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Face-processing timing differences may underlie visual social attention differences between autistic and non-autistic people, and males and females. This study investigates the timing of the effects of neurotype and sex on face-processing, and their dependence on age. We analysed EEG data during upright and inverted photographs of faces from 492 participants from the Longitudinal European Autism Project (141 neurotypical males, 76 neurotypical females, 202 autistic males, 73 autistic females; age 6–30 years). We detected timings of sex/diagnosis effects on event-related potential amplitudes at the posterior–temporal channel P8 with Bootstrapped Cluster-based Permutation Analysis and conducted Growth Curve Analysis (GCA) to investigate the timecourse and dependence on age of neural signals. The periods of influence of neurotype and sex overlapped but differed in onset (respectively, 260 and 310 ms post-stimulus), with sex effects lasting longer. GCA revealed a smaller and later amplitude peak in autistic female children compared to non-autistic female children; this difference decreased in adolescence and was not significant in adulthood. No age-dependent neurotype difference was significant in males. These findings indicate that sex and neurotype influence longer latency face processing and implicates cognitive rather than perceptual processing. Sex may have more overarching effects than neurotype on configural face processing. [ABSTRACT FROM AUTHOR]

Identifying factors linked to autism traits in the general population may improve our understanding of the mechanisms underlying divergent neurodevelopment. In this study we assess whether factors increasing the likelihood of childhood autism are related to early autistic trait emergence, or if other exposures are more important. We used data from 536 toddlers from London (UK), collected at birth (gestational age at birth, sex, maternal body mass index, age, parental education, parental language, parental history of neurodevelopmental conditions) and at 18 months (parents cohabiting, measures of socio-economic deprivation, measures of maternal parenting style, and a measure of maternal depression). Autism traits were assessed using the Quantitative Checklist for Autism in Toddlers (Q-CHAT) at 18 months. A multivariable model explained 20% of Q-CHAT variance, with four individually significant variables (two measures of parenting style and two measures of socio-economic deprivation). In order to address variable collinearity we used principal component analysis, finding that a component which was positively correlated with Q-CHAT was also correlated to measures of parenting style and socio-economic deprivation. Our results show that parenting style and socio-economic deprivation correlate with the emergence of autism traits at age 18 months as measured with the Q-CHAT in a community sample. [ABSTRACT FROM AUTHOR]

Background: Prostate-Specific Membrane Antigen (PSMA) PET/CT and multiparametric MRI (mpMRI) are well-established modalities for identifying intra-prostatic lesions (IPLs) in localised prostate cancer. This study aimed to investigate the use of PSMA PET/CT and mpMRI for biologically targeted radiation therapy treatment planning by: (1) analysing the relationship between imaging parameters at a voxel-wise level and (2) assessing the performance of radiomic-based machine learning models to predict tumour location and grade. Methods: PSMA PET/CT and mpMRI data from 19 prostate cancer patients were co-registered with whole-mount histopathology using an established registration framework. Apparent Diffusion Coefficient (ADC) maps were computed from DWI and semi-quantitative and quantitative parameters from DCE MRI. Voxel-wise correlation analysis was conducted between mpMRI parameters and PET Standardised Uptake Value (SUV) for all tumour voxels. Classification models were built using radiomic and clinical features to predict IPLs at a voxel level and then classified further into high-grade or low-grade voxels. Results: Perfusion parameters from DCE MRI were more highly correlated with PET SUV than ADC or T2w. IPLs were best detected with a Random Forest Classifier using radiomic features from PET and mpMRI rather than either modality alone (sensitivity, specificity and area under the curve of 0.842, 0.804 and 0.890, respectively). The tumour grading model had an overall accuracy ranging from 0.671 to 0.992. Conclusions: Machine learning classifiers using radiomic features from PSMA PET and mpMRI show promise for predicting IPLs and differentiating between high-grade and low-grade disease, which could be used to inform biologically targeted radiation therapy planning. [ABSTRACT FROM AUTHOR]

The ratio of T1-weighted/T2-weighted magnetic resonance images (T1w/T2w MRI) has been successfully applied at the cortical level since 2011 and is now one of the most used myelin mapping methods. However, no reports have explored the histological validity of T1w/T2w myelin mapping in white matter. Here we compare T1w/T2w with ex vivo postmortem histology and in vivo MRI methods, namely quantitative susceptibility mapping (QSM) and multi-echo T2 myelin water fraction (MWF) mapping techniques. We report a discrepancy between T1w/T2w myelin maps of the human corpus callosum and the histology and analyse the putative causes behind such discrepancy. T1w/T2w does not positively correlate with Luxol Fast Blue (LFB)-Optical Density but shows a weak to moderate, yet significant, negative correlation. On the contrary, MWF is strongly and positively correlated with LFB, whereas T1w/T2w and MWF maps are weakly negatively correlated. The discrepancy between T1w/T2w MRI maps, MWF and histological myelin maps suggests caution in using T1w/T2w as a white matter mapping method at the callosal level. While T1w/T2w imaging may correlate with myelin content at the cortical level, it is not a specific method to map myelin density in white matter. [ABSTRACT FROM AUTHOR]

Purpose: Albinism defines a group of genetic diseases which result from disordered melanin biosynthesis. Proliferative diabetic retinopathy (PDR) results from poorly controlled type 1 or 2 diabetes mellitus (DM) and can lead to blindness due to progressive neovascularisation. However, the treatment of PDR in patients with ocular/oculocutaneous albinism may be more challenging. In this study, we compared a group of patients with albinism and PDR, to a group with albinism and diabetes mellitus but no PDR, to examine the long-term implications. Methods: Retrospective observational study included all patients with ocular albinism (OA) or oculocutaneous albinism (OCA) and DM who presented at a single specialist centre. Participants were allocated into either group 1 (eyes with PDR) or group 2 (all eyes without PDR). Statistical analysis was performed using SPSS V26.0. Between-group differences were investigated. Results: Outcome data was available for 5 eyes from 3 participants in group 1 and 26 eyes from 13 participants in group 2. Despite interventions, a large and significant difference in vision at follow-up was observed between group 1 and group 2 (mean change in visual acuity: 1.11 (± 1.00) versus − 0.15 (± 0.46), respectively; p = < 0.0001). Conclusion: PDR is associated with poor long-term prognosis despite interventions for patients with albinism. Those without PDR appear to maintain stable vision. Alternative treatments for PDR and its complications may be required in this population. Measures to prevent the development of diabetic eye disease and progression towards PDR should be employed at an early stage. [ABSTRACT FROM AUTHOR]

Globally, 43 million people are living with HIV, 90% in developing countries. Increasing life expectancy with combination antiretroviral therapy (cART) results in chronic complications, including HIV-associated neurocognitive disorders (HAND) and eye diseases. HAND screening is currently challenging. Our aim was to evaluate clinical utility of retinopathy as a screening measure of HAND in older cART-treated individuals in Tanzania and feasibility of smartphone-based retinal screening in this low-resource setting. A cross-sectional systematic sample aged ≥ 50-years attending routine HIV follow-up in Tanzania were comprehensively assessed for HAND by American Academy of Neurology criteria and received ophthalmic assessment including smartphone-based retinal imaging. HAND and ophthalmic assessments were independent and blinded. Diagnostic accuracy was evaluated by AUROC curves. Of 129 individuals assessed, 69.8% were visually impaired. Thirteen had retinopathy. HAND prevalence was 66.7%. Retinopathy was significantly associated with HAND but HIV-disease factors (CD4, viral load) were not. Diagnostic accuracy of retinopathy for HAND was poor (AUROC 0.545-0.617) but specificity and positive predictive value were high. We conclude that ocular pathology and HAND appear highly prevalent in this low-resource setting. Although retinal screening cannot be used alone identify HAND, prioritization of individuals with abnormal retinal screening is a potential strategy in low-resource settings. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate outcomes for men with biochemically recurrent prostate cancer who were selected for transponder-guided salvage radiotherapy (SRT) to the prostate bed alone by 68Ga-labelled prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-PET). Methods: This is a single-arm, prospective study of men with a prostate-specific antigen (PSA) level rising to 0.1–2.5 ng/mL following radical prostatectomy. Patients were staged with 68Ga-PSMA-PET and those with a negative finding, or a positive finding localised to the prostate bed, continued to SRT only to the prostate bed alone with real-time target-tracking using electromagnetic transponders. The primary endpoint was freedom from biochemical relapse (FFBR, PSA > 0.2 ng/mL from the post-radiotherapy nadir). Secondary endpoints were time to biochemical relapse, toxicity and patient-reported quality of life (QoL). Results: Ninety-two patients (median PSA of 0.18 ng/ml, IQR 0.12–0.36), were screened with 68Ga-PSMA-PET and metastatic disease was found in 20 (21.7%) patients. Sixty-nine of 72 non-metastatic patients elected to proceed with SRT. At the interim (3-year) analysis, 32 (46.4%) patients (95% CI 34.3–58.8%) were FFBR. The median time to biochemical relapse was 16.1 months. The rate of FFBR was 82.4% for ISUP grade-group 2 patients. Rates of grade 2 or higher gastrointestinal and genitourinary toxicity were 0% and 15.2%, respectively. General health and disease-specific QoL remained stable. Conclusion: Pre-SRT 68Ga-PSMA-PET scans detect metastatic disease in a proportion of patients at low PSA levels but fail to improve FFBR. Transponder-guided SRT to the prostate bed alone is associated with a favourable toxicity profile and preserved QoL. Trial registration number: ACTRN12615001183572, 03/11/2015, retrospectively registered. [ABSTRACT FROM AUTHOR]

Anorexia nervosa (AN) is associated with difficulties in social and emotional functioning. A significant proportion of individuals with AN show autistic traits, which may influence social attention. This study examined attention to faces and facial features in AN, recovered AN (REC), and healthy controls, as well as relationships with comorbid psychopathology. One hundred and forty-eight participants' eye movements were tracked while watching a naturalistic social scene. Anxiety, depression, alexithymia, and autistic traits were assessed via self-report questionnaires. Participants with AN spent significantly less time looking at faces compared to REC and controls; patterns of attention to individual facial features did not differ across groups. Autistic traits mediated the relationship between group and time spent looking at faces. [ABSTRACT FROM AUTHOR]

Postnatal depression (PND) has an estimated prevalence of 6.5 to 12.9%. In addition to the direct consequences for women, PND also interferes with the maternal-infant interaction, contributing to long-term cognitive and emotional impairments in exposed offspring. It is unclear how PND differs from major depressive disorder (MDD) more generally, and if PND represents a distinct subtype of depression. We explored whether women with a history of PND have specific differences in brain activation associated with sex hormone changes during the late luteal phase of the menstrual cycle, compared to parous women with either a past history of MDD outside of the postnatal period, or an absent history of MDD ('never depressed'). Thirty mothers (history of PND (n = 10), history of MDD (n = 10), and 'never depressed' (n = 10)) underwent blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) acquisition during an emotional faces task. Amygdala activity was analysed using a region of interest (small volume correction) approach. There was a significant reduction in BOLD response to positive emotional faces in the right amygdala in women with a history of PND compared to women with a history of MDD. A similar but non-significant trend was found in the left amygdala in women with a history of PND compared to 'never depressed' women. Our findings support the hypothesis that women with vulnerability to PND represent a distinct subgroup of women with a differential sensitivity to changes in sex hormones. Further, albeit highly tentative, they provide a putative biomarker that could assist in detection of women at-risk to PND. [ABSTRACT FROM AUTHOR]

Purpose: We analysed quantitative biomarkers derived from both baseline whole-body imaging and blood serum to identify prognostic markers in patients treated within the lutetium-177 prostate-specific membrane antigen (LuPSMA) phase 2 trial. Methods: PET image analysis was carried out using whole-body segmentation quantifying molecular tumour volume (SUV > 3 threshold for PSMA, SUV > liver+2sd for fluorodeoxyglucose (FDG) including SUVmax and SUVmean. For baseline bone scans, EXINI bone scan index (BSI) was used to calculate the percentage of involved bone. Baseline alkaline phosphatase (ALP), lactate dehydrogenase (LDH), prostate specific antigen (PSA) and PSA doubling time were also used in this analysis. We used univariate cox regression analysis and log-rank comparison with optimised cut-offs to find suitable biomarkers prognostic of overall survival from time of enrolment. Results: This analysis identified FDG-positive tumour volume (FDGvol; HR 2.6; 95% CI, 1.4–4.8), mean intensity of PSMA-avid tumour uptake (PSMAmean; HR 0.89; 95% CI, 0.8–0.98), bone scan index (BSI; HR 2.3; 95% CI, 1.2–4.4), ALP (HR 1.1; 95% CI, 1–1.2) and LDH (HR 1.2; 95% CI, 1–1.5) as biomarkers prognostic of overall survival. Conclusions: In addition to established biomarkers, both FDG and PSMA PET/CT parameters have prognostic significance for survival in men undergoing LuPSMA therapy. [ABSTRACT FROM AUTHOR]

Neurodevelopmental disorders have a heritable component and are associated with region specific alterations in brain anatomy. However, it is unclear how genetic risks for neurodevelopmental disorders are translated into spatially patterned brain vulnerabilities. Here, we integrated cortical neuroimaging data from patients with neurodevelopmental disorders caused by genomic copy number variations (CNVs) and gene expression data from healthy subjects. For each of the six investigated disorders, we show that spatial patterns of cortical anatomy changes in youth are correlated with cortical spatial expression of CNV genes in neurotypical adults. By transforming normative bulk-tissue cortical expression data into cell-type expression maps, we link anatomical change maps in each analysed disorder to specific cell classes as well as the CNV-region genes they express. Our findings reveal organizing principles that regulate the mapping of genetic risks onto regional brain changes in neurogenetic disorders. Our findings will enable screening for candidate molecular mechanisms from readily available neuroimaging data. How neurodevelopmental disorder-associated risk genes are translated into spatially patterned brain vulnerabilities is unclear. Here, the authors show that disorder-specific patterns of neuroanatomical changes are aligned to brain expression maps of disease risk genes in healthy subjects. [ABSTRACT FROM AUTHOR]

Background: Extensive multi-visceral resection, including components of the urinary tract, is often required to achieve clear resection margins, which is now well established as a key predictor of long-term survival for locally advanced pelvic tumours. The aims of this study were to analyse major morbidity and factors predicting complications and long-term outcomes following a urological procedure within extended radical resections. Methods: Data were collected from prospective databases at two high-volume institutions specialising in extended radical resections for locally advanced and recurrent pelvic malignancies between 1990 and 2015. The primary endpoints were general major complications (Clavien–Dindo ≥ 3) and factors influencing complications and overall survival after urological resection. Results: A total of 646 consecutive patients requiring an extended radical resection for locally advanced or recurrent pelvic malignancies were identified. The median age was 63 years (range 19–89 years) and the majority were female (371; 57.4%). A urological resection was performed as part of the resection in 226 patients (35.0%). The overall 30-day major complication rate was significantly higher in the urological intervention group (23%; n = 52) compared to the non-urological group (12.9%; n = 54 patients; p = 0.001). Intestinal anastomotic leak (p = 0.001) and intra-abdominal collections (p = 0.001) were more common in the urological cohort. Ileal conduit formation was an independent predictor of major morbidity (OR 1.95; 95% CI 1.24–3.07; p = 0.004). Independent prognostic markers for poor 5-year survival following urological procedures were recurrent tumour, cardiovascular disease, previous thromboembolic event and postoperative pulmonary embolism. Conclusions: Extended radical resections which include a urological resection are associated with significantly more major morbidity than those without urological resection. Ileal conduit formation is independently associated with the development of major morbidity. Five-year overall survival is no different for patients who had or did not have urological resection as part of extended radical surgery for locally advanced or recurrent pelvic malignancy. [ABSTRACT FROM AUTHOR]

This study used the Camberwell Assessment of Need for adults with Developmental and Intellectual Disabilities (CANDID) to examine the social, physical health and mental health needs of 168 young people (aged 14-24 years) with neurodevelopmental disorders and compared young person and parent ratings of need. Agreement was poor in 21 out of 25 domains. Parents consistently reported higher levels of need than young people in the majority of domains although young people with ADHD reported significantly more needs in physical health, eyesight/hearing, seizures, other mental health problems and safety of others than their parents. Both parent and young person perspectives of needs are necessary to ensure that needs that are predictive of current or future poor outcomes are not missed. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate (1) the time interval between a decision to commence on active surveillance (AS) and grade progression in community practice; (2) factors predicting grade progression in localised prostate cancer (CaP) patients apparently undergoing AS. Methods: Data from the Prostate Cancer Outcomes Registry-Victoria were used to analyze men with Gleason 3 + 3 CaP or less who had at least one repeat biopsy. Unadjusted and adjusted 5-year Kaplan-Meier survival curves were used to assess the time to grade progression. Both univariate and multivariate analyses for grade progression were performed using Cox proportional hazards. Results: The cohort included 951 men. Overall, 39% of men had Gleason grade reclassified to a higher risk disease state with median of 2.2 years [IQR 1.2-3.7 years]. Men who harboured cT2 disease were 30% more likely to have upgrading compared to men with cT1 disease (adjusted HR: 1.3, 95% CI 1.0-1.6, p = 0.048). Half of the men with cT2 in our cohort had their Gleason grade reclassified within 1.6 years from diagnosis as compared with 2.7 years for the cT1 group. The presence of percentage of core involvement >25.0% and a PSA velocity of >1.01 ng/mL/year remained significant for a higher progression rate. The adjusted HR: 1.6; 95% CI [1.2-2.3], p = 0.004; adjusted HR: 1.6, 95% CI [1.2-2.4], p = 0.021, for percent of core involvement of 25.1-37.5%, and ≥37.6%, respectively. The adjusted HRs and p value associated with PSA velocity were 1.5; 95% CI [1.1-2.1], p = 0.016 and 1.6; 95% CI [1.2-2.3], p = 0.003 for PSA velocity values of 1.01-2 ng/mL per year and >2 ng/mL per year, respectively. Men who were diagnosed in regional hospital and subsequently had biopsy in metropolitan hospital were twice at risk of having Gleason upgrade compared to those whom both diagnostic and surveillance biopsies were carried out in metropolitan hospitals (adjusted HR: 1.9; 95% CI 1.1-3.3, p = 0.029). Conclusions: When placing men on AS and considering time to histologic progression, clinicians should pay particular attention to the likely accuracy of the diagnostic specimen, their tumour stage, volume of tumour (percent of core involvement), and rising PSA. Those diagnosed with T2 disease and had >25.0% of core involvement, and a PSA velocity greater than 1 ng/mL per year is at particular risk for more rapid disease progression and, for this reason, should be counselled on the importance of following the recommended surveillance regimen. For half of these men, their disease will have 'progressed' according to biopsy results in 2 years. [ABSTRACT FROM AUTHOR]

It is generally agreed that the human brain is responsive to environmental influences, and that the male brain may be particularly sensitive to early adversity. However, this is largely based on retrospective studies of older children and adolescents exposed to extreme environments in childhood. Less is understood about how normative variations in parent-child interactions are associated with the development of the infant brain in typical settings. To address this, we used magnetic resonance imaging to investigate the relationship between observational measures of mother-infant interactions and regional brain volumes in a community sample of 3- to 6-month-old infants ( N = 39). In addition, we examined whether this relationship differed in male and female infants. We found that lower maternal sensitivity was correlated with smaller subcortical grey matter volumes in the whole sample, and that this was similar in both sexes. However, male infants who showed greater levels of positive communication and engagement during early interactions had smaller cerebellar volumes. These preliminary findings suggest that variations in mother-infant interaction dimensions are associated with differences in infant brain development. Although the study is cross-sectional and causation cannot be inferred, the findings reveal a dynamic interaction between brain and environment that may be important when considering interventions to optimize infant outcomes. [ABSTRACT FROM AUTHOR]

The performance of a support vector machine (SVM) algorithm was investigated to predict prostate tumour location using multi-parametric MRI (mpMRI) data. The purpose was to obtain information of prostate tumour location for the implementation of bio-focused radiotherapy. In vivo mpMRI data were collected from 16 patients prior to radical prostatectomy. Sequences included T2-weighted imaging, diffusion-weighted imaging and dynamic contrast enhanced imaging. In vivo mpMRI was registered with 'ground truth' histology, using ex vivo MRI as an intermediate registration step to improve accuracy. Prostate contours were delineated by a radiation oncologist and tumours were annotated on histology by a pathologist. Five patients with minimal imaging artefacts were selected for this study. A Gaussian kernel SVM was trained and tested on different patient data subsets. Parameters were optimised using leave-oneout cross validation. Signal intensities of mpMRI were used as features and histology annotations as true labels. Prediction accuracy, as well as area under the curve (AUC) of the receiver operating characteristics (ROC) curve, were used to assess performance. Results demonstrated the prediction accuracy ranged from 70.4 to 87.1% and AUC of ROC ranged from 0.81 to 0.94. Additional investigations showed the apparent diffusion coefficient map from diffusion weighted imaging was the most important imaging modality for predicting tumour location. Future work will incorporate additional patient data into the framework to increase the sensitivity and specificity of the model, and will be extended to incorporate predictions of biological characteristics of the tumour which will be used in bio-focused radiotherapy optimisation. [ABSTRACT FROM AUTHOR]

Colophon is an understudied, rare and endangered stag beetle genus with all species endemic to isolated mountain peaks in South Africa's Western Cape. Geometric morphometrics was used to analyse intersexual and interspecific variation of size and shape in the mandibles, heads, pronota and elytra of two sympatric species: Colophon haughtoni and Colophon kawaii. All measured structures showed significant sexual dimorphism, which may result from male-male competition for females. Female mandibles were too small and featureless for analysis, but male Colophon beetles possess large, ornate mandibles for fighting. Males had significantly larger heads and pronota that demonstrated shape changes which may relate to resource diversion to the mandibles and their supporting structures. Females are indistinguishable across species, but males were accurately identified using mandibles, heads and pronota. Male C. kawaii were significantly larger than C. haughtoni for all structures. These results support the species status of C. kawaii, which is currently in doubt due to its hybridisation with C. haughtoni. We also demonstrate the value of geometric morphometrics as a tool which may aid Colophon conservation by providing biological and phylogenetic insights and enabling species identification. [ABSTRACT FROM AUTHOR]

Social media (SoMe) have become an integral part in many aspects of personal and professional life. With current uptake rates of 50-70 % among urologists, SoMe platforms merit huge potential for dissemination of information and professional exchange among stakeholders in urology. Application of SoMe includes conference conversations via tweet chats, health education via YouTube videos, and Twitter online journal clubs. In addition, a number of urology journals have embraced SoMe to allow rapid dissemination of their content and engagement with their readers. Guidance for the appropriate use of SoMe is provided to urologists by several organizations. Besides urology, other disciplines have adopted SoMe for a variety of areas: continuing professional development, awareness of rare diseases, recruitment of study participants, patient education and support, and publicizing research. Openness to new approaches is the basic prerequisite for a transfer of successful concepts embraced by other specialties, to the field of urology. [ABSTRACT FROM AUTHOR]

Children with conduct disorder (CD) are at increased risk of developing antisocial personality disorder and psychopathy in adulthood. Neuroimaging research has identified abnormal cortical volume (CV) in CD. However, CV comprises two genetically and developmentally separable components: cortical thickness (CT) and surface area (SA). Aim of this study is to explore the relationship between the cortical constituents of CV in boys with CD. We applied FreeSurfer software to structural MRI data to derive measures of CV, CT, and SA in 21 boys with CD and 19 controls. Relationships between these cortical measures were investigated. Boys with CD had significantly reduced CV and SA compared to non-CD boys in ventromedial and dorsolateral prefrontal cortex. We found no significant between-group differences in CT. Reduced prefrontal CV in boys with CD is associated with significantly reduced SA in the same regions. This finding may help to identify specific neurodevelopmental mechanisms underlying cortical deficits observed in CD. [ABSTRACT FROM AUTHOR]

The United Nations and World Health Organisation have identified autism spectrum disorder (ASD) as an important public health issue across global mental health services. Although a range of tools exist to identify and quantify ASD symptoms, there is a lack of information about which ASD measures are used in different services worldwide. This paper presents data from a large survey of measures used for patient characterisation in major ASD research and clinical centres across Europe collected between June 2013 and January 2014. The objective was to map the use of different instruments used to characterise ASD, comorbid psychopathology and cognitive and adaptive ability for patient diagnostic and characterisation purposes across Europe. Sixty-six clinical research sites diagnosing 14,844 patients per year contributed data. The majority of sites use the well-established Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview (ADI) instruments, though the proportion of sites in Western Europe using the ADI was almost double the rate in Eastern Europe. Approximately half the sites also used the Social Communication Questionnaire (SCQ) and Social Responsiveness Scale (SRS), although use of the SRS was over three times higher in Western Europe compared with Eastern Europe. The use of free/open access measures was lower than commercially available tools across all regions. There are clinical and scientific benefits in encouraging further convergence of clinical characterisation measures across ASD research and clinical centres in Europe to facilitate large-scale data sharing and collaboration, including clinical trials of novel medications and psychological interventions. [ABSTRACT FROM AUTHOR]

Rationale: Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are often comorbid and have both performance and brain dysfunctions during motor response inhibition. Serotonin agonists modulate motor response inhibition and have shown positive behavioural effects in both disorders. Aims: We therefore used functional magnetic resonance imaging (fMRI) to investigate the so far unknown shared and disorder-specific inhibitory brain dysfunctions in these two disorders, as well as the effects of a single dose of the selective serotonin reuptake inhibitor fluoxetine. Methods: Age-matched boys with ADHD (18), ASD (19) and healthy controls (25) were compared with fMRI during a stop task measuring motor inhibition. Patients were scanned twice, under either an acute dose of fluoxetine or placebo in a double-blind, placebo-controlled randomised design. Repeated measures analyses within patients assessed drug effects. To test for potential normalisation effects of brain dysfunctions, patients under each drug condition were compared to controls. Results: Under placebo, relative to controls, ASD boys showed overactivation in left and right inferior frontal cortex (IFC), while ADHD boys showed disorder-specific underactivation in orbitofrontal cortex (OFC) and basal ganglia. Under fluoxetine, the prefrontal dysfunctions were no longer observed, due to inverse effects of fluoxetine on these activations: fluoxetine downregulated IFC and OFC activation in ASD but upregulated them in ADHD. Conclusions: The findings show that fluoxetine normalises frontal lobe dysfunctions in both disorders via inverse effects, downregulating abnormally increased frontal activation in ASD and upregulating abnormally decreased frontal activation in ADHD, potentially reflecting inverse baseline serotonin levels in both disorders. [ABSTRACT FROM AUTHOR]

Background 22q11.2 deletion syndrome (22q11DS, velo-cardio-facial syndrome [VCFS]) is a genetic disorder associated with interstitial deletions of chromosome 22q11.2. In addition to high rates of neuropsychiatric disorders, children with 22q11DS have impairments of face processing, as well as IQ-independent deficits in visuoperceptual function and social and abstract reasoning. These face-processing deficits may contribute to the social impairments of 22q11DS. However, their neurobiological basis is poorly understood. Methods We used event-related functional magnetic resonance imaging (fMRI) to examine neural responses when children with 22q11DS (aged 9-17 years) and healthy controls (aged 8-17 years) incidentally processed neutral expressions and mild (50%) and intense (100%) expressions of fear and disgust. We included 28 right-handed children and adolescents: 14 with 22q11DS and 14 healthy (including nine siblings) controls. Results Within groups, contrasts showed that individuals significantly activated 'face responsive' areas when viewing neutral faces, including fusiform-extrastriate cortices. Further, within both groups, there was a significant positive linear trend in activation of fusiform-extrastriate cortices and cerebellum to increasing intensities of fear. There were, however, also between group differences. Children with 22q11DS generally showed reduced activity as compared to controls in brain regions involved in social cognition and emotion processing across emotion types and intensities, including fusiform-extrastriate cortices, anterior cingulate cortex (Brodmann area (BA) 24/32), and superomedial prefrontal cortices (BA 6). Also, an exploratory correlation analysis showed that within 22q11DS children reduced activation was associated with behavioural impairment--social difficulties (measured using the Total Difficulties Score from the Strengths and Difficulties Questionnaire [SDQ]) were significantly negatively correlated with brain activity during fear and disgust processing (respectively) in the left precentral gyrus (BA 4) and in the left fusiform gyrus (FG, BA 19), right lingual gyrus (BA 18), and bilateral cerebellum. Conclusions Regions involved in face processing, including fusiform-extrastriate cortices, anterior cingulate gyri, and superomedial prefrontal cortices (BA 6), are activated by facial expressions of fearful, disgusted, and neutral expressions in children with 22q11DS but generally to a lesser degree than in controls. Hypoactivation in these regions may partly explain the social impairments of children with 22q11DS. [ABSTRACT FROM AUTHOR]

Background Down syndrome (DS), or trisomy 21, is one of the most common autosomal mutations. People with DS have intellectual disability (ID) and are at significantly increased risk of developing Alzheimer's disease (AD). The biological associates of both ID and AD in DS are poorly understood, but glutamate has been proposed to play a key role. In non-DS populations, glutamate is essential to learning and memory and glutamate-mediated excitotoxicity has been implicated in AD. However, the concentration of hippocampal glutamate in DS individuals with and without dementia has not previously been directly investigated. Proton magnetic resonance spectroscopy (1H MRS) can be used to measure in vivo the concentrations of glutamate-glutamine (Glx). The objective of the current study was to examine the hippocampal Glx concentration in non-demented DS (DS-) and demented DS (DS+) individuals. Methods We examined 46 adults with DS (35 without dementia and 11 with dementia) and 39 healthy controls (HC) using 1H MRS and measured their hippocampal Glx concentrations. Results There was no significant difference in the hippocampal Glx concentration between DS+ and DS-, or between either of the DS groups and the healthy controls. Also, within DS, there was no significant correlation between hippocampal Glx concentration and measures of overall cognitive ability. Last, a sample size calculation based on the effect sizes from this study showed that it would have required 6,257 participants to provide 80% power to detect a significant difference between the groups which would indicate that there is a very low likelihood of a type 2 error accounting for the findings in this study. Conclusions Individuals with DS do not have clinically detectable differences in hippocampal Glx concentration. Other pathophysiological processes likely account for ID and AD in people with DS. [ABSTRACT FROM AUTHOR]

Sensory processing abnormalities are common in autism spectrum disorders (ASD), and now form part of the Diagnostic and Statistical Manual 5th Edition (DSM-5) diagnostic criteria, but it is unclear whether they characterize the 'broader phenotype' of the disorder. We recruited adults ( n = 772) with and without an ASD and administered the Autism Quotient (AQ) along with the Adult/Adolescent Sensory Profile (AASP), the Cardiff Anomalous Perceptions Scale (CAPS), and the Glasgow Sensory Questionnaire (GSQ), all questionnaire measures of abnormal sensory responsivity. Autism traits were significantly correlated with scores on all three sensory scales (AQ/GSQ r = 0.478; AQ/AASP r = 0.344; AQ/CAPS r = 0.333; all p < 0.001). This relationship was linear across the whole range of AQ scores and was true both in those with, and without, an ASD diagnosis. It survived correction for anxiety trait scores, and other potential confounds such as mental illness and migraine. [ABSTRACT FROM AUTHOR]

Rationale: Previous studies on psychotropic drugs prescribing in autism spectrum disorder (ASD) were from the USA or the UK. However, these studies may not be generalizable to other countries. There is a need to understand the extent of psychopharmacological prescribing for ASD treatment at a multinational level to identify areas of prescribing which lack evidence. Methods: We used the IMS Prescribing Insights database to investigate psychotropic drugs prescribing patterns for ASD treatment in children and adults in 2010-2012. Data were obtained from Europe (France, Germany, Italy, Spain and UK), South America (Mexico and Brazil), North America (Canada and USA) and Asia (Japan). Results: North American countries have the highest prescription rates, followed by the European and South American countries. Prescribing rates were higher in children compared to adults in individual countries. The most commonly prescribed drug for ASD was risperidone in young people (except in UK and Japan). In the UK, methylphenidate (34 %) was the most commonly prescribed for young people and haloperidol (44.1 %) in Japan. In adults, the most commonly prescribed drug class was antipsychotics and particularly risperidone (thioridazine and ziprasidone were the most prescribed antipsychotics in Brazil and USA, respectively). Conclusion: There is variation in medication prescription for people with ASD among countries, which may be attributable to diagnostic criteria, clinical guidelines or health care systems. However, there is a lack of evidence of efficacy and safety for many psychotropic drugs prescribed for people with ASD. Research is needed to bridge the evidence gaps in prescribing. [ABSTRACT FROM AUTHOR]

Rationale: Autism spectrum disorders (ASDs) affect 1 % of children, having significant impact on health and social outcomes. Psychotropic medication use by individuals with ASD in the USA increased over time, and polypharmacy occurred in >50 % of those prescribed. In the UK, no psychotropic drugs are approved in ASDs, and little is known about patterns of pharmacological treatment in the ASD population and associated co-morbidities. Methods: We used The Health Improvement Network, a nationally representative primary care database, to assess the prevalence of ASD diagnoses, psychotropic drug prescribing and neuropsychiatric co-morbidities of 0-24 year olds between 1992 and 2008. Results: ASD prevalence increased 65-fold from 0.01 % (1992) to 0.50 % (2008). Psychotropic drugs were prescribed to 29 % (1,619/5,651) of the ASD cohort; the most prescribed drugs were sleep medication (9.7 % of prescribed patients), psychostimulants (7.9 %) and antipsychotics (7.3 %). More patients were given psychostimulants and sleep medications over time from 1.5-6.3 % and 2.2-5.9 % respectively. Thirty-seven per cent of the cohort had ≥1 record of a neuropsychiatric co-morbidity, the most common being developmental difficulties and learning disabilities (12.6 %), behavioural, conduct and personality disorders (11.1 %) and attention deficit hyperactivity disorder (7.5 %). Conclusions: British physicians are more conservative in prescribing practice than American colleagues. However, use of psychostimulants and antipsychotics is much higher in those with ASD than in the general population. Polypharmacy was seen in 34 % of prescribed patients in 2008. Additional studies examining use, efficacy, and long-term safety of antipsychotics and psychostimulants in autistic individuals are warranted. [ABSTRACT FROM AUTHOR]

Over the past decade, human neuroimaging studies have provided invaluable insights into the neural substrates that underlie autism spectrum disorder (ASD). Although observations from multiple neuroimaging approaches converge in suggesting that changes in brain structure, functioning and connectivity are associated with ASD, the neurobiology of this disorder is complex, and considerable aetiological and phenotypic heterogeneity exists among individuals on the autism spectrum. Characterization of the neurobiological alterations that underlie ASD and development of novel pharmacotherapies for ASD, therefore, requires multidisciplinary collaboration. Consequently, pressure is growing to combine neuroimaging data with information provided by other disciplines to translate research findings into clinically useful biomarkers. So far, however, neuroimaging studies in patients with ASD have mainly been conducted in isolation, and the low specificity of neuroimaging measures has hindered the development of biomarkers that could aid clinical trials and/or facilitate patient identification. Novel approaches to acquiring and analysing data on brain characteristics are currently being developed to overcome these inherent limitations, and to integrate neuroimaging into translational research. Here, we discuss promising new studies of cortical pathology in patients with ASD, and outline how the novel insights thereby obtained could inform diagnosis and treatment of ASD in the future. [ABSTRACT FROM AUTHOR]

An Autism Spectrum Disorder (ASD) diagnosis is often used to access services. We investigated whether ASD diagnostic outcome varied when DSM-5 was used compared to ICD-10R and DSM-IV-TR in a clinical sample of 150 intellectually able adults. Of those diagnosed with an ASD using ICD-10R, 56 % met DSM-5 ASD criteria. A further 19 % met DSM-5 (draft) criteria for Social Communication Disorder. Of those diagnosed with Autistic Disorder/Asperger Syndrome on DSM-IV-TR, 78 % met DSM-5 ASD criteria. Sensitivity of DSM-5 was significantly increased by reducing the number of criteria required for a DSM-5 diagnosis, or by rating 'uncertain' criteria as 'present', without sacrificing specificity. Reduced rates of ASD diagnosis may mean some ASD individuals will be unable to access clinical services. [ABSTRACT FROM AUTHOR]

Background: Down's syndrome (DS) is the most common genetic cause of intellectual disability. People with DS are at an increased risk of Alzheimer's disease (AD) compared to the general population. Neuroimaging studies of AD have focused on medial temporal structures; however, to our knowledge, no in vivo case-control study exists comparing the anatomy of dementia in DS to people with AD in the general population. We therefore compared the in vivo brain anatomy of people with DS and dementia (DS+) to those with AD in the general population. Method: Using MRI in 192 adults, we compared the volume of whole brain matter, lateral ventricles, temporal lobes and hippocampus in DS subjects with and without dementia (DS+, DS-), to each other and to three non-DS groups. These included one group of individuals with AD and two groups of controls (each age-matched for their respective DS and general population AD cohorts). Results: AD and DS+ subjects showed significant reductions in the volume of the whole brain, hippocampus and temporal lobes and a significant elevation in the volume of the lateral ventricle, compared to their non-demented counterparts. People with DS+ had a smaller reduction in temporal lobe volume compared to individuals with AD. Conclusions: DS+ and AD subjects have a significant reduction in volume of the same brain regions. We found preliminary evidence that DS individuals may be more sensitive to tissue loss than others and have less 'cognitive reserve'. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorders (ASD) are associated with repetitive behaviours and often also with hyperactivity, aggression, self-injurious behaviour, irritability and lability of mood. There is emerging evidence that aripiprazole, an antipsychotic with partial agonist dopaminergic effect, may be effective in the treatment of these challenging behaviours. Nevertheless, there is little evidence for their efficacy in adults with ASD. Objectives: The aim of this article is to present preliminary data on the use of aripiprazole in the treatment of challenging behaviour in the setting of ASD. Methods: We present a consecutive series of five inpatients of normal intelligence with challenging behaviour associated with ASD, diagnosed according to ICD-10 criteria, which was resistant to treatment with other medical and behavioural interventions and which was treated with aripiprazole. Results: Four out of five patients were classified as 'much improved' or 'very much improved' according to the Clinical Global Impression-Improvement scale. Aripiprazole caused akathisia, at a dose of 30 mg in the one patient who was not classified as a responder but was otherwise well tolerated. Conclusions: This is the first case series of adults with ASD presenting with challenging behaviour who have been treated with aripiprazole. While the results are promising, controlled trials are required to confirm the findings. [ABSTRACT FROM AUTHOR]

Background: Robot-assisted laparoscopic surgery is being performed more frequently for the minimally invasive management of rectal cancer. The objective of this meta-analysis was to compare the clinical and oncologic safety and efficacy of robot-assisted versus conventional laparoscopic surgery. Methods: A search of the Medline and Embase databases was performed for studies that compared clinical or oncologic outcomes of conventional laparoscopic proctectomy with robot-assisted laparoscopic proctectomy for rectal cancer. The methodological quality of the selected studies was critically assessed to identify studies suitable for inclusion. Meta-analysis was performed by a random effects model and analyzed by Review Manager. Clinical outcomes evaluated were conversion rates, operation times, length of hospital stay, and complications. Oncologic outcomes evaluated were circumferential margin status, number of lymph nodes collected, and distal resection margin lengths. Results: Eight comparative studies were assessed for quality, and seven studies were included in the meta-analysis. Two studies were matched case-control studies, and five were unmatched. A total of 353 robot-assisted laparoscopic surgery proctectomy cases and 401 conventional laparoscopic surgery proctectomy cases were analyzed. Robotic surgery was associated with a significantly lower conversion rate ( P = 0.03; 95% confidence interval 1-12). There was no difference in complications, circumferential margin involvement, distal resection margin, lymph node yield, or hospital stay ( P = NS). Conclusions: Robot-assisted surgery decreased the conversion rate compared to conventional laparoscopic surgery. Other clinical outcomes and oncologic outcomes were equivalent. The benefits of robotic rectal cancer surgery may differ between population groups. [ABSTRACT FROM AUTHOR]

Studies of psychiatric disorders have traditionally focused on emotional symptoms such as depression, anxiety and hallucinations. However, poorly controlled cognitive deficits are equally prominent and severely compromise quality of life, including social and professional integration. Consequently, intensive efforts are being made to characterize the cellular and cerebral circuits underpinning cognitive function, define the nature and causes of cognitive impairment in psychiatric disorders and identify more effective treatments. Successful development will depend on rigorous validation in animal models as well as in patients, including measures of real-world cognitive functioning. This article critically discusses these issues, highlighting the challenges and opportunities for improving cognition in individuals suffering from psychiatric disorders. [ABSTRACT FROM AUTHOR]

Proton magnetic resonance spectroscopy (H-MRS) studies have previously reported reduced brain N-acetyl aspartate (NAA) and increased myo-inositol (mI) in people with established Alzheimer's disease (AD). The earliest structure affected by AD is the hippocampus but relatively few studies have examined its neuronal integrity by MRS in AD and fewer still in people with amnestic mild cognitive impairment (MCI). We measured the hippocampal concentration of NAA, mI, choline (Cho) and creatine + phosphocreatine (Cr + PCr) in 39 patients with AD, 21 subjects with MCI and 38 age matched healthy elderly controls. Patients with AD had a significantly lower hippocampal [NAA] than controls, with subjects with MCI intermediate between the other two groups. [NAA] was positively correlated with memory in the impaired groups. Using mean hippocampal [NAA] and [Cr + PCr] we correctly classified 72% of people with AD, and 75% of controls. Reductions in [NAA] can be detected in the hippocampi of subjects with MCI and hippocampal [NAA] and [Cr + PCr] can distinguish between mild AD and normal elderly controls. [ABSTRACT FROM AUTHOR]