Evaluation of the auto-refraction function of the Nidek OPD-Scan III

Background: The aim was to evaluate the validity and repeatability of the auto-refraction function of the Nidek OPD-Scan III (Nidek Technologies, Gamagori, Japan) compared with non-cycloplegic subjective refraction. The Nidek OPD-Scan III is a new aberrometer/corneal topographer workstation based on the skiascopy principle. It combines a wavefront aberrometer, topographer, autorefractor, auto keratometer and pupillometer/pupillographer. Methods: Objective refraction results obtained using the Nidek OPD-Scan III were compared with non-cycloplegic subjective refraction for 108 eyes of 54 participants (29 female) with a mean age of 23.7±9.5 years. Intra-session and inter-session variability were assessed on 14 subjects (28 eyes). Results: The Nidek OPD-Scan III gave slightly more negative readings than results obtained by subjective refraction (Nidek mean difference -0.19±0.36 DS, p<0.01 for sphere; -0.19±0.35 DS, p<0.01 for mean spherical equivalent; -0.002±0.23 DC, p=0.91 for cylinder; -0.06±0.38 DC, p=0.30 for J0 and -0.36±0.31 DC for J45, p=0.29). Auto-refractor results for 74 per cent of spherical readings and 60 per cent of cylindrical powers were within±0.25 of subjective refraction. There was high intra-session and inter-session repeatability for all parameters; 90 per cent of inter-session repeatability results were within 0.25 D. Conclusion: The Nidek OPD-Scan III gives valid and repeatable measures of objective refraction when compared with non-cycloplegic subjective refraction. © 2013 The Authors. Clinical and Experimental Optometry © 2013 Optometrists Association Australia.

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.

Measurement of scleral thickness in humans using anterior segment optical coherent tomography

Anterior segment optical coherent tomography (AS-OCT, Visante; Zeiss) is used to examine meridional variation in anterior scleral thickness (AST) and its association with refractive error, ethnicity and gender. Scleral cross-sections of 74 individuals (28 males; 46 females; aged between 18-40 years (27.7±5.3)) were sampled twice in random order in 8 meridians: [superior (S), inferior (I), nasal (N), temporal (T), superior-temporal (ST), superior-nasal (SN), inferior-temporal (IT) and inferior-nasal (IN)]. AST was measured in 1mm anterior-toposterior increments (designated the A-P distance) from the scleral spur (SS) over a 6mm distance. Axial length and refractive error were measured with a Zeiss IOLMaster biometer and an open-view binocular Shin-Nippon autorefractor. Intra- And inter-observer variability of AST was assessed for each of the 8 meridians. Mixed repeated measures ANOVAs tested meridional and A-P distance differences in AST with refractive error, gender and ethnicity. Only right eye data were analysed. AST (mean±SD) across all meridians and A-P distances was 725±46μm. Meridian SN was the thinnest (662±57μm) and I the thickest (806 ±60μm). Significant differences were found between all meridians (p<0.001), except S:ST, IT:IN, IT:N and IN:N. Significant differences between A-P distances were found except between SS and 6 mm and between 2 and 4mm. AST measurements at 1mm (682±48 μm) were the thinnest and at 6mm (818±49 μm) the thickest (p<0.001); a significant interaction occurred between meridians and A-P distances (p<0.001). AST was significantly greater (p<0.001) in male subjects but no significant differences were found between refractive error or ethnicity. Significant variations in AST occur with regard to meridian and distance from the SS and may have utility in selecting optimum sites for pharmaceutical or surgical intervention.

Source localization methods

One of the most pressing demands on electrophysiology applied to the diagnosis of epilepsy is the non-invasive localization of the neuronal generators responsible for brain electrical and magnetic fields (the so-called inverse problem). These neuronal generators produce primary currents in the brain, which together with passive currents give rise to the EEG signal. Unfortunately, the signal we measure on the scalp surface doesn't directly indicate the location of the active neuronal assemblies. This is the expression of the ambiguity of the underlying static electromagnetic inverse problem, partly due to the relatively limited number of independent measures available. A given electric potential distribution recorded at the scalp can be explained by the activity of infinite different configurations of intracranial sources. In contrast, the forward problem, which consists of computing the potential field at the scalp from known source locations and strengths with known geometry and conductivity properties of the brain and its layers (CSF/meninges, skin and skull), i.e. the head model, has a unique solution. The head models vary from the computationally simpler spherical models (three or four concentric spheres) to the realistic models based on the segmentation of anatomical images obtained using magnetic resonance imaging (MRI). Realistic models – computationally intensive and difficult to implement – can separate different tissues of the head and account for the convoluted geometry of the brain and the significant inter-individual variability. In real-life applications, if the assumptions of the statistical, anatomical or functional properties of the signal and the volume in which it is generated are meaningful, a true three-dimensional tomographic representation of sources of brain electrical activity is possible in spite of the ‘ill-posed’ nature of the inverse problem (Michel et al., 2004). The techniques used to achieve this are now referred to as electrical source imaging (ESI) or magnetic source imaging (MSI). The first issue to influence reconstruction accuracy is spatial sampling, i.e. the number of EEG electrodes. It has been shown that this relationship is not linear, reaching a plateau at about 128 electrodes, provided spatial distribution is uniform. The second factor is related to the different properties of the source localization strategies used with respect to the hypothesized source configuration.

Costs and benefits of orthographic inconsistency in reading:evidence from a cross-linguistic comparison

We compared reading acquisition in English and Italian children up to late primary school analyzing RTs and errors as a function of various psycholinguistic variables and changes due to experience. Our results show that reading becomes progressively more reliant on larger processing units with age, but that this is modulated by consistency of the language. In English, an inconsistent orthography, reliance on larger units occurs earlier on and it is demonstrated by faster RTs, a stronger effect of lexical variables and lack of length effect (by fifth grade). However, not all English children are able to master this mode of processing yielding larger inter-individual variability. In Italian, a consistent orthography, reliance on larger units occurs later and it is less pronounced. This is demonstrated by larger length effects which remain significant even in older children and by larger effects of a global factor (related to speed of orthographic decoding) explaining changes of performance across ages. Our results show the importance of considering not only overall performance, but inter-individual variability and variability between conditions when interpreting cross-linguistic differences.

Importance of storm events in controlling ecosystem structure and function in a Florida gulf coast estuary

From 8/95 to 2/01, we investigated the ecological effects of intra- and inter-annual variability in freshwater flow through Taylor Creek in southeastern Everglades National Park. Continuous monitoring and intensive sampling studies overlapped with an array of pulsed weather events that impacted physical, chemical, and biological attributes of this region. We quantified the effects of three events representing a range of characteristics (duration, amount of precipitation, storm intensity, wind direction) on the hydraulic connectivity, nutrient and sediment dynamics, and vegetation structure of the SE Everglades estuarine ecotone. These events included a strong winter storm in November 1996, Tropical Storm Harvey in September 1999, and Hurricane Irene in October 1999. Continuous hydrologic and daily water sample data were used to examine the effects of these events on the physical forcing and quality of water in Taylor Creek. A high resolution, flow-through sampling and mapping approach was used to characterize water quality in the adjacent bay. To understand the effects of these events on vegetation communities, we measured mangrove litter production and estimated seagrass cover in the bay at monthly intervals. We also quantified sediment deposition associated with Hurricane Irene's flood surge along the Buttonwood Ridge. These three events resulted in dramatic changes in surface water movement and chemistry in Taylor Creek and adjacent regions of Florida Bay as well as increased mangrove litterfall and flood surge scouring of seagrass beds. Up to 5 cm of bay-derived mud was deposited along the ridge adjacent to the creek in this single pulsed event. These short-term events can account for a substantial proportion of the annual flux of freshwater and materials between the mangrove zone and Florida Bay. Our findings shed light on the capacity of these storm events, especially when in succession, to have far reaching and long lasting effects on coastal ecosystems such as the estuarine ecotone of the SE Everglades.

Dynamics of ecosystem metabolism and flocculent detritus transport in estuarine Taylor River

Estuaries and estuarine wetlands are ecologically and societally important systems, exhibiting high rates of primary production that fuel offshore secondary production. Hydrological processes play a central role in shaping estuarine ecosystem structure and function by controlling nutrient loading and the relative contributions of marine and terrestrial influences on the estuary. The Comprehensive Everglades Restoration Plan includes plans to restore freshwater delivery to Taylor Slough, a shallow drainage basin in the southern Everglades, ultimately resulting in increased freshwater flow to the downstream Taylor River estuary. The existing seasonal and inter-annual variability of water flow and source in Taylor River affords the opportunity to investigate relationships between ecosystem function and hydrologic forcing. Estimates of aquatic ecosystem metabolism, derived from free-water, diel changes in dissolved oxygen, were combined with assessments of wetland flocculent detritus quality and transport within the context of seasonal changes in Everglades hydrology. Variation in ecosystem gross primary production and respiration were linked to seasonal changes in estuarine water quality using multiple autoregression models. Furthermore, Taylor River was observed to be net heterotrophic, indicating that an allochthonous source of carbon maintained ecosystem respiration in excess of autochthonous primary production. Wetland-derived detritus appears to be an important vector of energy and nutrients across the Everglades landscape; and in Taylor River, is seasonally flushed into ponded segments of the river where it is then respired. Lastly, seasonal water delivery appears to govern feedbacks regulating water column phosphorus availability in the Taylor River estuary.

Localising the auditory N1m with event-related beamformers:localisation accuracy following bilateral and unilateral stimulation

The auditory evoked N1m-P2m response complex presents a challenging case for MEG source-modelling, because symmetrical, phase-locked activity occurs in the hemispheres both contralateral and ipsilateral to stimulation. Beamformer methods, in particular, can be susceptible to localisation bias and spurious sources under these conditions. This study explored the accuracy and efficiency of event-related beamformer source models for auditory MEG data under typical experimental conditions: monaural and diotic stimulation; and whole-head beamformer analysis compared to a half-head analysis using only sensors from the hemisphere contralateral to stimulation. Event-related beamformer localisations were also compared with more traditional single-dipole models. At the group level, the event-related beamformer performed equally well as the single-dipole models in terms of accuracy for both the N1m and the P2m, and in terms of efficiency (number of successful source models) for the N1m. The results yielded by the half-head analysis did not differ significantly from those produced by the traditional whole-head analysis. Any localisation bias caused by the presence of correlated sources is minimal in the context of the inter-individual variability in source localisations. In conclusion, event-related beamformers provide a useful alternative to equivalent-current dipole models in localisation of auditory evoked responses.

Investigating metabolomic biomarkers of hypoxic ischaemic encephalopathy

Background An early objective biomarker to predict the severity of hypoxic-ischaemic encephalopathy (HIE) and identify infants suitable for intervention remains elusive. This thesis aims to progress metabolomic markers of HIE through a pipeline of biomarker discovery and validation by employing a novel untargeted mass spectrometry metabolomic method. Methodology Term infants with perinatal asphyxia were recruited, all having umbilical cord blood (UCB) drawn and biobanked within three hours of birth. HIE was defined by Sarnat score at 24hours and continuous multichannel-EEG. Infant neurodevelopment was assessed at 36-42 months using the Bayley Scales of Infant and Toddler Development Ed. III (BSID-III). Untargeted metabolomic analysis of UCB was performed using direct injection FT-ICR mass spectrometry (DI FT-ICR MS). Putative metabolite annotations and lipid classes were assigned and pathway analysis was performed. Results Untargeted metabolomic analysis: Thirty enrolled infants were diagnosed with HIE, including 17 mild, 8 moderate, and 5 severe cases. Pathway analysis revealed that ΔHIE was associated with a 50% and 75% perturbation of tryptophan and pyrimidine metabolism respectively, alongside alterations in amino acid pathways. Significant metabolite alterations were detected from six putatively identified lipid classes including fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterol lipids and prenol lipids. Outcome prediction: Metabolite model scores significantly correlated with outcome R=0.429 (model A) and R=0.549 (model B) respectively. Model B demonstrates the potential to predict both severe outcome (AUROC of 0.915) and intact survival (AUROC of 0.800). The effect of haemolysis: On average 5% of polar and 1.5% of non-polar features were altered between paired haemolysed and clean samples. However unsupervised multivariate analysis concluded that the preanalytical variability introduced by haemolysis was negligible compared with the inherent biological inter-individual variability. Conclusion This research has employed untargeted metabolomics to identify potential early cord blood biomarkers of HIE and has performed the technical validation of previously proposed markers.

Seawater carbonate chemistry and sperm swimming speed of the polychaete Galeolaria caespitosa in lab experiment

The rapidity of ocean acidification intensifies selection pressure for resilient phenotypes, particularly during sensitive early life stages. The scope for selection is greater in species with greater within-species variation in responses to changing environments, thus enhancing the potential for adaptation. We investigated among-male variation in sperm swimming responses (percent motility and swimming speeds) of the serpulid polychaete Galeolaria caespitosa to near- (delta pH 0.3) and far-future ocean acidification (delta pH 0.5). Responses of sperm swimming to acidification varied significantly among males and were overall negative. Robust sperm swimming behavior under near-future ocean acidification in some males may ameliorate climate change impacts, if traits associated with robustness are heritable, and thereby enhance the potential for adaptation to far-future conditions. Reduced sperm swimming in the majority of male G. caespitosa may decrease their fertilization success in a high CO2 future ocean. Resultant changes in offspring production could affect recruitment success and population fitness downstream.

Oxygen isotope ratios on calcite from the Piànico lake record

Stable oxygen isotope analyses at annual, 2-, 5-, 10- and 20-varve sample resolutions were carried out on two selected varve intervals from the interglacial sediment record of the Piànico palaeolake. These sediments are particularly suitable for ultra-high-resolution isotope analyses on lacustrine endogenic calcite because of the exceptionally well-preserved varve structure. A bias through detrital contamination can be excluded because microscopically controlled sampling enabled selecting detritus-free samples. The studied sediment intervals comprise 352 and 88 continuous varve series formed during periods of rapid climate change at the onset and end of a marked millennial-scale cool interval during the Piànico Interglacial. The most intriguing result is a pronounced short-term oscillation in the bi-annually resolved isotope record superimposed on the general decreasing and increasing d18O trends at the climatic transitions that is recorded at lower sample resolution. Spectral analyses of the bi-annual time series reveal periodicities indicating solar and NAO controls on the d18O record. Multiple d18O measurements from endogenic calcite of individual varves showed variations of up to 0.6 per mil, thus larger than the observed inter-annual variability and most likely explained by seasonal effects.

The relationship between changes in cardiovascular function and changes in VO2peak following SIT

Background: It is well known that sprint interval training (SIT), induces significant increases in peak oxygen uptake (VO2peak) at the group level. However, there have been only a few studies that have addressed the variability of VO2peak response following SIT, and precise mechanism(s) that may explain individual magnitude of response are unknown. Purpose: Therefore, the purpose of this thesis was to: 1) examine the inter-individual variability of the VO2peak response following SIT, 2) to inspect the relationship between changes in both central and peripheral measures and changes in VO2peak, and 3) to assess if peripheral or central adaptations play a role in whether an individual is a high or low responder with respect to VO2peak. Subjects: Twenty-two young, recreationally active males (age: 20.4 1.7 years; weight: 78.4 10.2 kg; VO2peak: 3.7 0.62 L/min) Methods: VO2peak (L/min), peak cardiac output (Qpeak [L/min]), and peak deoxygenated hemoglobin (HHbpeak [mM]) were measured before and after 16 sessions of SIT (Tabata Protocol) over four weeks. Peak a-vO2diff was calculated using a derivation of the Fick equation. Results: Due to a systematic error, HHbpeak could not be used to differentiate between individual responses. There was a large range of VO2peak response from pre to post testing (-4.75 to 32.18% change) and there was a significant difference between the Low Response Group (LRG) (n=8) and the High Response Group (HRG) (n=8) [f(1, 14)= 64.27, p<0.001]. Furthermore, there was no correlation between delta () VO2peak and Qpeak (r=-0.18, p=0.46) for all participants, nor was there an interaction effect between the Low and High Response Groups [f(1,11)=0.572, p=0.47]. Lastly, there was a significant correlation between VO2peak and peak a-vO2diff [r=0.692, p<0.001], and a significant interaction effect with peak a-vO2diff [f(1, 14)= 13.27, p<0.004] when comparing the HRG to the LRG. Conclusions: There was inter-individual variability of VO2peak response following 4 weeks of SIT, but central adaptations did not influence this variation. This suggests that peripheral adaptations may be responsible for VO2peak adaptation.

Revisiting the Late Jurassic-Early Cretaceous of the NW South Iberian Basin: new ages and sedimentary environments

The study of the Upper Jurassic-Lower Cretaceous deposits (Higueruelas, Villar del Arzobispo and Aldea de Cortés Formations) of the South Iberian Basin (NW Valencia, Spain) reveals new stratigraphic and sedimentological data, which have significant implications on the stratigraphic framework, depositional environments and age of these units. The Higueruelas Fm was deposited in a mid-inner carbonate platform where oncolitic bars migrated by the action of storms and where oncoid production progressively decreased towards the uppermost part of the unit. The overlying Villar del Arzobispo Fm has been traditionally interpreted as an inner platform-lagoon evolving into a tidal-flat. Here it is interpreted as an inner-carbonate platform affected by storms, where oolitic shoals protected a lagoon, which had siliciclastic inputs from the continent. The Aldea de Cortés Fm has been previously interpreted as a lagoon surrounded by tidal-flats and fluvial-deltaic plains. Here it is reinterpreted as a coastal wetland where siliciclastic muddy deposits interacted with shallow fresh to marine water bodies, aeolian dunes and continental siliciclastic inputs. The contact between the Higueruelas and Villar del Arzobispo Fms, classically defined as gradual, is also interpreted here as rapid. More importantly, the contact between the Villar del Arzobispo and Aldea de Cortés Fms, previously considered as unconformable, is here interpreted as gradual. The presence of Alveosepta in the Villar del Arzobispo Fm suggests that at least part of this unit is Kimmeridgian, unlike the previously assigned Late Tithonian-Middle Berriasian age. Consequently, the underlying Higueruelas Fm, previously considered Tithonian, should not be younger than Kimmeridgian. Accordingly, sedimentation of the Aldea de Cortés Fm, previously considered Valangian-Hauterivian, probably started during the Tithonian and it may be considered part of the regressive trend of the Late Jurassic-Early Cretaceous cycle. This is consistent with the dinosaur faunas, typically Jurassic, described in the Villar del Arzobispo and Aldea de Cortés Fms.

Los estilos de enseñanza: construyendo puentes para transitar las diferencias individuales del alumnado

Para progresar en el camino hacia una efectiva atención a la diversidad, es inevitable desarrollar un estilo de enseñanza que tenga en cuenta las diferencias individuales que presenta el alumnado, muy vinculadas a intereses, necesidades, aptitudes, potencialidades y estilos de aprendizaje particulares del educando. Rasgos, todos ellos, que los hace únicos y diferenciados. Así, desde el estudio de la variabilidad intersujeto y partiendo de un marco teórico multidimensional, se describen y analizan las diferencias interindividuales e intergrupales de 555 estudiantes de la Facultades de Ciencias de la Educación de Galicia pertenecientes a las Universidades de Coruña, Santiago de Compostela y Vigo, bajo el prisma de los siguientes estilos de enseñanza: reflexivo, cooperador, individualizador, innovador, indagador y académico. Los resultados obtenidos revelan la existencia de diferencias significativas en las preferencias sobre estilos de enseñanza en función de las variables propuestas: Universidad, especialidad, sexo y edad.

Influência da escala de cores na avaliação qualitativa das imagens de cintigrafia de perfusão do miocárdio

Introdução – A cintigrafia de perfusão do miocárdio (CPM) é utilizada no diagnóstico e seguimento de pacientes com doença arterial coronária, sendo a sua avaliação frequentemente realizada através da análise visual dos cortes tomográficos. A escala de cores selecionada é essencial na interpretação clínica das imagens de perfusão do miocárdio. Objetivo – Avaliar a influência de diferentes escalas de cores na avaliação qualitativa das imagens de CPM e estudar quais as mais adequadas para análise visual. Métodos – Trinta e cinco estudos de CPM foram avaliados visualmente por 16 estudantes da licenciatura em medicina nuclear nas escalas de cores Cool, Gray, Gray Invert, Thermal e Warm. Para a escala de cores Cool, a análise das imagens de CPM foi realizada através de um sistema de classificação semiquantitativo por scores. As restantes escalas de cores foram avaliadas por comparação com a análise das imagens efetuada com escala de cores Cool. Resultados/Discussão – Para a escala de cores Cool, a variabilidade interoperador revelou a existência de diferenças estatisticamente significativas entre todos os participantes (p<0,05), o que se pode atribuir à subjetividade da avaliação visual. Os resultados relativos às escalas de cores Gray e Gray Invert foram os mais próximos da perfusão do miocárdio observada com a escala Cool, considerando-se escalas de cores alternativas na análise visual dos estudos de CPM. Para as escalas de cores Thermal e Warm os resultados foram mais divergentes, não se considerando adequadas para a avaliação visual dos estudos de CPM. Conclusão – A escala de cores influencia a avaliação qualitativa da perfusão na CPM.