptic striatal dopamine function. Uptake values for the overall striatum and functional striatal subdivisions were determined by a Patlak analysis using a cerebellar reference region. Heritability, shared environmental effects and non-shared individual-specific effects were estimated using a region of interest (ROI) analysis and a confirmatory parametric analysis. Overall striatal heritability estimates from the ROI and parametric analyses were 0.44 and 0.33, respectively. We found a distinction between striatal heritability in the functional subdivisions, with the greatest heritability estimates occurring in the sensorimotor striatum and the greatest effect of individual-specific environmental factors in the limbic striatum. Our results indicate that variation in overall presynaptic striatal dopamine function is determined by a combination of genetic factors and individual-specific environmental factors, with familial environmental effects having no effect. These findings underline the importance of individual-specific environmental factors for striatal dopaminergic function, particularly in the limbic striatum, with implications for understanding neuropsychiatric disorders such as schizophrenia and addictions

Reconstructing the history of heavy metal pollution in the southern Pennines from the sedimentary record of reservoirs: methods and preliminary results

Although the southern Pennine uplands have experienced industrially derived heavy metal pollution for almost two hundred years, an historical analysis of its depositional records has not yet been undertaken. The area has no natural lakes but has many reservoirs, and despite the potential for sediment disturbance due to fluctuating water levels, reservoir sediments can be used as a record of heavy metal pollution. A methodology for the selection of reservoirs with undisturbed sedimentary records, and the verification of sediment stratigraphy is proposed. Preliminary results of metal analysis from the Howden reservoir indicate trace metal contamination with Zn > Pb > Cr > Ni = Cu