Correspondence between fMRI and SNP data by group sparse canonical correlation analysis

Both genetic variants and brain region abnormalities are recognized as important factors for complex diseases (e.g., schizophrenia). In this paper, we investigated the correspondence between single nucleotide polymorphism (SNP) and brain activity measured by functional magnetic resonance imaging (fMRI) to understand how genetic variation influences the brain activity. A group sparse canonical correlation analysis method (group sparse CCA) was developed to explore the correlation between these two datasets which are high dimensional-the number of SNPs/voxels is far greater than the number of samples. Different from the existing sparse CCA methods (sCCA), our approach can exploit structural information in the correlation analysis by introducing group constraints. A simulation study demonstrates that it outperforms the existing sCCA. We applied this method to the real data analysis and identified two pairs of significant canonical variates with average correlations of 0.4527 and 0.4292 respectively, which were used to identify genes and voxels associated with schizophrenia. The selected genes are mostly from 5 schizophrenia (SZ)-related signalling pathways. The brain mappings of the selected voxles also indicate the abnormal brain regions susceptible to schizophrenia. A gene and brain region of interest (ROI) correlation analysis was further performed to confirm the significant correlations between genes and ROIs.     

Signaling gradients in cascades of two-state reaction-diffusion systems

Biological networks frequently use cascades, generally defined as chain-like arrangements of similar modules. Spatially lumped cascades can serve as noise filters, time-delay, or thresholding elements. The operation and functional capabilities of spatially distributed cascades are much less understood. Motivated by studies of pattern formation in the early Drosophila embryo, we analyze cascades of 2-state reaction-diffusion systems. At each stage within such as a cascade, a diffusible particle is reversibly bound by immobile traps and can be annihilated in both mobile and immobile states. When trapped, these particles drive the next stage by converting mobile particles of a different type from a passive to active form. The cascade initiated by injection of mobile particles into the first stage. We derive analytical expressions for the steady-state concentration profiles of mobile and immobile particles and analyze how the output of a cascade is controlled by properties of the constituent stages.     

Colocolic intussusception secondary to submucosal lipoma

Adult intussusception is an uncommon cause of abdominal pain and poses diagnostic challenges for emergency physicians due to its varied presenting symptoms and time course. We report a case of chronic colocolic intussusception secondary to a lead point submucosal lipoma. Dedifferentiating intussusception with or without a lead point is important in determining appropriate management.     

Validation of the Physician’s Global Assessment of Fingernail Psoriasis by Rheumatologists Treating Psoriatic Arthritis

ObjectivesThis study aimed to assess the content validity and reliability of the Physician’s Global Assessment of Fingernail Psoriasis (PGA-F) by rheumatologists treating patients with psoriatic arthritis.MethodsThere were 3 stages of analyses with 3 clinician cohort groups. Stage 1 (concept confirmation) included rheumatologist qualitative data (cohort 1) to establish content validity, acceptability, utility, and feasibility of the PGA-F in assessing nail severity. Quantitative information regarding the response category utilization in nail abnormalities was assessed by photographs. Stage 2 (inter-rater reliability) involved quantitative analysis of PGA-F data from study investigators, including rheumatologists, involved in a phase III clinical study (cohort 2) and a cohort of newly recruited rheumatologists (cohort 3). Stage 3 included known-groups validity.ResultsQualitative analyses identified consensus that the PGA-F severity levels are comprehensive of real-world patient symptoms and the instrument is simple to use and understand. Psychometric analyses support the PGA-F as a clinical outcome assessment tool. Inter-rater reliability showed rheumatologist agreement across the fingernail psoriasis severity spectrum. They were monotonically ordered by the hypothesized severity structure with excellent fit to the clinicians who evaluated them. Agreement on the rank order of the severity of the photographs in this target rheumatologist population was consistent with previous reports by dermatologists.ConclusionsThe PGA-F was shown to be usable by rheumatologists to measure patients along the full range of the fingernail psoriasis severity spectrum, have a strong relationship with a conceptually similar reference measure, differentiate among patients based on fingernail psoriasis severity, and detect category severity change over a 24-week period.     

Risk factors of breakthrough aspergillosis in lung transplant recipients receiving itraconazole prophylaxis

IntroductionInvasive Aspergillus infection (IA) in lung transplantation can result in poor outcomes. Itraconazole has been shown to be effective for fungal prophylaxis in lung transplant recipients. However, IA remains a major cause of death after lung transplantation. Therefore, we aimed to clarify the risk factors for IA on itraconazole prophylaxis.MethodsWe examined 120 recipients to uncover their IA epidemiology, clinical characteristics, and outcomes. In addition, a case-control study was performed to identify risk factors of IA.ResultsOf the 120 patients, 12 developed IA under itraconazole prophylaxis. The patient demographics and clinical characteristics were compared among the following two groups: IA group, 12 patients, and control group, 108 patients. Significant differences were observed in age (p = 0.004), history of interstitial pneumonia (p = 0.032), and CMV infection (p < 0.001) between the groups. Before the onset of IA, 92% (11/12) of the patients received itraconazole with trough concentrations above the therapeutic range. IA developed at 272.9 ± 114.1 days after lung transplantation. Of the 12 patients who developed IA, 66.7% (8/12) had early cessation of cytomegalovirus (CMV) prophylaxis due to toxicity of valganciclovir, as follows: leukocytopenia in 4 patients, and renal dysfunction in 4 patients. Of the 8 patients who stopped valganciclovir, 75% (6/8) developed CMV infection subsequently.ConclusionThis study suggests that older age, history of interstitial pneumonia, and CMV infection may be important risk factors for IA on itraconazole prophylaxis. These results may help clinicians optimize prophylactic strategies for IA.     

RCT of mind reading as a component of a psychosocial treatment for high-functioning children with ASD

This randomized controlled trial evaluated the efficacy of mind reading as a component of a comprehensive psychosocial treatment for 36 high-functioning children, ages 7–12 years with ASD (HFASD). All participants received the comprehensive 5-week summer treatment (summerMAX), with half randomly assigned to also receive mind reading (emotion-recognition) computer instruction as part of the treatment (summerMAX + MR). Primary analyses of proximal measures indicated significantly better performance on face emotion-recognition testing for the summerMAX + MR group (vs. summerMAX alone), and significant gains in voice emotion-recognition child testing and parent- and clinician-rated emotion recognition skills for the overall group, but no between-groups differences. Secondary analyses of distal measures indicated significant improvements on broader emotion-recognition child testing and parent and clinician ratings of program-targeted social/social-communication skills, broad social skills, and ASD-related symptoms for the overall group (summerMAX + MR and summerMAX combined) and no significant differences between the conditions (summerMAX + MR vs. summerMAX). Results suggested that mind reading may result in significant but narrow gains when included as part of this intensive psychosocial treatment for children with HFASD.