Triglyceride-rich lipoproteins prevent septic death in rats.

Triglyceride-rich lipoproteins bind and inactive bacterial endotoxin in vitro and prevent death when given before a lethal dose of endotoxin in animals. However, lipoproteins have not yet been demonstrated to improve survival in polymicrobial gram-negative sepsis. We therefore tested the ability of triglyceride-rich lipoproteins to prevent death after cecal ligation and puncture (CLP) in rats. Animals were given bolus infusions of either chylomicrons (1 g triglyceride/kg per 4 h) or an equal volume of saline for 28 h after CLP. Chylomicron infusions significantly improved survival (measured at 96 h) compared with saline controls (80 vs 27%, P < or = 0.03). Chylomicron infusions also reduced serum levels of endotoxin, measured 90 min (26 +/- 3 vs 136 +/- 51 pg/ml, mean +/- SEM, P < or = 0.03) and 6 h (121 +/- 54 vs 1,026 +/- 459 pg/ml, P < or = 0.05) after CLP. The reduction in serum endotoxin correlated with a reduction in serum tumor necrosis factor, measured 6 h after CLP (0 +/- 0 vs 58 +/- 24 pg/ml, P < or = 0.03), suggesting that chylomicrons improve survival in this model by limiting macrophage exposure to endotoxin and thereby reducing secretion of inflammatory cytokines. Infusions of a synthetic triglyceride-rich lipid emulsion (Intralipid; KabiVitrum, Inc., Alameda, CA) (1 g triglyceride/kg) also significantly improved survival compared with saline controls (71 vs 27%, P < or = 0.03). These data demonstrate that triglyceride-rich lipoproteins can protect animals from lethal polymicrobial gram-negative sepsis

Profiling Vendor Performance

Giving a single wholesaler virtually all of the Knox College Library's firm orders, in return for promises of better delivery and discount, necessitated a change in the method of evaluating wholesaler performance. Unable to compare our vendor with his competitors, we instead attempted to profile the vendor's performance, coding the firm orders by response time in weeks and then arranging them by accounts (or subject areas) and by publishers. This method allowed us to identify specific strengths and weaknesses in our vendor's stock and to determine how well he could serve the particular needs of the library. About thirty-six hundred orders in twenty-nine accounts (or subject areas) and forty trade and academic publishers were analyzed, with the results indicating that, despite the vendor's claims for the comprehensiveness of his stock, in fact, only 40 to 50 percent of our orders could be filled from his stock, and, furthermore, his performance with regard to both subjects and publishers varied as much as 50 percent. The findings suggest that order periods should be shortened from twenty or twenty-four weeks to sixteen or twelve weeks to encourage delivery and that a vendor's performances with specific subjects and publishers should be considered before placing orders

Preliminary prediction of individual response to electroconvulsive therapy using whole-brain functional magnetic resonance imaging data.

Electroconvulsive therapy (ECT) works rapidly and has been widely used to treat depressive disorders (DEP). However, identifying biomarkers predictive of response to ECT remains a priority to individually tailor treatment and understand treatment mechanisms. This study used a connectome-based predictive modeling (CPM) approach in 122 patients with DEP to determine if pre-ECT whole-brain functional connectivity (FC) predicts depressive rating changes and remission status after ECT (47 of 122 total subjects or 38.5% of sample), and whether pre-ECT and longitudinal changes (pre/post-ECT) in regional brain network biomarkers are associated with treatment-related changes in depression ratings. Results show the networks with the best predictive performance of ECT response were negative (anti-correlated) FC networks, which predict the post-ECT depression severity (continuous measure) with a 76.23% accuracy for remission prediction. FC networks with the greatest predictive power were concentrated in the prefrontal and temporal cortices and subcortical nuclei, and include the inferior frontal (IFG), superior frontal (SFG), superior temporal (STG), inferior temporal gyri (ITG), basal ganglia (BG), and thalamus (Tha). Several of these brain regions were also identified as nodes in the FC networks that show significant change pre-/post-ECT, but these networks were not related to treatment response. This study design has limitations regarding the longitudinal design and the absence of a control group that limit the causal inference regarding mechanism of post-treatment status. Though predictive biomarkers remained below the threshold of those recommended for potential translation, the analysis methods and results demonstrate the promise and generalizability of biomarkers for advancing personalized treatment strategies

Joint and individual analysis of breast cancer histologic images and genomic covariates

A key challenge in modern data analysis is understanding connections between complex and differing modalities of data. For example, two of the main approaches to the study of breast cancer are histopathology (analyzing visual characteristics of tumors) and genetics. While histopathology is the gold standard for diagnostics and there have been many recent breakthroughs in genetics, there is little overlap between these two fields. We aim to bridge this gap by developing methods based on Angle-based Joint and Individual Variation Explained (AJIVE) to directly explore similarities and differences between these two modalities. Our approach exploits Convolutional Neural Networks (CNNs) as a powerful, automatic method for image feature extraction to address some of the challenges presented by statistical analysis of histopathology image data. CNNs raise issues of interpretability that we address by developing novel methods to explore visual modes of variation captured by statistical algorithms (e.g. PCA or AJIVE) applied to CNN features. Our results provide many interpretable connections and contrasts between histopathology and genetics

Parents, children and the porous boundaries of the sexual family in law and popular culture

This article focuses on a perceived ideological overlap between popular cultural and judicial treatments of sex and conjugality that contributes to a discursive construction of parenthood and parenting. The author perceives that in both legal and popular cultural texts, there is a sense in which notions of ‘natural’ childhood are discursively constituted as being put at risk by those who reproduce outside of dominant sexual norms, and that signs of normative sexuality (typically in the form of heterosexual coupling) may be treated as a sign of safety. These ideas are rooted in ancient associations between fertility, sexuality and femininity that can also be traced in the historical development of the English language. With the help of commentators such as Martha Fineman, the article situates parents and children within a discourse of family which prioritises conjugality, with consequences for the ways in which the internal and external boundaries of families are delineated

A longitudinal investigation of the relationship between unconditional positive self-regard and posttraumatic growth

The present study investigated whether unconditional positive self-regard (UPSR) is associated with subsequent posttraumatic growth (PTG) following the experience of a traumatic life event. A total of 143 participants completed an online questionnaire to assess the experience of traumatic life events, posttraumatic stress, well-being and UPSR (Time 1). Three months later, 76 of the participants completed measures of well-being and perceived PTG (Time 2). Analyses were conducted to test for association between UPSR at Time 1 and perceptions of PTG at Time 2. Results showed that higher UPSR at T1 was associated with higher perceived PTG at Time 2. To measure actual growth, individual differences in well-being were computed between Time 1 and Time 2. Results showed that higher UPSR at T1 was associated with higher actual PTG. Implications of these findings are discussed and future directions for research in this area considered. Specifically, results are consistent with a person-centered understanding of therapeutic approaches to the facilitation of PT