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The nervous system of C. elegans plays a role in the orchestration of systemic stress responses. One of these stress responses, the unfolded protein response of the endoplasmic reticulum (UPRER), is activated to re-establish protein homeostasis (proteostasis) upon the detection of ER stress. Overexpression of active, spliced XBP-1 (XBP-1s), a transcription factor that acts downstream of the UPRER kinase/endoribonuclease IRE-1, in the nervous system of C. elegans increases the lifespan and healthspan of worms through UPRER induction in the intestine cell non-autonomously. To investigate XBP-1s-dependent changes in the nervous system of these animals, we conducted tissue-specific RNA-Seq in neurons. This approach allowed us to characterise differentially regulated neuronal and synaptic components, which may mediate changes to the nervous system that cause the release of inter-tissue UPRER-activating signals. Furthermore, we extended our tissue-specific RNA-Seq analyses to the intestine, using intestinal cells from neuronal xbp-1s- or intestinal xbp-1s-overexpressing worms. We identified lysosomal gene upregulation in the intestine, which leads to activation of intestinal lysosomes downstream of neuronal xbp-1s. Moreover, comparison of cell autonomous and cell non-autonomous targets of XBP-1s within the intestine showed that XBP-1s has different but overlapping sets of target genes via different activation mechanisms. We also employed a candidate screening approach based on our previous finding that neurotransmitter secretion is required for intestinal UPRER activation upon neuronal xbp-1s overexpression, and identified positive and negative regulators of intestinal UPRER activation. This showed that distal UPRER activation relies on tyramine/octopamine production, and is modulated by the worm TGF-β homologue DAF-7. We then asked whether neuronal xbp-1s can affect other systemic outputs requiring neuron-specific functions, such as the regulation of behaviour. We found that a branch of the neuronal circuitry required to activate UPRER in the intestine following neuronal XBP-1s overexpression is also required to generate neuronal xbp-1s-dependent behavioural phenotypes in food-leaving and reproduction. These findings suggest that inter-tissue UPRER activation, increased longevity and healthspan can be coordinately regulated with stress-responsive behaviour by the activation of XBP-1s in the nervous system.

The treatment of serious mental illness has come a long way in just the last few decades, changing even what “mental health recovery” means. Parallel to this development, new measurements have evolved to capture the new meaning of recovery. The current study examined the reliability and validity, of a consumer-driven recovery measure, the Mental Health Recovery Measure (MHRM). The MHRM is a 30-item scale developed based on a grounded theory analysis (Young & Ensing, 1999) of information from individuals with severe and persistent mental illness regarding their understanding of the “lived experience” of recovery. The MHRM has previously been found (Bullock, 2005; Young, Ensing, & Bullock, 2000) to have good internal and test-retest reliability, convergent validity with other measures of recovery, and utility in the assessment of recovery following participation in recovery-focused treatment programs (Bullock, Sage, Hupp, O’Rourke, & Smith, 2009). The psychometric properties of the MHRM have been studied using classical statistical methods, which have limitations. The current study used the Rasch framework (Linacre, 2012a), which has significant advantages over the classical methods, including the ability to make sample-free examinations. The current study used data from 1116 individuals with severe and persistent mental illness who attended the introductory session of the Wellness Management and Recovery (WMR) program in a variety of community mental health centers, consumer operated sites, vocational rehabilitation services and state psychiatric hospitals across Ohio. Analyses revealed that the MHRM has acceptable item and person reliability. However, examination of the response category diagnostics revealed that the 5-point item response scale was not used as expected by participant respondents. A modification of the response categories in which a 3-point response scale was developed revealed improved category functioning. The current 30 items comprising the MHRM appear to measure a single construct and the Rasch analyses did not support deletion of any items or shortening of the measure. The order of item difficulties was consistent with the recovery model; however, problems were identified regarding targeting people with very high and low levels of recovery and potential solutions to these problems are discussed.

Seismic site response analysis is used to assess the effect of site-specific soil conditions on expected earthquake ground motions. For this purpose, input earthquake rock motions are propagated through a site-specific soil column to obtain motions at the ground surface. Due to the high variability in the expected input rock motions, a suite of input motions must be used and the number of motions should be relatively large to obtain a statistically stable estimate of the surface response spectrum. Unfortunately, the number of input motions used in practice in a site response evaluation is generally less than five, which results in uncertain predictions of the surface ground motion. An alternative to conventional site response analysis is a Random Vibration Theory (RVT) approach. Due to its stochastic nature, RVT analysis can provide an estimate of the site response without the need to choose any input time histories for analysis. Therefore, RVT is a potentially powerful tool for site response analysis that can provide fast and accurate estimates of the surface ground motion at a site. This study applies RVT to equivalent-linear site response analysis and provides site-specific comparisons between RVT site response analysis and traditional site response analysis, which uses time-domain input rock motions. Comparisons are made for various site conditions and earthquake scenarios. The site amplification predicted by RVT was similar to that predicted from the time domain simulations for most periods. However, at the fundamental site period, RVT-based analysis tended to overpredict amplification. A study was performed in which the time series parameters incorporated in RVT were computed from recorded ground motions and compared with those from RVT theoretical predictions. These comparisons were generally favorable, given that the duration of the forward directivity motions was appropriately characterized. RVT site response analysis for forward-directivity motions was performed by characterizing the near-fault, forward-directivity input motions via modified acceleration response spectra with enhanced long period spectral values. Time history site response analyses were performed with forward-directivity and non-directivity input rock motions. In general, the RVT analysis did not accurately predict the site response for the forward directivity motions, revealing that a more thorough characterization of the forwarddirectivity motions is required for input into RVT site response.