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Background\ud Children with intellectual disability frequently have multiple co-morbid neuropsychiatric conditions and poor physical health. Genomic testing is increasingly recommended as a first-line investigation for these children. We aim to determine the effect of genomics, inheritance, and socioeconomic deprivation on neuropsychiatric risk in children with intellectual disability of genetic origin as compared with the general population.\ud Methods\ud IMAGINE is a prospective cohort study using online mental health and medical assessments in a cohort of 3407 UK participants with intellectual disability and pathogenic genomic variants as identified by the UK's National Health Service (NHS). Our study is on a subset of these participants, including all children aged 4–19 years. We collected diagnostic genomic reports from NHS records and asked primary caregivers to provide an assessment of their child using the Development and Well-Being Assessment (DAWBA), the Strengths and Difficulties Questionnaire (SDQ), the Adaptive Behaviour Assessment System 3 (ABAS-3), and a medical history questionnaire. Each child was assigned a rank based on their postcode using the index of multiple deprivation (IMD). We compared the IMAGINE cohort with the 2017 National Survey of Children's Mental Health in England. The main outcomes of interest were mental health and neurodevelopment according to the DAWBA and SDQ.\ud Findings\ud We recruited 2770 children from the IMAGINE study between Oct 1, 2014 and June 30, 2019, of whom 2397 (86·5%) had a basic assessment of their mental health completed by their families and 1277 (46·1%) completed a medical history questionnaire. The mean age of participants was 9·2 years (SD 3·9); 1339 (55·9%) were boys and 1058 (44·1%) were girls. 355 (27·8%) of 1277 reported a seizure disorder and 814 (63·7%) reported movement or co-ordination problems. 1771 (73·9%) of 2397 participants had a pathogenic copy number variant (CNV) and 626 (26·1%) had a pathogenic single nucleotide variant (SNV). Participants were representative of the socioeconomic spectrum of the UK general population. The relative risk (RR) of co-occurring neuropsychiatric diagnoses, compared with the English national population, was high: autism spectrum disorder RR 29·2 (95% CI 23·9–36·5), ADHD RR 13·5 (95% CI 11·1–16·3). In children with a CNV, those with a familial variant tended to live in more socioeconomically deprived areas than those with a de novo variant. Both inheritance and socioeconomic deprivation contributed to neuropsychiatric risk in those with a CNV.\ud Interpretation\ud Children with genomic variants and intellectual disability are at an increased risk of neuropsychiatric difficulties. CNV variant inheritance and socioeconomic deprivation also contribute to the risk. Early genomic investigations of children with intellectual disability could facilitate the identification of the most vulnerable children. Additionally, harnessing parental expertise using online DAWBA assessments could rapidly identify children with exceptional needs to child mental health services.

Summary Background Disparities in involuntary psychiatric hospitalisation between population subgroups have been identified in adults, but little is known about the factors associated with involuntary hospitalisation in children or adolescents. We did a systematic review, meta-analysis, and narrative synthesis to investigate the social and clinical factors associated with involuntary psychiatric hospitalisation among children and adolescents. Methods We searched MEDLINE, PsycINFO, Embase, and the Cochrane Central Register of Controlled Trials for studies of any type up to July 22, 2020, that compared the characteristics of voluntary and involuntary psychiatric inpatients (mean age of sample ≤18 years). We synthesised results using random effects meta-analysis on unadjusted data and by narrative synthesis. Heterogeneity between studies was calculated using I2. This study is registered on PROSPERO, CRD42020099892. Findings 23 studies from 11 countries were included in the systematic review and narrative synthesis, of which 19 studies (n=31 212) were included in the meta-analysis. On meta-analysis, involuntary rather than voluntary hospitalisation of minors was associated with a diagnosis of psychosis (eight studies; odds ratio 3·63, 95% CI 2·43–5·44, p

Summary Objective To compare early hip osteoarthritis (OA) features on magnetic resonance imaging (MRI) in high-impact athletes with and without hip and/or groin pain, and to evaluate associations between early hip OA features, the International Hip Outcome Tool (iHOT33) and Copenhagen Hip and Groin Outcome Score (HAGOS). Design This case-control study evaluated data of the femoroacetabular impingement and hip osteoarthritis cohort (FORCe). One hundred and eighty-two symptomatic (hip and/or groin pain >6 months and positive flexion-adduction-internal-rotation (FADIR) test) and 55 pain-free high-impact athletes (soccer or Australian football (AF)) without definite radiographic hip OA underwent hip MRI. The Scoring Hip Osteoarthritis with MRI (SHOMRI) method quantified and graded the severity of OA features. Each participant completed the iHOT33 and HAGOS. Results Hip and/or groin pain was associated with higher total SHOMRI (0–96) (mean difference 1.4, 95% CI: 0.7–2.2), labral score (adjusted incidence rate ratio (aIRR) 1.33, 95% CI: 1.1–1.6). Differences in prevalence of cartilage defects, labral tears and paralabral cysts between symptomatic and pain-free participants were inconclusive. There was a lower prevalence of effusion-synovitis in symptomatic participants when compared to pain-free participants (adjusted odds ratio (aOR) 0.46 (95% CI: 0.3–0.8). Early hip OA features were not associated with iHOT33 or HAGOS. Conclusions A complex and poorly understood relationship exists between hip and/or groin pain and early hip OA features present on MRI in high-impact athletes without radiographic OA. Hip and/or groin pain was associated with higher SHOMRI and labral scores.

Developmental trauma is associated with an increased risk of psychosis and predicts poor prognosis. Despite this association, little is known about which treatments work best for survivors of developmental trauma with psychosis. We sought to do the first review, to our knowledge, to investigate treatments for people with psychotic and dissociative symptoms who have a history of developmental trauma. We searched MEDLINE, PsychINFO, and Google Scholar for studies reporting psychological and pharmacological treatments of psychotic or dissociative symptoms in adult survivors of developmental trauma. We identified 24 studies, most of which investigated various modalities of psychotherapy with two case reports of pharmacological treatments. There is preliminary evidence in favour of third wave cognitive therapies. However, because of low methodological quality and reporting in most of the studies found, it remains unknown which treatments are most effective in this clinical group. Nonetheless, our findings of potential treatment targets, including emotion regulation, acceptance, interpersonal skills, trauma re-processing, and the integration of dissociated ego states, could guide future work in this area. Methodologically rigorous studies are needed to enable clinicians and patients to collaboratively form evidence-based treatment plans. Our Review is registered with PROSPERO, number CRD42018104533.

Summary Background Evidence exists that maternal depression in the perinatal period has an adverse effect on a range of early childhood outcomes and increases the risk of offspring depression during adolescence. However, the association between maternal depression during the perinatal period and offspring psychotic experiences has not been investigated. We aimed to investigate whether there is an association between maternal antenatal or postnatal depression and offspring psychotic experiences at 18 years of age. Methods This longitudinal study used data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective birth cohort, which recruited 14 541 pregnant women with an estimated delivery date between April 1, 1991, and Dec 31, 1992. Perinatal depression was measured using the Edinburgh Postnatal Depression Scale (EPDS); offspring psychotic experiences at 18 years of age were measured using the Psychosis-Like Symptom Interview. Offspring of mothers with complete data on maternal perinatal depression measures, and complete data on outcome (psychotic experiences) and confounding variables were included in the main analysis. For the main analysis, we used logistic regression to examine the associations between maternal depression (antenatal and postnatal) and offspring psychotic experiences at the age of 18 years. We used biprobit regression to model the association between maternal antenatal depression and the two offspring outcomes (psychotic experiences and depression) at 18 years of age jointly. Findings 3067 offspring for whom data were available on maternal perinatal depression and offspring psychotic experiences aged 18 years were included in analyses. Maternal antenatal depressive symptoms were associated with offspring psychotic experiences at 18 years of age, with an unadjusted odds ratio (OR) of 1·38 (95% CI 1·18–1·61, p=0·0001) and after adjustment for confounders, an OR of 1·26 (1·06–1·49, p=0·0074). Maternal antenatal depressive symptoms were associated with both offspring psychotic experiences at the age of 18 years (n=2830, OR for a 5-point increase in EPDS score: 1·32 [95% CI 1·16–1·51], p

Importance People with anorexia nervosa often experience difficulties regulating their emotions. There is no longitudinal evidence as to whether these differences are already present in childhood or when they begin to emerge.Objective To investigate the association between emotion regulation trajectories from 3 to 7 years of age and symptoms of anorexia nervosa and atypical anorexia nervosa in adolescence.Design, Setting, and Participants This cohort study included all children with complete exposure data in the Millennium Cohort Study, a UK general population birth cohort. Data were acquired from June 2001 to March 2016 and analyzed from June to November 2020.Exposures Mothers reported on their children’s emotion regulation skills at 3, 5, and 7 years of age using the Children’s Social Behavior Questionnaire. Multilevel models were used to derive early childhood emotion regulation scores (ie, predicted intercept) and within-child changes in emotion regulation scores from 3 to 7 years of age (ie, predicted slope).Main Outcome and Measures Symptoms consistent with a DSM-5 diagnosis of anorexia nervosa or atypical anorexia nervosa at 14 years of age, defined using a range of questions relative to body image, weight perception, and dieting behaviors (hereinafter referred to as broad anorexia nervosa). Univariable and multivariable logistic regression models tested the association between exposures and outcome. Regression models were adjusted for child and family sociodemographic and socioeconomic characteristics and mental health difficulties, prenatal and perinatal factors, child’s cognitive development, and maternal attachment.Results A total of 15 896 participants (85.7% of total sample; 51.0% boys; 84.5% White individuals) had complete data on the exposure and were included in the main analyses. Among those with complete exposure and outcome data (9912 of the analytical sample [62.4%]), 97 participants (1.0%; 86 [88.7%] girls and 85 [87.6%] White individuals) had symptoms consistent with a diagnosis of broad anorexia nervosa at 14 years of age. No evidence suggested that children with lower emotion regulation ability at 3 years of age had greater odds of later reporting symptoms of broad anorexia nervosa (odds ratio [OR], 1.21; 95% CI, 0.91-1.63). However, children whose emotion regulation skills did not improve over childhood and who had greater problems regulating emotions at 7 years of age had higher odds of having broad anorexia nervosa at 14 years of age (OR, 1.45; 95% CI, 1.16-1.83).Conclusions and Relevance These findings suggest that difficulties in developing age-appropriate emotion regulation skills in childhood are associated with experiencing broad anorexia nervosa in adolescence. Interventions to support the development of emotion regulation skills across childhood may help reduce the incidence of anorexia nervosa.

ObjectivesThis study aimed to explore the experiences of parents caring for children with intellectual and developmental disabilities (IDD) during the UK national lockdown in spring 2020, resulting from the COVID-19 pandemic.DesignParticipants were identified using opportunity sampling from the IMAGINE-ID national (UK) cohort and completed an online survey followed by a semistructured interview. Interviews were analysed using thematic analysis.SettingInterviews were conducted over the telephone in July 2020 as the first UK lockdown was ending.Participants23 mothers of children with intellectual and developmental disabilities aged 5–15 years were recruited.ResultsThemes reported by parents included: managing pre-existing challenges during a time of extreme change, having mixed emotions about the benefits and difficulties that arose during the lockdown and the need for appropriate, individualised support.ConclusionsOur findings confirm observations previously found in UK parents of children with IDD and provide new insights on the use of technology during the pandemic for schooling and healthcare, as well as the need for regular check-ins.

BACKGROUND Accurate interpretation of hip MRI is time-intensive and difficult, prone to inter- and intrareviewer variability, and lacks a universally accepted grading scale to evaluate morphological abnormalities. PURPOSE To 1) develop and evaluate a deep-learning-based model for binary classification of hip osteoarthritis (OA) morphological abnormalities on MR images, and 2) develop an artificial intelligence (AI)-based assist tool to find if using the model predictions improves interreader agreement in hip grading. STUDY TYPE Retrospective study aimed to evaluate a technical development. POPULATION A total of 764 MRI volumes (364 patients) obtained from two studies (242 patients from LASEM [FORCe] and 122 patients from UCSF), split into a 65-25-10% train, validation, test set for network training. FIELD STRENGTH/SEQUENCE 3T MRI, 2D T2 FSE, PD SPAIR. ASSESSMENT Automatic binary classification of cartilage lesions, bone marrow edema-like lesions, and subchondral cyst-like lesions using the MRNet, interreader agreement before and after using network predictions. STATISTICAL TESTS Receiver operating characteristic (ROC) curve, area under curve (AUC), specificity and sensitivity, and balanced accuracy. RESULTS For cartilage lesions, bone marrow edema-like lesions and subchondral cyst-like lesions the AUCs were: 0.80 (95% confidence interval [CI] 0.65, 0.95), 0.84 (95% CI 0.67, 1.00), and 0.77 (95% CI 0.66, 0.85), respectively. The sensitivity and specificity of the radiologist for binary classification were: 0.79 (95% CI 0.65, 0.93) and 0.80 (95% CI 0.59, 1.02), 0.40 (95% CI -0.02, 0.83) and 0.72 (95% CI 0.59, 0.86), 0.75 (95% CI 0.45, 1.05) and 0.88 (95% CI 0.77, 0.98). The interreader balanced accuracy increased from 53%, 71% and 56% to 60%, 73% and 68% after using the network predictions and saliency maps. DATA CONCLUSION We have shown that a deep-learning approach achieved high performance in clinical classification tasks on hip MR images, and that using the predictions from the deep-learning model improved the interreader agreement in all pathologies. LEVEL OF EVIDENCE 3 TECHNICAL EFFICACY STAGE: 1 J. Magn. Reson. Imaging 2020;52:1163-1172.

This study presents deterministic and probabilistic human health risk assessment using Monte Carlo simulations on exposure to an Indian river, Kaveri, which has been contaminated by non-steroidal anti-inflammatory drugs (NSAIDs). The NSAIDs of concern are naproxen, ibuprofen, aspirin, ketoprofen, and diclofenac. We have considered three exposure scenarios (water ingestion, dermal exposure, and fish ingestion) for four different age groups (0-5, 6-10, 11-18, and 19-70 years). Deterministic risk assessment revealed teenagers to be the most sensitive receptors and water ingestion to be the most crucial pathway contributing to maximum health risk (79 to 86%). Based on the results of Monte Carlo simulations, it was found that the probability of exceeding the deterministic mean risks ranged from 17 to 39% for different exposure routes. High end risk estimates such as 95th percentiles and maximum values of HQ for the entire population did not exceed the USEPA allowable risk. This implies that the NSAIDs at the detected concentrations in the Kaveri river may not pose adverse health effects even in the worst-case scenario. Among the five NSAIDs, diclofenac was found to be the major contributor for health risk. Moreover, the concentration of diclofenac was just one order less than the estimated site-specific threshold concentrations. From sensitivity analysis, the most and the least impactful parameters were found to be water ingestion rate and fish ingestion rate respectively.

Purpose The purpose of this paper is to assess whether clinicians have an accurate perception of the preventability of their patients’ mortality. Case note review estimates that approximately 5 percent of inpatient deaths are preventable. Design/methodology/approach The design involved in the study is a prospective audit of inpatient mortality in a single NHS hospital trust. The case study includes 979 inpatient mortalities. A number of outcome measures were recorded, including a Likert scale of the preventability of death- and NCEPOD-based grading of care quality. Findings Clinicians assessed only 1.4 percent of deaths as likely to be preventable. This is significantly lower than previously published values (p Research limitations/implications The implications of objective assessment of the preventability of mortality are essential to drive quality improvement in this area. Practical implications There is a wide disparity between independent case note review and clinicians assessing the care of their own patients. This may be due to a “knowledge gap” between reviewers and treating clinicians, or an “objectivity gap” meaning clinicians may not recognize preventability of death of patients under their care. Social implications This study gives some insight into deficiencies in clinical governance processes. Originality/value No similar study has been performed. This has significant implications for the idea of the preventability of mortality.

Group social skills interventions (GSSIs) are a commonly offered treatment for children with high functioning ASD. We critically evaluated GSSI randomised controlled trials for those aged 6-25 years. Our meta-analysis of outcomes emphasised internal validity, thus was restricted to trials that used the parent-report social responsiveness scale (SRS) or the social skills rating system (SSRS). Large positive effect sizes were found for the SRS total score, plus the social communication and restricted interests and repetitive behaviours subscales. The SSRS social skills subscale improved with moderate effect size. Moderator analysis of the SRS showed that GSSIs that include parent-groups, and are of greater duration or intensity, obtained larger effect sizes. We recommend future trials distinguish gains in children's social knowledge from social performance.

Purpose Non-epileptic seizures are paroxysmal events which to an observer resemble epileptic seizures. Proposed risk factors incorporate biopsychosocial aspects including factors in the affected individual. Unexpectedly high rates of autism spectrum disorder (ASD) occurred in the clinical population reported here. Although elevated levels of psychiatric co-morbidity are known to be present in patients with NES, ASD has only been previously described in a single case report. Methods This case series captures rates of ASD in 59 children and young people who were referred to a specialist paediatric mental health service at Great Ormond Street Hospital, London, UK for assessment and treatment of non-epileptic seizures between 2012 and 2016. Results 10/59 (16.9%) of the children and young people with non-epileptic seizures also had ASD, with 5/10 (50%) of these undiagnosed with ASD before referral. Children and young people with ASD were significantly more likely to have tics or attention-deficit hyperactivity disorder than those without ASD. Conclusion ASD may be a common co-morbidity in non-epileptic seizures. Careful clinical assessment with consideration of ASD traits is therefore important in the non-epileptic seizures population. It is beneficial to diagnose ASD early as its presence is likely to require a modified approach to assessment and treatment of non-epileptic seizures. Study of the development of non-epileptic seizures in ASD may suggest hypotheses for the pathogenesis of non-epileptic seizures in the wider population.

PURPOSE Novel sensitive methods for early detection of relapse and for monitoring therapeutic efficacy may have a huge impact on risk stratification, treatment, and ultimately outcome for patients with bladder cancer. We addressed the prognostic and predictive impact of ultra-deep sequencing of cell-free DNA in patients before and after cystectomy and during chemotherapy. PATIENTS AND METHODS We included 68 patients with localized advanced bladder cancer. Patient-specific somatic mutations, identified by whole-exome sequencing, were used to assess circulating tumor DNA (ctDNA) by ultra-deep sequencing (median, 105,000×) of plasma DNA. Plasma samples (n = 656) were procured at diagnosis, during chemotherapy, before cystectomy, and during surveillance. Expression profiling was performed for tumor subtype and immune signature analyses. RESULTS Presence of ctDNA was highly prognostic at diagnosis before chemotherapy (hazard ratio, 29.1; P = .001). After cystectomy, ctDNA analysis correctly identified all patients with metastatic relapse during disease monitoring (100% sensitivity, 98% specificity). A median lead time over radiographic imaging of 96 days was observed. In addition, for high-risk patients (ctDNA positive before or during treatment), the dynamics of ctDNA during chemotherapy was associated with disease recurrence ( P = .023), whereas pathologic downstaging was not. Analysis of tumor-centric biomarkers showed that mutational processes (signature 5) were associated with pathologic downstaging ( P = .024); however, no significant correlation for tumor subtypes, DNA damage response mutations, and other biomarkers was observed. Our results suggest that ctDNA analysis is better associated with treatment efficacy compared with other available methods. CONCLUSION ctDNA assessment for early risk stratification, therapy monitoring, and early relapse detection in bladder cancer is feasible and provides a basis for clinical studies that evaluate early therapeutic interventions.

Background\ud \ud The phenotype of children with XXYY has predominantly been defined by comparison to other sex chromosome aneuploidies trisomies affecting male children; however, the intellectual ability of children with XXYY is lower than children with other sex chromosome aneuploidies trisomies. It is not known to what extent the phenotype identified to date is specific to XXYY, rather than a reflection of lower IQ. This study evaluates the mental health and behaviour of children with XXYY, in comparison to children with intellectual disabilities of heterogeneous genetic origin.\ud \ud \ud Methods\ud \ud Fifteen children with XXYY and 30 controls matched for age (4–14 years), sex and intellectual ability were ascertained from the IMAGINE ID study. IMAGINE ID participants have intellectual disabilities due to genetic anomalies confirmed by National Health Service Regional Genetic Centre laboratories. The mental health and behaviour of participants was examined with the Development and Well‐being Assessment and the Strengths and Difficulties Questionnaire.\ud \ud \ud Results\ud \ud Children with XXYY experienced significantly more frequent and intense temper outbursts than the control group.\ud \ud \ud Conclusion\ud \ud Our results suggest that temper outbursts may be specifically associated with the XXYY phenotype. These problems have a significant impact on the daily lives of boys with XXYY and their families. It is crucial to ensure that families are well supported to manage these difficulties.

The purpose of this study was to evaluate the sensitivity, tumor conspicuity, and image quality of different material decomposition images of phantoms and patients with nearly isodense bone metastases using rapid-kilovoltage-switching dual-energy CT (DECT).Fifty-one semianthropomorphic lumbar spine phantoms embedded with 75 simulated tumors were scanned without and with outer torso-attenuating encasement under the same scan settings. Two radiologists independently reviewed the 70-keV virtual monochromatic and material decomposition images (hydroxyapatite-water, water-hydroxyapatite, cortical bone-water, water-cortical bone). The sensitivity of tumor detection, tumor conspicuity (on a 3-point scale), and image quality (on a 3-point scale) were recorded by two independent readers. McNemar and Wilcoxon signed rank tests were used to compare results between the image reconstructions. Six clinical abdominopelvic DECT scans (three men, three women; mean age, 52 years) with nine nearly isodense lumbar spine tumors missed in the clinical report but confirmed on other scans were also evaluated.The hydroxyapatite-water material decomposition algorithm showed improved sensitivity for isodense lesion detection (without torso phantom encasement, 94% vs 82%, p = 0.031; with torso phantom encasement, 38% vs 18%, p = 0.013), and higher tumor conspicuity scores (p0.0001) compared with 70-keV virtual monoenergetic images. Artifacts were more prevalent with all material decomposition images than with 70-keV virtual monoenergetic images. Similar results were seen in the patient study.Dual-energy CT with hydroxyapatite-water material decomposition may improve the detection of bone marrow metastases, especially for subtle isodense tumors. Further study in prospective clinical scans is warranted.

Background There are few population-based cohort studies of the emergence, development, and persistence of mental health problems in sexual minorities compared with heterosexuals. We compared trajectories of depressive symptoms in sexual-minority adolescents and heterosexual adolescents from when they were aged 10 to 21 years, and examined self-harm at ages 16 and 21 years. Methods The study included 4828 adolescents born between April 1, 1991, and Dec 31, 1992, from the Avon Longitudinal Study of Parents and Children birth cohort (Bristol, UK) who reported their sexual orientation when aged 16 years. Depressive symptoms were assessed with the short Mood and Feelings Questionnaire at seven timepoints between ages 10 and 21 years. A self-harm questionnaire was completed at ages 16 and 21 years. Analyses were linear multilevel models with growth curves (depressive symptoms), logistic multilevel models (self-harm in the previous year at ages 16 and 21 years), and multinomial regression (lifetime self-harm with and without suicidal intent at age 21 years). Findings At age 10, depressive symptoms were higher in sexual minorities than in heterosexuals and increased with age to a larger extent. Depressive symptoms increased at each timepoint by 0·31 points in hetereosexuals, and by 0·49 points in sexual minorities. Sexual-minority adolescents were more likely than heterosexual adolescents to report self-harm in the previous year at ages 16 and 21 years, with no evidence that this estimate decreased with age. At aged 21, sexual minorities were more likely to report lifetime self-harm (ie, on at least one previous occasion) with suicidal intent than heterosexuals. Interpretation Mental health disparities between heterosexuals and sexual minorities are present early in adolescence and increase throughout the school years, persisting to young adulthood. Prevention of these mental health problems and early intervention must be a priority.

Anterior cruciate ligament (ACL) tears are common injuries that if left untreated can result in chronic instability, cartilage damage, meniscal tears, and ligamentous injuries, eventually leading to early osteoarthritis. ACL reconstruction surgeries are therefore increasingly being performed. Despite the fact that most patients achieve excellent postoperative results, patients can present with recurrent instability and pain. These patients often undergo imaging with radiographs, magnetic resonance imaging, and/or computed tomography. An understanding of the imaging appearance of the normal ACL reconstruction and common causes of failure is therefore essential for the interpreting radiologist. This article reviews surgical techniques for ACL reconstruction, highlighting recent technical advances, the normal imaging appearance after ACL reconstruction, etiologies for reconstruction failure, and the diagnosis of these with the aid of imaging.

Bacterial gene islands add to the genetic repertoire of opportunistic pathogens. Here, we perform comparative analyses of three Pseudomonas aeruginosa strains isolated sequentially over a 3-week period from a patient with ventilator-associated pneumonia (VAP) who received clindamycin and piperacillin-tazobactam as part of their treatment regime. While all three strains appeared to be clonal by standard pulsed-field gel electrophoresis, whole-genome sequencing revealed subtle alterations in the chromosomal organization of the last two strains; specifically, an inversion event within a novel 124-kb gene island (PAGI 12) composed of 137 open reading frames [ORFs]. Predicted ORFs in the island included metabolism and virulence genes. Overexpression of a gene island-borne putative β-lactamase gene was observed following piperacillin-tazobactam exposure and only in those strains that had undergone the inversion event, indicating altered gene regulation following genomic remodeling. Examination of a separate cohort of 76 patients with VAP for integration at this tRNA lys recombination site demonstrated that patients exhibiting evidence of integration at this site had significantly higher 28-day mortality. These findings provide evidence that P. aeruginosa can integrate, rapidly remodel, and express exogenous genes, which likely contributes to its fitness in a clinical setting.

The first metatarsophalangeal joint and hallucal-sesamoid complex are critical structures in weightbearing and susceptible to several pathologies including turf toe, sesamoiditis, degenerative or inflammatory arthritides, infection, and avascular necrosis. This review article summarizes the complex anatomy of the region, covers common pathologies while clarifying terms such as turf toe and sesamoiditis, reviews imaging techniques, and discusses management.

Setting: A specialist multi-disciplinary outpatient eating disorders centre in Australia. Patients: Adolescents aged 12-18 years with a diagnosis of anorexia nervosa (AN) or partial AN based on DSM-IV criteria (excluding amenorrhoea) living with at least one parent. Those who presented with severe medical or psychiatric comorbidity were excluded. Those who had previously received family-based treatment (FBT) were also excluded. Intervention: Manualised outpatient treatment delivered as 18 sessions over 6 months. FBT which included the entire family and the adolescent in treatment sessions was compared with PFT. This involved sessions with the same focus as FBT but attended by the parents only, without the adolescent or siblings present. Outcomes: Remission was defined as increase in weight to >95% median BMI at the end of treatment and Global Eating Disorder Examination (EDE) within 1 SD of community norms. Follow-up period: Participants were …

The purpose of this study was to validate the utility of dual-source dual-energy MDCT in quantifying iodine concentration in a phantom and in renal masses.A series of tubes containing solutions of varying iodine concentration were imaged with dual-source dual-energy MDCT. Iodine concentration was calculated and compared with known iodine concentration. Single-phase contrast-enhanced dual-source dual-energy MDCT data on 15 patients with renal lesions then were assessed independently by two readers. Dual-energy postprocessing was used to generate iodine-only images. Regions of interest were placed on the iodine image over the lesion and, as a reference, over the aorta, for recording of iodine concentration in the lesion and in the aorta. Another radiologist determined lesion enhancement by comparing truly unenhanced with contrast-enhanced images. Mixed-model analysis of variance based on ranks was used to compare lesion types (simple cyst, hemorrhagic cyst, enhancing mass) in terms of lesion iodine concentration and lesion-to-aorta iodine ratio.In the phantom study, there was excellent correlation between calculated and true iodine concentration (R(2) = 0.998, p0.0001). In the patient study, 13 nonenhancing (10 simple and three hyperdense cysts) and eight enhancing renal masses were evaluated in 15 patients. The lesion iodine concentration and lesion-to-aorta iodine ratio in enhancing masses were significantly higher than in hyperdense and simple cysts (p0.0001).Iodine quantification with dual-source dual-energy MDCT is accurate in a phantom and can be used to determine the presence and concentration of iodine in a renal lesion. Characterization of renal masses may be possible with a single dual-source dual-energy MDCT acquisition without unenhanced images or reliance on a change in attenuation measurements.

Pseudomonas aeruginosa is an opportunistic pathogen that can, like other bacterial species, exist in antimicrobial resistant sessile biofilms and as free-swimming, planktonic cells. Specific virulence factors are typically associated with each lifestyle and several two component response regulators have been shown to reciprocally regulate transition between biofilm-associated chronic, and free-swimming acute infections. Quorum sensing (QS) signal molecules belonging to the las and rhl systems are known to regulate virulence gene expression by P. aeruginosa. However the impact of a recently described family of novel quorum sensing signals produced by the Pseudomonas Quinolone Signal (PQS) biosynthetic pathway, on the transition between these modes of infection is less clear. Using clonal isolates from a patient developing ventilator-associated pneumonia, we demonstrated that clinical observations were mirrored by an in vitro temporal shift in isolate phenotype from a non-secreting, to a Type III cytotoxin secreting (TTSS) phenotype and further, that this phenotypic change was PQS-dependent. While intracellular type III cytotoxin levels were unaffected by PQS concentration, cytotoxin secretion was dependent on this signal molecule. Elevated PQS concentrations were associated with inhibition of cytotoxin secretion coincident with expression of virulence factors such as elastase and pyoverdin. In contrast, low concentrations or the inability to biosynthesize PQS resulted in a reversal of this phenotype. These data suggest that expression of specific P. aeruginosa virulence factors appears to be reciprocally regulated and that an additional level of PQS-dependent post-translational control, specifically governing type III cytotoxin secretion, exists in this species.

Setting: 15 National Health Service (NHS) child and adolescent mental health service (CAMHS) clinics in three regions of England: East Anglia, North London and North-West England. Patients: 470 adolescents aged 11 to 17 years with a diagnosis of DSM IV major depressive disorder.1 Interventions: A manualised cognitive behavioural therapy (CBT) model adapted for adolescents delivered by clinical psychologists or CAMHS clinicians for up to 20 sessions over 30 weeks. Short-term psychoanalytical psychotherapy (STPP) comprised a planned programme of 28 sessions over 30 weeks, delivered by CAMHS clinicians with psychoanalytical psychotherapy training. Parents or carers were offered up to seven sessions with a separate parent worker. Brief psychosocial intervention (BPI) was a manualised intervention based on routine specialist clinical care, consisting of 12 sessions over 20 weeks and included up to 4 family sessions. Outcomes: …

markdownabstractIntroduction: Femoroacetabular impingement syndrome is a common cause of hip-related pain in active young adults. It comprises a triad of imaging findings, symptoms and signs, and is usually characterised by extra bone formation at the femoral head-neck junction known as ‘cam morphology’. Cam morphology is theorised to create hip impingement in hip flexion activities, place stress on hip joint structures, and increase the risk of hip osteoarthritis over time.

OBJECTIVE. We conducted a prospective, observational study in a tertiary care pediatric center to determine risk factors for the development of and outcomes from ventilator-associated pneumonia. METHODS. From November 2004 to June 2005, all NICU and PICU patients mechanically ventilated for >24 hours were eligible for enrollment after parental consent. The primary outcome measure was the development of ventilator-associated pneumonia, which was defined by both Centers for Disease Control and Prevention/National Nosocomial Infections Surveillance criteria and clinician diagnosis. Secondary outcome measures were length of mechanical ventilation, hospital and ICU length of stay, hospital cost, and death. RESULTS. Fifty-eight patients were enrolled. The median age was 6 months, and 57% were boys. The most common ventilator-associated pneumonia organisms identified were Gram-negative bacteria (42%), Staphylococcus aureus (22%), and Haemophilus influenzae (11%). On multivariate analysis, female gender, postsurgical admission diagnosis, presence of enteral feeds, and use of narcotic medications were associated with ventilator-associated pneumonia. Patients with ventilator-associated pneumonia had greater need for mechanical ventilation (12 vs 22 median ventilator-free days), longer ICU length of stay (6 vs 13 median ICU-free days), higher total median hospital costs ($308534 vs $252652), and increased absolute hospital mortality (10.5% vs 2.4%) than those without ventilator-associated pneumonia. CONCLUSIONS. In mechanically ventilated, critically ill children, those with ventilator-associated pneumonia had a prolonged need for mechanical ventilation, a longer ICU stay, and a higher mortality rate. Female gender, postsurgical diagnosis, the use of narcotics, and the use of enteral feeds were associated with an increased risk of developing ventilator-associated pneumonia in these patients.

According to World Health Organization statistics of 2011, infectious diseases remain in the top five causes of mortality worldwide. However, despite sophisticated research tools for microbial detection, rapid and accurate molecular diagnostics for identification of infection in humans have not been extensively adopted. Time-consuming culture-based methods remain to the forefront of clinical microbial detection. The 16S rRNA gene, a molecular marker for identification of bacterial species, is ubiquitous to members of this domain and, thanks to ever-expanding databases of sequence information, a useful tool for bacterial identification. In this study, we assembled an extensive repository of clinical isolates (n = 617), representing 30 medically important pathogenic species and originally identified using traditional culture-based or non-16S molecular methods. This strain repository was used to systematically evaluate the ability of 16S rRNA for species level identification. To enable the most accurate species level classification based on the paucity of sequence data accumulated in public databases, we built a Naïve Bayes classifier representing a diverse set of high-quality sequences from medically important bacterial organisms. We show that for species identification, a model-based approach is superior to an alignment based method. Overall, between 16S gene based and clinical identities, our study shows a genus-level concordance rate of 96% and a species-level concordance rate of 87.5%. We point to multiple cases of probable clinical misidentification with traditional culture based identification across a wide range of gram-negative rods and gram-positive cocci as well as common gram-negative cocci.

To identify the variety of second and third intermetatarsal space (IS) lesions that may coexist with and without adjacent metatarsophalangeal joint (MTP) plantar plate (PP) tears. One hundred forefoot MRIs in 96 patients with metatarsalgia obtained between 30 September 2011 and 21 July 2012 using 1.5- or 3-T MRI were retrospectively reviewed in consensus by two MSK radiologists and one podiatrist (DPM). MRI was evaluated for second and third MTP PP tear and the presence/nature of second and third IS lesions. Second and third IS neuromas were measured in transverse (trans) dimension. A total of 40 PP tears were identified: 36 at the second and 4 at the third MTP. Second MTP PP tear was identified in 33 % of females and 40.5 % of males. In the 63 female feet there were 21 second MTP PP tears, all of which also had second IS lesions: pericapsular fibrosis (16), bursitis (4), and ganglion (1). In the 37 male feet there were 15 second MTP PP tears, 14 of which had second IS lesions: pericapsular fibrosis (8), bursitis (5), and ganglion (1). There was no definite second IS neuroma adjacent to any second MTP PP tear. In females without PP tear, there were 24 second (3 mm trans average) and 43 third IS neuromas (4.1 mm trans average). In males without PP tear, there were 9 second (3.4 mm trans average) and 16 third IS neuromas (4.1 mm trans average). MTP PP tears occurred in 40 % of our cases, 90 % of which occurred at the second MTP. Almost all coexisted with non-neuromatous second IS lesions.

Acute appendicitis is the most common condition requiring emergency surgery in children. Differentiation of perforated from nonperforated appendicitis is important because perforated appendicitis may initially be managed conservatively whereas nonperforated appendicitis requires immediate surgical intervention. CT has been proved effective in identifying appendiceal perforation. The purpose of this study was to determine whether perforated and nonperforated appendicitis in children can be similarly differentiated with ultrasound.This retrospective study included 161 consecutively registered children from two centers who had acute appendicitis and had undergone ultra-sound and appendectomy. Ultrasound images were reviewed for appendiceal size, appearance of the appendiceal wall, changes in periappendiceal fat, and presence of free fluid, abscess, or appendicolith. The surgical report served as the reference standard for determining whether perforation was present. The specificity and sensitivity of each ultrasound finding were determined, and binary models were generated.The patients included were 94 boys and 67 girls (age range, 1-20 years; mean, 11 ± 4.4 [SD] years) The appendiceal perforation rate was significantly higher in children younger than 8 years (62.5%) compared with older children (29.5%). Sonographic findings associated with perforation included abscess (sensitivity, 36.2%; specificity, 99%), loss of the echogenic submucosal layer of the appendix in a child younger than 8 years (sensitivity, 100%; specificity, 72.7%), and presence of an appendicolith in a child younger than 8 years (sensitivity, 68.4%; specificity, 91.7%).Ultrasound is effective for differentiation of perforated from nonperforated appendicitis in children.

To compare the ability of four biomarkers to distinguish between those with ventilator-associated pneumonia (VAP) vs. lower respiratory tract bacterial colonization in mechanically ventilated intensive care unit (ICU) pediatric patients.Prospective, pilot cohort study.Tertiary care children's hospital, pediatric ICU.All pediatric ICU patients mechanically ventilated48 hrs were eligible for enrollment between April 2006 to May 2007. Thirty-three patients were consecutively screened and enrolled after institutional consent process.None.VAP was defined by both Centers for Disease and Prevention/National Nosocomial Infections Surveillance criteria and clinician diagnosis; those not meeting the criteria were considered to be colonized. Plasminogen activation inhibitor (PAI-1), soluble triggering receptor expressed on myeloid cells, receptor for advanced glycation end-products, and surfactant protein D levels were measured in bronchoalveolar lavage samples on average within 24 hrs of suspicion for VAP, i.e., a positive screening endotracheal Gram stain. Sixteen patients were diagnosed with VAP and 17 met the criteria for colonization. PAI-1 was associated with VAP independent of age, sex, race, acute lung injury/acute respiratory distress syndrome, Pediatric Risk of Mortality 3 score, pediatric logistic organ dysfunction score, and duration of intubation. The receiver operating characteristics for PAI-1 showed good discrimination with an area under the curve of 0.82. PAI-1 levels of ≥ 2.8 ng/mL had a sensitivity of 81.3%, specificity of 76.5%, and positive likelihood ratio of 3.5. Levels of soluble triggering receptor expressed on myeloid cells, receptor for advanced glycation end-products, and surfactant protein D were not significantly associated with VAP.In mechanically ventilated pediatric ICU patients, PAI-1 is independently associated with the diagnosis of VAP. Real-time measurement of PAI-1 levels in bronchoalveolar lavage fluid may be of benefit in the early diagnosis and subsequent treatment of VAP in ICU patients.