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Autistic youth frequently experience interfering anxiety, and schools may be an ideal setting to deliver mental health care. A type 1 hybrid-effectiveness, cluster randomized trial was used to examine the effectiveness of school-based Facing Your Fears compared to usual care. Change in provider cognitive behavior therapy knowledge and treatment fidelity (adherence and provider competence) were also examined. Seventy-seven interdisciplinary school providers across 25 elementary/middle schools were trained via a train-the-trainer approach. Eighty-one students, ages 8-14 years, with autism or suspected autism and anxiety participated. Students who received school-based Facing Your Fears displayed significantly greater reductions in anxiety compared to students in usual care according to caregiver and child report (Screen for Anxiety and Related Emotional Disorders). Significant reductions in total anxiety (p = 0.012), separation (p = 0.002), and social anxiety (p = 0.003) subscales occurred, according to parent report. Student self-report indicated significant reductions on the social anxiety subscales (p = 0.001). Interdisciplinary school providers demonstrated significantly increased cognitive behavior therapy knowledge following training (p < 0.001). Mean adherence and competence ratings were strong. The positive effectiveness and implementation outcomes are encouraging. Training interdisciplinary school providers to deliver school-based Facing Your Fears has the potential to increase access to care for anxious autistic students. Future directions and limitations are discussed.

: Background The effects of xenon on regional cerebral blood flow (rCBF) are controversial. Moreover, the precise sites of action at which xenon exerts its effects in the human brain remain to be established. : Methods rCBF was sequentially assessed by H215O positron emission tomography in six volunteers. rCBF was determined at baseline and during general anaesthesia induced with propofol and maintained with one minimum alveolar concentration xenon. rCBF measurements were started after the calculated plasma concentration of propofol had decreased to subanaesthetic levels (<1.0 µg ml−1). Changes in rCBF were calculated for 13 cerebral volumes of interest by measurement of a semi-quantitative perfusion index (PI). In addition, voxel-wise changes in rCBF were analysed using statistical parametric mapping. : Results Xenon had only minor effects on PI in grey matter volumes of interest. In contrast, PI was increased in white matter [from 1.01 (0.11) to 1.24 (0.15) kcnt ml−1 MBq−1, P=0.05, mean (sd)]. Voxel-based analysis showed an increase of rCBF in white matter and a relative decrease of rCBF during xenon anaesthesia in distinct grey matter regions, particularly the orbito- and mesiofrontal cortex, cingulate gyrus, thalamus, hippocampus and bilateral cerebellum (P<0.05 corrected). When correlating PI with cerebral metabolic rate of glucose (previously obtained in another group of six volunteers using 18F-fluorodeoxyglucose as tracer), the flow–metabolism coupling was preserved during xenon anaesthesia. : Conclusions Xenon exerted distinct regional effects on CBF: relative decreases in several cortical, subcortical, and cerebellar areas were accompanied by an increase in white matter. Flow–metabolism coupling was not impaired during xenon anaesthesia. [ABSTRACT FROM AUTHOR]

Radiotracers incorporating the urea-based Glu-NH-C(O)-NH-Lys group have gained prominence due to their role in targeting prostate-specific membrane antigen (PSMA)-a clinical biomarker of prostate cancer. Here, the synthesis, radiolabeling, and in vitro and in vivo characterization of two 68 Ga-radiolabeled Glu-NH-C(O)-NH-Lys radiotracers conjugated to the desferrioxamine B (DFO) chelate were evaluated. Two linker groups based on amide bond and thiourea coupling chemistries were employed to develop 68 Ga-DFO-Nsucc-PSMA ( 68 Ga-4) and 68 Ga-DFO- pNCS-Bn-PSMA ( 68 Ga-7), respectively. Radiosynthesis proceeded quantitatively at room temperature with high radiochemical yields, chemical/radiochemical purities, and specific activities. Pharmacokinetic profiles of 68 Ga-4 and 68 Ga-7 were assessed using positron-emission tomography (PET) in mice bearing subcutaneous LNCaP tumors. Data were compared to the current clinical benchmark radiotracer 68 Ga-HBED-CC-PSMA ( 68 Ga-1) (HBED = N,N'-Bis(2-hydroxy-5-(ethylene-beta-carboxy)benzyl)ethylenediamine N,N'-diacetic acid). Results indicated that the target binding affinity, protein association, blood pool and background organ clearance properties, and uptake in PSMA-positive lesions are strongly dependent on the nature of the chelate, the linker, and the spacer groups. Protein dissociation constants ( K d values) were found to be predictive of pharmacokinetics in vivo. Compared to 68 Ga-1, 68 Ga-4 and 68 Ga-7 resulted in decreased tumor uptake but enhanced blood pool clearance and reduced residence time in the kidney. The study highlights the importance of maximizing protein binding affinity during radiotracer optimization.