Chronic low-grade inflammation has been observed in major depression and other major psychiatric disorders and has been implicated in metabolic changes that are commonly associated with these disorders. This raises the possibility that the effects of dysfunctional metabolism may facilitate changes in neuronal structure and function which contribute to neuroprogression. Such changes may have implications for the progress from major depression to dementia in the elderly patient. The purpose of this review is to examine the contribution of inflammation and hypercortisolaemia, which are frequently associated with major depression, to neurodegeneration and how they detrimentally impact on brain energy metabolism. A key factor in these adverse events is insulin insensitivity caused by pro-inflammatory cytokines in association with desensitised glucocorticoid receptors. Identifying the possible metabolic changes initiated by inflammation opens new targets to ameliorate the adverse metabolic changes. This has resulted in the identification of dietary and drug targets which are of interest in the development of a new generation of psychotropic drugs.

OBJECTIVES/SPECIFIC AIMS: (1) Assess if the total duration of EEG suppression during a protocolized exposure to general anesthesia predicts cognitive performance in multiple cognitive domains immediately following emergence from anesthesia. (2) Assess if the total duration of EEG suppression in the same individuals predicts the rate of cognitive recovery in a three-hour period following emergence from anesthesia. METHODS/STUDY POPULATION: This was a non-specified substudy of NCT01911195, a multicenter investigation taking place at the University of Michigan, University of Pennsylvania, and Washington University in St. Louis. 30 healthy volunteers aged 20-40 years were recruited to receive general anesthesia. Participants in the anesthesia arm were anesthetized for three hours at isoflurane levels compatible with surgery (1.3 MAC). Multichannel sensor nets were used for EEG acquisition during the anesthetic exposure. EEG suppression was detected through automated voltage-thresholded classification of 2-second signal epochs, with concordance assessed across sensors. Following return of responsiveness to verbal commands, participants completed up to three hours of serial cognitive tests assessing executive function, reaction time, cognitive throughput, and working memory. Non-linear mixed effects models will be used to estimate the initial cognitive deficit and the rate of cognitive recovery following anesthetic exposure; these measures of cognitive function will be assessed in relation to total duration of suppression during anesthesia. RESULTS/ANTICIPATED RESULTS: Participants displayed wide variability in the total amount of suppression during anesthesia, with a median of 31.2 minutes and range from 0 minutes to 115.2 minutes. Initial analyses suggest that greater duration of burst suppression had a weak relationship with participants’ initial cognitive deficits upon return of responsiveness from anesthesia. Model generation of rate of recovery following anesthetic exposure is pending, but we anticipate this will also have a weak relationship with burst suppression. DISCUSSION/SIGNIFICANCE OF IMPACT: In healthy adults receiving a standardized exposure to anesthesia without surgery, burst suppression appears to be a poor predictor of post-anesthesia cognitive task performance. This suggests that burst suppression may have limited utility as a predictive marker of post-operative cognitive functioning, particularly in young adults without significant illness.

This paper discusses a pulse electroplating method for preparing copper (Cu)-coated gas diffusion electrodes (GDEs) for the electrochemical conversion of carbon dioxide (CO2) to hydrocarbons such as ethylene. Ionomer coating and air-plasma surface pre-treatments were explored as means of hydrophilizing the carbon surface to enable adhesion of electrodeposited material. The pulsed-current electrodeposition method used successfully generated copper and copper oxide micro- and nano-particles on the prepared surfaces. Copper(I) species identified on the ionomer-treated GDEs are presumed to be highly active for the selective generation of ethylene as compared to other gaseous byproducts of CO2 reduction. Conversely, copper catalysts deposited onto plasma-treated GDEs were found to have poor activity for hydrocarbon production, likely due to substantial metallic character. Of note, plasma treatment of an ionomer-treated GDE after copper plating yielded further improvements in catalytic activity and durability towards ethylene production.

This review summarises the evidence that chronic low grade inflammation triggers changes that contribute to the mental and physical ill health of patients with major depression. Inflammation, and the activation of the hypothalamic pituitary axis by stress, are normal components of the stress response but when stress is prolonged and the endocrine and immune system become chronic resulting in the activation of the peripheral macrophages, the central microglia and hypercortisolemia, the neuronal networks are damaged and become dysfunctional. The proinflammatory cytokines, in addition to activating the hypothalamic–pituitary–adrenal axis and thereby increasing cortisol synthesis, also activate the tryptophan–kynurenine pathway. This results in the synthesis of the neurotoxic N-methyl-d-aspartate (NMDA) glutamate agonist quinolinic acid and 3-hydroxykynurenine thereby enhancing oxidative stress and contributes to neurodegeneration which characterise major depression particularly in late life.While antidepressants attenuate some of the endocrine and immune changes caused by inflammation, not all therapeutically effective antidepressants do so. This suggests that drugs which specifically target the immune, endocrine and neurotransmitter systems may be more effective antidepressants.The preliminary clinical evidence that some non-steroidal anti-inflammatory drugs, such as the cyclooxygenase 2 inhibitor celecoxib, can enhance the response to standard antidepressant treatment is therefore considered and a critical assessment made of the possible limitations of such an approach to novel antidepressant development.

Objectives: The aim of this study was to describe cognitive, academic, and psychosocial outcomes after an incident demyelinating event (acquired demyelinating syndromes, ADS) in childhood and to investigate the contribution of brain lesions and confirmed MS diagnosis on outcome. Methods: Thirty-six patients with ADS (mean age=12.2 years, SD=2.7, range: 7–16 years) underwent brain MRI scans at presentation and at 6-months follow-up. T2-weighted lesions on MRI were assessed using a binary classification. At 6-months follow-up, patients underwent neuropsychological evaluation and were compared with 42 healthy controls. Results: Cognitive, academic, and behavioral outcomes did not differ between the patients with ADS and controls. Three of 36 patients (8.3%) were identified with cognitive impairment, as determined by performance falling ≤1.5 SD below normative values on more than four independent tests in the battery. Poor performance on a visuomotor integration task was most common, observed among 6/32 patients, but this did not differ significantly from controls. Twelve of 36 patients received a diagnosis of MS within 3 years post-ADS. Patients with MS did not differ from children with monophasic ADS in terms of cognitive performance at the 6-months follow-up. Fatigue symptoms were reported in 50% of patients, irrespective of MS diagnosis. Presence of brain lesions at onset and 6 months post-incident demyelinating event did not associate with cognitive outcome. Conclusions: Children with ADS experience a favorable short-term neurocognitive outcome, even those confirmed to have MS. Longitudinal evaluations of children with monophasic ADS and MS are required to determine the possibility of late-emerging sequelae and their time course. (JINS, 2016, 22, 1050–1060)

Crop producers might be able to better manage field bindweed, an aggressive perennial weed, by utilizing tillage to bring roots to the surface where they can be consumed by ruminant livestock. The objectives of this study were to provide first perspectives on forage nutritive value of field bindweed roots and to determine root chemistry responses to Aceria malherbae, an eriophyid mite that has been released for field bindweed biocontrol in the western United States and Canada. To accomplish these objectives, root systems were sampled from A. malherbae-infested and noninfested plants occurring in an agricultural field in eastern New Mexico. Sampling took place during autumn and spring of each year for 3 consecutive yr. Results indicated that A. malherbae reduced taproot diameter and increased root concentrations of Ca, P, and Mg. However, A. malherbae did not affect root concentrations of acid detergent fiber, nonfiber carbohydrates, neutral detergent fiber (NDF), crude protein (CP), and total digestible nutrients (TDN). Overall means for NDF (33.8%), CP (11.6%), and TDN (72.1%) were similar to those reported for forages commonly grown in the region, suggesting that field bindweed roots might positively contribute to nutritional programs of ruminant livestock. These results justify subsequent studies on livestock responses to field bindweed roots and field bindweed responses to targeted root grazing.

Since our earliest days as a profession, regularities of politics have been described in terms of laws of political behavior (Bryce 1909), but not without controversy. Reviewing a century of efforts to identify laws of politics yields numerous offerings, including Duverger's (1954) and Michels' (1915) well-known contributions. Following the structure embodied in Newton's Laws of Motion, I propose three general laws of politics and government in America: (1) political objects in motion tend to stay in motion, (2) the relationship between a candidate and his or her political force is the product of campaign funding and personal likability or appeal to the press, and (3) for every political action, there is an equal and opposite reaction (i.e., “Craig Leonard Brians Law of Unintended Political Consequences”). Each law is illustrated and discussed using examples drawn from US politics. Finally, I note several potential research limitations of these proposed laws, as well as their possible utility in teaching introductory political science courses.

The idea that the cohomology of finite groups might be fruitfully approached via the cohomology of ambient semisimple algebraic groups was first shown to be viable in the papers [E. Cline, B. Parshall, and L. Scott, Cohomology of finite groups of Lie type, I, Publ. Math. Inst. Hautes Études Sci. 45 (1975), 169–191] and [E. Cline, B. Parshall, L. Scott and W. van der Kallen, Rational and generic cohomology, Invent. Math. 39 (1977), 143–163]. The second paper introduced, through a limiting process, the notion of generic cohomology, as an intermediary between finite Chevalley group and algebraic group cohomology. The present paper shows that, for irreducible modules as coefficients, the limits can be eliminated in all but finitely many cases. These exceptional cases depend only on the root system and cohomological degree. In fact, we show that, for sufficiently large $r$, depending only on the root system and $m$, and not on the prime $p$ or the irreducible module $L$, there are isomorphisms ${\mathrm{H} }^{m} (G({p}^{r} ), L)\cong {\mathrm{H} }^{m} (G({p}^{r} ), {L}^{\prime } )\cong { \mathrm{H} }_{\mathrm{gen} }^{m} (G, {L}^{\prime } )\cong {\mathrm{H} }^{m} (G, {L}^{\prime } )$, where the subscript ‘gen’ refers to generic cohomology and ${L}^{\prime } $ is a constructibly determined irreducible ‘shift’ of the (arbitrary) irreducible module $L$ for the finite Chevalley group $G({p}^{r} )$. By a famous theorem of Steinberg, both $L$ and ${L}^{\prime } $ extend to irreducible modules for the ambient algebraic group $G$ with ${p}^{r} $-restricted highest weights. This leads to the notion of a module or weight being ‘shifted $m$-generic’, and thus to the title of this paper. Our approach is based on questions raised by the third author in [D. I. Stewart, The second cohomology of simple ${\mathrm{SL} }_{3} $-modules, Comm. Algebra 40 (2012), 4702–4716], which we answer here in the cohomology cases. We obtain many additional results, often with formulations in the more general context of ${ \mathrm{Ext} }_{G({p}^{r} )}^{m} $ with irreducible coefficients.

Given a quasi-hereditary algebra , we present conditions which guarantee that the algebra obtained by grading by its radical filtration is Koszul and at the same time inherits the quasi-hereditary property and other good Lie-theoretic properties that might possess. The method involves working with a pair consisting of a quasi-hereditary algebra and a (positively) graded subalgebra . The algebra arises as a quotient of by a defining ideal of . Along the way, we also show that the standard (Weyl) modules for have a structure as graded modules for . These results are applied to obtain new information about the finite dimensional algebras (e.g., the -Schur algebras) which arise as quotients of quantum enveloping algebras. Further applications, perhaps the most penetrating, yield results for the finite dimensional algebras associated with semisimple algebraic groups in positive characteristic . These results require, at least at present, considerable restrictions on the size of .

We consider the neglected importance of temperature as an explanatory variable. We show that: (1) colder states have turnout that is high relative to the national average; (2) the coldest states in the United States were more likely to adopt Election Day Registration (EDR) than other states, and very hot states never did so; and (3) those who live in colder states live longer.