Gene Expression Responses of Larval Gopher (Sebastes carnatus) and Blue (S. mystinus) Rockfish to Ocean Acidification and Hypoxia

Global climate change is driving shifts in ocean chemistry, which combined with intensification of coastal upwelling, reduces ocean pH and dissolved oxygen (DO) content in the nearshore habitats of the California Current System. Physiological plasticity, within and across generations, might be especially important for long-lived, late-to-mature species, like rockfishes (genus Sebastes), that may be unable to keep pace with climate change via genetic adaptation. Rockfishes exhibit matrotrophic viviparity and may be able to buffer their offspring from environmental stress through early developmental exposure or transgenerational plasticity (non-genetic inheritance of phenotypes). In this study, mature female gopher (S. carnatus) and blue (S. mystinus) rockfish were pre-exposed to one of four treatments; 1) control conditions, 2) low pH, 3) low DO, or 4) combined low pH/DO stressors during embryonic growth (i.e. fertilization and gestation), followed by a 5-day larval exposure after birth in either the same or a different treatment received by mothers. I used RNA sequencing to determine how the maternal environment affected larval rockfish gene expression (GE) at birth, after the 5-day larval exposure in either the same maternal treatment or a novel pH/DO environment, and between larvae sampled at birth and after the 5-day larval exposure within each treatment. For both species, I found that the maternal exposure drove larval GE patterns regardless of sampling time point or treatment. Furthermore, the maternal environment continued to strongly influence larval GE for at least the first five days after birth. In gopher rockfish, larvae differentially expressed fewer genes at birth between the control and hypoxic groups than larvae that gestated in and remained in the same treatment and were sampled after the 5-day larval exposure. Gene functions also shifted; at day 5, there was an increase in differentially expressed genes that were related to metabolic pathways, implying that the larvae in the hypoxic treatment are responding to the stressor. In both species, I found that larvae which experienced a pH and/or hypoxic stressor during the maternal exposure had fewer differentially expressed genes across time compared to larvae that experienced control conditions. This pattern remained consistent, even if the larvae were placed into control conditions for the 5-day larval exposure, indicating that exposure to low pH/DO stressors might cause a delay in development. These data suggest that rockfish may not be able to buffer their offspring from environmental stressors, highlighting the important role of the maternal environment during gestation. Between the two species, however, blue rockfish may in fact fare better in future conditions as their reproductive season occurs before the onset of strong spring upwelling, when more hypoxic and low pH water intrudes the nearshore. However, if future climate models are correct, shifts in the timing and intensity of upwelling season may overlap with the reproductive season in blue rockfish. Elucidating the critical role of the maternal environment on offspring physiology can help us better understand how economically and ecologically important species will fare in the face of climate change

Developing a health state classification system from NEWQOL for epilepsy using classical psychometric techniques and Rasch analysis: a technical report

Aims: Resource allocation amongst competing health care interventions is informed by evidence of both clinical- and cost-effectiveness. Cost-utility analysis is increasingly used to assess cost effectiveness through the use of Quality Adjusted Life Years (QALYs). This requires health state values. Generic measures of health related quality of life (HRQL) are usually used to produce these values, but there are concerns about their relevance and sensitivity in epilepsy. This study develops a health state classification system for epilepsy from the NEWQOL battery, a validated questionnaire measuring QoL in epilepsy. The classification system will be amenable to valuation for calculating QALYs. Methods: Factor and other psychometric analyses were undertaken to investigate the factor structure of the battery, and assess the validity and responsiveness of the items. These analyses were used alongside Rasch analysis to select the dimensions included in the classification system, and the items used to represent each domain. Analysis was carried out on a trial dataset of patients with epilepsy (n=1611). Rasch and factor analysis were performed on one half of the sample and validated on the remaining half. Dimensions and items were selected that performed well across all analyses. Results: The battery was found to demonstrate reliability and validity but responsiveness across time periods for many of the items was low. A six dimension classification system was developed: worry about seizures, depression, memory, cognition, stigmatism and control, each with four response levels. Conclusions: It is feasible to develop a health state classification system from a battery of instruments using a combination of classical psychometric, factor and Rasch analysis. This is the first condition-specific health state classification developed for epilepsy and the next stage will produce preference weights to enable the measure to be used in cost-utility analysis.quality adjusted life years; health related quality of life; Rasch analysis; preference-based measures of health; health states; epilepsy

Developing a health state classification system from NEWQOL for epilepsy using classical psychometric techniques and Rasch analysis: A technical report

Aims: Resource allocation amongst competing health care interventions is informed by evidence of both clinical- and cost-effectiveness. Cost-utility analysis is increasingly used to assess cost effectiveness through the use of Quality Adjusted Life Years (QALYs). This requires health state values. Generic measures of health related quality of life (HRQL) are usually used to produce these values, but there are concerns about their relevance and sensitivity in epilepsy. This study develops a health state classification system for epilepsy from the NEWQOL battery, a validated questionnaire measuring QoL in epilepsy. The classification system will be amenable to valuation for calculating QALYs. Methods: Factor and other psychometric analyses were undertaken to investigate the factor structure of the battery, and assess the validity and responsiveness of the items. These analyses were used alongside Rasch analysis to select the dimensions included in the classification system, and the items used to represent each domain. Analysis was carried out on a trial dataset of patients with epilepsy (n=1611). Rasch and factor analysis were performed on one half of the sample and validated on the remaining half. Dimensions and items were selected that performed well across all analyses. Results: The battery was found to demonstrate reliability and validity but responsiveness across time periods for many of the items was low. A six dimension classification system was developed: worry about seizures, depression, memory, cognition, stigmatism and control, each with four response levels. Conclusions: It is feasible to develop a health state classification system from a battery of instruments using a combination of classical psychometric, factor and Rasch analysis. This is the first condition-specific health state classification developed for epilepsy and the next stage will produce preference weights to enable the measure to be used in cost-utility analysis