Prospective study of insulin-like growth factor-I, insulin-like growth factor-binding protein 3, genetic variants in the IGF1 and IGFBP3 genes and risk of coronary artery disease.

Although experimental studies have suggested that insulin-like growth factor I (IGF-I) and its binding protein IGFBP-3 might have a role in the aetiology of coronary artery disease (CAD), the relevance of circulating IGFs and their binding proteins in the development of CAD in human populations is unclear. We conducted a nested case-control study, with a mean follow-up of six years, within the EPIC-Norfolk cohort to assess the association between circulating levels of IGF-I and IGFBP-3 and risk of CAD in up to 1,013 cases and 2,055 controls matched for age, sex and study enrolment date. After adjustment for cardiovascular risk factors, we found no association between circulating levels of IGF-I or IGFBP-3 and risk of CAD (odds ratio: 0.98 (95% Cl 0.90-1.06) per 1 SD increase in circulating IGF-I; odds ratio: 1.02 (95% Cl 0.94-1.12) for IGFBP-3). We examined associations between tagging single nucleotide polymorphisms (tSNPs) at the IGF1 and IGFBP3 loci and circulating IGF-I and IGFBP-3 levels in up to 1,133 cases and 2,223 controls and identified three tSNPs (rs1520220, rs3730204, rs2132571) that showed independent association with either circulating IGF-I or IGFBP-3 levels. In an assessment of 31 SNPs spanning the IGF1 or IGFBP3 loci, none were associated with risk of CAD in a meta-analysis that included EPIC-Norfolk and eight additional studies comprising up to 9,319 cases and 19,964 controls. Our results indicate that IGF-I and IGFBP-3 are unlikely to be importantly involved in the aetiology of CAD in human populations.

Improving Information Problem Solving skills in Secondary Education through embedded instruction

This empirical study consists in an investigation of the effects, on the development of Information Problem Solving (IPS) skills, of a long-term embedded, structured and supported instruction in Secondary Education. Forty secondary students of 7th and 8th grades (13–15 years old) participated in the 2-year IPS instruction designed in this study. Twenty of them participated in the IPS instruction, and the remaining twenty were the control group. All the students were pre- and post-tested in their regular classrooms, and their IPS process and performance were logged by means of screen capture software, to warrant their ecological validity. The IPS constituent skills, the web search sub-skills and the answers given by each participant were analyzed. The main findings of our study suggested that experimental students showed a more expert pattern than the control students regarding the constituent skill ‘defining the problem’ and the following two web search sub-skills: ‘search terms’ typed in a search engine, and ‘selected results’ from a SERP. In addition, scores of task performance were statistically better in experimental students than in control group students. The paper contributes to the discussion of how well-designed and well-embedded scaffolds could be designed in instructional programs in order to guarantee the development and efficiency of the students’ IPS skills by using net information better and participating fully in the global knowledge society.

Radio continuum and near-infrared study of the MGRO J2019+37 region

MGRO J2019+37 is an unidentified extended source of very high energy gamma-rays originally reported by the Milagro Collaboration as the brightest TeV source in the Cygnus region. Its extended emission could be powered by either a single or several sources. The GeV pulsar AGL J2020.5+3653 , discovered by AGILE and associated with PSR J2021+3651 , could contribute to the emission from MGRO J2019+37 . Aims. Our aim is to identify radio and near-infrared sources in the field of the extended TeV source MGRO J2019+37 , and study potential counterparts to explain its emission. Methods. We surveyed a region of about 6 square degrees with the Giant Metrewave Radio Telescope (GMRT) at the frequency 610 MHz. We also observed the central square degree of this survey in the near-infrared -band using the 3.5 m telescope in Calar Alto. Archival X-ray observations of some specific fields are included. VLBI observations of an interesting radio source were performed. We explored possible scenarios to produce the multi-TeV emission from MGRO J2019+37 and studied which of the sources could be the main particle accelerator. Results. We present a catalogue of 362 radio sources detected with the GMRT in the field of MGRO J2019+37 , and the results of a cross-correlation of this catalog with one obtained at near-infrared wavelengths, which contains ~3105 sources, as well as with available X-ray observations of the region. Some peculiar sources inside the ~1° uncertainty region of the TeV emission from MGRO J2019+37 are discussed in detail, including the pulsar PSR J2021+3651 and its pulsar wind nebula PWN G75.2+0.1 , two new radio-jet sources, the H II region Sh 2-104 containing two star clusters, and the radio source NVSS J202032+363158 . We also find that the hadronic scenario is the most likely in case of a single accelerator, and discuss the possible contribution from the sources mentioned above. Conclusions. Although the radio and GeV pulsar PSR J2021+3651 / AGL J2020.5+3653 and its associated pulsar wind nebula PWN G75.2+0.1 can contribute to the emission from MGRO J2019+37 , extrapolation of the GeV spectrum does not explain the detected multi-TeV flux. Other sources discussed here could contribute to the emission of the Milagro source.

Radio continuum and near-ingrared study of the MGRO J2019+37 region

Context. MGRO J2019+37 is an unidentified extended source of very high energy gamma-rays originally reported by the Milagro Collaboration as the brightest TeV source in the Cygnus region. Its extended emission could be powered by either a single or several sources. The GeV pulsar AGL J2020.5+3653, discovered by AGILE and associated with PSR J2021+3651, could contribute to the emission from MGRO J2019+37. Our aim is to identify radio and near-infrared sources in the field of the extended TeV source MGRO J2019+37, and study potential counterparts to explain its emission. Methods: We surveyed a region of about 6 square degrees with the Giant Metrewave Radio Telescope (GMRT) at the frequency 610 MHz. We also observed the central square degree of this survey in the near-infrared Ks-band using the 3.5 m telescope in Calar Alto. Archival X-ray observations of some specific fields are included. VLBI observations of an interesting radio source were performed. We explored possible scenarios to produce the multi-TeV emission from MGRO J2019+37 and studied which of the sources could be the main particle accelerator. Results: We present a catalogue of 362 radio sources detected with the GMRT in the field of MGRO J2019+37, and the results of a cross-correlation of this catalog with one obtained at near-infrared wavelengths, which contains ∼3 × 105 sources, as well as with available X-ray observations of the region. Some peculiar sources inside the ∼1◦ uncertainty region of the TeV emission from MGRO J2019+37 are discussed in detail, including the pulsar PSR J2021+3651 and its pulsar wind nebula PWN G75.2+0.1, two new radio-jet sources, the Hii region Sh 2-104 containing two star clusters, and the radio source NVSS J202032+363158. We also find that the hadronic scenario is the most likely in case of a single accelerator, and discuss the possible contribution from the sources mentioned above. Conclusions: Although the radio and GeV pulsar PSR J2021+3651 / AGL J2020.5+3653 and its associated pulsar wind nebula PWN G75.2+0.1 can contribute to the emission from MGRO J2019+37, extrapolation of the GeV spectrum does not explain the detected multi-TeV flux. Other sources discussed here could contribute to the emission of the Milagro source

Electrochemical study and dependence of 'transition state' in Co(II) and Ni(II) complexes with some antibiotics and cephalothin

Electrode kinetics and study of 'transition state' with applied potential in case of [M - antibiotics - cephalothin] system were reported at pH = 7.30 ± 0.01 at suitable supporting electrolyte at 25.0ºC. The M = Co or Ni and antibiotics were doxycycline, chlortetracycline, oxytetracycline, tetracycline, minocycline, amoxicillin and chloramphenicol used as primary ligands and cephalothin as secondary ligand. Kinetic parameters viz. transfer coefficient (a), degree of irreversibility (l), diffusion coefficient (D) and rate constant (k) were determined. The values of a and k varied from 0.41 to 0.59 and 2.60 X 10-3 cm s-1 to 9.67 X 10-3 cm s-1 in case of [Co - antibiotics - cephalothin] system. In case of [Ni - antibiotics - cephalothin], a and k varied from 0.41 to 0.58 and 2.34 X 10-3 cm s-1 to 9.19 X 10-3 cm s-1 respectively confirmed that transition state behaves between oxidant and reductant response to applied potential and it adjusts it self in such a way that the same is located midway between dropping mercury electrode and solution interface. The values of rate constant confirmed the quasireversible nature of electrode processes. The stability constants (logb) of complexes were also determined.

Thinking Outside the Box: Enhancing Science Teaching by Combining (Instead of Contrasting) Laboratory and Simulation Activities

The focus of the present work was on 10- to 12-year-old elementary school students’ conceptual learning outcomes in science in two specific inquiry-learning environments, laboratory and simulation. The main aim was to examine if it would be more beneficial to combine than contrast simulation and laboratory activities in science teaching. It was argued that the status quo where laboratories and simulations are seen as alternative or competing methods in science teaching is hardly an optimal solution to promote students’ learning and understanding in various science domains. It was hypothesized that it would make more sense and be more productive to combine laboratories and simulations. Several explanations and examples were provided to back up the hypothesis. In order to test whether learning with the combination of laboratory and simulation activities can result in better conceptual understanding in science than learning with laboratory or simulation activities alone, two experiments were conducted in the domain of electricity. In these experiments students constructed and studied electrical circuits in three different learning environments: laboratory (real circuits), simulation (virtual circuits), and simulation-laboratory combination (real and virtual circuits were used simultaneously). In order to measure and compare how these environments affected students’ conceptual understanding of circuits, a subject knowledge assessment questionnaire was administered before and after the experimentation. The results of the experiments were presented in four empirical studies. Three of the studies focused on learning outcomes between the conditions and one on learning processes. Study I analyzed learning outcomes from experiment I. The aim of the study was to investigate if it would be more beneficial to combine simulation and laboratory activities than to use them separately in teaching the concepts of simple electricity. Matched-trios were created based on the pre-test results of 66 elementary school students and divided randomly into a laboratory (real circuits), simulation (virtual circuits) and simulation-laboratory combination (real and virtual circuits simultaneously) conditions. In each condition students had 90 minutes to construct and study various circuits. The results showed that studying electrical circuits in the simulation–laboratory combination environment improved students’ conceptual understanding more than studying circuits in simulation and laboratory environments alone. Although there were no statistical differences between simulation and laboratory environments, the learning effect was more pronounced in the simulation condition where the students made clear progress during the intervention, whereas in the laboratory condition students’ conceptual understanding remained at an elementary level after the intervention. Study II analyzed learning outcomes from experiment II. The aim of the study was to investigate if and how learning outcomes in simulation and simulation-laboratory combination environments are mediated by implicit (only procedural guidance) and explicit (more structure and guidance for the discovery process) instruction in the context of simple DC circuits. Matched-quartets were created based on the pre-test results of 50 elementary school students and divided randomly into a simulation implicit (SI), simulation explicit (SE), combination implicit (CI) and combination explicit (CE) conditions. The results showed that when the students were working with the simulation alone, they were able to gain significantly greater amount of subject knowledge when they received metacognitive support (explicit instruction; SE) for the discovery process than when they received only procedural guidance (implicit instruction: SI). However, this additional scaffolding was not enough to reach the level of the students in the combination environment (CI and CE). A surprising finding in Study II was that instructional support had a different effect in the combination environment than in the simulation environment. In the combination environment explicit instruction (CE) did not seem to elicit much additional gain for students’ understanding of electric circuits compared to implicit instruction (CI). Instead, explicit instruction slowed down the inquiry process substantially in the combination environment. Study III analyzed from video data learning processes of those 50 students that participated in experiment II (cf. Study II above). The focus was on three specific learning processes: cognitive conflicts, self-explanations, and analogical encodings. The aim of the study was to find out possible explanations for the success of the combination condition in Experiments I and II. The video data provided clear evidence about the benefits of studying with the real and virtual circuits simultaneously (the combination conditions). Mostly the representations complemented each other, that is, one representation helped students to interpret and understand the outcomes they received from the other representation. However, there were also instances in which analogical encoding took place, that is, situations in which the slightly discrepant results between the representations ‘forced’ students to focus on those features that could be generalised across the two representations. No statistical differences were found in the amount of experienced cognitive conflicts and self-explanations between simulation and combination conditions, though in self-explanations there was a nascent trend in favour of the combination. There was also a clear tendency suggesting that explicit guidance increased the amount of self-explanations. Overall, the amount of cognitive conflicts and self-explanations was very low. The aim of the Study IV was twofold: the main aim was to provide an aggregated overview of the learning outcomes of experiments I and II; the secondary aim was to explore the relationship between the learning environments and students’ prior domain knowledge (low and high) in the experiments. Aggregated results of experiments I & II showed that on average, 91% of the students in the combination environment scored above the average of the laboratory environment, and 76% of them scored also above the average of the simulation environment. Seventy percent of the students in the simulation environment scored above the average of the laboratory environment. The results further showed that overall students seemed to benefit from combining simulations and laboratories regardless of their level of prior knowledge, that is, students with either low or high prior knowledge who studied circuits in the combination environment outperformed their counterparts who studied in the laboratory or simulation environment alone. The effect seemed to be slightly bigger among the students with low prior knowledge. However, more detailed inspection of the results showed that there were considerable differences between the experiments regarding how students with low and high prior knowledge benefitted from the combination: in Experiment I, especially students with low prior knowledge benefitted from the combination as compared to those students that used only the simulation, whereas in Experiment II, only students with high prior knowledge seemed to benefit from the combination relative to the simulation group. Regarding the differences between simulation and laboratory groups, the benefits of using a simulation seemed to be slightly higher among students with high prior knowledge. The results of the four empirical studies support the hypothesis concerning the benefits of using simulation along with laboratory activities to promote students’ conceptual understanding of electricity. It can be concluded that when teaching students about electricity, the students can gain better understanding when they have an opportunity to use the simulation and the real circuits in parallel than if they have only the real circuits or only a computer simulation available, even when the use of the simulation is supported with the explicit instruction. The outcomes of the empirical studies can be considered as the first unambiguous evidence on the (additional) benefits of combining laboratory and simulation activities in science education as compared to learning with laboratories and simulations alone.

Responding to Changing Student Demographics in Finland: A Study of Teachers’ Developing Cultural Competence

The aim of this dissertation was to examine the skills and knowledge that pre-service teachers and teachers have and need about working with multilingual and multicultural students from immigrant backgrounds. The specific goals were to identify pre-service teachers’ and practising teachers’ current knowledge and awareness of culturally and linguistically responsive teaching, identify a profile of their strengths and needs, and devise appropriate professional development support and ways to prepare teachers to become equitable culturally responsive practitioners. To investigate these issues, the dissertation reports on six original empirical studies within two groups of teachers: international pre-service teacher education students from over 25 different countries as well as pre-service and practising Finnish teachers. The international pre-service teacher sample consisted of (n = 38, study I; and n = 45, studies II-IV) and the pre-service and practising Finnish teachers sample encompassed (n = 89, study V; and n = 380, study VI). The data used were multi-source including both qualitative (students’ written work from the course including journals, final reflections, pre- and post-definition of key terms, as well as course evaluation and focus group transcripts) and quantitative (multi-item questionnaires with open-ended options), which enhanced the credibility of the findings resulting in the triangulation of data. Cluster analytic procedures, multivariate analysis of variance (MANOVA), and qualitative analyses mostly Constant Comparative Approach were used to understand pre-service teachers’ and practising teachers’ developing cultural understandings. The results revealed that the mainly white / mainstream teacher candidates in teacher education programmes bring limited background experiences, prior socialisation, and skills about diversity. Taking a multicultural education course where identity development was a focus, positively influenced teacher candidates’ knowledge and attitudes toward diversity. The results revealed approaches and strategies that matter most in preparing teachers for culturally responsive teaching, including but not exclusively, small group activities and discussions, critical reflection, and field immersion. This suggests that there are already some tools to address the need for the support needed to teach successfully a diversity of pupils and provide in-service training for those already practising the teaching profession. The results provide insight into aspects of teachers’ knowledge about both the linguistic and cultural needs of their students, as well as what constitutes a repertoire of approaches and strategies to assure students’ academic success. Teachers’ knowledge of diversity can be categorised into sound awareness, average awareness, and low awareness. Knowledge of diversity was important in teachers’ abilities to use students’ language and culture to enhance acquisition of academic content, work effectively with multilingual learners’ parents/guardians, learn about the cultural backgrounds of multilingual learners, link multilingual learners’ prior knowledge and experience to instruction, and modify classroom instruction for multilingual learners. These findings support the development of a competency based model and can be used to frame the studies of pre-service teachers, as well as the professional development of practising teachers in increasingly diverse contexts. The present set of studies take on new significance in the current context of increasing waves of migration to Europe in general and Finland in particular. They suggest that teacher education programmes can equip teachers with the necessary attitudes, skills, and knowledge to enable them work effectively with students from different ethnic and language backgrounds as they enter the teaching profession. The findings also help to refine the tools and approaches to measuring the competencies of teachers teaching in mainstream classrooms and candidates in preparation.

School funding and education policy-making models in Ontario /

The purpose of this thesis is to examine various policy implementation models, and to determine what use they are to a government. In order to insure that governmental proposals are created and exercised in an effective manner, there roust be some guidelines in place which will assist in resolving difficult situations. All governments face the challenge of responding to public demand, by delivering the type of policy responses that will attempt to answer those demands. The problem for those people in positions of policy-making responsibility is to balance the competitive forces that would influence policy. This thesis examines provincial government policy in two unique cases. The first is the revolutionary recommendations brought forth in the Hall -Dennis Report. The second is the question of extending full -funding to the end of high school in the separate school system. These two cases illustrate how divergent and problematic the policy-making duties of any government may be. In order to respond to these political challenges decision-makers must have a clear understanding of what they are attempting to do. They must also have an assortment of policy-making models that will insure a policy response effectively deals with the issue under examination. A government must make every effort to insure that all policymaking methods are considered, and that the data gathered is inserted into the most appropriate model. Currently, there is considerable debate over the benefits of the progressive individualistic education approach as proposed by the Hall -Dennis Committee. This debate is usually intensified during periods of economic uncertainty. Periodically, the province will also experience brief yet equally intense debate on the question of separate school funding. At one level, this debate centres around the efficiency of maintaining two parallel education systems, but the debate frequently has undertones of the religious animosity common in Ontario's history. As a result of the two policy cases under study we may ask ourselves these questions: a) did the policies in question improve the general quality of life in the province? and b) did the policies unite the province? In the cases of educational instruction and finance the debate is ongoing and unsettling. Currently, there is a widespread belief that provincial students at the elementary and secondary levels of education are not being educated adequately to meet the challenges of the twenty-first century. The perceived culprit is individual education which sees students progressing through the system at their own pace and not meeting adequate education standards. The question of the finance of Catholic education occasionally rears its head in a painful fashion within the province. Some public school supporters tend to take extension as a personal religious defeat, rather than an opportunity to demonstrate that educational diversity can be accommodated within Canada's most populated province. This thesis is an attempt to analyze how successful provincial policy-implementation models were in answering public demand. A majority of the public did not demand additional separate school funding, yet it was put into place. The same majority did insist on an examination of educational methods, and the government did put changes in place. It will also demonstrate how policy if wisely created may spread additional benefits to the public at large. Catholic students currently enjoy a much improved financial contribution from the province, yet these additional funds were taken from somewhere. The public system had it funds reduced with what would appear to be minimal impact. This impact indicates that government policy is still sensitive to the strongly held convictions of those people in opposition to a given policy.

Metal music as critical dystopia : humans, technology and the future in 1990s science fiction metal

Metal Music as Critical Dystopia: Humans, Technology and the Future in 1990s Science Fiction Metal seeks to demonstrate that the dystopian elements in metal music are not merely or necessarily a sonic celebration of disaster. Rather, metal music's fascination with dystopian imagery is often critical in intent, borrowing themes and imagery from other literary and cinematic traditions in an effort to express a form of social commentary. The artists and musical works examined in this thesis maintain strong ties with the science fiction genre, in particular, and tum to science fiction conventions in order to examine the long-term implications of humanity's complex relationship with advanced technology. Situating metal's engagements with science fiction in relation to a broader practice of blending science fiction and popular music and to the technophobic tradition in writing and film, this thesis analyzes the works of two science fiction metal bands, VOlvod and Fear Factory, and provides close readings of four futuristic albums from the mid to late 1990s that address humanity's relationship with advanced technology in musical and visual imagery as well as lyrics. These recorded texts, described here as cyber metal for their preoccupation with technology in subject matter and in sound, represent prime examples of the critical dystopia in metal music. While these albums identify contemporary problems as the root bf devastation yet to come, their musical narratives leave room for the possibility of hope , allowing for the chance that dystopia is not our inevitable future.

You get what you pay for : independent music and Canadian public policy

The aim of this MA thesis is to demonstrate how corporate concentration within the global music industry specifically affects the Canadian music industry's ability to compete for its own national audience as well as audiences worldwide. Federal public policies, regulatory regimes and subsidies are considered within the context of the structure of the global marketplace which is, in effect, an oligopoly controlled by four major corporations. Through an extensive literature review of political economy theory, Canadian public policies and music studies, as well as personal interviews conducted with Canadian musicians, entrepreneurs and public servants, I will situate my research within the body of political economy theory; present a detailed report of the structure of the global music industry; address the key players within the industry; describe the relationship between the major corporations and the independent companies operating in the industry; discuss how new technologies affect said relationships; consider the effectiveness of Canadian public policies in safeguarding the national music industry; and recommend steps that can be taken to remedy the shortcomings of Federal policies and regulatory regimes.

A Temporal Analysis of Emotions in Girls' Secondary School Physical Education Games and Fitness Classes

Female enthusiasm towards engaging in physical education (PE) significantly decreases with age as it provides females with positive and negative emotional experiences. This study examined emotions within four grade nine female PE soccer and fitness classes (N = 67). Emotional patterns were studied over time and across two units of instruction and in relation to student grades. A mixed-method approach was utilized assessing the state emotions of shame, enjoyment, anxiety, and social physique anxiety (SPA). Results revealed unsatisfactory internal consistency for shame and thus it was removed. Statistical analysis revealed no significant changes in emotions over time, whereas qualitative analysis found that state emotions were inconsistent. Statistical analysis indicated that students in the fitness classes reported significantly higher levels of anxiety and SPA on the final class (p < .01). Qualitative analysis signaled different origins and themes of students‟ emotions. No predictive relationship between emotion and students‟ grade was found.

The Transfer of Wilderness Trips to the Everyday Lives of Young People: A Case Study

There has been considerable research that investigates the outcomes, benefits, and perceptions of wilderness trip experiences. However, the transfer of learning from a wilderness trip to the everyday lives of youth trip participants, that has deliberately explored post-trip experience, is minimal. Using a qualitative multi-case study approach, methods of data collection included interviews with six youth program participants, six parents/legal guardians, and three program staff, as well as document solicitation. Reports from the participants suggested that the key content transferred to a post-wilderness trip context were interpersonal skills; life skills; and instances of personal growth. Participants applied their learning content from the wilderness trip to school; sports; community and international volunteering; work and career aspirations; family and home life; and social life contexts. Implications for adventure programming and curriculum design, instruction, and transfer are considered.

A Needs Assessment: Language Instruction Stakeholders Engaging in Project Based Learning Outside the Classroom for Effective Strategic Problem Solving

Abstract A noted benefit of Project Based Learning (PBL) as a teaching strategy is how it engages the student and enhances learning outcomes as a result of working through challenges intended to depict dilemmas outside the classroom. PBL has seldom been applied outside the parameters of the classroom curriculum. The current needs assessment carried out in this research project examined current practices of language instruction and International Administrative Professionals of both the private and public Language Industry. Participants responded to survey questions on their current administrative practices, strategies, and program characteristics. The study investigated the usefulness of a handbook on the procedure of assisting administrative service teams in language instruction settings to an engaged approach to PBL for student service issues. The diverse opinions, beliefs, and ideas, along with institutional policy, can provide beneficial framework ideas for future tools.

Metaphorical Interpretation: Measuring and Facilitating Growth.

Abstract A total of 378 grade 9 students participated in this study to address the problem that although metaphorical literacy and thought are expected and necessary for success in junior and senior high school and beyond, metaphorical concepts and thought are not required to be explicitly taught to these students. The students were from 20 different classes from 4 levels: English language learners (ELL), school to work (SSTW), applied, and academic. All were from 7 secondary schools within a board in southern Ontario. Nine classes made up the control group and 11 classes made up the treatment group. All classes were given 3 pretests and the posttest. The treatment group was given Socratic lessons and direct instruction on metaphorical thought and expressions during 1 semester and in conjunction with their other classroom material. The pretest scores (TOLD, Peabody, preproverbs concrete, and preproverbs abstract) did not reveal any effect of gender, but the academic students had higher scores than the applied students. The SSTW student results are more variable: (a) for the TOLD test, SSTW scores were between those of the academic and applied students; (b) for Peabody scores, SSTW students’ scores are the same as academic and are greater than applied; (c) for preproverbs concrete and preproverbs abstract, the SSTW scores are not different from the applied scores. The postproverbs concrete and postproverbs abstract scores for the treatment groups also showed no effect of gender but revealed that all students who received the treatment did better on their post scores. The positive changes of the treatment group illustrate a measured movement from literal understanding to abstract understanding using direct Socratic instruction and proverbs as a medium.

In Vitro Ketamine CYP3A Mediated Metabolism Study using Mammalian Liver S9 Fractions, cDNA Expressed Enzymes and Liquid Chromatography Tandem Mass Spectrometry

Ketamine is widely used in medicine in combination with several benzodiazepines including midazolam. The objectives of this study were to develop a novel HPLC-MS/SRM method capable of quantifying ketamine and norketamine using an isotopic dilution strategy in biological matrices and study the formation of norketamine, the principal metabolite of ketamine with and without the presence of midazolam, a well-known CYP3A substrate. The chromatographic separation was achieved using a Thermo Betasil Phenyl 100 x 2 mm column combined with an isocratic mobile phase composed of acetonitrile, methanol, water and formic acid (60:20:20:0.4) at a flow rate of 300 μL/min. The mass spectrometer was operating in selected reaction monitoring mode and the analytical range was set at 0.05–50 μM. The precision (%CV) and accuracy (%NOM) observed were ranging from 3.9–7.8 and 95.9.2–111.1% respectively. The initial rate of formation of norketamine was determined using various ketamine concentration and Km values of 18.4 μM, 13.8 μM and 30.8 μM for rat, dog and human liver S9 fractions were observed respectively. The metabolic stability of ketamine on liver S9 fractions was significantly higher in human (T1/2 = 159.4 min) compared with rat (T1/2 = 12.6 min) and dog (T1/2 = 7.3 min) liver S9 fractions. Moreover significantly lower IC50 and Ki values observed in human compared with rat and dog liver S9 fractions. Experiments with cDNA expressed CYP3A enzymes showed the formation of norketamine is mediated by CYP3A but results suggest an important contribution from others isoenzymes, most likely CYP2C particularly in rat.