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Statement of problem Bilateral balanced occlusion has been advocated over nonbalanced occlusion for improved removable complete denture stability and function. However, assessments of quality of life and patient satisfaction studies between the 2 occlusion schemes are lacking. Purpose The objective of this parallel randomized control trial was to determine the difference in quality of life and patient satisfaction between the nonbalanced and bilaterally balanced occlusal schemes. Material and methods Sixty participants were included in the parallel randomized control trial of nonbalanced and bilaterally balanced complete dentures. Thirty were recruited into each group with definitive inclusion and exclusion criteria as per the Consolidated Standards of Reporting Trials (CONSORT) guidelines. Quality of life was estimated from the oral health quality of life (Oral Health Impact profile) for edentulous patients questionnaire, and patient satisfaction was analyzed from a visual analog scale. The estimation was made at 0, 3, and 6 months after denture insertion. The data were statistically analyzed with the Friedman, Mann-Whitney, and t test (α=.05). Results The mean ±standard deviation Oral Health Impact profile score was 60.81 ±8.87 for nonbalanced dentures and 64.12 ±8.98 for bilaterally balanced dentures. The mean ±standard deviation visual analog scale score was 2.84 ±0.28 for nonbalanced dentures and 2.90 ±0.31 for bilaterally balanced dentures. The Mann-Whitney and t test indicated nonsignificant differences between the 2 groups and at different time intervals for Oral Health Impact profile and visual analog scale scores (P>.05). Conclusions The study detected no significant differences between the 2 occlusal schemes in quality of life or patient satisfaction.

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.

While the cholesterol biosynthesis pathway has been extensively studied, recent work has forged new links between inhibition of specific sterol pathway enzymes, accumulation of their unique sterol substrates, and biological areas as diverse as cancer, immunology, and neurodegenerative disease. We recently reported that dozens of small molecules enhance formation of oligodendrocytes, a glial cell type lost in multiple sclerosis, by inhibiting CYP51, Sterol 14-reductase, or EBP and inducing cellular accumulation of their 8,9-unsaturated sterol substrates. Several adjacent pathway enzymes also have 8,9-unsaturated sterol substrates but have not yet been evaluated as potential targets for oligodendrocyte formation or in many other biological contexts, in part due to a lack of available small-molecule probes. Here, we show that genetic suppression of SC4MOL or HSD17B7 increases the formation of oligodendrocytes. Additionally, we have identified and optimized multiple potent new series of SC4MOL and HSD17B7 inhibitors and shown that these small molecules enhance oligodendrocyte formation. SC4MOL inhibitor CW4142 induced accumulation of SC4MOL's sterol substrates in mouse brain and represents an in vivo probe of SC4MOL activity. Mechanistically, the cellular accumulation of these 8,9-unsaturated sterols represents a central driver of enhanced oligodendrocyte formation, as exogenous addition of purified SC4MOL and HSD17B7 substrates but not their 8,9-saturated analogs promotes OPC differentiation. Our work validates SC4MOL and HSD17B7 as novel targets for promoting oligodendrocyte formation, underlines a broad role for 8,9-unsaturated sterols as enhancers of oligodendrocyte formation, and establishes the first high-quality small molecules targeting SC4MOL and HSD17B7 as novel tools for probing diverse areas of biology., Inhibition of two additional cholesterol biosynthesis enzymes, SC4MOL and HSD17B7, and accumulation of their 8,9-unsaturated sterols enhance formation of oligodendrocytes. We have also identified novel inhibitors of SC4MOL and HSD17B7.

A survey for practitioners.

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

This article provides an organization of various kinds of biases that can occur in the AI pipeline starting from dataset creation and problem formulation to data analysis and evaluation. It highlights the challenges associated with the design of bias-mitigation strategies, and it outlines some best practices suggested by researchers. Finally, a set of guidelines is presented that could aid ML developers in identifying potential sources of bias, as well as avoiding the introduction of unwanted biases. The work is meant to serve as an educational resource for ML developers in handling and addressing issues related to bias in AI systems.

BackgroundCognitive mechanisms that characterize or precede depressive symptoms are poorly understood. We investigated cross-sectional and longitudinal associations between risk taking to obtain reward and adolescent depressive symptoms in a large prospective cohort, using the Cambridge Gambling Task (CGT). We also explored sex differences.MethodsThe Millennium Cohort Study (MCS) is an ongoing UK study, following the lives of 19 000 individuals born 2000/02. The CGT was completed at ages 11 (n = 12 355) and 14 (n = 10 578). Our main exposure was the proportion of points gambled, when the odds of winning were above chance (risk-taking to obtain reward). Outcomes were emotional symptoms (Strengths and Difficulties Questionnaire, SDQ) at age 11 and depressive symptoms (short Mood and Feelings Questionnaire, sMFQ) at age 14. We calculated cross-sectional and longitudinal associations, using linear regressions.ResultsIn univariable models, there was evidence of cross-sectional associations between risk-taking and SDQ/sMFQ scores, but these associations disappeared after we adjusted for sex. Longitudinally, there was weak evidence of an association between risk-taking and depressive symptoms in females only [a 20-point increase in risk-taking at age 11 was associated with a reduction of 0.31 sMFQ points at age 14 (95% CI −0.60 to −0.02)]. At both time-points, females were less risk-taking than males.ConclusionsWe found no convincing evidence of a relationship between risk-taking to obtain reward and depressive symptoms. There were large sex differences in risk-taking, but these do not appear to contribute to the female preponderance of depressive symptoms in adolescence.

Fallopian tube fistula with the bladder can mimic an enterovaginal fistula. A 34-year-old woman presented with continuous urinary incontinence after hysterectomy. A cystogram confirmed a vesicovaginal fistula and a possible additional intestinal communication. Further imaging, however, ruled out an enterovaginal fistula and diagnosed a fallopian tube prolapse with salpingovesicovaginal fistula. This case demonstrates the importance of multiple imaging modalities in identifying and clearly delineating the anatomy of gynecologic fistulous connections. The case illustrates the fact that while salpingovesical fistula is a rare complication of hysterectomy, it is an important consideration in one's differential diagnosis.

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.

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.

Pharmaceutical contaminants present in wastewaters cause severe health hazards among chronically exposed population. Emerging pharmaceutically active contaminants pose a serious challenge to conventional treatment technologies. Employing advanced treatment technologies for the abatement of such contaminants is usually energy-intensive. In this study, a complex pharmaceutical wastewater from a pharmaceutical industry in California, USA, was treated by employing a novel bio-electrochemical treatment train system. Labeled “Bio-electroperoxone,” our proposed system comprises (i) an electrically bound biofilm reactor (EBBR) that accelerates bacterial adhesion for the removal of biodegradable and persistent organics and (ii) an electroperoxone reactor that removes recalcitrant organics with minimal energy uptake. The EBBR comprises a platinum-coated titanium cathode and a conductive nematic liquid crystal display electrode (NLCE) obtained from electronic waste that serves as the anode. Characterization of functional groups, morphology, and elemental mapping of NLCE were carried out to explain mechanisms for rapid biofilm attachment. The concomitant electroperoxone reactor comprises a platinum-coated titanium (Pt-Ti) anode and a reticulated vitreous carbon (RVC) cathode that catalyzes the two-electron reduction of oxygen to form in situ H2O2. The bio-electroperoxone system (i) inactivated 99.99% of the micro-organisms, removed (ii) 92.20% of the color, (iii) 84.72% of the total suspended solids, and (iv) 89% of the total organic carbon (TOC). Possible mechanisms for the degradation of organic contaminants are elucidated. Bio-electroperoxone thus paves the way for an efficient and sustainable approach for the efficient removal of both biodegradable and recalcitrant, persistent organic contaminants from pharmaceutical and possibly other complex wastewaters.

While virtual reality (VR) is emerging as an interactive tool for chemical education, its application and assessment for chemical education are still limited. Thus, an educational VR activity based...

ObjectiveTo 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).DesignA cross-sectional analysis 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.ResultsHip and/or groin pain was associated with higher total SHOMRI (0 to 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.ConclusionsA 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.

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.

With growing adoption of AI across fields such as healthcare, finance, and the justice system, explaining an AI decision has become more important than ever before. Development of human-centric explainable AI (XAI) systems necessitates an understanding of the requirements of the human-in-the-loop seeking the explanation. This includes the cognitive behavioral purpose that the explanation serves for its recipients, and the structure that the explanation uses to reach those ends. An understanding of the psychological foundations of explanations is thus vital for the development of effective human-centric XAI systems. Towards this end, we survey papers from the cognitive science literature that address the following broad questions: (1) what is an explanation, (2) what are explanations for, and 3) what are the characteristics of good and bad explanations. We organize the insights gained therein by means of highlighting the advantages and shortcomings of various explanation structures and theories, discuss their applicability across different domains, and analyze their utility to various types of humans-in-the-loop. We summarize the key takeaways for human-centric design of XAI systems, and recommend strategies to bridge the existing gap between XAI research and practical needs. We hope this work will spark the development of novel human-centric XAI systems.

In this study, ferrocene functionalized electrochemically reduced graphene oxide (Fc-ErGO) was used as electro-Fenton catalyst in rotating disc electrode system for the continuous generation of reactive oxygen species without external aeration. The nature of Fc-ErGO was evaluated using X-ray photoelectron spectroscopy, Raman spectroscopy, scanning electron microscopy and energy-dispersive X-ray spectroscopy analysis. Degradation of ciprofloxacin and carbamazepine were carried out to evaluate the performance of reactor. Enhanced removal rate was achieved at a wider range of pH as compared to the unmodified and ErGO modified graphite felt electrode systems. An increase in rotational speed of the disc electrodes resulted in enhanced removal rate due to improved mass transfer activity. At neutral condition, the removal rate was found to be 0.199 min−1 and 0.082 min−1 for ciprofloxacin and carbamazepine, respectively. Quantification of reactive oxygen species was also done. The Fc-ErGO modified cathode showed 644 μM, 264 μM, and 163 μM of •OH radicals at pH 3.0, 7.0 and 9.0 respectively; it confirms that ferrocene efficiently catalyses the conversion of H2O2 to •OH radicals and facilitates the degradation of contaminants. Stable catalytic activity was achieved even upto 10 cycles of repeatable experimental runs. A highly efficient, cleaner electro-Fenton system without external aeration and chemical addition was successfully demonstrated.

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.

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.

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.

© 2015 IEEE. This article explores the feasibility of face-recognition technologies for analyzing works of portraiture and, in the process, provides a quantitative source of evidence to art historians in answering many of their ambiguities concerning identity of the subject in some portraits and in understanding artists? styles. Works of portrait art bear the mark of visual interpretation of the artist. Moreover, the number of samples available to model these effects is often limited. Based on an understanding of artistic conventions, we show how to learn and validate features that are robust in distinguishing subjects in portraits (sitters) and that are also capable of characterizing an individual artist?s style. This can be used to learn a feature space called portrait feature space (PFS) that is representative of quantitative measures of similarities between portrait pairs known to represent same/different sitters. Through statistical hypothesis tests, we analyze uncertain portraits against known identities and explain the significance of the results from an art historian?s perspective. Results are shown on our data consisting of over 270 portraits belonging largely to the Renaissance era.

Part 5: MAKE Explainable AI; International audience; The transparent AI initiative has ignited several academic and industrial endeavors and produced some impressive technologies and results thus far. Many state-of-the-art methods provide explanations that mostly target the needs of AI engineers. However, there is very little work on providing explanations that support the needs of business owners, software developers, and consumers who all play significant roles in the service development and use cycle. By considering the overall context in which an explanation is presented, including the role played by the human-in-the-loop, we can hope to craft effective explanations. In this paper, we introduce the notion of the “cognitive value” of an explanation and describe its role in providing effective explanations within a given context. Specifically, we consider the scenario of a business owner seeking to improve sales of their product, and compare explanations provided by some existing interpretable machine learning algorithms (random forests, scalable Bayesian Rules, causal models) in terms of the cognitive value they offer to the business owner. We hope that our work will foster future research in the field of transparent AI to incorporate the cognitive value of explanations in crafting and evaluating explanations.

In this paper, we set out to explore the level of programming experience present among the masses (the last mile end-user programmers), the influence of various factors such as early exposure to software, as well as age, on programming experience, their effects on the types of software people might want to create, and the software development approaches they prefer.

In nano-meter scale Integrated Circuits, via fails due to random defects is a well-known yield detractor, and via redundancy insertion is a common method to help enhance semiconductors yield. For the case of Self Aligned Double Patterning (SADP), which might require unidirectional design layers as in the case of some advanced technology nodes, the conventional methods of inserting redundant vias don’t work any longer. This is because adding redundant vias conventionally requires adding metal shapes in the non-preferred direction, which will violate the SADP design constraints in that case. Therefore, such metal layers fabricated using unidirectional SADP require an alternative method for providing the needed redundancy. This paper proposes a post-layout Design for Manufacturability (DFM) redundancy insertion method tailored for the design requirements introduced by unidirectional metal layers. The proposed method adds redundant wires in the preferred direction - after searching for nearby vacant routing tracks - in order to provide redundant paths for electrical signals. This method opportunistically adds robustness against failures due to silicon defects without impacting area or incurring new design rule violations. Implementation details of this redundancy insertion method will be explained in this paper. One known challenge with similar DFM layout fixing methods is the possible introduction of undesired electrical impact, causing other unintentional failures in design functionality. In this paper, a study is presented to quantify the electrical impacts of such redundancy insertion scheme and to examine if that electrical impact can be tolerated. The paper will show results to evaluate DFM insertion rates and corresponding electrical impact for a given design utilization and maximum inserted wire length. Parasitic extraction and static timing analysis results will be presented. A typical digital design implemented using GLOBALFOUNDRIES 7nm technology is used for demonstration. The provided results can help evaluate such extensive DFM insertion method from an electrical standpoint. Furthermore, the results could provide guidance on how to implement the proposed method of adding electrical redundancy such that intolerable electrical impacts could be avoided.

Antibiotics are majorly used in food animals for growth promotion and prophylactic purposes in public health and environment. The aim of this review is mainly to discuss about the antibiotics usage in poultry, livestock and aquaculture sectors, particularly in India, and the identification of antibiotic resistance in animals, their corresponding antibiotic resistance genes (ARGs) (if investigated) and their dissemination among environmental compartments in various parts of the country. It also discusses about the classification and mechanism of action of different antibiotics. It reports the risks, benefits, ARGs development mechanisms from food animals to humans and to the environment. Most of the current studies are done in the medical field on regulating/restricting antibiotic usage and tracking the propagation of ARGs in bacterial samples of sick patients and also report the identification of antibiotics and ARGs in wastewater treatment plant effluents across various countries. This study mainly reviews the evolution and transportation of ARGs in detail for Indian scenario.

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.

Background Circulating tumor DNA (ctDNA) analysis is an emerging field for diagnosis, monitoring of treatment efficacy and detection of disease recurrence in various cancers. In bladder cancer, previous work has demonstrated prognostic value of ctDNA for early stage cancers and early detection of recurrence following radical cystectomy (CX), however more extensive investigation of the potential impact of ctDNA analysis on clinical decision making remains to be carried out. Methods A total of 68 patients with localized advanced bladder cancer to be treated with neoadjuvant chemotherapy (NAC) and CX were prospectively included. We performed RNA-Seq to identify RNA subtypes and whole exome sequencing to identify somatic mutations for ctDNA analysis. Based on allele frequency and sequence context, 16 somatic mutations were selected for each patient for multiplex PCR and subsequent ultra-deep sequencing (median coverage of 114,000x). The sample-level analytical sensitivity was determined to be >95% at 0.01% ctDNA concentration level when at least 2/16 mutations were detected. The protocol was applied to detect ctDNA in 618 blood samples procured at diagnosis, during NAC, before CX and during surveillance following CX. Results The presence of ctDNA was highly prognostic already at diagnosis before initiation of NAC (HR=31.7, p=0.001). Analysis of ctDNA dynamics during NAC revealed that clearance of ctDNA was associated with pathological downstaging (≤TaN0 at CX) and reduced disease recurrence. Conversely, continually detectable ctDNA during NAC was associated with lack of pathological downstaging and later disease recurrence (p=0.023). Our results suggest that ctDNA dynamics during NAC may offer superior predictive value compared to clinical parameters and tumor centric molecular markers such as DNA damage response mutations and RNA subtypes. Following CX, ctDNA analysis identified 92% of metastatic relapse (100% specificity) during disease monitoring (100% positive- and 98% negative predictive value). The positive lead-time over radiographic imaging was 100 days on average (range: -17-245 days). Conclusions ctDNA analysis of blood samples procured throughout the disease course of patients with bladder cancer demonstrates novel evidence of early risk stratification and monitoring of treatment efficacy, which adds to the already strong evidence of ctDNA-based recurrence detection. Collectively, this paves the way for novel ctDNA-based clinical trials. Citation Format: Emil Christensen, Karin Birkenkamp-Demtröder, Himanshu Sethi, Svetlana Shchegrova, Raheleh Salari, Iver Nordentoft, Hsin-Ta Wu, Michael Knudsen, Philippe Lamy, Sia V. Lindskrog, Ann Taber, Mustafa Balcioglu, Søren Vang, Zoe Assaf, Shruti Sharma, Antony S. Tin, Ramya Srinivasan, Dina Hafez, Thomas Reinert, Samantha Navarro, Alexander Olson, Rosie Ram, Scott Dashner, Matthew Rabinowitz, Paul Billings, Styrmir Sigurjonsson, Claus L. Andersen, Ryan Swenerton, Alexey Aleshin, Bernhard G. Zimmermann, Mads Agerbæk, Cheng-Ho J. Lin, Jørgen B. Jensen, Lars Dyrskjøt. Early detection of metastatic relapse and monitoring of therapeutic efficacy by ultra-deep sequencing of plasma cell-free DNA in patients with urothelial bladder carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 913.

Conversational user interfaces (CUIs) are rapidly evolving towards being ubiquitous as human-machine interfaces. Often, CUI backends are powered by a combination of human and machine intelligence, to address queries efficiently. Depending on the type of conversation issue, human-to-human conversations in CUIs (i.e. a human end-user conversing with the human in the CUI backend) could involve varying amounts of emotional content. While some of these emotions could be expressed through the conversation, others are experienced internally within the individual. Understanding the relationship between these two emotion modalities in the end-user could help to analyze and address the conversation issue better. Towards this, we propose an emotion analytic metric that can estimate experienced emotions based on its knowledge about expressed emotions in a user. Our findings point to the possibility of augmenting CUIs with an algorithmically guided emotional sense, which would help in having more effective conversations with end-users.

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.

With advancements in wireless technologies, location based services (LBS) have become ubiquitous and are fundamental to services that provide emergency response to those that enhance the quality of daily life. Location tracking applications include traffic congestion management, waste management, indoor navigation in malls/airports, receiving coupons/advertisements by retailers, applications to allow parents to track their children, providing centimeter-level guidance to visually impaired users in indoor environments etc. Location tracking also enables applications in device-free situations - intrusion detection by means of tracking people and their movements through walls, monitoring the heartbeat of a person(ex: elderly citizen) through walls etc. In conjunction with location based services, the development of the Internet of Things (IoT) provides rich contextual information which is key to the scalability of smart cities. Managing these technologies along with establishing effective countermeasures against security and privacy concerns of individual citizens as well as service providers and government agencies is essential for their adoption. In this paper we envision a feature of the emergency response system of a smart city whereby critical contextual information from the emergency site is made available to the emergency service provider to enable effective first response strategy. We use the example of a smart building with an infrastructure that consists of an indoor hybrid wireless environment for identifying individuals, tracking their location, monitoring vital statistics and measuring ambient conditions. This information is critical to rescue teams and paramedics. We provide an architecture that addresses the security and privacy issues associated with the highly sensitive information generated by this system.

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: …

Introduction: Liquid biopsy-based detection and monitoring of tumor-specific somatic mutations in cell-free DNA has great potential to improve patient care by detecting cancer early, assisting adjuvant therapy decision-making, monitoring residual disease, determining treatment effects, assessing relapse and the consequent need for follow-up intervention. We have developed a novel highly sensitive and specific approach for the detection and quantification of circulating tumor DNA (ctDNA) by tracking personalized cancer signatures in plasma. We recently described our ability to detect ctDNA presence longitudinally in patients with non-small cell lung cancer (NSCLC) and have validated this personalized approach for detection of tumor DNA in plasma, and made it available for research use only (RUO). Summary of Experimental Procedures: This study describes results of the Signatera RUO assay's analytical validation test titrations of cancer cell lines and their matched normal counterparts. Multiplex-PCR (mPCR) assay pools specific to the tumor mutational signatures were derived from whole-exome data analysis of the tumor cell line and its corresponding matched normal cell line. Tumor DNA spike-in mixtures were amplified using the mPCR assays and then barcoded and sequenced at ultra-high depth on the Illumina HiSeq instrument (average > 100,000 reads per target). This study also demonstrates the ability to detect ctDNA using Signatera RUO assay's personalized somatic mutations in patients with epithelial and non-epithelial ovarian cancer. Results/Data Summary: The Signatera RUO analytical validation results demonstrate a variant-level sensitivity of ~60% at spiked-in tumor DNA concentrations of 0.03% along with an assay specificity of 99.9% in wild-type DNA. By targeting 16 somatic mutations present in the tumor, an estimated LOD of 0.01% tumor DNA in a patient's plasma is achieved. The Signatera RUO assay also demonstrates the ability to detect ctDNA in plasma down to less than 0.1% VAF at baseline (prior to treatment) in epithelial and non-epithelial ovarian cancer. Conclusion: The Signatera RUO assay provides a unique method to noninvasively detect ctDNA by assaying for personalized cancer signatures in plasma by ultra-high-depth sequencing of custom-made multiplex PCR assays, with high sensitivity and high specificity. Our study demonstrates the potential of this technology to improve the current standard of care by enabling early recurrence detection and the monitoring of treatment effectiveness across several tumor types. Citation Format: Himanshu Sethi, Raheleh Salari, Samantha Navarro, Prashanthi Natarajan, Ramya Srinivasan, Scott Dashner, Tony Tin, Mustafa Balcioglu, Ryan Swenerton, Bernhard Zimmermann. Analytical validation of the SignateraTM RUO assay, a highly sensitive patient-specific multiplex PCR NGS-based noninvasive cancer recurrence detection and therapy monitoring assay [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4542.

Minimally invasive methods for assessment of tumor burden, early detection of disease relapse and for monitoring therapeutic efficacy are needed to improve individualized follow-up and treatment for patients diagnosed with bladder cancer. The ability to predict pathologic complete response after neoadjuvant chemotherapy (NAC) through detection of ctDNA in plasma may enable strategies for bladder preservation. The aim of the study was to use patient-specific mutations to identify residual disease, metastatic relapse and to monitor treatment response in longitudinally collected plasma samples. For this, 50 patients diagnosed with locally advanced muscle-invasive bladder cancer (MIBC) and scheduled for chemotherapy were prospectively recruited between 2013 and 2017. In total, 42 patients received four cycles of cisplatin-based NAC prior to cystectomy and 82% showed response (pathologic downstaging). Eight patients received 2-6 cycles of cisplatin-based first-line chemotherapy due to diagnosis of T4b or lymph node metastasis prior to cystectomy (3CR, 2PR, 2PD, 1 ongoing). So far, 8/50 patients (16%) experienced disease relapse and three patients had metastatic progression. The mean follow-up time after radical cystectomy (RC) was 320 days (65-973); the mean follow-up time for disease-free patients was 397 days (119-778). Whole-exome sequencing (106x mean target coverage) of tumor and germline DNA was performed from a time point before systemic treatment. MUTECT2 identified a mean of 33 high (6-121), 340 (67-2838) moderate and 223 (29-2955) low-impact SNVs or insertion-deletions (InDels) per tumor. High-impact mutations in known cancer genes such as TP53 (60%), KDM6A (34%), ARID1A (32%), RB1 (28%), BRCA2 (26%), FGFR3 (22%) and ERCC2 (20%) were identified with no significant difference between responders vs nonresponders. Signatures 2, 13 (APOBEC), and 3 (BRCA) were frequently identified, with signature 13 being more prevalent in nonresponders (p=0.05). Personalized, multiplex-PCR assay-panels were individually designed, targeting each patient's tumor-specific mutations in plasma. Targeted sequencing was performed using cfDNA from 4-16 longitudinally collected plasma from each patient taken pre- and post-systemic therapy and at scheduled control visits after RC. In a blinded fashion, ctDNA was analyzed and results were compared to pathologic response and radiographic imaging data for each patient. Conclusion: Preliminary results indicated that analysis of plasma cfDNA is an appropriate method to detect metastatic relapse after RC and to monitor treatment efficacy. Here we perform a larger ctDNA study, applying direct sequencing of plasma cfDNA using highly sensitive NGS methods to determine clinical applicability of the method. Data collection is ongoing and all details will be presented at the AACR 2018 meeting. Citation Format: Karin Birkenkamp-Demtröder, Emil Christensen, Shruti Sharma, Ann Taber, Mads Agerbæk, Himanshu Sethi, Hsin-Ta Wu, Svetlana Shchegrova, Philippe Lamy, Iver Nordentoft, Ryan Swenerton, Samantha Navarro, Tony Tin, Ramya Srinivasan, John So, Spenser Alexander, Solomon Moshkevich, Bernhard Zimmermann, Cheng-Ho Jimmy Lin, Jørgen Bjerggaard Jensen, Lars Dyrskjøt. Sequencing of plasma cfDNA from patients with locally advanced bladder cancer for surveillance and therapeutic efficacy monitoring [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3653.