Low autocorrelated multi-phase sequences

The interplay between the ground state energy of the generalized Bernasconi model to multi-phase, and the minimal value of the maximal autocorrelation function, $C_{max}=\max_K{|C_K|}$, $K=1,..N-1$, is examined analytically and the main results are: (a) The minimal value of $\min_N{C_{max}}$ is $0.435\sqrt{N}$ significantly smaller than the typical value for random sequences $O(\sqrt{\log{N}}\sqrt{N})$. (b) $\min_N{C_{max}}$ over all sequences of length N is obtained in an energy which is about 30% above the ground-state energy of the generalized Bernasconi model, independent of the number of phases m. (c) The maximal merit factor $F_{max}$ grows linearly with m. (d) For a given N, $\min_N{C_{max}}\sim\sqrt{N/m}$ indicating that for m=N, $\min_N{C_{max}}=1$, i.e. a Barker code exits. The analytical results are confirmed by simulations.Comment: 4 pages, 4 figure

A better understanding of the impact of childhood trauma on depression in early psychosis: A differential item functioning approach.

Childhood trauma (CT) has been shown to impact depressive symptoms measured broadly in early psychosis patients. Beyond the broad intensity of such impact, less is known about which depressive features are more impacted. Patients of a specialized early intervention programme were evaluated after the first two and six months of treatment with the Montgomery-Asberg Depression Rating Scale (MADRS). We used the first assessment available. We estimated an Item-response model to reveal potential differential item functioning (DIF) in order to highlight depressive features that could be impacted differently than others by experiences of abuse (sexual physical and emotional) and neglect (physical and emotional). Two hundred and sixty-two recent onset patients with psychosis were assessed. Results at the beginning of the Treatment and Early Intervention in Psychosis Program (TIPP) showed that abuse but not neglect was associated with more severe depression levels, measured at a global MADRS score. Concerning specific depressive symptoms, concentration difficulties were left largely unaffected by abuse in contrast with other aspects of depression. The cognitive item of the depressive dimension assessed by the MADRS was not impacted by experiences of abuse, while the remaining subdomains involving anxiety, suicidality, somatic symptoms, and anhedonia were. Trials focusing on improving the impact of depression in traumatised individuals should account for the possible diluting effect of concentration when measuring the depression broadly. DIF is a promising method to better understand the impact many variables may have on various psychological dimensions at the item level

Six months functional response to early psychosis intervention program best predicts outcome after three years.

Not all patients respond well to early interventions for their psychosis. The present study's goal was to evaluate whether patients' responses in the first six months of treatment in a specialised three-year programme could predict final outcomes. 206 early psychosis patients were assessed at baseline, using a large set of sociodemographic and clinical variables, and then monitored for 36 months. Among those variables, changes in their Global Assessment of Functioning (GAF) scores during the first six months were used to predict outcomes after three years. Changes in GAF scores during the first six months were the only variables that predicted every symptom of functional outcome. GAF scores were also always the first or second most important predictor for every outcome. This finding held for both high- and low-functioning patients at baseline. Predicting poor long-term outcomes after only six months should help clinicians to improve treatments

Symptom dimensions stability over time in recent onset psychosis: A prospective study.

The factorial structure of schizophrenia symptoms has been much debated but little is known on its degree of unicity, specificity as well as its dynamic over time. Symptom differentiation is a phenomenon according to which patients' symptoms could differentiate from one another during illness to form more independent, distinct dimensions. On the contrary, symptom dedifferentiation is an increase in the correlations between those symptoms over time. The goal of this study was to investigate symptom differentiation or dedifferentiation over time in recent onset psychosis using the Positive and Negative Syndrome Scale. A confirmatory factor analysis model based on the consensus five-factor model of the Positive and Negative Syndrome Scale for schizophrenia was estimated on seven different time points over a three-year period. A general factor capturing common variance between every symptom was also included. Explained common variance was computed for the general factor and each specific factor. Three hundred and sixty-two recent onset psychosis patients were assessed. Results showed no evidence for either symptom differentiation or dedifferentiation over time. Specific symptoms accounted for >70 % of the variance suggesting a high degree of specificity of the symptomatology. Overall, this study adds support for a highly multidimensional approach to clinical symptom assessment with an explicit focus on depression. The premise behind the staging approach being inherently one-dimensional, implications for further research is discussed

The differential impact of duration of untreated psychosis on functioning and quality of life: a threshold analysis

AIM: Reduction of duration of untreated psychosis (DUP) remains a key goal of early intervention programs. While a significant body of literature suggests that a short DUP has a positive impact on outcome, little is known regarding the threshold above which various dimensions of outcome are impaired. In this study, we explore the DUP threshold that best discriminates subgroups with poorer outcome regarding global functioning and quality of life after 3 years of treatment. METHOD: A total of 432 patients were followed-up prospectively over 3 years. Several hypothetical cut-off points for DUP were tested in order to maximize differences in effect size for quality of life and general functioning. RESULTS: While a DUP cut-off of 86 weeks defined two subpopulations with a difference of greatest effect size in quality of life after 3 years, it is already at a cut-off of 3 weeks of DUP that two subpopulations with a difference in global functioning of the greatest effect size was reached. CONCLUSION: DUP seems to have a differential impact on the various components of outcome, and in particular on quality of life and global functioning. Our data suggest that aiming at very short DUP is justified, but that DUP over 3 weeks are still compatible with good quality of life after 3 years of treatment

ESR Statement on the Validation of Imaging Biomarkers

Medical imaging capable of generating imaging biomarkers, specifically radiology and nuclear medicine image acquisition and analysis processes, differs from frequently used comparators like blood or urine biomarkers. This difference arises from the sample acquisition methodology. While different analysis methodologies and equipment provide slightly different results in any analytical domain, unlike blood or urine analysis where the samples are obtained by simple extraction or excretion, in radiology the acquisition of the sample is heterogeneous by design, since complex equipment from different vendors is used. Therefore, with this additional degree of freedom in medical imaging, there is still risk of persistent heterogeneity of image quality through time, due to different technological implementations across vendors and protocols used in different centres. Quantitative imaging biomarkers have yet to demonstrate an impact on clinical practice due to this lack of comprehensive standardisation in terms of technical aspects of image acquisition, analysis algorithms, processes and clinical validation. The aim is establishing a standard methodology based on metrology for the validation of image acquisition and analysis methods used in the extraction of biomarkers and radiomics data. The appropriate implementation of the guidelines herein proposed by radiology departments, research institutes and industry will allow for a significant reduction in inter-vendor & inter-centre variability in imaging biomarkers and determine the measurement error obtained, enabling them to be used in imaging-based criteria for diagnosis, prognosis or treatment response, ultimately improving clinical workflows and patient care. The validation of developed analytical methods must be based on a technical performance validation and clinical validation

Age at the time of onset of psychosis: A marker of specific needs rather than a determinant of outcome?

While there is suggestion that early onset of psychosis is a determinant of outcome; knowledge regarding correlates of later onset age is more limited. This study explores the characteristics of patients developing psychosis after age 26, towards the end of the usual age range of early intervention programs, in order to identify potential specific needs of such patients. Two hundred and fifty-six early psychosis patients aged 18-35 were followed-up prospectively over 36 months. Patients with onset after 26 ("later onset", LO) were compared to the rest of the sample. LO patients (32% of the sample) had shorter DUP, were less likely to be male, had better premorbid functioning and were more likely to have been exposed to trauma. They had greater insight at presentation and less negative symptoms overall. The trajectories for positive and depressive symptoms were similar in both groups. Evolution of functional level was similar in both groups, but while LO patients recovered faster, they were significantly less likely to return to premorbid functional level. Later psychosis onset correlates with better premorbid functioning and higher rate of trauma exposure; the latter should therefore be a treatment focus in such patients. LO patients were less likely to return to premorbid functional level, which suggests that current treatment strategies may not be efficient to help patients maintain employment. The possibility of distinct illness mechanisms according to onset age and the more central role for trauma in patients with onset after age 26 needs to be further explored

Association of overcrowding and turnover with self-harm in a swiss pre-trial prison

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Self-harm is a common issue in detention and includes both suicidal and non-suicidal behaviours. Beyond well-known individual risk factors, institutional factors such as overcrowding (i.e., when the prison population exceeds its capacity) and turnover (i.e., the rate at which the prison population is renewed), may also increase the risk of self-harm. However, these factors are understudied or previous studies reported inconsistent findings. This study investigated the association of self-harm with overcrowding and turnover in the largest pre-trial Swiss prison in Geneva. Data were collected yearly between 2011 and 2017. Measures included self-harm (all kinds of self-injuring acts requiring medical attention, including self-strangulations and self-hangings). We performed meta-regressions to analyse the relationships between self-harm and institutional factors. Self-harm events were frequent, with a prevalence estimate of 26.4%. Overcrowding and turnover were high (average occupation rate of 177% and average turnover of 73%, respectively). Overcrowding and turnover were significantly associated with self-harm (respectively b = 0.068, p < 0.001 and (b = 1.257, p < 0.001). In both cases, self-harm was higher when overcrowding and turnover increased. Overcrowding and turnover raise important human rights concerns and have damaging effects on the health of people living in detention. Identification of and care for this vulnerable population at risk of self-harm are needed and institutional factors should be addressed

Influence of density and salinity on larval development of salt-adapted and salt-naïve frog populations

Environmental change and habitat fragmentation will affect population densities for many species. For those species that have locally adapted to persist in changed or stressful habitats, it is uncertain how density dependence will affect adaptive responses. Anurans (frogs and toads) are typically freshwater organisms, but some coastal populations of green treefrogs (Hyla cinerea) have adapted to brackish, coastal wetlands. Tadpoles from coastal populations metamorphose sooner and demonstrate faster growth rates than inland populations when reared solitarily. Although saltwater exposure has adaptively reduced the duration of the larval period for coastal populations, increases in densities during larval development typically in-crease time to metamorphosis and reduce rates of growth and survival. We test how combined stressors of density and salinity affect larval development between salt-adapted (“coastal�) and nonsalt-adapted (“inland�) populations by measuring various developmental and metamorphic phenotypes. We found that increased tadpole density strongly affected coastal and inland tadpole populations similarly. In high-density treatments, both coastal and inland populations had reduced growth rates, greater exponential decay of growth, a smaller size at metamorphosis, took longer to reach metamorphosis, and had lower survivorship at metamorphosis. Salinity only exaggerated the effects of density on the time to reach metamorphosis and exponential decay of growth. Location of origin affected length at metamorphosis, with coastal tadpoles metamorphosing slightly longer than inland tadpoles across densities and salinities. These findings confirm that density has a strong and central influence on larval development even across divergent populations and habitat types and may mitigate the expression (and therefore detection) of locally adapted phenotypes

Complement Activation Determines the Therapeutic Activity of Rituximab In Vivo

Rituximab is an anti-CD20 chimeric mAb effective for the treatment of B-NHL. It can lyse lymphoma cells in vitro through both C- and Ab-dependent cellular cytotoxicity. The mechanism of action of rituximab in vivo is however still unclear. We have set up a new in vivo model in nonimmunodeficient mice by stable transduction of the human CD20 cDNA in the murine lymphoma line EL4. Animals injected i.v. with the EL4-CD20+ lymphoma cells died within 30 days with evident liver, spleen, and bone marrow involvement, confirmed by immunohistochemistry and PCR analysis. A single injection of rituximab or the murine anti-CD20 Ab 1F5, given i.p. 1 day after the tumor, cured 100% of the animals. Indeed, at week 4 after tumor cell inoculation, CD20+ cells were undetectable in all organs analyzed in rituximab-treated animals, as determined by immunohistochemistry and PCR. Rituximab had no direct effect on tumor growth in vitro. Depletion of either NK cells or neutrophils or both in tumor-injected animals did not affect the therapeutic activity of the drug. Similarly, rituximab was able to eradicate tumor cells in athymic nude mice, suggesting that its activity is T cell independent. In contrast, the protective activity of rituximab or the 1F5 Ab was completely abolished in syngeneic knockout animals lacking C1q, the first component of the classical pathway of C (C1qa−/−). These data demonstrate that C activation is fundamental for rituximab therapeutic activity in vivo