The Long-Term Impact of COVID-19 on Presentations to a Specialist Child and Adolescent Eating Disorder Program.

Aim Explore the impact of COVID-19 on numbers and clinical profile of Eating Disorder (ED) presentations to a specialist ED program pre- and during COVID-19. Methods Retrospective chart review of referrals pre- COVID-19 (January 2018 - February 2020) and during COVID-19 (March 2020 - August 2021) were compared. Results 128 youth were assessed with significantly higher rates of referrals each month during COVID-19 compared to pre- COVID-19 (3.78 vs. 2.31, p = 0.02). Youth referred during COVID-19 showed a higher rate of % Ideal Body Weight (IBW) loss (4.8% = vs. 2.6%, p = < 0.001) and had a shorter duration of illness pre-referral (4.8 months vs. 7.4 months, p = 0.001). Fewer youth during COVID- 19 (19% vs. 43%, p = 0.011) were prescribed psychotropic medication. Many youth (80%), self-declared COVID-19 as a contributory factor in the development of their ED. Conclusion This study supports the growing consensus of a COVID-19 specific impact on ED services with higher rates of referrals, youth presenting with a faster pace of weight loss and earlier referral to specialist services. Whether this represents a true increase in EDs or an overall increase in CAMHS referrals with a faster transfer to ED services requires further exploration.

Mental health care and resistance to fascism.

Mental health nurses have a critical stake in resisting the right-wing ideology of British fascism. Particularly concerning is the contemporary effort of the British National Party (BNP) to gain credibility and electoral support by the strategic re-packaging of a racist and divisive political manifesto. Evidence that some public sector workers are affiliated with the BNP has relevance for nursing at a series of levels, not least the incompatibility of party membership with a requirement of the Professional Code to avoid discrimination. Progressive advances, though, need to account for deep rooted institutionalized racism in the discourse and practice of healthcare services. The anomalous treatment of black people within mental health services, alongside racial abuse experienced by ethnic minority staff, is discussed in relation to the concept of race as a powerful social category and construction. The murder of the mentally ill and learning disabled in Nazi Germany, as an adjunct of racial genocide, is presented as an extreme example where professional ethics was undermined by dominant political ideology. Finally, the complicity of medical and nursing staff in the state sanctioned, bureaucratic, killing that characterized the Holocaust is revisited in the context of ethical repositioning for contemporary practice and praxis.

Joint amplitude and connectivity compensatory mechanisms in Parkinson's disease.

Neuroimaging studies in Parkinson's disease (PD) have previously demonstrated several regions of hypo- and hyper-activation during voluntary movement. How these patterns of amplitude changes at multiple discrete foci relate to changes within functional networks recruited by a given task is unclear. Changes in both amplitude and connectivity have both been individually shown within the striato-thalamo-cortical (STC) loop in PD, as well as other regions, most consistently in the cerebellum and primary motor cortex. We have previously shown overactivation of the cerebellum and motor cortex in PD subjects off medication during a visuo-motor tracking task performed at three frequencies. Here, we show that this change in activation amplitude is also accompanied by significant changes in functional connectivity between regions of interest (ROIs), with enhanced connectivity within the cerebello-thalamo-cortical (CTC) loop as well as increased inter-hemispheric communication between several basal ganglia structures. Although changes in activation amplitude were influenced by the frequency of movement performed in the tracking task, functional connectivity changes were robustly present across all three task frequencies performed, suggesting that functional connectivity analysis in PD may be a more sensitive means of detecting plastic changes which are relatively invariant to the particulars of the experimental task. Additionally, we demonstrate amplitude and connectivity changes in structures that are typically active during the resting state, or "default-mode," in PD. Unlike in STC/CTC loops, where the direction of change was the same for amplitude and connectivity, default-mode regions showed increased amplitude but decreased connectivity. Our results further support that the CTC is recruited in PD to compensate for dysfunctional basal ganglia circuits, and that this recruitment involves both amplitude and connectivity changes. The differing relationship between amplitude and connectivity changes within individual loops highlights the importance of jointly examining them in order to fully elucidate functional changes in Parkinson's disease.

Partial directed coherence-based information flow in Parkinson's disease patients performing a visually-guided motor task.

We propose a partial directed coherence (PCD) method based on a sparse multivariate autoregressive (mAR) model to investigate patterns of information flow in electroencephalography (EEG) recordings in Parkinson's disease (PD) patients performing a visually-guided motor task. The use of a sparsity constraint on the mAR matrix addresses issues such as sample size, model order selection and number of parameters to be estimated, particularly when the number of EEG channels used is large and the window size is small in order to capture dynamic changes. The proposed PDC-based information flow analysis demonstrated distinctly altered patterns of connectivity between PD patients off medication and healthy subjects, particularly with respect to net information outflow from the left sensorimotor (L Sm) region, which might indicate excessive spreading of activity in the diseased state. Disrupted patterns of connectivity in PD were partially restored by levodopa medication. In addition, PDC-based analysis proved to be more sensitive to temporally-dynamic connectivity changes as compared to traditional spectral analysis, which might be influenced primarily by large-scale changes. We suggest that the proposed sparse-PDC method is a suitable technique to investigate altered connectivity in Parkinson's disease.

Asymmetrical lateral ventricular enlargement in Parkinson's disease.

BACKGROUND: A recent case report suggested the presence of asymmetrical lateral ventricular enlargement associated with motor asymmetry in Parkinson's disease (PD). The current study explored these associations further. METHODS: Magnetic resonance imaging (3T) scans were obtained on 17 PD and 15 healthy control subjects at baseline and 12-43 months later. Baseline and longitudinal lateral ventricular volumetric changes were compared between contralateral and ipsilateral ventricles in PD subjects relative to symptom onset side and in controls relative to their dominant hand. Correlations between changes in ventricular volume and United Parkinson's disease rating scale motor scores (UPDRS-III) whilst on medication were determined. RESULTS: The lateral ventricle contralateral to symptom onset side displayed a faster rate of enlargement compared to the ipsilateral (P = 0.004) in PD subjects, with no such asymmetry detected (P = 0.312) in controls. There was a positive correlation between ventricular enlargement and worsening motor function assessed by UPDRS-III scores (r = 0.96, P < 0.001). DISCUSSION: There is asymmetrical lateral ventricular enlargement that is associated with PD motor asymmetry and progression. Further studies are warranted to investigate the underlying mechanism(s), as well as the potential of using volumetric measurements as a marker for PD progression.

Levodopa-sensitive, dynamic changes in effective connectivity during simultaneous movements in Parkinson's disease.

Changes in effective connectivity during the performance of a motor task appear important for the pathogenesis of motor symptoms in Parkinson's disease (PD). One type of task that is typically difficult for individuals with PD is simultaneous or bimanual movement, and here we investigate the changes in effective connectivity as a potential mechanism. Eight PD subjects off and on l-DOPA medication and 10 age-matched healthy control subjects performed both simultaneous and unimanual motor tasks in an fMRI scanner. Changes in effective connectivity between regions of interest (ROIs) during simultaneous and unimanual task performance were determined with structural equation modeling (SEM), and changes in the temporal dynamics of task performance were determined with multivariate autoregressive modeling (MAR). PD subjects demonstrated alterations in both effective connectivity and temporal dynamics compared with control subjects during the performance of a simultaneous task. l-DOPA treatment was able to partially normalize effective connectivity and temporal patterns of activity in PD, although some connections remained altered in PD even after medication. Our results suggest that difficulty performing simultaneous movements in PD is at least in part mediated by a disruption of effective communication between widespread cortical and subcortical areas, and l-DOPA assists in normalizing this disruption. These results suggest that even when the site of neurodegeneration is relatively localized, study of how disruption in a single region affects connectivity throughout the brain can lead to important advances in the understanding of the functional deficits caused by neurodegenerative disease.

Task specific influences of Parkinson's disease on the striato-thalamo-cortical and cerebello-thalamo-cortical motor circuitries.

The motor deficits in Parkinson's disease (PD) have been primarily associated with internally guided (IG), but not externally guided (EG), tasks. This study investigated the functional mechanisms underlying this phenomenon using genetically-matched twins. Functional magnetic resonance images were obtained from a monozygotic twin pair discordant for clinical PD. Single-photon emission computed tomography neuroimaging using [(123)I](-)-2-beta-carboxymethoxy-3-beta-(4-iodophenyl)tropane confirmed their disease-discordant status by demonstrating a severe loss of transporter binding in the PD-twin, whereas the non-PD-twin was normal. Six runs of functional magnetic resonance imaging (fMRI) data were acquired from each twin performing EG and IG right-hand finger sequential tasks. The percentage of voxels activated in each of several regions of interest (ROI) was calculated. Multiple analysis of variance was used to compare each twin's activity in ROIs constituting the striato-thalamo-cortical motor circuits [basal ganglia (BG)-cortical circuitry, but including the globus pallidus/putamen, thalamus, supplementary motor area, and primary motor cortex] and cerebello-thalamo-cortical circuits (cerebellar-cortical circuitry, including the cerebellum, thalamus, somatosensory cortex, and lateral premotor cortex). During the EG task, there were no significant differences between the twins in bilateral BG-cortical pathways, either basally or after levodopa, whereas the PD-twin had relatively increased activity in the cerebellar-cortical pathways basally that was normalized by levodopa. During the IG task, the PD-twin had less activation than the non-PD-twin in ROIs of the bilateral BG-cortical and cerebellar-cortical pathways. Levodopa normalized the hypoactivation in the contralateral BG-cortical pathway, but "over-corrected" the activation in the ipsilateral BG-cortical and bilateral cerebellar-cortical pathways. In this first fMRI study of twins discordant for PD, the data support the hypothesis that BG-cortical and cerebellar-cortical pathways are task-specifically influenced by PD. The levodopa-induced "over-activation" of BG-cortical and cerebellar-cortical pathways, and its relevance to both compensatory changes in PD and the long-term effects of levodopa in PD, merit further exploration.

Cortical muscle coupling in Parkinson's disease (PD) bradykinesia.

OBJECTIVES: To determine if novel methods establishing patterns in EEG-EMG coupling can infer subcortical influences on the motor cortex, and the relationship between these subcortical rhythms and bradykinesia. BACKGROUND: Previous work has suggested that bradykinesia may be a result of inappropriate oscillatory drive to the muscles. Typically, the signal processing method of coherence is used to infer coupling between a single channel of EEG and a single channel of rectified EMG, which demonstrates 2 peaks during sustained contraction: one, approximately 10 Hz, which is pathologically increased in PD, and a approximately 30 Hz peak which is decreased in PD, and influenced by pharmacological manipulation of GABAA receptors in normal subjects. MATERIALS AND METHODS: We employed a novel multiperiodic squeezing paradigm which also required simultaneous movements. Seven PD subjects (on and off L-Dopa) and five normal subjects were recruited. Extent of bradykinesia was inferred by reduced relative performance of the higher frequencies of the squeezing paradigm and UPDRS scores. We employed Independent Component Analysis (ICA) and Empirical Mode Decomposition (EMD) to determine EEG/EMG coupling. RESULTS: Corticomuscular coupling was detected during the continually changing force levels. Different components included those over the primary motor cortex (ipsilaterally and contralaterally) and over the midline. Subjects with greater bradykinesia had a tendency towards increased approximately 10 Hz coupling and reduced approximately 30 Hz coupling that was erratically reversed with L-dopa. CONCLUSIONS: These results suggest that lower approximately 10 Hz peak may represent pathological oscillations within the basal ganglia which may be a contributing factor to bradykinesia in PD.

The service architecture of the TeraGyroid experiment.

We describe the service architecture of the successful TeraGyroid experiment. In particular we discuss the use of the open Grid service infrastructure (OGSI) to build the services used during the experiment and illustrate the problems we encountered.

Gender politics and secure services for women: reflections on a study of staff understandings of challenging behaviour.

This paper discusses the findings of a Q methodological study that investigated the complexity of professional understandings of (attitudes towards) residents in a secure unit for women with learning disabilities and challenging behaviours. Particular attention is afforded to the critical debate regarding women in psychiatric and secure care, including the significant contribution made to this literature by feminist perspectives. A multiprofessional group of staff (n = 38) participated in the study and nine distinct accounts of women's challenging behaviour are described. Despite a considerable amount of recent policy concern with the position of women in psychiatric services, the findings of this research suggest that many front line staff are reluctant to highlight gender in their explanations of women's behaviour. This supports the assertion by Williams et al. (2001), who were involved in the National Gender Training Initiative (NGTI), that most critical theorizing about women's mental health has had minimal impact at the level of individuals' understandings of these important issues. This state of affairs suggests a powerful case for the expansion of staff training as provided in the NGTI, which makes gender central to understanding and emphasizes feminist perspectives.

Selection of genomic target RNAs by iterative screening.

A growing number of proteins are known to exert their regulatory or biological functions via RNA binding. In some cases genetic interactions allow us to infer candidate targets for RNA directed regulation, but in many other cases identification of potential regulatory targets is problematic. We have developed an in vitro biochemical screen, SETIS (SElection of <> Target RNAs by Iterative Screening) that allows screening of a major portion of the genome for identification of potential targets for RNA binding proteins.

Identification and characterization of DAlk: a novel Drosophila melanogaster RTK which drives ERK activation in vivo.

BACKGROUND: The mammalian receptor protein tyrosine kinase (RTK), Anaplastic Lymphoma Kinase (ALK), was first described as the product of the t(2;5) chromosomal translocation found in non-Hodgkin's lymphoma. While the mechanism of ALK activation in non-Hodgkin's lymphoma has been examined, to date, no in vivo role for this orphan insulin receptor family RTK has been described. RESULTS: We describe here a novel Drosophila melanogaster RTK, DAlk, which we have mapped to band 53 on the right arm of the second chromosome. Full-length DAlk cDNA encodes a phosphoprotein of 200 kDa, which shares homology not only with mammalian ALK but also with the orphan RTK LTK. Analysis of both mammalian and Drosophila ALK reveals that the ALK family of RTKs contains a newly identified MAM domain within their extracellular domains. Like its mammalian counterpart, DAlk appears to be expressed in the developing CNS by in situ analysis. However, in addition to expression of DAlk in the Drosophila brain, careful analysis reveals an additional early role for DAlk in the developing visceral mesoderm where its expression is coincident with activated ERK. CONCLUSION: In this paper we describe a Drosophila melanogaster Alk RTK which is expressed in the developing embryonic mesoderm and CNS. Our data provide evidence for the existence of a DAlk RTK pathway in Drosophila. We show that ERK participates in this pathway, and that it is activated by DAlk in vivo. Expression patterns of dALK, together with activated ERK, suggest that DAlk fulfils the criteria of the missing RTK pathway, leading to ERK activation in the developing visceral mesoderm.

Phasic and tonic coupling between EEG and EMG demonstrated with independent component analysis.

The authors describe a method for demonstrating the tonic and phasic couplings between suitably time-aligned surface eletromyographs (sEMGs) and the simultaneously recorded EEGs. The method, based on independent component analysis, was applied to data recorded from two normal subjects performing sustained submaximal contractions or continual repetitive movements of the arm. Augmented datasets, consisting of the EEG and either the sEMG from a single muscle (subject 1) or a combination of sEMGs from several muscles (subject 2), were analyzed with independent component analysis to determine the EEG/sEMG coupling. Each derived coupling consisted of a spatial distribution on the scalp and a waveform representing an EEG channel combination coactivating with the sEMG. The combinations of sEMGs, derived by applying independent component analysis to the simultaneous sEMG recordings from several muscles to create sEMG independent components (ICs), were either tonic or phasic with differing periods of activation. The topographic distributions on the scalp of the couplings between the EEG and sEMG ICs were different for each sEMG IC. The spatial distributions of the couplings between tonic sEMG ICs or single-muscle sEMGs and the EEG followed topographic patterns in sensorimotor regions. Phasic couplings were bifrontal, lateral, and bioccipital. Calculation of coherence between the sEMG ICs and calculated EEG combinations agreed well with the frequency spectra of the independent component analysis-derived coupling waveforms. These preliminary results demonstrate that detection of both the tonic and phasic coupling between the sEMG and the EEG is possible when monitoring unpaced proximal arm movement. This may thus be a practical means of exploring the dynamic cortical/muscle relationships in subjects unable to perform fine finger movements, such as patients recovering from stroke.

The dual role of ultraspiracle, the Drosophila retinoid X receptor, in the ecdysone response.

The Drosophila homolog of the retinoid X receptor, ultraspiracle (USP), heterodimerizes with the ecdysone receptor (EcR) to form a functional complex that mediates the effects of the steroid molting hormone ecdysone by activating and repressing expression of ecdysone response genes. As with other retinoid X receptor heterodimers, EcR/USP affects gene transcription in a ligand-modulated manner. We used in vivo, cell culture, and biochemical approaches to analyze the functions of two usp alleles, usp(3) and usp(4), which encode stable proteins with defective DNA-binding domains. We observed that USP is able to activate as well as repress the Z1 isoform of the ecdysone-responsive broad complex (BrC-Z1). Activation of BrC-Z1 as well as EcR, itself an ecdysone response gene, can be mediated by both the USP3 and USP4 mutant proteins. USP3 and USP4 also activate an ecdysone-responsive element, hsp27EcRE, in cultured cells. These results differ from the protein null allele, usp(2), which is unable to mediate activation [Schubiger, M. & Truman, J. W. (2000) Development 127, 1151--1159]. BrC-Z1 repression is compromised in all three usp alleles, suggesting that repression involves the association of USP with DNA. Our results distinguish two mechanisms by which USP modulates the properties of EcR: one that involves the USP DNA-binding domain and one that can be achieved solely through the ligand-binding domain. These newly revealed properties of USP might implicate similar properties for retinoid X receptor.

Removing electroencephalographic artifacts by blind source separation.

Eye movements, eye blinks, cardiac signals, muscle noise, and line noise present serious problems for electroencephalographic (EEG) interpretation and analysis when rejecting contaminated EEG segments results in an unacceptable data loss. Many methods have been proposed to remove artifacts from EEG recordings, especially those arising from eye movements and blinks. Often regression in the time or frequency domain is performed on parallel EEG and electrooculographic (EOG) recordings to derive parameters characterizing the appearance and spread of EOG artifacts in the EEG channels. Because EEG and ocular activity mix bidirectionally, regressing out eye artifacts inevitably involves subtracting relevant EEG signals from each record as well. Regression methods become even more problematic when a good regressing channel is not available for each artifact source, as in the case of muscle artifacts. Use of principal component analysis (PCA) has been proposed to remove eye artifacts from multichannel EEG. However, PCA cannot completely separate eye artifacts from brain signals, especially when they have comparable amplitudes. Here, we propose a new and generally applicable method for removing a wide variety of artifacts from EEG records based on blind source separation by independent component analysis (ICA). Our results on EEG data collected from normal and autistic subjects show that ICA can effectively detect, separate, and remove contamination from a wide variety of artifactual sources in EEG records with results comparing favorably with those obtained using regression and PCA methods. ICA can also be used to analyze blink-related brain activity.

Detection of consistently task-related activations in fMRI data with hybrid independent component analysis.

fMRI data are commonly analyzed by testing the time course from each voxel against specific hypothesized waveforms, despite the fact that many components of fMRI signals are difficult to specify explicitly. In contrast, purely data-driven techniques, by focusing on the intrinsic structure of the data, lack a direct means to test hypotheses of interest to the examiner. Between these two extremes, there is a role for hybrid methods that use powerful data-driven techniques to fully characterize the data, but also use some a priori hypotheses to guide the analysis. Here we describe such a hybrid technique, HYBICA, which uses the initial characterization of the fMRI data from Independent Component Analysis and allows the experimenter to sequentially combine assumed task-related components so that one can gracefully navigate from a fully data-derived approach to a fully hypothesis-driven approach. We describe the results of testing the method with two artificial and two real data sets. A metric based on the diagnostic Predicted Sum of Squares statistic was used to select the best number of spatially independent components to combine and utilize in a standard regressional framework. The proposed metric provided an objective method to determine whether a more data-driven or a more hypothesis-driven approach was appropriate, depending on the degree of mismatch between the hypothesized reference function and the features in the data. HYBICA provides a robust way to combine the data-derived independent components into a data-derived activation waveform and suitable confounds so that standard statistical analysis can be performed.