Classification of first-episode psychosis using cortical thickness: A large multicenter MRI study.

Machine learning classifications of first-episode psychosis (FEP) using neuroimaging have predominantly analyzed brain volumes. Some studies examined cortical thickness, but most of them have used parcellation approaches with data from single sites, which limits claims of generalizability. To address these limitations, we conducted a large-scale, multi-site analysis of cortical thickness comparing parcellations and vertex-wise approaches. By leveraging the multi-site nature of the study, we further investigated how different demographical and site-dependent variables affected predictions. Finally, we assessed relationships between predictions and clinical variables. 428 subjects (147 females, mean age 27.14) with FEP and 448 (230 females, mean age 27.06) healthy controls were enrolled in 8 centers by the ClassiFEP group. All subjects underwent a structural MRI and were clinically assessed. Cortical thickness parcellation (68 areas) and full cortical maps (20,484 vertices) were extracted. Linear Support Vector Machine was used for classification within a repeated nested cross-validation framework. Vertex-wise thickness maps outperformed parcellation-based methods with a balanced accuracy of 66.2% and an Area Under the Curve of 72%. By stratifying our sample for MRI scanner, we increased generalizability across sites. Temporal brain areas resulted as the most influential in the classification. The predictive decision scores significantly correlated with age at onset, duration of treatment, and positive symptoms. In conclusion, although far from the threshold of clinical relevance, temporal cortical thickness proved to classify between FEP subjects and healthy individuals. The assessment of site-dependent variables permitted an increase in the across-site generalizability, thus attempting to address an important machine learning limitation.

Long-term trajectories of cognitive deficits in schizophrenia: A critical overview.

BACKGROUND: Cognitive disturbances are widely pronounced in schizophrenia and schizophrenia spectrum disorders. Whilst cognitive deficits are well established in the prodromal phase and are known to deteriorate at the onset of schizophrenia, there is a certain discrepancy of findings regarding the cognitive alterations over the course of the illness. METHODS: We bring together the results of the longitudinal studies identified through PubMed which have covered more than 3 years follow-up and to reflect on the potential factors, such as sample characteristics and stage of the illness which may contribute to the various trajectories of cognitive changes. RESULTS: A summary of recent findings comprising the changes of the cognitive functioning in schizophrenia patients along the longitudinal course of the illness is provided. The potential approaches for addressing cognition in the course of schizophrenia are discussed. CONCLUSIONS: Given the existing controversies on the course of cognitive changes in schizophrenia, differentiated approaches specifically focusing on the peculiarities of the clinical features and changes in specific cognitive domains could shed light on the trajectories of cognitive deficits in schizophrenia and spectrum disorders.

Uncertainties in internal doses calculated for Mayak workers--a study of 63 cases.

This study makes use of 63 cases of Mayak workers exposed to Pu-239 with autopsy data and some late-time urine bioassay data. In addition, air-concentration data--used to construct monthly average values--are available for each case, which provide the time dependence and potential magnitudes of normal inhalation intakes for each case. The purpose of the study is to develop and test Bayesian methods of dose calculation for the Mayak workers. The first part of the study was to quantitatively characterise the uncertainties of the bioassay data. Then, starting with three different published biokinetic models, the data are fit by varying intake and model perturbation parameters, e.g., parameters influencing the lung, thoracic lymph nodes, liver and bone retention. Statistical self-consistency arguments are used to check the measurement uncertainty parameters within the Poisson-lognormal model. The second part of the study is to set up and test Bayesian dose calculations, which use the point determinations of biokinetic parameters from the study cases within a discrete, empirical Bayes approximation. The main conclusion of the study is that these methods are now ready to be applied to the entire Mayak worker population.

Plutonium microdistribution in the lungs of Mayak workers.

The degree of nonuniform distribution of plutonium in the human lung has not been determined; thus current dosimetric models do not account for nonuniform irradiation. A better scientific basis is needed for assessing the risk of developing radiation-induced disease from inhaled alpha-particle-emitting radionuclides. We measured the distribution of plutonium activity in the lung by autoradiography and related the activity to specific compartments of the lung. The study materials were lung specimens from deceased workers employed by the Mayak Production Association. The approach to analyzing these lung samples used contemporary stereological sampling and analysis techniques together with quantitative alpha-particle autoradiography. For the first time, plutonium distribution has been quantified in the human lung. The distribution of long-term retained plutonium is nonuniform, and a significant portion of plutonium was retained in pulmonary scars. In addition, a large fraction of plutonium was present in the parenchyma, where it was retained much longer than was estimated previously. The sequestration of plutonium particles in scars would greatly reduce the radiation exposure of the critical target cells and tissues for lung cancer. Thus the prolonged retention of plutonium in lung scars may not increase the dose or risk for lung cancer.

Distribution of plutonium particles in the lungs of Mayak workers.

Lung tissues from workers at the Mayak Production Association were examined to determine the distribution of plutonium (Pu) activity in various lung compartments. Stereological sampling methods and autoradiography were used. Pu particles were identified by microscopic examination of autoradiographs and localised in one of six normal anatomic sites and two sites of fibrosis (parenchymal, non-parenchymal). Particle activity was determined by counting the number of tracks emanating from the particles. Over 50% of the Pu activity was localised in sites of fibrosis, which had significantly higher than average activity for the lung. Over 40% of the activity was in lung parenchyma. Activity in the bronchovascular interstitium was significantly lower than average. These results support the hypothesis that Pu activity is not uniformly distributed in the lung, with long-term retained particles concentrated in scars of the lung. The results may significantly affect estimates of dose from inhaled Pu.

Modifying the ICRP 66 dosimetry model based on results obtained from Mayak plutonium workers.

Results obtained in a study of the microscopic distribution of plutonium in the lungs of deceased Pu workers from the Mayak Production Association showed that the long-term retention of Pu was greater than predicted by the current ICRP 66 respiratory tract dosimetry model (HRTM). These data were therefore applied to the HRTM by modifying selected parameters, namely the transfer rate of Pu from the transformed state compartment and the fraction of Pu that transfers to the bound state compartment. Invoking the latter compartment into the modelling allowed a better representation of the long-term Pu retention as well as providing a convenient means of describing the workplace-specific characteristics of the different Pu aerosols found in the Mayak plant. In particular, the present model describes a significantly greater long-term retention of Pu nitrate aerosols in the lung compared with the Type M default.

Assessing the uniformity of plutonium alpha radiation dose in human lung: the Mayak experience.

Radiation-induced lung cancer risk is currently estimated based on epidemiological data from populations exposed either to relatively uniform, low-LET radiation, or from uranium miners who inhaled radon and its progeny. Inhaled alpha-emitting radionuclides (e.g. Pu and Am) produce distinctive dose patterns that may not be adequately modelled at present. Thus the distribution of Pu is being measured in formalin-fixed autopsy lung tissue from former workers at the Mayak Production Association, and which is maintained in a tissue archive at SUBI. Lungs are sampled using contemporary stereological techniques and Pu particle activities and locations are determined using quantitative autoradiography and morphological identification of lung structures. To date, > 80% of Pu particles have been observed in parenchymal lung tissues with higher concentrations being found in scar tissue. Concentrations of Pu particles in conducting airways are uniformly low, thus indicating that long-term-retained Pu particles are non-uniformly distributed in human lung, mostly in the parenchyma.