title: Effect of novel ketamine-analogue R5 on brain activation and select behavioural parameters

authors: Head, Mitchell Antony

subjects: anaesthetic

abstract: Ketamine is a common anaesthetic that works through complex neural mechanisms, including multiple molecular and circuitry targets. Importantly, it promotes analgesia, though it also induces undesirable effects, such as agitation, disorientation, hallucinations and nausea. Thus, there is an ongoing search for novel ketamine analogues that influence a similar repertoire of brain targets as ketamine, whose beneficial effects are potentiated. The present project, utilizing rats as an animal model, focused on examining functional properties of the ester-analogue of ketamine, R5, whose potentially beneficial profile had been suggested by preliminary studies. First, brain activation patterns following R5 compared to ketamine (and another ester-analogue control compound, R1) were assessed by employing immunohistochemical detection of an immediate-early gene product, c-Fos. R5 produced a somewhat similar pattern of activity as ketamine, whereas more profound differences in c-Fos were detected after R1. It was particularly striking in areas related to pain and addiction, including the anterior insular cortex (AIC) and paraventricular nucleus (PVN). Therefore, in the subsequent set of experiments, effects of R5 on pain- and addiction-related behavioral parameters were assessed in rats injected with R5 intracerebroventricularly (ICV) or intraparenchymally. It was found that BaCl attenuated ICV R5-induced analgesia. AIC administration of R5 produced modest analgesia in the tail-flick test. Finally, PVN R5 reduced naltrexone-precipitated exercise-induced withdrawal. In sum, R5 shows an analgesic effect similar to ketamine, most likely by targeting a similar subset of brain sites, which suggests that this particular ester-analogue can be considered as a good candidate for conceptualizing future pain management strategies.

text: Effect of novel ketamine-analogue R5 on brain activation and select behavioural parameters Ketamine is a common anaesthetic that works through complex neural mechanisms, including multiple molecular and circuitry targets. Importantly, it promotes analgesia, though it also induces undesirable effects, such as agitation, disorientation, hallucinations and nausea. Thus, there is an ongoing search for novel ketamine analogues that influence a similar repertoire of brain targets as ketamine, whose beneficial effects are potentiated. The present project, utilizing rats as an animal model, focused on examining functional properties of the ester-analogue of ketamine, R5, whose potentially beneficial profile had been suggested by preliminary studies. First, brain activation patterns following R5 compared to ketamine (and another ester-analogue control compound, R1) were assessed by employing immunohistochemical detection of an immediate-early gene product, c-Fos. R5 produced a somewhat similar pattern of activity as ketamine, whereas more profound differences in c-Fos were detected after R1. It was particularly striking in areas related to pain and addiction, including the anterior insular cortex (AIC) and paraventricular nucleus (PVN). Therefore, in the subsequent set of experiments, effects of R5 on pain- and addiction-related behavioral parameters were assessed in rats injected with R5 intracerebroventricularly (ICV) or intraparenchymally. It was found that BaCl attenuated ICV R5-induced analgesia. AIC administration of R5 produced modest analgesia in the tail-flick test. Finally, PVN R5 reduced naltrexone-precipitated exercise-induced withdrawal. In sum, R5 shows an analgesic effect similar to ketamine, most likely by targeting a similar subset of brain sites, which suggests that this particular ester-analogue can be considered as a good candidate for conceptualizing future pain management strategies.

year: 2017

title: Cross-cultural validation of the stroke riskometer using generalizability theory (vol 11, 19064, 2021)

authors: Medvedev, Oleg N.

subjects: Science & Technology

abstract: The Stroke Riskometer mobile application is a novel, validated way to provide personalized stroke risk assessment for individuals and motivate them to reduce their risks. Although this app is being used worldwide, its reliability across different countries has not yet been rigorously investigated using appropriate methodology. The Generalizability Theory (G-Theory) is an advanced statistical method suitable for examining reliability and generalizability of assessment scores across different samples, cultural and other contexts and for evaluating sources of measurement errors. G-Theory was applied to the Stroke Riskometer data sampled from 1300 participants in 13 countries using two-facet nested observational design (person by item nested in the country). The Stroke Riskometer demonstrated strong reliability in measuring stroke risks across the countries with coefficients G relative and absolute of 0.84, 95%CI [0.79; 0.89] and 0.82, 95%CI [0.76; 0.88] respectively. D-study analyses revealed that the Stroke Riskometer has optimal reliability in its current form in measuring stroke risk for each country and no modifications are required. These results suggest that the Stroke Riskometer’s scores are generalizable across sample population and countries permitting cross-cultural comparisons. Further studies investigating reliability of the Stroke Riskometer over time in longitudinal study design are warranted.

text: Cross-cultural validation of the stroke riskometer using generalizability theory (vol 11, 19064, 2021) The Stroke Riskometer mobile application is a novel, validated way to provide personalized stroke risk assessment for individuals and motivate them to reduce their risks. Although this app is being used worldwide, its reliability across different countries has not yet been rigorously investigated using appropriate methodology. The Generalizability Theory (G-Theory) is an advanced statistical method suitable for examining reliability and generalizability of assessment scores across different samples, cultural and other contexts and for evaluating sources of measurement errors. G-Theory was applied to the Stroke Riskometer data sampled from 1300 participants in 13 countries using two-facet nested observational design (person by item nested in the country). The Stroke Riskometer demonstrated strong reliability in measuring stroke risks across the countries with coefficients G relative and absolute of 0.84, 95%CI [0.79; 0.89] and 0.82, 95%CI [0.76; 0.88] respectively. D-study analyses revealed that the Stroke Riskometer has optimal reliability in its current form in measuring stroke risk for each country and no modifications are required. These results suggest that the Stroke Riskometer’s scores are generalizable across sample population and countries permitting cross-cultural comparisons. Further studies investigating reliability of the Stroke Riskometer over time in longitudinal study design are warranted.

year: 2021-10-11

title: Is there a lack of science resources and specialists for kaiako at Kura reo o Waikato?

authors: Hopkins, Aareka

subjects: Kura kaupapa

abstract: The New Zealand debates on culture and science education for Maaori are grounded in the concern for the under-achievement of tauira in science. In 1995, a lack of subject experts, specialists and resources to implement the Ministry of Education’s science curriculum was identified. I investigated the concept of a mobile science laboratory to provide subject experts, specialists and resources to Kura Reo o Tainui as a way of improving and enhancing tauira literacy and engagement in puutaiao. This study used a semi-structured survey to elicit the whakaaro and perceptions of kaiako puutaiao from four Wharekura, three Kura Kaupapa Maaori, and three Rumaki Total Immersion classes in Waikato-Tainui, using registered participants in the inaugural Kura Reo o Tainui Waananga in 2008 to select survey participants.

text: Is there a lack of science resources and specialists for kaiako at Kura reo o Waikato? The New Zealand debates on culture and science education for Maaori are grounded in the concern for the under-achievement of tauira in science. In 1995, a lack of subject experts, specialists and resources to implement the Ministry of Education’s science curriculum was identified. I investigated the concept of a mobile science laboratory to provide subject experts, specialists and resources to Kura Reo o Tainui as a way of improving and enhancing tauira literacy and engagement in puutaiao. This study used a semi-structured survey to elicit the whakaaro and perceptions of kaiako puutaiao from four Wharekura, three Kura Kaupapa Maaori, and three Rumaki Total Immersion classes in Waikato-Tainui, using registered participants in the inaugural Kura Reo o Tainui Waananga in 2008 to select survey participants.

year: 2010-08