Clinical and pharmacokinetic evaluation of S-ketamine for intravenous general anaesthesia in horses undergoing field castration.

BACKGROUND Intravenous anaesthetic drugs are the primary means for producing general anaesthesia in equine practice. The ideal drug for intravenous anaesthesia has high reliability and pharmacokinetic properties indicating short elimination and lack of accumulation when administered for prolonged periods. Induction of general anaesthesia with racemic ketamine preceded by profound sedation has already an established place in the equine field anaesthesia. Due to potential advantages over racemic ketamine, S-ketamine has been employed in horses to induce general anaesthesia, but its optimal dose remains under investigation. The objective of this study was to evaluate whether 2.5 mg/kg S-ketamine could be used as a single intravenous bolus to provide short-term surgical anaesthesia in colts undergoing surgical castration, and to report its pharmacokinetic profile. RESULTS After premedication with romifidine and L-methadone, the combination of S-ketamine and diazepam allowed reaching surgical anaesthesia in the 28 colts. Induction of anaesthesia as well as recovery were good to excellent in the majority (n = 22 and 24, respectively) of the colts. Seven horses required additional administration of S-ketamine to prolong the duration of surgical anaesthesia. Redosing did not compromise recovery quality. Plasma concentration of S-ketamine decreased rapidly after administration, following a two-compartmental model, leading to the hypothesis of a consistent unchanged elimination of the parent compound into the urine beside its conversion to S-norketamine. The observed plasma concentrations of S-ketamine at the time of first movement were various and did not support the definition of a clear cut-off value to predict the termination of the drug effect. CONCLUSIONS The administration of 2.5 mg/kg IV S-ketamine after adequate premedication provided good quality of induction and recovery and a duration of action similar to what has been reported for racemic ketamine at the dose of 2.2 mg/kg. Until further investigations will be provided, close monitoring to adapt drug delivery is mandatory, particularly once the first 10 minutes after injection are elapsed. Taking into account rapid elimination of S-ketamine, significant inter-individual variability and rapid loss of effect over a narrow range of concentrations a sudden return of consciousness has to be foreseen.

Visual Perception and Acuity of Hand Surgeons Using Loupes.

PURPOSE To assess the visual performance of Swiss hand surgeons in an environment similar to their workplace. The influence of Galilean (lenses only) and Keplerian loupes (lenses and prisms), the surgeon's age, and the credibility of a self-assessment of his or her own optical performance were evaluated. METHODS Sixty-three hand surgeons between 29 and 68 years of age with 70 loupes were included in the study (Galilean n = 35, Keplerian n = 35). The visual performance as surgeons was self-assessed on a modified visual analog scale and objectively measured with miniaturized visual tests in a simulated clinical setting. We evaluated the influence of the optical device by comparing Galilean and Keplerian loupes and the influence of the surgeon's age by comparing 2 subgroups: < 40 years and ≥ 40 years. RESULTS The correlation between self-assessment and objective visual performance was weak, with a Spearman rank correlation coefficient of 0.25. The near visual acuity with habitual optical aids showed considerable variability, with a range of 300% in the dimension of the smallest detected structure. The near visual acuity was significantly lower in the older group ≥ 40 years than in the younger group < 40 years with both Galilean and Keplerian loupes. Keplerian loupes allowed a significantly higher visual performance than Galilean loupes. Surgeons 40 years or older using Keplerian loupes had a similar visual acuity to surgeons younger than 40 years with Galilean loupes. CONCLUSIONS The magnified near vision of hand surgeons showed an important individual variability. Self-assessment was not a valuable instrument for surgeons to estimate their own near vision. Hand surgeons older than 40 years should use higher magnification loupes. TYPE OF STUDY/LEVEL OF EVIDENCE Diagnostic III.

Final Syllable Lengthening (FSL) in Infant Vocalizations

Final Syllable Lengthening (FSL) has been extensively examined in infant vocalizations in order to determine whether its basis is biological or learned. Findings suggest there may be a U-shaped developmental trajectory for FSL. The present study sought to verify this pattern and to determine whether vocal maturity and deafness influence FSL. Eight normally hearing infants, aged 0 ; 3 to 1 ; 0, and eight deaf infants, aged 0 ; 8 to 4 ; 0, were examined at three levels of prelinguistic vocal development: precanonical, canonical, and postcanonical. FSL was found at all three levels suggesting a biological basis for this phenomenon. Individual variability was, however, considerable. Reduction in the magnitude of FSL across the three sessions provided some support for a downward trend for FSL in infancy. Findings further indicated that auditory deprivation can significantly affect temporal aspects of infant speech production.

(Table 1) Characteristics of South Pole personnel according to forced expiratory flow (FEF25-75) response to altitude

The impact of acute altitude exposure on pulmonary function is variable. A large inter-individual variability in the changes in forced expiratory flows (FEFs) is reported with acute exposure to altitude, which is suggested to represent an interaction between several factors influencing bronchial tone such as changes in gas density, catecholamine stimulation, and mild interstitial edema. This study examined the association between FEF variability, acute mountain sickness (AMS) and various blood markers affecting bronchial tone (endothelin-1, vascular endothelial growth factor (VEGF), catecholamines, angiotensin II) in 102 individuals rapidly transported to the South Pole (2835 m). The mean FEF between 25 and 75% (FEF25-75) and blood markers were recorded at sea level and after the second night at altitude. AMS was assessed using Lake Louise questionnaires. FEF25-75 increased by an average of 12% with changes ranging from -26 to +59% from sea level to altitude. On the second day, AMS incidence was 36% and was higher in individuals with increases in FEF25-75 (41 vs. 22%, P = 0.05). Ascent to altitude induced an increase in endothelin-1 levels, with greater levels observed in individuals with decreased FEF25-75. Epinephrine levels increased with ascent to altitude and the response was six times larger in individuals with decreased FEF25-75. Greater levels of endothelin-1 in individuals with decreased FEF25-75 suggest a response consistent with pulmonary hypertension and/or mild interstitial edema, while epinephrine may be upregulated in these individuals to clear lung fluid through stimulation of beta2-adrenergic receptors.

Ocean acidification impacts on sperm mitochondrial membrane potential bring sperm swimming behaviour near its tipping point

Broadcast spawning marine invertebrates are susceptible to environmental stressors such as climate change, as their reproduction depends on the successful meeting and fertilization of gametes in the water column. Under near-future scenarios of ocean acidification, the swimming behaviour of marine invertebrate sperm is altered. We tested whether this was due to changes in sperm mitochondrial activity by investigating the effects of ocean acidification on sperm metabolism and swimming behaviour in the sea urchin Centrostephanus rodgersii. We used a fluorescent molecular probe (JC-1) and flow cytometry to visualize mitochondrial activity (measured as change in mitochondrial membrane potential, MMP). Sperm MMP was significantly reduced in delta pH -0.3 (35% reduction) and delta pH -0.5 (48% reduction) treatments, whereas sperm swimming behaviour was less sensitive with only slight changes (up to 11% decrease) observed overall. There was significant inter-individual variability in responses of sperm swimming behaviour and MMP to acidified seawater. We suggest it is likely that sperm exposed to these changes in pH are close to their tipping point in terms of physiological tolerance to acidity. Importantly, substantial inter-individual variation in responses of sperm swimming to ocean acidification may increase the scope for selection of resilient phenotypes, which, if heritable, could provide a basis for adaptation to future ocean acidification.

(Table 2) Carbon and nitrogen isotopic ratios in blood sampled from arctic foxes (Vulpes lagopus) on Bylot Island between 2003-2008

Inter-individual variation in diet within generalist animal populations is thought to be a widespread phenomenon but its potential causes are poorly known. Inter-individual variation can be amplified by the availability and use of allochthonous resources, i.e., resources coming from spatially distinct ecosystems. Using a wild population of arctic fox as a study model, we tested hypotheses that could explain variation in both population and individual isotopic niches, used here as proxy for the trophic niche. The arctic fox is an opportunistic forager, dwelling in terrestrial and marine environments characterized by strong spatial (arctic-nesting birds) and temporal (cyclic lemmings) fluctuations in resource abundance. First, we tested the hypothesis that generalist foraging habits, in association with temporal variation in prey accessibility, should induce temporal changes in isotopic niche width and diet. Second, we investigated whether within-population variation in the isotopic niche could be explained by individual characteristics (sex and breeding status) and environmental factors (spatiotemporal variation in prey availability). We addressed these questions using isotopic analysis and Bayesian mixing models in conjunction with linear mixed-effects models. We found that: i) arctic fox populations can simultaneously undergo short-term (i.e., within a few months) reduction in both isotopic niche width and inter-individual variability in isotopic ratios, ii) individual isotopic ratios were higher and more representative of a marine-based diet for non-breeding than breeding foxes early in spring, and iii) lemming population cycles did not appear to directly influence the diet of individual foxes after taking their breeding status into account. However, lemming abundance was correlated to proportion of breeding foxes, and could thus indirectly affect the diet at the population scale.

Identidade profissional: como se veem os professores na escola atual

Dissertação apresentada para a obtenção do grau de mestre em Ciências da Educação - área de Supervisão e Orientação Pegagógica

Stress management in mothers of children with Autism Spectrum Disorder : psychological characteristics, coping strategies and biological correlates

Un figlio con un Disturbo dello Spettro Autistico, caratterizzato da gravi difficoltà nelle relazioni, nei comportamenti e nella comunicazione, costringe tutto il sistema familiare a gestire un notevole stress dovuto alla gestione quotidiana di una patologia così complessa. Per questi motivi, i genitori necessitano di un sostegno il più possibile personalizzato rispetto alle caratteristiche del loro contesto familiare. Per fare questo sarebbe importante individuare quali siano i parametri correlati ai livelli di stress nei familiari di pazienti con autismo e che potrebbero avere un’influenza sul benessere familiare. Lo scopo di questo studio è quello di valutare quali caratteristiche di personalità, stili di coping e capacità di gestire le emozioni possano essere in relazione con la reattività individuale alle situazioni di stress, valutata attraverso alcuni correlati biologici, quali il livello di cortisolo (l’ormone dello stress) e la variabilità della frequenza cardiaca. L’ottica di ricerca applicata fa sì che gli obiettivi ultimi di questo lavoro siano anche quelli di diminuire l’accesso ai servizi per questi soggetti, considerando il fatto che progetti individualizzati di sostegno genitoriale costituiscono un fattore protettivo rispetto a conseguenze fisiche e psicologiche di disagio se implementati tenendo conto della variabilità individuale rispetto alle caratteristiche sopra citate.

Identidade profissional: como se veem os professores na escola atual

Dissertação apresentada para a obtenção do grau de mestre em Ciências da Educação - área de Supervisão e Orientação Pegagógica

Fatigue and Co-occurring Symptoms in Women with Irritable Bowel Syndrome

Thesis (Ph.D.)--University of Washington, 2016-06

Reflections on the statistical analysis of personality and norms in war, peace, and prejudice: Are deviant minorities the problem?

The compelling quality of the Global Change simulation study (Altemeyer, 2003), in which high RWA (right-wing authoritarianism)/high SDO (social dominance orientation) individuals produced poor outcomes for the planet, rests on the inference that the link between high RWA/SDO scores and disaster in the simulation can be generalized to real environmental and social situations. However, we argue that studies of the Person × Situation interaction are biased to overestimate the role of the individual variability. When variables are operationalized, strongly normative items are excluded because they are skewed and kurtotic. This occurs both in the measurement of predictor constructs, such as RWA, and in the outcome constructs, such as prejudice and war. Analyses of normal linear statistics highlight personality variables such as RWA, which produce variance, and overlook the role of norms, which produce invariance. Where both normative and personality forces are operating, as in intergroup contexts, the linear analysis generates statistics for the sample that disproportionately reflect the behavior of the deviant, antinormative minority and direct attention away from the baseline, normative position. The implications of these findings for the link between high RWA and disaster are discussed.

Interindividual Differences in Leg Muscle Mass and Pyruvate Kinase Activity Correlate with Interindividual Differences in Jumping Performance of Hyla multilineata

Frog jumping is an excellent model system for examining the structural basis of interindividual variation in burst locomotor performance. Some possible factors that affect jump performance, such as total body size, hindlimb length, muscle mass, and muscle mechanical and biochemical properties, were analysed at the interindividual (intraspecies) level in the tree frog Hyla multilineata. The aim of this study was to determine which of these physiological and anatomical variables both vary between individuals and are correlated with interindividual variation in jump performance. The model produced via stepwise linear regression analysis of absolute data suggested that 62% of the interindividual variation in maximum jump distance could be explained by a combination of interindividual variation in absolute plantaris muscle mass, total hindlimb muscle mass ( excluding plantaris muscle), and pyruvate kinase activity. When body length effects were removed, multiple regression indicated that the same independent variables explained 43% of the residual interindividual variation in jump distance. This suggests that individuals with relatively large jumping muscles and high pyruvate kinase activity for their body size achieved comparatively large maximal jump distances for their body size.

Accuracy and applications of group MEG studies using cortical source locations estimated from participants' scalp surfaces

We contend that powerful group studies can be conducted using magnetoencephalography (MEG), which can provide useful insights into the approximate distribution of the neural activity detected with MEG without requiring magnetic resonance imaging (MRI) for each participant. Instead, a participant's MRI is approximated with one chosen as a best match on the basis of the scalp surface from a database of available MRIs. Because large inter-individual variability in sulcal and gyral patterns is an inherent source of blurring in studies using grouped functional activity, the additional error introduced by this approximation procedure has little effect on the group results, and offers a sufficiently close approximation to that of the participants to yield a good indication of the true distribution of the grouped neural activity. T1-weighted MRIs of 28 adults were acquired in a variety of MR systems. An artificial functional image was prepared for each person in which eight 5 × 5 × 5 mm regions of brain activation were simulated. Spatial normalisation was applied to each image using transformations calculated using SPM99 with (1) the participant's actual MRI, and (2) the best matched MRI substituted from those of the other 27 participants. The distribution of distances between the locations of points using real and substituted MRIs had a modal value of 6 mm with 90% of cases falling below 12.5 mm. The effects of this -approach on real grouped SAM source imaging of MEG data in a verbal fluency task are also shown. The distribution of MEG activity in the estimated average response is very similar to that produced when using the real MRIs. © 2003 Wiley-Liss, Inc.

Dynamic causal modeling of load-dependent modulation of effective connectivity within the verbal working memory network

Neuroimaging studies have consistently shown that working memory (WM) tasks engage a distributed neural network that primarily includes the dorsolateral prefrontal cortex, the parietal cortex, and the anterior cingulate cortex. The current challenge is to provide a mechanistic account of the changes observed in regional activity. To achieve this, we characterized neuroplastic responses in effective connectivity between these regions at increasing WM loads using dynamic causal modeling of functional magnetic resonance imaging data obtained from healthy individuals during a verbal n-back task. Our data demonstrate that increasing memory load was associated with (a) right-hemisphere dominance, (b) increasing forward (i.e., posterior to anterior) effective connectivity within the WM network, and (c) reduction in individual variability in WM network architecture resulting in the right-hemisphere forward model reaching an exceedance probability of 99% in the most demanding condition. Our results provide direct empirical support that task difficulty, in our case WM load, is a significant moderator of short-term plasticity, complementing existing theories of task-related reduction in variability in neural networks. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.

Population pharmacokinetic and pharmacogenetic analysis of tacrolimus in paediatric liver transplant patients

Aims - To build a population pharmacokinetic model that describes the apparent clearance of tacrolimus and the potential demographic, clinical and genetically controlled factors that could lead to inter-patient pharmacokinetic variability within children following liver transplantation. Methods - The present study retrospectively examined tacrolimus whole blood pre-dose concentrations (n = 628) of 43 children during their first year post-liver transplantation. Population pharmacokinetic analysis was performed using the non-linear mixed effects modelling program (nonmem) to determine the population mean parameter estimate of clearance and influential covariates. Results - The final model identified time post-transplantation and CYP3A5*1 allele as influential covariates on tacrolimus apparent clearance according to the following equation: TVCL = 12.9 x (Weight/13.2)0.35 x EXP (-0.0058 x TPT) x EXP (0.428 x CYP3A5) where TVCL is the typical value for apparent clearance, TPT is time post-transplantation in days and the CYP3A5 is 1 where *1 allele is present and 0 otherwise. The population estimate and inter-individual variability (%CV) of tacrolimus apparent clearance were found to be 0.977 l h−1 kg−1 (95% CI 0.958, 0.996) and 40.0%, respectively, while the residual variability between the observed and predicted concentrations was 35.4%. Conclusion Tacrolimus apparent clearance was influenced by time post-transplantation and CYP3A5 genotypes. The results of this study, once confirmed by a large scale prospective study, can be used in conjunction with therapeutic drug monitoring to recommend tacrolimus dose adjustments that take into account not only body weight but also genetic and time-related changes in tacrolimus clearance.