Generative Embedding for Model-Based Classification of fMRI Data

Decoding models, such as those underlying multivariate classification algorithms, have been increasingly used to infer cognitive or clinical brain states from measures of brain activity obtained by functional magnetic resonance imaging (fMRI). The practicality of current classifiers, however, is restricted by two major challenges. First, due to the high data dimensionality and low sample size, algorithms struggle to separate informative from uninformative features, resulting in poor generalization performance. Second, popular discriminative methods such as support vector machines (SVMs) rarely afford mechanistic interpretability. In this paper, we address these issues by proposing a novel generative-embedding approach that incorporates neurobiologically interpretable generative models into discriminative classifiers. Our approach extends previous work on trial-by-trial classification for electrophysiological recordings to subject-by-subject classification for fMRI and offers two key advantages over conventional methods: it may provide more accurate predictions by exploiting discriminative information encoded in 'hidden' physiological quantities such as synaptic connection strengths; and it affords mechanistic interpretability of clinical classifications. Here, we introduce generative embedding for fMRI using a combination of dynamic causal models (DCMs) and SVMs. We propose a general procedure of DCM-based generative embedding for subject-wise classification, provide a concrete implementation, and suggest good-practice guidelines for unbiased application of generative embedding in the context of fMRI. We illustrate the utility of our approach by a clinical example in which we classify moderately aphasic patients and healthy controls using a DCM of thalamo-temporal regions during speech processing. Generative embedding achieves a near-perfect balanced classification accuracy of 98% and significantly outperforms conventional activation-based and correlation-based methods. This example demonstrates how disease states can be detected with very high accuracy and, at the same time, be interpreted mechanistically in terms of abnormalities in connectivity. We envisage that future applications of generative embedding may provide crucial advances in dissecting spectrum disorders into physiologically more well-defined subgroups

Early growth patterns and cardiometabolic function at the age of 5 in a multiethnic birth cohort: the ABCD study

<p>Abstract</p> <p>Background</p> <p>The relation between fetal growth retardation and cardiovascular and metabolic diseases in later life has been demonstrated in many studies. However, debate exists around the potential independent role of postnatal growth acceleration. Furthermore, it is unknown whether a potential effect of growth acceleration on cardiovascular and metabolic function is confined to certain timeframes.</p> <p>The present study assesses the (predictive) role of prenatal and postnatal growth on 5 components of cardiovascular and metabolic function in children aged 5. The potential association of timing of postnatal growth acceleration with these outcomes will be explored.</p> <p>Methods and design</p> <p>Prospective multiethnic community-based cohort study of 8266 pregnancies (Amsterdam Born Children and their Development, ABCD study). Up till now, anthropometry of 5104 children from the original cohort was followed during the first 5 years of life, with additional information about birth weight, pregnancy duration, and various potential confounding variables.</p> <p>At age 5, various components of cardiovascular and metabolic function are being measured. Outcome variables are body size, body composition and fat distribution, insulin sensitivity, lipid profile, blood pressure and autonomic regulation of cardiovascular function.</p> <p>Discussion</p> <p>This study will be one of the first population-based prospective cohort studies to address the association between measures of both prenatal and postnatal growth and various components of cardiovascular and metabolic function. Specific attention is paid to the timing of acceleration in growth and its potential association with the outcome variables. Importantly, the longitudinal design of this study gives us the opportunity to gain more insight into growth trajectories associated with adverse outcomes in later life. If identified as an independent risk factor, this provides further basis for the hypothesis that accelerated growth during the first years of life is a modifiable factor for the prevention of cardiovascular and metabolic disorders in later life. Moreover, identification of specific vulnerable periods during development may reveal suitable timeframes for early interventions.</p

Defining genetic risk factors for scleroderma-associated interstitial lung disease

Although several genetic associations with scleroderma (SSc) are defined, very little is known on genetic susceptibility to SSc-associated interstitial lung disease (SSc-ILD). A number of common polymorphisms have been associated with SSc-ILD, but most have not been replicated in separate populations. Four SNPs in IRF5, and one in each of STAT4, CD226 and IRAK1, selected as having been previously the most consistently associated with SSc-ILD, were genotyped in 612 SSc patients, of European descent, of whom 394 had ILD. The control population (n = 503) comprised individuals of European descent from the 1000 Genomes Project. After Bonferroni correction, two of the IRF5 SNPs, rs2004640 (OR (95% CI)1.30 (1.10–1.54), p^{corr} = 0.015) and rs10488631 (OR 1.48 (1.14–1.92), p^{corr} = 0.022), and the STAT4 SNP rs7574865 (OR 1.43 (1.18–1.73), p^{corr} = 0.0015) were significantly associated with SSc compared with controls. However, none of the SNPs were significantly different between patients with SSc-ILD and controls. Two SNPs in IRF5, rs10488631 (OR 1.72 (1.24–2.39), p^{corr} = 0.0098), and rs2004640 (OR 1.39 (1.11–1.75), p^{corr} = 0.03), showed a significant difference in allele frequency between controls and patients without ILD, as did STAT4 rs7574865 (OR 1.86 (1.45–2.38), p^{corr} = 6.6 × 10^{-6}). A significant difference between SSc with and without ILD was only observed for STAT4 rs7574865, being less frequent in patients with ILD (OR 0.66 (0.51–0.85), p^{corr} = 0.0084). In conclusion, IRF5 rs2004640 and rs10488631, and STAT4 rs7574865 were significantly associated with SSc as a whole. Only STAT4 rs7574865 showed a significant difference in allele frequency in SSc-ILD, with the T allele being protective against ILD

Inhibition of the tyrosine phosphatase SHP-2 suppresses angiogenesis in vitro and in vivo

Endothelial cell survival is indispensable to maintain endothelial integrity and initiate new vessel formation. We investigated the role of SHP-2 in endothelial cell survival and angiogenesis in vitro as well as in vivo. SHP-2 function in cultured human umbilical vein and human dermal microvascular endothelial cells was inhibited by either silencing the protein expression with antisense-oligodesoxynucleotides or treatment with a pharmacological inhibitor (PtpI IV). SHP-2 inhibition impaired capillary-like structure formation (p < 0.01; n = 8) in vitro as well as new vessel growth ex vivo (p < 0.05; n = 10) and in vivo in the chicken chorioallantoic membrane (p < 0.01, n = 4). Additionally, SHP-2 knock-down abrogated fibroblast growth factor 2 (FGF-2)-dependent endothelial proliferation measured by MTT reduction ( p ! 0.01; n = 12). The inhibitory effect of SHP-2 knock-down on vessel growth was mediated by increased endothelial apoptosis ( annexin V staining, p ! 0.05, n = 9), which was associated with reduced FGF-2-induced phosphorylation of phosphatidylinositol 3-kinase (PI3-K), Akt and extracellular regulated kinase 1/2 (ERK1/2) and involved diminished ERK1/2 phosphorylation after PI3-K inhibition (n=3). These results suggest that SHP-2 regulates endothelial cell survival through PI3-K-Akt and mitogen-activated protein kinase pathways thereby strongly affecting new vessel formation. Thus, SHP-2 exhibits a pivotal role in angiogenesis and may represent an interesting target for therapeutic approaches controlling vessel growth. Copyright (C) 2007 S. Karger AG, Basel

Current challenges in software solutions for mass spectrometry-based quantitative proteomics

This work was in part supported by the PRIME-XS project, grant agreement number 262067, funded by the European Union seventh Framework Programme; The Netherlands Proteomics Centre, embedded in The Netherlands Genomics Initiative; The Netherlands Bioinformatics Centre; and the Centre for Biomedical Genetics (to S.C., B.B. and A.J.R.H); by NIH grants NCRR RR001614 and RR019934 (to the UCSF Mass Spectrometry Facility, director: A.L. Burlingame, P.B.); and by grants from the MRC, CR-UK, BBSRC and Barts and the London Charity (to P.C.

2019 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations : summary from the basic life support; advanced life support; pediatric life support; neonatal life support; education, implementation, and teams; and first aid task forces

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research

Genetic Markers of Obesity Risk: Stronger Associations with Body Composition in Overweight Compared to Normal-Weight Children

Genetic factors are important determinants of overweight. We examined whether there are differential effect sizes depending on children's body composition. We analysed data of n = 4,837 children recorded in the Avon Longitudinal Study of Parents and Children (ALSPAC), applying quantile regression with sex- and age-specific standard deviation scores (SDS) of body mass index (BMI) or with body fat mass index and fat-free mass index at 9 years as outcome variables and an "obesity-risk-allele score" based on eight genetic variants known to be associated with childhood BMI as the explanatory variable. The quantile regression coefficients increased with increasing child's BMI-SDS and fat mass index percentiles, indicating larger effects of the genetic factors at higher percentiles. While the associations with BMI-SDS were of similar size in medium and high BMI quantiles (40th percentile and above), effect sizes with fat mass index increased over the whole fat mass index distribution. For example, the fat mass index of a normal-weight (50th percentile) child was increased by 0.13 kg/m(2) (95% confidence interval (CI): 0.09, 0.16) per additional allele, compared to 0.24 kg/m(2) per allele (95% CI: 0.15, 0.32) in children at the 90th percentile. The genetic associations with fat-free mass index were weaker and the quantile regression effects less pronounced than those on fat mass index. Genetic risk factors for childhood overweight appear to have greater effects on fatter children. Interaction of known genetic factors with environmental or unknown genetic factors might provide a potential explanation of these findings

A multicentric study on stigma towards people with mental illness in health sciences students

BackgroundThere is evidence of negative attitudes among health professionals towards people with mental illness but there is also a knowledge gap on what training must be given to these health professionals during their education. The purpose of this study is to compare the attitudes of students of health sciences: nursing, medical, occupational therapy, and psychology.MethodsA comparative and cross-sectional study in which 927 final-year students from health sciences university programmes were evaluated using the Mental Illness: Clinicians' Attitudes (both MICA-2 and MICA-4) scale. The sample was taken in six universities from Chile and Spain.ResultsWe found consistent results indicating that stigma varies across university programmes. Medical and nursing students showed more negative attitudes than psychology and occupational therapy students in several stigma-related themes: recovery, dangerousness, uncomfortability, disclosure, and discriminatory behaviour.ConclusionsOur study presents a relevant description of the attitudes of each university programme for education against stigma in the formative years. Results show that the biomedical understanding of mental disorders can have negative effects on attitudes, and that education based on the psychosocial model allows a more holistic view of the person over the diagnosis

Clinical Relevance and Discriminatory Value of Elevated Liver Aminotransferase Levels for Dengue Severity

Dengue is a global public health problem, as the incidence of the disease has reached hyperendemic proportions in recent decades. Infection with dengue can cause acute, febrile illness or severe disease, which can lead to plasma leakage, bleeding, and organ impairment. One of the most prominent clinical characteristics of dengue patients is increased aspartate and alanine aminotransferase liver enzyme levels. The significance of this is uncertain, as it is transient in the majority of cases, and most patients recover uneventfully without liver damage. In this study, we characterized this phenomenon in the context of dengue severity and found that, although liver enzyme levels increased concurrently with dengue severity, they could not sufficiently discriminate between dengue fever and dengue hemorrhagic fever or between non-severe and severe dengue. Therefore clinicians may need to use other parameters to distinguish dengue severity in patients during early illness

Study of the reaction e^{+}e^{-} -->J/psi\pi^{+}\pi^{-} via initial-state radiation at BaBar

We study the process $e^+e^-\to J/\psi\pi^{+}\pi^{-}$ with initial-state-radiation events produced at the PEP-II asymmetric-energy collider. The data were recorded with the BaBar detector at center-of-mass energies 10.58 and 10.54 GeV, and correspond to an integrated luminosity of 454 $\mathrm{fb^{-1}}$. We investigate the $J/\psi \pi^{+}\pi^{-}$ mass distribution in the region from 3.5 to 5.5 $\mathrm{GeV/c^{2}}$. Below 3.7 $\mathrm{GeV/c^{2}}$ the $\psi(2S)$ signal dominates, and above 4 $\mathrm{GeV/c^{2}}$ there is a significant peak due to the Y(4260). A fit to the data in the range 3.74 -- 5.50 $\mathrm{GeV/c^{2}}$ yields a mass value $4244 \pm 5$ (stat) $\pm 4$ (syst)$\mathrm{MeV/c^{2}}$ and a width value $114 ^{+16}_{-15}$ (stat)$\pm 7$(syst)$\mathrm{MeV}$ for this state. We do not confirm the report from the Belle collaboration of a broad structure at 4.01 $\mathrm{GeV/c^{2}}$. In addition, we investigate the $\pi^{+}\pi^{-}$ system which results from Y(4260) decay