Assessing and managing hallucinations in children and adolescents

Children and young people who disclose sensory experiences suggestive of hallucinations do pose a diagnostic and therapeutic challenge to mental health clinicians in their daily practice. Hallucinations, defined as erroneous percepts in the absence of identifiable stimuli, are a key feature of psychotic states, but they had also long been known to present in children with non-psychotic psychiatric disorders. The recent upsurge of interest in childhood hallucinations has arisen out of epidemiological studies of child populations, where comprehensive symptom enquiry has included screening questions on abnormal perceptions. This has resulted in what seemed surprisingly high rates of hallucinatory experiences among other psychotic-like symptoms. Children and ado lescents show a prevalence rate of self-reported hallucinatory experiences of about 10% and are reported as more common in childhood than in adolescence. These hallucinatory phenomena are most likely to occur in the absence of any psychiatric disorder and would be expected more often than not to be simpler, less elaborate and distressing than those observed in clinical samples of children with psychiatric disorders. Longitudinal studies have in fact shown that only a small proportion of children in the general population with hallucinations (less than 10%) will suffer from a psychotic disorder later in life. In clinical settings, presentations with hallucinations can be an expression of a psychotic state, or alternatively of a symptom constellation co-occurr ing along other psychiatric conditions. Associations have been found between hallucinations and traumatic stressors (i.e. bullying and sexual assault), severity of psychopathology and suicidal symptoms. These associations could be mediated by individual vulnerability, involving neurodevelopmental anomalies and a tendency to mental dissociation and mood dysregulation. This review details the clinical assessment of hallucinations in children and adolescents taking into account developmental considerations and paediatric organic associations. It describes hallucinations in young people with psychoses (schizophrenic spectrum and mood disorders) and other non-psychotic psychiatric disorders (emotional and behavioural disorders), and it addresses therapeutic aspects

Whole Exome Sequencing Suggests Much of Non-BRCA1/BRCA2 Familial Breast Cancer Is Due to Moderate and Low Penetrance Susceptibility Alleles

The identification of the two most prevalent susceptibility genes in breast cancer, BRCA1 and BRCA2, was the beginning of a sustained effort to uncover new genes explaining the missing heritability in this disease. Today, additional high, moderate and low penetrance genes have been identified in breast cancer, such as P53, PTEN, STK11, PALB2 or ATM, globally accounting for around 35 percent of the familial cases. In the present study we used massively parallel sequencing to analyze 7 BRCA1/BRCA2 negative families, each having at least 6 affected women with breast cancer (between 6 and 10) diagnosed under the age of 60 across generations. After extensive filtering, Sanger sequencing validation and co-segregation studies, variants were prioritized through either control-population studies, including up to 750 healthy individuals, or case-control assays comprising approximately 5300 samples. As a result, a known moderate susceptibility indel variant (CHEK2 1100delC) and a catalogue of 11 rare variants presenting signs of association with breast cancer were identified. All the affected genes are involved in important cellular mechanisms like DNA repair, cell proliferation and survival or cell cycle regulation. This study highlights the need to investigate the role of rare variants in familial cancer development by means of novel high throughput analysis strategies optimized for genetically heterogeneous scenarios. Even considering the intrinsic limitations of exome resequencing studies, our findings support the hypothesis that the majority of non-BRCA1/BRCA2 breast cancer families might be explained by the action of moderate and/or low penetrance susceptibility alleles

Prospective Observational Study of Pazopanib in Patients with Advanced Renal Cell Carcinoma (PRINCIPAL Study)

Background: Real-world data are essential to accurately assessing efficacy and toxicity of approved agents in everyday practice. PRINCIPAL, a prospective, observational study, was designed to confirm the real-world safety and efficacy of pazopanib in patients with advanced renal cell carcinoma (RCC). Subjects, Materials, and Methods: Patients with clear cell advanced/metastatic RCC and a clinical decision to initiate pazopanib treatment within 30 days of enrollment were eligible. Primary objectives included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), relative dose intensity (RDI) and its effect on treatment outcomes, change in health-related quality of life (HRQoL), and safety. We also compared characteristics and outcomes of clinical-trial-eligible (CTE) patients, defined using COMPARZ trial eligibility criteria, with those of non-clinical-trial-eligible (NCTE) patients. Secondary study objectives were to evaluate clinical efficacy, safety, and RDI in patient subgroups. Results: Six hundred fifty-seven patients were enrolled and received ≥1 dose of pazopanib. Median PFS and OS were 10.3 months (95% confidence interval [CI], 9.2–12.0) and 29.9 months (95% CI, 24.7 to not reached), respectively, and the ORR was 30.3%. HRQoL showed no or little deterioration over time. Treatment-related serious adverse events (AEs) and AEs of special interest occurred in 64 (9.7%), and 399 (60.7%) patients, respectively. More patients were classified NCTE than CTE (85.2% vs. 14.8%). Efficacy of pazopanib was similar between the two groups. Conclusion: PRINCIPAL confirms the efficacy and safety of pazopanib in patients with advanced/metastatic RCC in a real-world clinical setting. Implications for Practice: PRINCIPAL is the largest (n = 657) prospective, observational study of pazopanib in patients with advanced/metastatic renal cell carcinoma, to the authors’ knowledge. Consistent with clinical trial results that often contain specific patient types, the PRINCIPAL study demonstrated that the effectiveness and safety of pazopanib is similarly safe and effective in patients with advanced kidney cancer in a real-world clinical setting. The PRINCIPAL study showed that patients with advanced kidney cancer who are treated with first-line pazopanib generally do not show disease progression for approximately 10 months and generally survive for nearly 30 months

Euclid preparation: XXXIII. Characterization of convolutional neural networks for the identification of galaxy-galaxy strong-lensing events

Forthcoming imaging surveys will increase the number of known galaxy-scale strong lenses by several orders of magnitude. For this to happen, images of billions of galaxies will have to be inspected to identify potential candidates. In this context, deep-learning techniques are particularly suitable for finding patterns in large data sets, and convolutional neural networks (CNNs) in particular can efficiently process large volumes of images. We assess and compare the performance of three network architectures in the classification of strong-lensing systems on the basis of their morphological characteristics. In particular, we implemented a classical CNN architecture, an inception network, and a residual network. We trained and tested our networks on different subsamples of a data set of 40 000 mock images whose characteristics were similar to those expected in the wide survey planned with the ESA mission Euclid, gradually including larger fractions of faint lenses. We also evaluated the importance of adding information about the color difference between the lens and source galaxies by repeating the same training on single- and multiband images. Our models find samples of clear lenses with ≳90% precision and completeness. Nevertheless, when lenses with fainter arcs are included in the training set, the performance of the three models deteriorates with accuracy values of ~0.87 to ~0.75, depending on the model. Specifically, the classical CNN and the inception network perform similarly in most of our tests, while the residual network generally produces worse results. Our analysis focuses on the application of CNNs to high-resolution space-like images, such as those that the Euclid telescope will deliver. Moreover, we investigated the optimal training strategy for this specific survey to fully exploit the scientific potential of the upcoming observations. We suggest that training the networks separately on lenses with different morphology might be needed to identify the faint arcs. We also tested the relevance of the color information for the detection of these systems, and we find that it does not yield a significant improvement. The accuracy ranges from ~0.89 to ~0.78 for the different models. The reason might be that the resolution of the Euclid telescope in the infrared bands is lower than that of the images in the visual band

Euclid preparation: XXVI. the Euclid Morphology Challenge: Towards structural parameters for billions of galaxies

The various Euclid imaging surveys will become a reference for studies of galaxy morphology by delivering imaging over an unprecedented area of 15 000 square degrees with high spatial resolution. In order to understand the capabilities of measuring morphologies from Euclid-detected galaxies and to help implement measurements in the pipeline of the Organisational Unit MER of the Euclid Science Ground Segment, we have conducted the Euclid Morphology Challenge, which we present in two papers. While the companion paper focusses on the analysis of photometry, this paper assesses the accuracy of the parametric galaxy morphology measurements in imaging predicted from within the Euclid Wide Survey. We evaluate the performance of five state-of-the-art surface-brightness-fitting codes, DeepLeGATo, Galapagos-2, Morfometryka, ProFit and SourceXtractor++, on a sample of about 1.5 million simulated galaxies (350 000 above 5σ) resembling reduced observations with the Euclid VIS and NIR instruments. The simulations include analytic Sérsic profiles with one and two components, as well as more realistic galaxies generated with neural networks. We find that, despite some code-specific differences, all methods tend to achieve reliable structural measurements (< 10% scatter on ideal Sérsic simulations) down to an apparent magnitude of about IE = 23 in one component and IE = 21 in two components, which correspond to a signal-to-noise ratio of approximately 1 and 5, respectively. We also show that when tested on non-analytic profiles, the results are typically degraded by a factor of 3, driven by systematics. We conclude that the official Euclid Data Releases will deliver robust structural parameters for at least 400 million galaxies in the Euclid Wide Survey by the end of the mission. We find that a key factor for explaining the different behaviour of the codes at the faint end is the set of adopted priors for the various structural parameters

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

What Do We Know About Neuropsychological Aspects Of Schizophrenia?

Application of a neuropsychological perspective to the study of schizophrenia has established a number of important facts about this disorder. Some of the key findings from the existing literature are that, while neurocognitive impairment is present in most, if not all, persons with schizophrenia, there is both substantial interpatient heterogeneity and remarkable within-patient stability of cognitive function over the long-term course of the illness. Such findings have contributed to the firm establishment of neurobiologic models of schizophrenia, and thereby help to reduce the social stigma that was sometimes associated with purely psychogenic models popular during parts of the 20th century. Neuropsychological studies in recent decades have established the primacy of cognitive functions over psychopathologic symptoms as determinants of functional capacity and independence in everyday functioning. Although the cognitive benefits of both conventional and even second generation antipsychotic medications appear marginal at best, recognition of the primacy of cognitive deficits as determinants of functional disability in schizophrenia has catalyzed recent efforts to develop targeted treatments for the cognitive deficits of this disorder. Despite these accomplishments, however, some issues remain to be resolved. Efforts to firmly establish the specific neurocognitive/neuropathologic systems responsible for schizophrenia remain elusive, as do efforts to definitively demonstrate the specific cognitive deficits underlying specific forms of functional impairment. Further progress may be fostered by recent initiatives to integrate neuropsychological studies with experimental neuroscience, perhaps leading to measures of deficits in cognitive processes more clearly associated with specific, identifiable brain systems

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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