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We sought to determine the utility of a new performance validity index that was recently proposed. In particular, we wanted to determine if this index would be associated with a specificity of at least.90, a sensitivity of at least.40, and an Area Under the Curve of at least.70 in a traumatic brain injury (TBI) sample. We used logistic regression to investigate how well this new index could distinguish persons with TBI (n = 148) who were evaluated within 1–36 months after injury. All participants had been classified on the basis of at least two independent performance validity tests as having provided valid performance (n = 128) or invalid performance (n = 20). The new performance validity index had acceptable specificity (.96) but had suboptimal sensitivity (.35) and Area Under the Curve (.66). It was concerning that almost half (5/12) of the cases that were identified by this index as providing invalid effort were false positives. Although a slightly more liberal cut-off improved sensitivity, the problem with poor positive predictive power remained. The conventional Forced Choice index had relatively better classification accuracy. Differences in base rates between the original sample of Martin et al. and the current one most likely affected positive predictive power of the new index. Although their performance validity has excellent specificity, the current results do not support the application of this index in the clinical evaluation of patients with traumatic brain injury when base rates of invalid performance differ markedly from those in the original study. [ABSTRACT FROM AUTHOR]

The technologies of communication saturate our life-worlds. Nowhere is this more evident than on college and university campuses where mediated communication often displaces the face-to-face variety. While college students sometimes lament that our "howzitgoing" greetings reflect shallowness and transience, their use of technologies designed to connect them with others can also produce disconnect and disenchantment. Echoing Neil Postman's (1993) contention that technology is neither additive nor subtractive, but rather "ecological" - it changes the whole - this article develops some of the implications that student technology use has for colleges as learning "communities." Calling for greater clarity in technology use-norms, and focusing on the meanings our technology has for us, it concludes with an informal experiment aimed at drawing students into decisions about how technology might be used in the classroom. [ABSTRACT FROM AUTHOR]

The article discusses various papers published in this issue including one by Carolyn Stauffer on the sexual politics of gender-based violence in South Africa, one by Savvas Daniel Georgiades on the Greek Orthodox Christian Faith, and one by David Moberg on Christian sociology.

Infusion of 13C-labeled metabolites provides a gold standard for understanding the metabolic processes used by T cells during immune responses in vivo. Through infusion of 13C-labeled metabolites (glucose, glutamine, and acetate) in Listeria monocytogenes-infected mice, we demonstrate that CD8 T effector (Teff) cells use metabolites for specific pathways during specific phases of activation. Highly proliferative early Teff cells in vivo shunt glucose primarily toward nucleotide synthesis and leverage glutamine anaplerosis in the tricarboxylic acid (TCA) cycle to support adenosine triphosphate and de novo pyrimidine synthesis. In addition, early Teff cells rely on glutamic-oxaloacetic transaminase 1 (Got1)--which regulates de novo aspartate synthesis--for effector cell expansion in vivo. CD8 Teff cells change fuel preference over the course of infection, switching from glutamine-to acetate-dependent TCA cycle metabolism late in infection. This study provides insights into the dynamics of Teff metabolism, illuminating distinct pathways of fuel consumption associated with CD8 Teff cell function in vivo. [ABSTRACT FROM AUTHOR]

The progressive decline of CD8 T cell effector function-also known as terminal exhaustion-is a major contributor to immune evasion in cancer. Yet, the molecular mechanisms that drive CD8 T cell dysfunction remain poorly understood. Here, we report that the Kelch-like ECH-associated protein 1 (KEAP1)-Nuclear factor erythroid 2-related factor 2 (NRF2) signaling axis, which mediates cellular adaptations to oxidative stress, directly regulates CD8 T cell exhaustion. Transcriptional profiling of dysfunctional CD8 T cells from chronic infection and cancer reveals enrichment of NRF2 activity in terminally exhausted (Tex term ) CD8 T cells. Increasing NRF2 activity in CD8 T cells (via conditional deletion of KEAP1) promotes increased glutathione production and antioxidant defense yet accelerates the development of terminally exhausted (PD-1 + TIM-3 + ) CD8 T cells in response to chronic infection or tumor challenge. Mechanistically, we identify PTGIR, a receptor for the circulating eicosanoid prostacyclin, as an NRF2-regulated protein that promotes CD8 T cell dysfunction. Silencing PTGIR expression restores the anti-tumor function of KEAP1-deficient T cells. Moreover, lowering PTGIR expression in CD8 T cells both reduces terminal exhaustion and enhances T cell effector responses (i.e. IFN-γ and granzyme production) to chronic infection and cancer. Together, these results establish the KEAP1-NRF2 axis as a metabolic sensor linking oxidative stress to CD8 T cell dysfunction and identify the prostacyclin receptor PTGIR as an NRF2-regulated immune checkpoint that regulates CD8 T cell fate decisions between effector and exhausted states., Competing Interests: Competing interests: RGJ is a scientific advisor for Servier Pharmaceuticals and is a member of the Scientific Advisory Board of Immunomet Therapeutics.

Infusion of 13C-labeled metabolites provides a gold-standard for understanding the metabolic processes used by T cells during immune responses in vivo . Through infusion of 13C-labeled metabolites (glucose, glutamine, acetate) in Listeria monocytogenes ( Lm )-infected mice, we demonstrate that CD8+ T effector (Teff) cells utilize metabolites for specific pathways during specific phases of activation. Highly proliferative early Teff cells in vivo shunt glucose primarily towards nucleotide synthesis and leverage glutamine anaplerosis in the tricarboxylic acid (TCA) cycle to support ATP and de novo pyrimidine synthesis. Additionally, early Teff cells rely on glutamic-oxaloacetic transaminase 1 (Got1)-which regulates de novo aspartate synthesis-for effector cell expansion in vivo . Importantly, Teff cells change fuel preference over the course of infection, switching from glutamine- to acetate-dependent TCA cycle metabolism late in infection. This study provides insights into the dynamics of Teff metabolism, illuminating distinct pathways of fuel consumption associated with Teff cell function in vivo ., Competing Interests: Competing interests: RGJ is a scientific advisor for Agios Pharmaceuticals and Servier Pharmaceuticals and is a member of the Scientific Advisory Board of Immunomet Therapeutics.