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Background: The clinical staging model states that psychosis develops through subsequent stages of illness severity. To better understand what drives illness progression, more extensive comparison across clinical stages is needed. The current paper presents an in-depth characterization of individuals with different levels of risk for psychosis (i.e., different early clinical stages), using a multimethod approach of cross-sectional assessments and daily diary reports.Methods: Data came from the Mirorr study that includes N = 96 individuals, divided across four subgroups (n1 = 25, n2 = 27, n3 = 24, and n4 = 20). These subgroups, each with an increasing risk for psychosis, represent clinical stages 0-1b. Cross-sectional data and 90-day daily diary data on psychopathology, well-being, psychosocial functioning, risk and protective factors were statistically compared across subgroups (stages) and descriptively compared across domains and assessment methods.Results: Psychopathology increased across subgroups, although not always linearly and nuanced differences were seen between assessment methods. Well-being and functioning differed mostly between subgroup 1 and the other subgroups, suggesting differences between non-clinical and clinical populations. Risk and protective factors differed mostly between the two highest and lowest subgroups, especially regarding need of social support and coping, suggesting differences between those with and without substantial psychotic experiences. Subgroup 4 (stage 1b) reported especially high levels of daily positive and negative psychotic experiences.Conclusions: Risk for psychosis exists in larger contexts of mental health and factors of risk and protection that differ across stages and assessment methods. Taking a broad, multi-method approach is an important next step to understand the complex development of youth mental health problems.

Findings show virtual therapy (conducted using internet-based videoconferencing techniques) to be a viable alternative to in-person therapy for a variety of mental-health problems. COVID-19 social-distancing imperatives required us to substitute virtual interventions for in-person sessions routinely offered in our outpatient eating disorder (ED) program-and afforded us an opportunity to compare the two treatment formats for clinical efficacy.Using self-report assessments, we compared outcomes in a historical sample of 49 adults with heterogeneous EDs (treated in-person over 10-14 weeks in individual and group therapies) to those of 76 patients receiving comparable virtual treatments, at distance, during the COVID-19 outbreak. Linear mixed models were used to study symptom changes over time and to test for differential effects of treatment modality.Participants in both groups showed similar improvements on eating symptoms, levels of weight gain (in individuals in whom gain was indicated), and satisfaction with services.Our results suggest that short-term clinical outcomes with virtual and in-person ED therapies are comparable, and point to potentials of virtual therapy for situations in which geographical distance or other barriers impede physical access to trained therapists or specialized treatments.

Objective The relationship between eating disorders (EDs) and substance use (SU) has only been briefly described in literature using mainly adult populations. This study examined the prevalence and characteristics of SU among patients of an adolescent ED outpatient treatment program. Method A retrospective chart analysis was conducted to determine and subsequently compare medical status, psychosocial factors, treatment course and outcome between patients with and without SU. Results Over 60% of patients with SU status (n = 203) reported regularly consuming substances. 33.4% of substance users received a diagnosis involving purging behaviors compared to 5.9% of nonusers. Females composed 96.4% and 81.7% of users and nonusers, respectively. Users reported significantly more self-harm (57.7% of users vs. 38.6% of nonusers) but did not differ significantly in terms of trauma (abuse or victimization; 48.3% of users vs. 44.9% of nonusers). The percentage of ideal body weight significantly improved throughout treatment and did not differ by SU with a mean increase of 5.29% (SD = 13.6) among nonusers compared to 5.45% (SD = 7.5) of users. While users and nonusers did not differ before and after treatment in ED severity, users were more likely than nonusers to drop-out of treatment (41.5% of users vs. 25.2% of nonusers). Discussion Adolescents with SU benefit from ED outpatient treatment as much as those without SU, however, users are more likely to drop-out. Therefore, treatment should target these adolescents' emotional dysregulation to improve treatment compliance. Further research is necessary to determine the efficacy of such an approach.

The effects of changing hydrodynamic conditions and changing temperatures on polar organic chemical integrative sampler (POCIS) sampling rates (Rs ) were investigated for 12 crop protection chemicals. Exposure concentration was held constant in each laboratory experiment, and flow velocities were calculated from measured mass transfer coefficients of the water boundary layer near the surface of POCIS devices. At a given temperature Rs generally increased by a factor of 2 to 5 between a stagnant condition and higher flow velocities (6-21 cm/s), but Rs for most compounds was essentially constant between the higher flow velocities. When temperature was varied between 8 and 39 °C for a given flow condition, Rs increased linearly. In general, Rs increased by a factor of 2 to 4 and 2 to 8 over this temperature range under flow and stagnant conditions, respectively. An Arrhenius model was used to describe the dependence of POCIS sampling rates on temperature. Adjustments of Rs for temperature did not fully explain observed differences between time-weighted average concentrations of atrazine determined from POCIS and from composite water sampling in a field setting, suggesting that the effects of other competing factors still need to be evaluated. Environ Toxicol Chem 2018;37:2331-2339. © 2018 SETAC.

Eye movement desensitization and reprocessing (EMDR), a form of psychotherapy for individuals with post-traumatic stress disorder (PTSD), has long been a controversial topic, hampered in part by a lack of understanding of the neural mechanisms that contribute to its remedial effect. Here, we review current theories describing EMDR's potential neurobiological mechanisms of action involving working memory, interhemispheric communication, de-arousal, and memory reconsolidation. We then discuss recent studies describing the temporal and spatial aspects of smooth pursuit and predictive saccades, which resemble those made during EMDR, and their neural correlates within the default mode network (DMN) and cerebellum. We hypothesize that if the production of bilateral predictive eye movements is supportive of DMN and cerebellum activation, then therapies that shift the brain towards this state correspondingly would benefit the processes regulated by these structures (i.e., memory retrieval, relaxation, and associative learning), all of which are essential components for PTSD recovery. We propose that the timing of sensory stimulation may be relevant to treatment effect and could be adapted across different patients depending on their baseline saccade metrics. Empirical data in support of this model are reviewed and experimental predictions are discussed.

Background Idiopathic REM sleep behavior disorder is a prodromal stage of Parkinson's disease and dementia with Lewy bodies. Hyposmia, reduced dopamine transporter binding, and expression of the brain metabolic PD-related pattern were each associated with increased risk of conversion to PD. The objective of this study was to study the relationship between the PD-related pattern, dopamine transporter binding, and olfaction in idiopathic REM sleep behavior disorder. Methods In this cross-sectional study, 21 idiopathic REM sleep behavior disorder subjects underwent 18F-fluorodeoxyglucose PET, dopamine transporter imaging, and olfactory testing. For reference, we included 18F-fluorodeoxyglucose PET data of 19 controls, 20 PD patients, and 22 patients with dementia with Lewy bodies. PD-related pattern expression z-scores were computed from all PET scans. Results PD-related pattern expression was higher in idiopathic REM sleep behavior disorder subjects compared with controls (P = 0.048), but lower compared with PD (P = 0.001) and dementia with Lewy bodies (P

Introduction Case reports of life-threatening cardiac arrhythmias and sudden cardiac arrest (SCA) among amphetamine users have raised serious concerns about the cardiac safety of this class of drugs. This is important in light of the high prevalence of dexamphetamine (dAMPH) prescription for attention-deficit/hyperactivity disorder (ADHD), and its rising use as a recreational drug. The objective was to investigate electrocardiogram (ECG) parameters upon intravenous administration of a single dAMPH dose in habitual recreational dAMPH users (users) and healthy gender/age/IQ-matched controls (non-users). Methods and Results ECG recordings were made in 18 users and 18 non-users during administration of dAMPH (0.3 mg/kg body weight). Baseline ECG was normal in both groups. dAMPH elicited increased heart rate (HR) and QTc prolongation in both groups (all p

Mass transfer coefficients of the water boundary layer (kw) were measured using alabaster dissolution kinetics in a diffusion cell that was operated at stirring rates between 90 min−1 and 600 min−1, aiming to provide a more robust characterization of the effect of hydrodynamics on the uptake of polar compounds by passive samplers, as compared with characterizations in terms of stirring rates and water flow velocities. The measured kw helped to quantitatively understand calcium sulfate transport through a poly(ethersulfone) membrane and 2 water boundary layers (at both sides of the membrane). Alabaster-based kw value were used to understand atrazine transport in the diffusion cell, allowing the conclusion that atrazine transport in the membrane is via the pore space, rather than via the polymer matrix. The merits of measuring alabaster dissolution rates for passive sampler calibration and application in the field are discussed. The authors propose that passive sampler calibrations be carried out under controlled kw conditions, rather than under controlled stirring rates or flow velocities. This would facilitate the interpretation of passive sampler calibration studies and the translation of laboratory-based water sampling rates to flow conditions that apply in the field. Environ Toxicol Chem 2017;36:1517–1524. © 2016 SETAC

Background Several studies have shown that the in utero environment, which can be indexed by birth weight (BW), is associated with cortical morphology in adolescence and adulthood. Work in monozygotic (MZ) twins suggests that this association is driven by non-shared environmental factors. This correlation could be the result of in utero impacts on DNA methylation. The aim of the present study with MZ twins is to replicate the association between discordance in BW and brain morphology and test whether discordance in DNA methylation mediates this relationship. Methods One hundred and four adolescent MZ twins (52 pairs, of which 42% were male pairs) who have been followed regularly since birth underwent T1 weighted structural MRI, and epigenome-wide assessment of DNA methylation from saliva at age 15. Results Co-twins had very similar measures of DNA methylation and cortical morphology. Higher BW members of a twin pair had increased total cortical surface area, and decreased cortical thickness compared to their lower BW sibling. BW Discordance was positively associated with both cortical surface area and cortical volume discordance. Genes involved in neurodevelopment were tentatively identified as mediators of both the BW - cortical volume, and BW- cortical surface area relationships. Conclusions The association between BW and cortical morphology in adolescence appears to be attributable to in utero environmental effects, and DNA methylation may play a role in mediating this relationship. Hum Brain Mapp 38:2037-2050, 2017. © 2017 Wiley Periodicals, Inc.

Two laboratory performance studies with 21 and 11 participants were carried out for passive sampling of nonpolar chemicals in water, using silicone samplers that were deployed for 7 wk and 13 wk at 2 river sites in the Netherlands. Target analytes were polychlorinated biphenyls, polycyclic aromatic hydrocarbons (PAHs), polybrominated diphenyl ethers (PBDEs), hexachlorobutadiene, hexachlorobenzene, and a number of performance reference compounds (PRCs). Calculation of aqueous concentrations based on prescribed input values and a prescribed uptake model was also included. Between-laboratory coefficients of variation (CVs) in the analysis of target compounds were approximately 20% at concentrations of 100ngg-1 and approximately 100% at concentrations of 0.01ngg-1, which was similar to previous results for the analysis of biota samples. The analysis of PRCs yielded water sampling rates with a between-laboratory CV of 18% to 30%. The sampling rate model showed a nearly perfect match with the consensus values of retained PRCs. The implications of the present study for future interlaboratory exercises are discussed.

The purpose of this study was to assess whether there was an agreement between quantitative cerebral blood flow (CBF) and arterial cerebral blood volume (CBVA) measurements by [15O]H2O positron emission tomography (PET) and model-free QUASAR MRI. Twelve healthy subjects were scanned within a week in separate MRI and PET imaging sessions, after which quantitative and qualitative agreement between both modalities was assessed for gray matter, white matter and whole brain region of interests (ROI). The correlation between CBF measurements obtained with both modalities was moderate to high (r2: 0.28–0.60, P

Background Little is known about the underlying mechanisms of clinical symptoms in dementia with Lewy bodies. The aim of this study was to explore the association between loss of striatal dopamine transporter binding and symptoms in dementia with Lewy bodies. Methods Thirty-five patients with dementia with Lewy bodies underwent single-photon emission computerized tomography brain imaging with N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ([123I]FP-CIT). Associations between striatal binding ratios and motor (UPDRS), psychiatric (Neuropsychiatric Inventory; [NPI]), and cognitive (Mini–Mental State Examination [MMSE] and neuropsychological tests) symptoms were assessed by linear regression analysis. Results The explorative analysis showed that the motor UPDRS was negatively associated with putamen dopamine transporter binding, whereas no association with striatal dopamine transporter binding was found for total NPI, hallucinations, apathy, depression, anxiety, and MMSE scores. However, in post-hoc analysis, executive impairment was positively associated with dopamine transporter loss after adjustment of age and gender. Conclusions Dopamine deficiency in patients with dementia with Lewy bodies was associated with severity of motor symptoms, but did not correlate significantly with ratings of neurobehavioral disturbances or overall cognition. © 2015 International Parkinson and Movement Disorder Society

Conventional high-grade osteosarcoma is the most common primary bone sarcoma, with relatively high incidence in young people. In this study we found that expression of Aven correlates inversely with metastasis-free survival in osteosarcoma patients and is increased in metastases compared to primary tumours. Aven is an adaptor protein that has been implicated in anti-apoptotic signalling and serves as an oncoprotein in acute lymphoblastic leukaemia. In osteosarcoma cells, silencing Aven triggered G2 cell-cycle arrest; Chk1 protein levels were attenuated and ATR-Chk1 DNA damage response signalling in response to chemotherapy was abolished in Aven-depleted osteosarcoma cells, while ATM, Chk2 and p53 activation remained intact. Osteosarcoma is notoriously difficult to treat with standard chemotherapy, and we examined whether pharmacological inhibition of the Aven-controlled ATR-Chk1 response could sensitize osteosarcoma cells to genotoxic compounds. Indeed, pharmacological inhibitors targeting Chk1/Chk2 or those selective for Chk1 synergized with standard chemotherapy in 2D cultures. Likewise, in 3D extracellular matrix-embedded cultures, Chk1 inhibition led to effective sensitization to chemotherapy. Together, these findings implicate Aven in ATR-Chk1 signalling and point towards Chk1 inhibition as a strategy to sensitize human osteosarcomas to chemotherapy.

Objective Evidence associates anorexia nervosa (AN) with epigenetic alterations that could contribute to illness risk or entrenchment. We investigated the extent to which AN is associated with a distinct methylation profile compared to that seen in normal-eater women. Method Genome-wide methylation profiles, obtained using DNA from whole blood, were determined in 29 women currently ill with AN (10 with AN-restrictive type, 19 with AN-binge/purge type) and 15 normal-weight, normal-eater control women, using 450 K Illumina bead arrays. Results Regardless of type, AN patients showed higher and less-variable global methylation patterns than controls. False Discovery Rate corrected comparisons identified 14 probes that were hypermethylated in women with AN relative to levels obtained in normal-eater controls, representing genes thought to be associated with histone acetylation, RNA modification, cholesterol storage and lipid transport, and dopamine and glutamate signaling. Age of onset was significantly associated with differential methylation in gene pathways involved in development of the brain and spinal cord, while chronicity of illness was significantly linked to differential methylation in pathways involved with synaptogenesis, neurocognitive deficits, anxiety, altered social functioning, and bowel, kidney, liver and immune function. Discussion Although pre-existing differences cannot be ruled out, our findings are consistent with the idea of secondary alterations in methylation at genomic regions pertaining to social-emotional impairments and physical sequelae that are commonly seen in AN patients. Further investigation is needed to establish the clinical relevance of the affected genes in AN, and, importantly, reversibility of effects observed with nutritional rehabilitation and treatment. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2015; 48:874–882)

Objectives To compare the effective radiation dose (ERD) needed to obtain information on coronary anatomy and physiology by a non-invasive versus an invasive diagnostic strategy. Background Knowledge of anatomy and physiology is needed for management of patients with coronary artery disease (CAD). There is, however, a growing concern about detrimental long-term effects of radiation associated with diagnostic procedures. Methods In a total of 671 patients with suspected CAD, we compared the ERD needed to obtain anatomical and physiological information through a non-invasive strategy or an invasive strategy. The non-invasive strategy consisted of coronary computed tomography angiography (CCTA) and single photon emission computed tomography (SPECT). The invasive strategy included coronary angiography (CA) and fractional flow reserve (FFR) measurement. In 464 patients, the data were acquired in Period 2009 and in 207 the data were acquired in Period 2011 (after each period, the CCTA- and the CA-equipment had been upgraded). Results For the Period 2009 total ERD of the non-invasive approach was significantly larger compared to the invasive approach (28.45 ± 5.37 mSv versus 15.79 ± 7.95 mSv, respectively; P