15 resultados para Rh-Hr blood-group system

em Brock University, Canada


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The ability of the cardiovascular system to quickly and efficiently adapt to an orthostatic stress is vital for the human body to function on earth. The way in which the various aspects of the cardiovascular system work together to counteract an orthostatic stress has been previously quantified in the adult population. However, there are still many unknowns surrounding the topic of how the cardiovascular system functions to cope with this same stress in children. The purpose of this study was to describe the cardiovascular hemodynamic adaptations to various levels of orthostatic stress induced using a lower body negative pressure (LBNP) chamber in pre-pubertal boys. A secondary purpose was to determine indices of baroreceptor sensitivity (BRS) at both rest and during low levels of LBNP in this same pediatric sample. Finally, this study aimed to compare the relative responses to LBNP between the children and adults. To complete the study 20 healthy pre-pubertal boys and adult males (9.3 ± 1.1 and 23 ± 1.8 years of age respectively) were recruited and randomly exposed to three levels of LBNP (15, 20 and 25 mmHg). At rest and during the application of the LBNP heart rate (HR), manual and bcat-by-beat systolic (SBP), diastolic (DBP) and mean arterial blood pressure (MAP) were monitored continuously. Aortic diameter was measured at rest and peak aortic blood velocity (PV) was recorded continuously for at least I minute during each baseline and LBNP condition. From the raw data HR, stroke volume (SV), cardiac output (Q), total peripheral resistance (TPR), low frequency baroreceptor sensitivity (LF BRS), high frequency baroreceptor sensitivity (HF BRS) and LFIIIF ratio were calculated. At rest, llR wa'i higher and SBP, SV, Q and LF/HF ratio were lower in the children compared to the adult males (pgJ.05). In response to the increasing LEN!> IIR and TPR increased, and LF BRS. SV and Q decreased in the adult group (pSf).05). while the same levels of LBNP caused an increase in TPR and a decrease in SBP, SV and Q in the children (pSf).05). Although not significant, the LF/HF ratio in the adult group showed an increasing trend in response to increased negative pressure (p=O.088). As for resting BRS, there were no significant differences in LF or HF BRS between the children and the adults despite a tendency for both measures to be 18% lower in the children. Also the LF/HF ratio was almost significantly greater in the adults compared to the children (p=O.057). In addition, a comparison between the relative adult and child responses to LBNP yielded no significant group by level interactions. This result should be taken with caution though, as the low sample size and high measurement variability generated very low statistical power for this analysis. In conclusion, the results of this study suggest that the hemodynamic adaptations to an orthostatic stress were less pronounced in the prepubertal males, most likely due to an underdeveloped autonomic system. These results need to be strengthened by further research before any implications can be derived for health care purposes.

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Four groups of rainbow trout, Salmo gairdneri, were acclimated to 2°, 10°, and 18°e, and to a diurnal temperature cycle (100 ± 4°C). To evaluate the influence of cycling temperatures in terms of an immediate as opposed to acclimatory response various ventilatory-cardiovascular rate functions were observed for trout, either acclimated to cycling temperatures or acclimated to constant temperatures and exposed to a diurnal temperature cycle for the first time (10° ± 4°C for trout acclimated to 10°C; 18°+ 4°C for trout acclimated to l8°e). Gill resistance and the cardiac to ventilatory rate ratio were then calculated. Following a post preparatory recovery period of 36 hr, measurements were made over a 48 hour period with the first 24 hours being at constant temperature in the case of statically-acclimated fish followed by 24 hours under cyclic temperature conditions. Trout exhibited marked changes in oxygen consumption (Vo ) with temp- 2 erature both between acclimation groups, and in response to the diurnal temperature cycle. This increase in oxygen uptake appears to have been achieved by adjustment of ventilatory and, to some extent, cardiovascular activity. Trout exhibited significant changes in ventilatory rate (VR), stroke volume (Vsv), and flow (VG) in response to temperature. Marked changes in cardiac rate were also observed. These findings are discussed in relation to their importance in convective oxygen transport via water and blood at the gills and tissues. Trout also exhibited marked changes in pressure waveforms associated with the action of the resp; ratory pumps with temperature. Mean differenti a 1 pressure increased with temperature as did gill resistance and utilization. This data is discussed in relation to its importance in diffusive oxygen transport and the conditions for gas exchange at the gills. With one exception, rainbow trout were able to respond to changes in oxygen demand and availability associated with changes in temperature by means of adjustments in ventilation, and possibly pafusion, and the conditions for gas exchange at the gills. Trout acclimated to 18°C, however, and exposed to high cyclic temperatures, showed signs of the ventilatory and cardiovascular distress problems commonly associated with low circulating levels of oxygen in the blood. It appears these trout were unable to fully meet the oxygen requirements associated with c~ling temperatures above 18°C. These findings were discussed in relation to possible limitations in the cardiovascular-ventilatory response at high temperatures. The response of trout acclimated to cycling temperatures was generally similar to that for trout acclimated to constant temperatures and exposed to cycling temperatures for the first time. This result suggested that both groups of fish may have been acclimated to a similar thermal range, regardless of the acclimation regime employed. Such a phenomenon would allow trout of either acclimation group to respond equally well to the imposed temperature cycle. Rainbow trout showed no evidence of significant diurnal rhythm in any parameters observed at constant temperatures (2°, 10°, and 18° C), and under a 12/12 light-dark photoperiod regime. This was not taken to indicate an absence of circadian rhythms in these trout, but rather a deficiency in the recording methods used in the study.

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Hematological status in rainbow trout, Salmo gairdneri, was examined in relation to eight combinations of three environmental fa ctors; temperature (5°, 20°C), oxygen availability «35%, >70% saturation) and photoperiod (16L:8D, 8L:16D) and evaluated by 3-factor analysis of variance. Hemog l obin and hematocrit , indicators of oxygenc arrying capacity increased significantly at the higher temperature, following exposure to hypoxia and in relation to reduced light period. Significant variations in mean corpuscular hemoglobin concentration were not detected. The effects of temperature and oxygen availability were more pronounced than that of photoperiod which was generally masked. Although oxygen availability and photoperiod did not interact with temperature, the interaction of the former fac tors was significant. Elec trophoresis revealed twelve hemoglobin isomorphs. Relative concentration changes were found in re lation to the factors c onsidered with temperature>hypoxia>photoperiod. Howeve r , in terms of absolute concentration, effects were hypoxia>temperature>photoperiod. Photoperiod effects were again masked by temperature and (or) hypoxia. Red cell +2 l eve ls of [CI ] and [Mg ], critical elements in the hemoglobin-oxygen affinity regulating system, were also significantly altered. Red cell CI +2 was influenced only by temperature ; Mg by temper ature and oxygen. No photoperiod influence on either ions was observed. Under nominal 'summer' conditions, these changes point to the likelihood of increases in oxygen-c arrying c apac ity coupled with low Hb-02 affinity adjustments which would be expected to increase oxygen delivery rates to their more rapidly metabolising tissues.

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Vagal baroreflex sensitivity (BRS) is a measure of short term blood pressure (BP) regulation through alterations in heart rate. Low BRS reflects impaired autonomic system regulation and has been found to be a surrogate marker for cardiovascular health. In particular, it has found to be associated with the pathogenesis of adult hypertension. However, only limited information exists as to the negative consequences of childhood BP on baroreflex function. The objective of this study was to investigate BRS in children with 2 different BP profiles while controlling for the effects of age, maturation, sex, and body composition. A preliminary subsample of 11-14 year-old children from the HBEAT (Heart Behavioural Environmental Assessment Team) Study was selected. The children were divided into 2 BP groups; high BP (HBP; 2:95tl1 percentile, n=21) and normal BP (NBP; <90th percentile, n=85). Following an initial 15 minutes of supine rest, 5 minutes of continuous beat-to-beat BP (Finapres) and RR interval (RRI) were recorded (standard ECG). Spectral indices were computed using Fast Fourier Transform and transfer function analysis was used to compute BRS. High frequency (HF) and low frequency (LF) power spectral areas were set to 0.15-0.4 Hz and 0.04-0.15 Hz, respectively. Body composition was measured using body mass index. After adjusting for body composition, maturation, age and sex ANCOV A results were as follows; LF and HF BRS, LF and HF RRI, and RRI total power were lower in the HBP versus NBP participants (p<0.05). As well, LF IHF SBP ratio was significantly higher in the HBP compared to the NBP group (p<0.05). The regression coefficients (unstandardized B) indicated that in changing groups (NBP to HBP) LF and HF BRS decreases by 4.04 and 6.18 ms/mmHg, respectively. Thus, as BP increases, BRS decreases. These data suggest that changes in autonomic activity occur in children who have HBP, regardless of age, sex, maturation, and body composition. Thus, despite their young age and relatively short amount of time having high BP compared with adults, these children are already demonstrating poor BP regulation and reduced cardiovagal activity. Given that childhood BP is associated with hypertension in adulthood, there is a growing concern in regards to the current cardiovascular health of our children and future adults.

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Physical inactivity poses a huge burden on Canada's health care system and is detrimental to the health of Canadians (Katzmarzyk & Janssen, 2004). Walking is a viable option for individuals to become physically active on a daily basis and is in fact the most commonly reported leisure time physical activity. It has been associated with many health benefits including weight loss/weight control, reduced risk of coronary artery disease and diabetes, lowered blood pressure, and improved psychological wellbeing (Brisson & Tudor-Locke, 2004). Specifically, individuals' stage of change, selfefficacy and health related quality of life (HRQL) are three psychological constructs that can be greatly improved with increased physical activity (Dishman, 1991; Penedo & Dahn, 2005; Poag & McAuley, 1992). Public health physical activity recommendations exist but many individuals find these difficult to meet due to overly busy lifestyles (Public Health Agency of Canada, 2003). Pedometers are inexpensive devices that can monitor individual bouts of walking so that the incorporation of physical activity into one's daily life is more plausible. They are also excellent tools for motivation, goalsetting, and immediate feedback (Brisson & Tudor-Locke, 2004). Since many people spend a large proportion of their time at their places of employment, workplaces have begun to be a common site for the development of physical activity interventions. These programs have been growing in popUlarity and have shown numerous benefits for both employees and employers (Voit, 2001). The purpose of the current study was to implement and evaluate the use of a pedometer-based physical activity intervention incorporating goal-setting and physical activity logs in a workplace setting, and to examine the relationship between different types of self-efficacy (task, barrier, and scheduling) and different phases of the intervention. Twenty male participants from a local steel manufacturing plant who exhibited health risk factors (e.g. hypertension, diabetes, etc.) were assigned to one of two groups (group A or group B). All participants were asked to wear pedometers on their waists, record their daily steps, set goals that were outlined on a step-tracking sheet (detennined by their baseline number of steps), and keep track of their work days, wakelbed time, sedentary time, and time spent doing other physical activity. Group A began the intervention immediately following the baseline measures, whereas group B continued with their regular routine for 4 weeks before beginning. Physiological measures (height, weight, blood pressure, relative body fat, waist and hip circumference, and body mass index) were taken and a battery of questionnaires that assessed barrier, task and scheduling self-efficacy, HRQL, and stage of change administered at baseline, week 5 (end of intervention for group A), week 9 (end of intervention for group B; follow-up for group A) and week 13 (follow-up for both groups). Results showed that this workplace physical activity intervention was successful at increasing the participants' daily steps, that task self-efficacy is a significant predictor of participants' exercise adherence during the initial stages of participation (intervention phase), and that the participants felt that this intervention was effective. Finally, further exploratory analyses showed that this intervention was effective for all participants, but most valuable for participants most in need of improvement - that is, those who were most sedentary prior to the intervention. This intervention is an inexpensive use of simple and effective tools (e.g. pedometers), has the potential to attract a wide variety of participants and become a pennanent part of any health promotion initiative.

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The "Java Intelligent Tutoring System" (JITS) research project focused on designing, constructing, and determining the effectiveness of an Intelligent Tutoring System for beginner Java programming students at the postsecondary level. The participants in this research were students in the School of Applied Computing and Engineering Sciences at Sheridan College. This research involved consistently gathering input from students and instructors using JITS as it developed. The cyclic process involving designing, developing, testing, and refinement was used for the construction of JITS to ensure that it adequately meets the needs of students and instructors. The second objective in this dissertation determined the effectiveness of learning within this environment. The main findings indicate that JITS is a richly interactive ITS that engages students on Java programming problems. JITS is equipped with a sophisticated personalized feedback mechanism that models and supports each student in his/her learning style. The assessment component involved 2 main quantitative experiments to determine the effectiveness of JITS in terms of student performance. In both experiments it was determined that a statistically significant difference was achieved between the control group and the experimental group (i.e., JITS group). The main effect for Test (i.e., pre- and postiest), F( l , 35) == 119.43,p < .001, was qualified by a Test by Group interaction, F( l , 35) == 4.98,p < .05, and a Test by Time interaction, F( l , 35) == 43.82, p < .001. Similar findings were found for the second experiment; Test by Group interaction revealed F( 1 , 92) == 5.36, p < .025. In both experiments the JITS groups outperformed the corresponding control groups at posttest.

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This case study examines the impact of a computer information system as it was being implemented in one Ontario hospital. The attitudes of a cross section of the hospital staff acted as a barometer to measure their perceptions of the implementation process. With The Mississauga Hospital in the early stages of an extensive computer implementation project, the opportunity existed to identify staff attitudes about the computer system, overall knowledge and compare the findings with the literature. The goal of the study was to develop a greater base about the affective domain in the relationship between people and the computer system. Eight exploratory questions shaped the focus of the investigation. Data were collected from three sources: a survey questionnaire, focused interviews, and internal hospital documents. Both quantitative and qualitative data were analyzed. Instrumentation in the study consisted of a survey distributed at two points in time to randomly selected hospital employees who represented all staff levels.Other sources of data included hospital documents, and twenty-five focused interviews with staff who replied to both surveys. Leavitt's socio-technical system, with its four subsystems: task, structure, technology, and people was used to classify staff responses to the research questions. The study findings revealed that the majority of respondents felt positive about using the computer as part of their jobs. No apparent correlations were found between sex, age, or staff group and feelings about using the computer. Differences in attitudes, and attitude changes were found in potential relationship to the element of time. Another difference was found in staff group and perception of being involved in the decision making process. These findings and other evidence about the role of change agents in this change process help to emphasize that planning change is one thing, managing the transition is another.

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Geochemical examination of the rock matrix and cements from core material extracted from four oil wells within southwestern Ontario suggest various stages of diagenetic alteration and preservation of the Trenton Group carbonates. The geochemical compositions of Middle Ordovician (LMC) brachiopods reflect the physicochemical water conditions of the ambient depositional environment. The sediments appear to have been altered in the presence of mixed waters during burial in a relatively open diagenetic microenvironment. Conodont CAl determination suggests that the maturation levels of the Trenton Group carbonates are low and proceeded at temperatures of about 30 - 50°C within the shallow burial environment. The Trenton Group carbonates are characterized by two distinct stages of dolomitization which proceeded at elevated temperatures. Preexisting fracture patterns, and block faulting controlled the initial dolomitization of the precursor carbonate matrix. Dolomitization progressed In the presence of warm fluids (60 75°C) with physicochemical conditions characteristic of a progressively depleted basinal water. The matrix is mostly Idiotopic-S and Idiotopic-E dolomite, with Xenotopic-A dolomite dominating the matrix where fractures occur. The second stage of dolomitization involved hydrothermal basinal fluid(s) with temperatures of about 60 - 70°C. These are the postulated source for the saddle dolomite and blocky calcite cements occurring in pore space and fractures. Rock porosity was partly occluded by Idiotopic-E type dolomite. Late stage saddle dolomite, calcite, anhydrite, pyrite, marcasite and minor sphalerite and celestite cements effectively fill any remaining porosity within specific horizons. Based on cathode luminescence, precipitation of the different diagenetic phases probably proceeded in open diagenetic systems from chemically homogeneous fluids. Ultraviolet fluorescence of 11 the matrix and cements demonstrated that hydrocarbons were present during the earliest formation of saddle dolomite. Oxygen isotope values of -7.6 to -8.5 %0 (PDB), and carbon isotope values of - 0.5 and -3.0 %0 (PDB) from the latest stage dog-tooth calcite cement suggest that meteoric water was introduced into the system during their formation. This is estimated to have occurred at temperatures of about 25 - 40°C. Specific facies associations within the Trenton Group carbonates exhibit good hydrocarbon generating potential based on organic carbon preservation (1-3.5%). Thermal maturation and Lopatin burial-history evaluations suggest that hydrocarbons were generated within the Trenton Group carbonates some time after 300 Ma . Progressively depleted vanadium trends measured from hydrocarbon samples within southwestern Ontario suggests its potential use as a hydrocarbon migration indicator on local (within an oilfield) and on regional scales.

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It has previously been recognized that the major biochemical toxicity induced by sulphide is due to an inhibition of cytochrome ~ oxidase. Inhibition of this enzyme occurs at 30°C and pH 7.4 with a Ki of approximately 0.2 ~M, and a kon of 104 M-1 s-l, under catalytic conditions. However, the equimo1ar mixture of sulphide and the enzyme shows identical catalytic behaviour to that of the native enzyme. This cannot readily be attributed to rapid dissociation of sulphide, as both spectroscopic and plot analysis indicate the koff value is low. The addition of stoichiometric sulphide to the resting oxidized enzyme gives rise to the appearance of a low-spin ferric-type spectrum not identical with that seen on the addition of excess sulphide to the enzyme aerobically. Sulphide added to the enzyme anaerobically gives rise to another low-spin, probably largely ferric, form which upon admission of oxygen is then converted into a 607 nm species closely resembling Compound C. The 607 nm form is probably the precursor of oxyferricytochrome aa3. The addition of successive a1iquots of Na2S solution to the enzyme induces initial uptake of approximately 3 moles of oxygen per mole of the enzyme. Thus, it is concluded that: 1. the initial product of sulphide-cytochrome c oxidase interaction is not an inhibited form of the enzyme, but the low-spin (oxyferri) ~3+~+ species; 2. a subsequent step in which sulphide reduces cytochrome ~ occurs; 3. the final inhibitory step, in which a further molecule of sulphide binds to the cytochrome ~ iron centre in the cytochrome ~2+~+ species, gives the cytochrome a2+~+-H2S form which is a half-reduced fully inhibited species;4. a 607 run form of the enzyme is produced which may be converted into a catalytically active low-spin (oxyferri) state; and therefore 5. liganded sulphide may be able to reduce the cytochrome 33 -Cu centre without securing the prior reduction of the cytochrome a_ haem group or the Cud centre associated with it.

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Hypertension is thought to exist in up to five percent of children. A select number of studies have investigated the role elevated blood pressure plays in pediatric atherosclerotic progression. However these studies contain significant methodological flaws and fail to recognize important confounding factors. Therefore, the influence of elevated blood pressure on arterial health in children remains to be clearly understood. The purpose of this study was to investigate the association between blood pressure (BP) and arterial thickness and stiffuess in children. Common carotid artery (CCA) intima-media thickness (IMT) and distensibility (Dist), as well as systemic pulse wave velocity (PWV) were measured in 21 elevated blood pressure (EBP; BP ~ 95th percentile) and 83 normal blood pressure (NBP; BP < 90th percentile) children 11-14 years of age. Both EBP and NBP groups demonstrated BP within the normal clinical range, but EBP showed significantly elevated BP as compared to the NBP group. Independent t-tests failed to show significant differences between the EBP and NBP groups for CCA IMT (0.43 ± 0.05 mm and 0.42 ± 0.06 mm, respectively) and Dist (0.0058 ± 0.0024 mmHg-1 and 0.0064 ± 0.0019 mmHil respectively). In contrast, a significantly elevated PWV (psystemic arterial stiffuess as measured through PWV. This may be the result of sympathetic predominance and its significant influence on the peripheral vasculature. More studies are needed to clearly illustrate the temporal sequence of pediatric atherosclerotic progression in response to elevated BP.

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The vascular adventitia is recognized as a dynamic mediator of vascular structure and function, yet its role in aging is not understood. The purpose of this thesis was to examine the age-related changes of the vascular adventitia and determine the underlying mediators responsible. Male Sprague-Dawley rats were aged to 15, 30, 50 and 80 weeks before being anesthetised and euthanized by exsanguination. Thoracic aortas, mesenteric and pudental arteries were isolated, formalin fixed, and embedded in paraffin then sectioned at 5μm. Vessels were examined by microscopy and protein expression was determined by indirect immunofluorescence. The thickness of the adventitia increased dramatically with age. Immunofluorescence revealed a robust expression of endothelin system proteins in the adventitia. Additionally, extracellular matrix proteins collagen and fibronectin, and the proliferation marker Ki67 showed strong adventitial origin. The changes observed in the vascular adventitia with aging clearly demonstrate an important role in the process of vascular aging.

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The vascular adventitia is recognized as a dynamic mediator of vascular structure and function, yet its role in aging is not understood. The purpose of this thesis was to examine the age-related changes of the vascular adventitia and determine the underlying mediators responsible. Male Sprague-Dawley rats were aged to 15,30,50 and 80 weeks before being anesthetised and euthanized by exsanguination. Thoracic aortas, mesenteric and pudental arteries were isolated, formalin fixed, and embedded in paraffin then sectioned at 51lm. Vessels were examined by microscopy and protein expression was determined by indirect immunofluorescence. The thickness of the adventitia increased dramatically with age. Immunofluorescence revealed a robust expression of endothelin system proteins in the adventitia. Additionally, extracellular matrix proteins collagen and fibronectin, and the proliferation marker Ki67 showed strong adventitial origin. The changes observed in the vascular adventitia with aging clearly demonstrate an important role in the process of vascular aging.

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Rats produce ultrasonic vocalizations that can be categorized into two types of ultrasonic calls based on their sonographic structure. One group contains 22-kHz ultrasonic vocalization (USVs), characterized by relatively constant (flat) frequency with peak frequency ranging from 19 to 28-kHz, and a call duration ranging between 100 – 3000 ms. These vocalization can be induced by cholinomimetic agents injected into the ascending mesolimbic cholinergic system that terminates in the anterior hypothalamic-preoptic area (AH-MPO) and lateral septum (LS). The other group of USVs contains 50-kHz USVs, characterized by high peak frequency, ranging from 39 to 90-kHz, short duration ranging from 10-90 ms, and varying frequency and complex sonographic morphology. These vocalizations can be induced by dopaminergic agents injected into the nucleus accumbens, the target area for the mesolimbic dopaminergic system. 22-kHz USVs are emitted in situations that are highly aversive, such as proximity of a predator or anticipation of a foot shock, while 50 kHz USVs are emitted in rewarding and appetitive situations, such as juvenile play behaviour or anticipation of rewarding electrical brain stimulation. The activities of these two mesolimbic systems were postulated to be antagonistic to each other. The current thesis is focused on the interaction of these systems indexed by emission of relevant USVs. It was hypothesized that emission of 22 kHz USVs will be antagonized by prior activation of the dopaminergic system while emission of 50 kHz will be antagonized by prior activation of the cholinergic system. It was found that injection of apomorphine into the shell of the nucleus accumbens significantly decreased the number of carbachol-induced 22 kHz USVs from both AH-MPO and LS. Injection of carbachol into the LS significantly decreased the number of apomorphine-induced 50 kHz USVs from the shell of the nucleus accumbens. The results of the study supported the main hypotheses that the mesolimbic dopaminergic and cholinergic systems function in antagonism to each other.

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The purpose of this project was to raise awareness surrounding child and adolescent mental health in an effort to reduce preconceived stigmas in relation to this specialized field. This project presented a literature review of the current state of child and adolescent mental health in Canada today, including the prevalence and several treatment options for young people confronting mental health challenges. Consideration of the powerful role of the education system upon youth with mental health issues became evident, specifically regarding early identification and prevention. A needs assessment was conducted to gather feedback from the clinical practitioners of a Section 23 classroom within a Southern Ontario hospital. This assessment was used to develop an informational and pedagogical workshop resource to extend practitioner understanding of this pertinent issue and support the social and emotional needs of young people confronting mental heath challenges. Results of the assessment indicated the significant need for such a workshop resource, and these responses were used to guide the development of Group Chat: A Workshop to Support the Emotional and Social Needs of Youth. The latter was subsequently presented to participants, whereby evaluative questionnaires indicated the efficacy and usefulness of this workshop resource to both practitioners and students alike.

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Although reductions in cerebral blood flow (CBF) may be implicated in the development of central fatigue during environmental stress, the contribution from hypocapnia-induced reductions in CBF versus reductions in CBF per se has yet to be isolated. The current research program examined the influence of CBF, with and without consequent hypocapnia, on neuromuscular responses during hypoxia and passive heat stress. To this end, neuromuscular responses, as indicated by motor evoked potentials (MEP), maximal M-wave (Mmax) and cortical voluntary activation (cVA) of the flexor carpi radialis muscle during isometric wrist flexion, was assessed in three separate projects: 1) hypocapnia, independent of concomitant reductions in CBF; 2) altered CBF during severe hypoxia and; 3) thermal hyperpnea-mediated reductions in CBF, independent of hypocapnia. All projects employed a custom-built dynamic end-tidal forcing system to control end-tidal PCO2 (PETCO2), independent of the prevailing environmental conditions, and cyclooxygenase inhibition using indomethacin (Indomethacin, 1.2 mg·Kg-1) to selectively reduce CBF (estimated using transcranial Doppler ultrasound) without changes in PETCO2. A primary finding of the present research program is that the excitability of the corticospinal tract is inherently sensitive to changes in PaCO2, as demonstrated by a 12% increase in MEP amplitude in response to moderate hypocapnia. Conversely, CBF mediated reductions in cerebral O2 delivery appear to decrease corticospinal excitability, as indicated by a 51-64% and 4% decrease in MEP amplitude in response to hypoxia and passive heat stress, respectively. The collective evidence from this research program suggests that impaired voluntary activation is associated with reductions in CBF; however, it must be noted that changes in cVA were not linearly correlated with changes in CBF. Therefore, other factors independent of CBF, such as increased perception of effort, distress or discomfort, may have contributed to the reductions in cVA. Despite the functional association between reductions in CBF and hypocapnia, both variables have distinct and independent influence on the neuromuscular system. Therefore, future studies should control or acknowledge the separate mechanistic influence of these two factors.