30 Years on: How the Neurodevelopmental Hypothesis of Schizophrenia Morphed into the Developmental Risk Factor Model of Psychosis

At its re-birth 30 years ago, the neurodevelopment hypothesis of schizophrenia focussed on aberrant genes and early neural hazards, but then it grew to include ideas concerning aberrant synaptic pruning in adolescence. The hypothesis had its own stormy development and it endured some difficult teenage years when a resurgence of interest in neurodegeneration threatened its survival. In early adult life, it over-reached itself with some reductionists claiming that schizophrenia was simply a neurodevelopmental disease. However, by age 30, the hypothesis has matured sufficiently to incorporated childhood and adult adversity, urban living and migration, as well as heavy cannabis use, as important risk factors. Thus, it morphed into the developmental risk factor model of psychosis and integrated new evidence concerning dysregulated striatal dopamine as the final step on the pathway linking risk factors to psychotic symptoms

Hematologic toxicity of radium-223 in elderly patients with metastatic Castration Resistant Prostate Cancer: a real-life experience

Background: Treatment with radium-223 has been shown to increase survival and to delay skeletal events related to bone metastases of patients with metastatic Castration Resistant Prostate Cancer (mCRPC). This treatment has also proved to be well tolerated, and hematological toxicity, in particular anemia, represents the most represented adverse event. Materials and methods: We evaluated the hematologic toxicity of Ra-223 treatment in a real-life experience of 38 patients from two Italian cancer centers, with bone metastases from mCRPC. The main endpoint of the study was the evaluation of the efficacy and tolerability of treatment with radium-223, with greater reference to hematological toxicity (especially anemia) as the cause of interruption of treatment, specifically in the elderly patient. Results: From August 2016 to October 2017, a total of 38 consecutive nonselected patients, 20 of them aged >75 years, with mCRPC symptomatic bone metastases, were enrolled for radium-223 at standard doses. Hematologic adverse events were recorded more frequently (72.4% with AE), and 36.8% had anemia. The most frequent cause of treatment discontinuation due to AEs was anemia [8/10 patients (80%)], followed by thrombocytopenia (2 patients) and neutropenia (1 patient). Hematologic AEs were more represented in elderly patients with greater disease burden and previously treated with docetaxel. Conclusions: Anemia is the most represented AE related to radium-223 treatment in elderly patients with greater disease burden and previously treated with docetaxel, besides representing the main reason for interruption of treatment. Correct patient selection, appropriate timing, and adequate supportive care are elements that could facilitate successful treatment with radium-223, preventing premature interruption of the same. The results of this experience support the opportunity to propose treatment with radium-223 mostly in patients in the earliest stages

A microfabricated physical sensor for atmospheric mercury monitoring,”

Abstract A new microfabricated physical sensor for elemental gaseous mercury (Hg 0 ) determinations has been developed and experimentally tested by the authors. Hg 0 represents 90-99% of atmospheric mercury forms. The sensor is based on the technique of resistivity variation of thin gold film, characterised by high selectivity and absence of optical parts. The sensor consists of four identical thin gold film resistors mounted in Wheatstone bridge configuration. Two resistors work as sensitive elements and the others as reference, in order to minimise the influence of temperature variation. The absorption of Hg 0 on the gold film produces a change in the resistivity of the amalgam. Far from the saturation, this change is proportional to the amount of the absorbed Hg 0 . The adsorption behaviour of the sensor deposited by sputtering on two different substrates (glass and Printed Circuit Board (PCB)) have been investigated. The sensors showed to work in a large range of linearity and need a low power during the regeneration process. Sensors on glass and PCB substrates underwent numerous regeneration cycles without inflicting any mechanical or electrical damages to the resistors. The presented experimental results describe the features of both sensors pointing out advantages and drawbacks of the used substrates. The PCB substrate seems to have more suitable characteristics for developing a new mercury 'smart' sensor

Strategies to develop radiomics and machine learning models for lung cancer stage and histology prediction using small data samples

Predictive models based on radiomics and machine-learning (ML) need large and annotated datasets for training, often difficult to collect. We designed an operative pipeline for model training to exploit data already available to the scientific community. The aim of this work was to explore the capability of radiomic features in predicting tumor histology and stage in patients with non-small cell lung cancer (NSCLC). We analyzed the radiotherapy planning thoracic CT scans of a proprietary sample of 47 subjects (L-RT) and integrated this dataset with a publicly available set of 130 patients from the MAASTRO NSCLC collection (Lung1). We implemented intra- and inter-sample cross-validation strategies (CV) for evaluating the ML predictive model performances with not so large datasets. We carried out two classification tasks: histology classification (3 classes) and overall stage classification (two classes: stage I and II). In the first task, the best performance was obtained by a Random Forest classifier, once the analysis has been restricted to stage I and II tumors of the Lung1 and L-RT merged dataset (AUC = 0.72 ± 0.11). For the overall stage classification, the best results were obtained when training on Lung1 and testing of L-RT dataset (AUC = 0.72 ± 0.04 for Random Forest and AUC = 0.84 ± 0.03 for linear-kernel Support Vector Machine). According to the classification task to be accomplished and to the heterogeneity of the available dataset(s), different CV strategies have to be explored and compared to make a robust assessment of the potential of a predictive model based on radiomics and ML

Comparing microphysical/dynamical outputs by different cloud resolving models: impact on passive microwave precipitation retrieval from satellite

International audienceMesoscale cloud resolving models (CRM's) are often utilized to generate consistent descriptions of the microphysical structure of precipitating clouds, which are then used by physically-based algorithms for retrieving precipitation from satellite-borne microwave radiometers. However, in principle, the simulated upwelling brightness temperatures (TB's) and derived precipitation retrievals generated by means of different CRM's with different microphysical assumptions, may be significantly different even when the models simulate well the storm dynamical and rainfall characteristics. In this paper, we investigate this issue for two well-known models having different treatment of the bulk microphysics, i.e. the UW-NMS and the MM5. To this end, the models are used to simulate the same 24-26 November 2002 flood-producing storm over northern Italy. The model outputs that best reproduce the structure of the storm, as it was observed by the Advanced Microwave Scanning Radiometer (AMSR) onboard the EOS-Aqua satellite, have been used in order to compute the upwelling TB's. Then, these TB's have been utilized for retrieving the precipitation fields from the AMSR observations. Finally, these results are compared in order to provide an indication of the CRM-effect on precipitation retrieval

Nonorographic generation of Arctic polar stratospheric clouds during

[1] During December 1999, polar stratospheric clouds (PSCs) were observed in the absence of conditions conducive to generation by topographic gravity waves. The possibility is explored that PSCs can be generated by inertia gravity waves (IGW) radiating from breaking synoptic-scale Rossby waves on the polar front jet. The aerosol features on 7 and 12 December are selected for comparison with theory and with simulations using the University of Wisconsin Nonhydrostatic Modeling System (UWNMS). Consistent with Rossby adjustment theory, a common feature in the UWNMS simulations is radiation of IGW from the tropopause polar front jet, especially from sectors which are evolving rapidly in the Rossby wave breaking process. Packets of gravity wave energy radiate upward and poleward into the cold pool, while individual wave crests propagate poleward and downward, causing mesoscale variations in vertical motion and temperature. On 12 December the eastbound DC-8 lidar observations exhibited a fairly uniform field of six waves in aerosol enhancement in the 14-20 km layer, consistent with vertical displacement by a field of IGW propagating antiparallel to the flow, with characteristic horizontal and vertical wavelengths of $300 and$10 km. UWNMS simulations show emanation of a field of IGW upward and southwestward from a northward incursion of the polar front jet. The orientation and evolution of the aerosol features on 7 December are consistent with a single PSC induced by an IGW packet propagating from a breaking Rossby wave over western Russia toward the northeast into the coldest part of the base of the polar vortex, with characteristic period $9 hours, vertical wavelength$12 km, and horizontal wavelength $1000 km. Linear theory shows that for both of these cases, IGW energy propagates upward at$1 km/hour and horizontally at $100 km/hour, with characteristic trace speed$30 m/s. The spatial orientation of the PSC along IGW phase lines is contrasted with the nearly horizontal filamentary structures in the PSC, which are indicative of flow streamlines. It is suggested that vertical displacement is a crucial factor in determining whether a PSC will form and that most PSCs are relatable to specific synoptic and mesoscale motions

Nonorographic generation of Arctic polar stratospheric clouds during

[1] During December 1999, polar stratospheric clouds (PSCs) were observed in the absence of conditions conducive to generation by topographic gravity waves. The possibility is explored that PSCs can be generated by inertia gravity waves (IGW) radiating from breaking synoptic-scale Rossby waves on the polar front jet. The aerosol features on 7 and 12 December are selected for comparison with theory and with simulations using the University of Wisconsin Nonhydrostatic Modeling System (UWNMS). Consistent with Rossby adjustment theory, a common feature in the UWNMS simulations is radiation of IGW from the tropopause polar front jet, especially from sectors which are evolving rapidly in the Rossby wave breaking process. Packets of gravity wave energy radiate upward and poleward into the cold pool, while individual wave crests propagate poleward and downward, causing mesoscale variations in vertical motion and temperature. On 12 December the eastbound DC-8 lidar observations exhibited a fairly uniform field of six waves in aerosol enhancement in the 14-20 km layer, consistent with vertical displacement by a field of IGW propagating antiparallel to the flow, with characteristic horizontal and vertical wavelengths of $300 and$10 km. UWNMS simulations show emanation of a field of IGW upward and southwestward from a northward incursion of the polar front jet. The orientation and evolution of the aerosol features on 7 December are consistent with a single PSC induced by an IGW packet propagating from a breaking Rossby wave over western Russia toward the northeast into the coldest part of the base of the polar vortex, with characteristic period $9 hours, vertical wavelength$12 km, and horizontal wavelength $1000 km. Linear theory shows that for both of these cases, IGW energy propagates upward at$1 km/hour and horizontally at $100 km/hour, with characteristic trace speed$30 m/s. The spatial orientation of the PSC along IGW phase lines is contrasted with the nearly horizontal filamentary structures in the PSC, which are indicative of flow streamlines. It is suggested that vertical displacement is a crucial factor in determining whether a PSC will form and that most PSCs are relatable to specific synoptic and mesoscale motions

The Antioxidant Potential of the Mediterranean Diet in Patients at High Cardiovascular Risk: An In-Depth Review of the PREDIMED

Cardiovascular disease (CVD) is the leading global cause of death. Diet is known to be important in the prevention of CVD. The PREDIMED trial tested a relatively low-fat diet versus a high-fat Mediterranean diet (MedDiet) for the primary prevention of CVD. The resulting reduction of the CV composite outcome resulted in a paradigm shift in CV nutrition. Though many dietary factors likely contributed to this effect, this review focuses on the influence of the MedDiet on endogenous antioxidant systems and the effect of dietary polyphenols. Subgroup analysis of the PREDIMED trial revealed increased endogenous antioxidant and decreased pro-oxidant activity in the MedDiet groups. Moreover, higher polyphenol intake was associated with lower incidence of the primary outcome, overall mortality, blood pressure, inflammatory biomarkers, onset of new-onset type 2 diabetes mellitus (T2DM), and obesity. This suggests that polyphenols likely contributed to the lower incidence of the primary event in the MedDiet groups. In this article, we summarize the potential benefits of polyphenols found in the MedDiet, specifically the PREDIMED cohort. We also discuss the need for further research to confirm and expand the findings of the PREDIMED in a non-Mediterranean population and to determine the exact mechanisms of action of polyphenols

Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis: The EU-GEI study

BACKGROUND: A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone. METHODS: We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case–control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)exposure and PRS − ORexposure − ORPRS + 1] with adjustment for potential confounders. RESULTS: There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) −1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI −6.25 to 20.88). CONCLUSIONS: Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates

Jumping to conclusions, general intelligence, and psychosis liability: Findings from the multi-centre EU-GEI case-control study

BackgroundThe 'jumping to conclusions' (JTC) bias is associated with both psychosis and general cognition but their relationship is unclear. In this study, we set out to clarify the relationship between the JTC bias, IQ, psychosis and polygenic liability to schizophrenia and IQ.MethodsA total of 817 first episode psychosis patients and 1294 population-based controls completed assessments of general intelligence (IQ), and JTC, and provided blood or saliva samples from which we extracted DNA and computed polygenic risk scores for IQ and schizophrenia.ResultsThe estimated proportion of the total effect of case/control differences on JTC mediated by IQ was 79%. Schizophrenia polygenic risk score was non-significantly associated with a higher number of beads drawn (B = 0.47, 95% CI-0.21 to 1.16, p = 0.17); whereas IQ PRS (B = 0.51, 95% CI 0.25-0.76, p < 0.001) significantly predicted the number of beads drawn, and was thus associated with reduced JTC bias. The JTC was more strongly associated with the higher level of psychotic-like experiences (PLEs) in controls, including after controlling for IQ (B =-1.7, 95% CI-2.8 to-0.5, p = 0.006), but did not relate to delusions in patients.ConclusionsOur findings suggest that the JTC reasoning bias in psychosis might not be a specific cognitive deficit but rather a manifestation or consequence, of general cognitive impairment. Whereas, in the general population, the JTC bias is related to PLEs, independent of IQ. The work has the potential to inform interventions targeting cognitive biases in early psychosis