Parental involvement in sport: psychometric development and empirical test of a theoretical model

The purposes of the present multistudy were to develop and provide initial construct validity for measures based on the model of parental involvement in sport (Study 1) and examine structural relationships among the constructs of the model (Study 2). In Study 1 (nparents = 342, nathletes = 223), a confirmatory factor analysis was used to verify the psychometric properties of the measures. Content and construct validity were evaluated, as well individual and composite reliability. Multi-group analysis with two independent samples provided evidence of factorial invariance. In Study 2 (nparents = 754, nathletes = 438), structural equation modeling analysis supported the hypothesised model in which athletes’ perceptions of parents’ behaviours mediated the relationship between parents’ reported behaviours and the athletes’ psychological variables conducive to their achievement in sport. The findings provide support for the parental involvement in sport model and demonstrate the role of perceptions of parents’ behaviours on young athletes’ cognitions in sport.

Structural Time Series Modeling: an Application to Environmental Variables

A structural time series model is one which is set up in terms of components which have a direct interpretation. In this paper, the discussion focuses on the dynamic modeling procedure based on the state space approach (associated to the Kalman filter), in the context of surface water quality monitoring, in order to analyze and evaluate the temporal evolution of the environmental variables, and thus identify trends or possible changes in water quality (change point detection). The approach is applied to environmental time series: time series of surface water quality variables in a river basin. The statistical modeling procedure is applied to monthly values of physico- chemical variables measured in a network of 8 water monitoring sites over a 15-year period (1999-2014) in the River Ave hydrological basin located in the Northwest region of Portugal.

Incorporation of Hysteretic Effects in Model-Order Reduction Analysis of Magnetic Devices

The ability to predict the properties of magnetic materials in a device is essential to ensuring the correct operation and optimization of the design as well as the device behavior over a wide range of input frequencies. Typically, development and simulation of wide-bandwidth models requires detailed, physics-based simulations that utilize significant computational resources. Balancing the trade-offs between model computational overhead and accuracy can be cumbersome, especially when the nonlinear effects of saturation and hysteresis are included in the model. This study focuses on the development of a system for analyzing magnetic devices in cases where model accuracy and computational intensity must be carefully and easily balanced by the engineer. A method for adjusting model complexity and corresponding level of detail while incorporating the nonlinear effects of hysteresis is presented that builds upon recent work in loss analysis and magnetic equivalent circuit (MEC) modeling. The approach utilizes MEC models in conjunction with linearization and model-order reduction techniques to process magnetic devices based on geometry and core type. The validity of steady-state permeability approximations is also discussed.

Investigating the role of N-WASP in the development of colorectal cancer

Colorectal cancer (CRC) is the second most common cancer in Europe, with the second highest mortality rate. Although prognosis is improving, survival rates remain poor for those presenting with the most advanced stages of the disease. There is therefore a need for improved early diagnosis and thus a greater understanding of the early stages of the development of colorectal tumours is desirable. Additionally, as most deaths in colorectal cancer are due to advanced metastatic disease, it is of great interest to explore any potential mechanisms by which metastatic disease can be inhibited. N-WASP is a ubiquitously expressed protein with multiple intracellular roles including actin regulation and maintaining stability of epithelial cell-cell junctions. Through its role as an actin regulator, it has been implicated in the processes of invasion and metastasis of multiple cancer types. Its role in the development and progression of colorectal cancer however has not been fully explored. This thesis will present a series of in vitro and in vivo studies that were carried out with the aim of answering the following questions: • Does N-Wasp have a role in normal intestinal homeostasis? • Does N-Wasp knockout affect the development of tumours in a mouse model of intestinal tumourigenesis? • Does N-Wasp knockout affect the invasive properties of intestinal cancer in vitro? • Does N-WASP correlate with prognosis or other indicators in human colorectal cancer TMAs? Findings from the in vivo experiments, using an inducible, gut-specific knockout model, have uncovered potential roles for N-Wasp in regulating differentiation and migration of intestinal epithelial cells. Although it had no effect in short term models of intestinal hyperproliferation, N-Wasp knockout increased tumour burden and decreased survival in an established in vivo model of intestinal tumourigenesis, in which there is heterozygous loss of Apc (Apcfl/+). No effect was seen on tumour development or survival when additional N-WASP knockout was introduced into a more rapid model, with heterozygous loss of Apc and mutation of Kras (Apcfl/+ KrasG12D/+). N-WASP expression in human colorectal cancer was assessed using immunohistochemical staining of two tissue microarrays. Low levels of N-WASP expression were found to be associated with presence of MMR deficiency. There was no statistically significant difference in overall or cancer specific survival based on N-WASP expression. Collectively, the data presented here suggest a previously unreported role for N-WASP in regulation of intestinal epithelial differentiation and indicate that it may act as a tumour suppressor against development of benign precursor lesions of colorectal cancer. Further research is warranted to delineate the mechanisms underlying these processes.

Exotic dynamics in a firing rate model of neural tissue with threshold accommodation

Many of the equations describing the dynamics of neural systems are written in terms of firing rate functions, which themselves are often taken to be threshold functions of synaptic activity. Dating back to work by Hill in 1936 it has been recognized that more realistic models of neural tissue can be obtained with the introduction of state-dependent dynamic thresholds. In this paper we treat a specific phenomenological model of threshold accommodation that mimics many of the properties originally described by Hill. Importantly we explore the consequences of this dynamic threshold at the tissue level, by modifying a standard neural field model of Wilson-Cowan type. As in the case without threshold accommodation classical Mexican-Hat connectivity is shown to allow for the existence of spatially localized states (bumps) in both one and two dimensions. Importantly an analysis of bump stability in one dimension, using recent Evans function techniques, shows that bumps may undergo instabilities leading to the emergence of both breathers and traveling waves. Moreover, a similar analysis for traveling pulses leads to the conditions necessary to observe a stable traveling breather. In the regime where a bump solution does not exist direct numerical simulations show the possibility of self-replicating bumps via a form of bump splitting. Simulations in two space dimensions show analogous localized and traveling solutions to those seen in one dimension. Indeed dynamical behavior in this neural model appears reminiscent of that seen in other dissipative systems that support localized structures, and in particular those of coupled cubic complex Ginzburg-Landau equations. Further numerical explorations illustrate that the traveling pulses in this model exhibit particle like properties, similar to those of dispersive solitons observed in some three component reaction-diffusion systems. A preliminary account of this work first appeared in S Coombes and M R Owen, Bumps, breathers, and waves in a neural network with spike frequency adaptation, Physical Review Letters 94 (2005), 148102(1-4).

A kinetic energy budget and internal instabilities in the Fine Resolution Antarctic Model

An energy analysis of the Fine Resolution Antarctic Model (FRAM) reveals the instability processes in the model. The main source of time-mean kinetic energy is the wind stress and the main sink is transfer to mean potential energy. The wind forcing thus helps maintain the density structure. Transient motions result from internal instabilities of the Bow rather than seasonal variations of the forcing. Baroclinic instability is found to be an important mechanism in FRAM. The highest values of available potential energy are found in the western boundary regions as well as in the Antarctic Circumpolar Current (ACC) region. All subregions with predominantly zonal flow are found to be baroclinically unstable. The observed deficit of eddy kinetic energy in FRAM occurs as a result of the high lateral friction, which decreases the growth rates of the most unstable waves. This high friction is required for the numerical stability of the model and can only be made smaller by using a finer horizontal resolution. A grid spacing of at least 10-15 km would be required to resolve the most unstable waves in the southern part of the domain. Barotropic instability is also found to be important for the total domain balance. The inverse transfer (that is, transfer from eddy to mean kinetic energy) does not occur anywhere, except in very localized tight jets in the ACC. The open boundary condition at the northern edge of the model domain does not represent a significant source or sink of eddy variability. However, a large exchange between internal and external mode energies is found to occur. It is still unclear how these boundary conditions affect the dynamics of adjacent regions.

Change-point detection in environmental time series based on the informational approach

In this study, the Schwarz Information Criterion (SIC) is applied in order to detect change-points in the time series of surface water quality variables. The application of change-point analysis allowed detecting change-points in both the mean and the variance in series under study. Time variations in environmental data are complex and they can hinder the identification of the so-called change-points when traditional models are applied to this type of problems. The assumptions of normality and uncorrelation are not present in some time series, and so, a simulation study is carried out in order to evaluate the methodology’s performance when applied to non-normal data and/or with time correlation.

Characterizing, modelling and understanding the climate variability of the deep water formation in the North-Western Mediterranean Sea

Observing, modelling and understanding the climate-scale variability of the deep water formation (DWF) in the North-Western Mediterranean Sea remains today very challenging. In this study, we first characterize the interannual variability of this phenomenon by a thorough reanalysis of observations in order to establish reference time series. These quantitative indicators include 31 observed years for the yearly maximum mixed layer depth over the period 1980–2013 and a detailed multi-indicator description of the period 2007–2013. Then a 1980–2013 hindcast simulation is performed with a fully-coupled regional climate system model including the high-resolution representation of the regional atmosphere, ocean, land-surface and rivers. The simulation reproduces quantitatively well the mean behaviour and the large interannual variability of the DWF phenomenon. The model shows convection deeper than 1000 m in 2/3 of the modelled winters, a mean DWF rate equal to 0.35 Sv with maximum values of 1.7 (resp. 1.6) Sv in 2013 (resp. 2005). Using the model results, the winter-integrated buoyancy loss over the Gulf of Lions is identified as the primary driving factor of the DWF interannual variability and explains, alone, around 50 % of its variance. It is itself explained by the occurrence of few stormy days during winter. At daily scale, the Atlantic ridge weather regime is identified as favourable to strong buoyancy losses and therefore DWF, whereas the positive phase of the North Atlantic oscillation is unfavourable. The driving role of the vertical stratification in autumn, a measure of the water column inhibition to mixing, has also been analyzed. Combining both driving factors allows to explain more than 70 % of the interannual variance of the phenomenon and in particular the occurrence of the five strongest convective years of the model (1981, 1999, 2005, 2009, 2013). The model simulates qualitatively well the trends in the deep waters (warming, saltening, increase in the dense water volume, increase in the bottom water density) despite an underestimation of the salinity and density trends. These deep trends come from a heat and salt accumulation during the 1980s and the 1990s in the surface and intermediate layers of the Gulf of Lions before being transferred stepwise towards the deep layers when very convective years occur in 1999 and later. The salinity increase in the near Atlantic Ocean surface layers seems to be the external forcing that finally leads to these deep trends. In the future, our results may allow to better understand the behaviour of the DWF phenomenon in Mediterranean Sea simulations in hindcast, forecast, reanalysis or future climate change scenario modes. The robustness of the obtained results must be however confirmed in multi-model studies.

Simulating customer experience and word-of-mouth in retail: a case study

Agents offer a new and exciting way of understanding the world of work. In this paper we describe the development of agent-based simulation models, designed to help to understand the relationship between people management practices and retail performance. We report on the current development of our simulation models which includes new features concerning the evolution of customers over time. To test the features we have conducted a series of experiments dealing with customer pool sizes, standard and noise reduction modes, and the spread of customers’ word of mouth. To validate and evaluate our model, we introduce new performance measure specific to retail operations. We show that by varying different parameters in our model we can simulate a range of customer experiences leading to significant differences in performance measures. Ultimately, we are interested in better understanding the impact of changes in staff behavior due to changes in store management practices. Our multi-disciplinary research team draws upon expertise from work psychologists and computer scientists. Despite the fact we are working within a relatively novel and complex domain, it is clear that intelligent agents offer potential for fostering sustainable organizational capabilities in the future.

In vitro-in vivo Pharmacokinetic correlation model for quality assurance of antiretroviral drugs

Introduction: The In vitro-in vivo pharmacokinetic correlation models (IVIVC) are a fundamental part of the drug discovery and development process. The ability to accurately predict the in vivo pharmacokinetic profile of a drug based on in vitro observations can have several applications during a successful development process. Objective: To develop a comprehensive model to predict the in vivo absorption of antiretroviral drugs based on permeability studies, in vitro and in vivo solubility and demonstrate its correlation with the pharmacokinetic profile in humans. Methods: Analytical tools to test the biopharmaceutical properties of stavudine, lamivudine y zidovudine were developed. The kinetics of dissolution, permeability in caco-2 cells and pharmacokinetics of absorption in rabbits and healthy volunteers were evaluated. Results: The cumulative areas under the curve (AUC) obtained in the permeability study with Caco-2 cells, the dissolution study and the pharmacokinetics in rabbits correlated with the cumulative AUC values in humans. These results demonstrated a direct relation between in vitro data and absorption, both in humans and in the in vivo model. Conclusions: The analytical methods and procedures applied to the development of an IVIVC model showed a strong correlation among themselves. These IVIVC models are proposed as alternative and cost/effective methods to evaluate the biopharmaceutical properties that determine the bioavailability of a drug and their application includes the development process, quality assurance, bioequivalence studies and pharmacosurveillance.

FACTORS AFFECTING DIPOREIA GROWTH RATES IN LAKE SUPERIOR

An ability to predict population dynamics of the amphipod Diporeia is important in understanding how energy pathways in the Lake Superior food web might be altered by disturbances to the ecosystem. Estimating growth rates for this prominent prey item for fish requires information on the physiological effects of changes to its environment. These effects have been investigated for Diporeia in other Great Lakes, but little is known about Lake Superior populations. The primary objective of this study is to obtain quantitative data for rates of Diporeia respiration and consumption that can be incorporated into a bioenergetics model for Lake Superior. Benthic communities in Lake Superior were sampled bimonthly from April through September during 2011 and 2012 to investigate spatial and temporal trends of Diporeia abundances as well as size class structures of the population. Additional samples of Diporeia were collected and kept alive in natural sediment for laboratory experiments. Respiration rates for Diporeia were measured by monitoring dissolved oxygen concentrations in microcosoms using microelectrodes. Additionally, a series of experiments to estimate consumption rates based on food availability were conducted using 14C-labeled algae (Selenastrum capricornutum). Amphipod population densities are highest between 30-110 m (slope) compared to 0-30 m (shelf) or >110 m (profundal) regions in Lake Superior. This heterogeneous distribution of Diporeia in Lake Superior is an important component to quantifying lake-wide biomass. Rates of oxygen consumption by Diporeia range from 32.0 to 44.7 mgO2*gDW-1*d-1, and do not vary significantly with body size per individual. The predicted consumption rate corresponding to average Lake Superior algal carbon fluxes was 0.08 ± SE mgC*gDW-1*d-1. Data on Lake Superior Diporeia biomass and bioenergetics found in this study can be incorporated in a model used to estimate the viability of this population under potential future environmental stressors.

Applicability of an assessment model for healthcare information systems in a public hospital

Assessment processes are essential to guarantee quality and continuous improvement of software in healthcare, as they measure software attributes in their lifecycle, verify the degree of alignment between the software and its objectives and identify unpredicted events. This article analyses the use of an assessment model based on software metrics for three healthcare information systems from a public hospital that provides secondary and tertiary care in the region of Ribeirão Preto. Compliance with the metrics was investigated using questionnaires in guided interviews of the system analysts responsible for the applications. The outcomes indicate that most of the procedures specified in the model can be adopted to assess the systems that serves the organization, particularly in the attributes of compatibility, reliability, safety, portability and usability.

Trends in NE Atlantic landings (southern Portugal): identifying the relative importance of fisheries and environmental variables

Time series of commercial landings from the Algarve (southern Portugal) from 1982 to 1999 were analyzed using min/max autocorrelation factor analysis (MAFA) and dynamic factor analysis (DFA). These techniques were used to identify trends and explore the relationships between the response variables (annual landings of 12 species) and explanatory variables [sea surface temperature, rainfall, an upwelling index, Guadiana river (south-east Portugal) flow, the North Atlantic oscillation, the number of licensed fishing vessels and the number of commercial fishermen]. Landings were more highly correlated with non-lagged environmental variables and in particular with Guadiana river flow. Both techniques gave coherent results, with the most important trend being a steady decline over time. A DFA model with two explanatory variables (Guadiana river flow and number of fishermen) and three common trends (smoothing functions over time) gave good fits to 10 of the 12 species. Results of other models indicated that river flow is the more important explanatory variable in this model. Changes in the mean flow and discharge regime of the Guadiana river resulting from the construction of the Alqueva dam, completed in 2002, are therefore likely to have a significant and deleterious impact on Algarve fisheries landings.

Longitudinal Micro CT-driven biomarkers as a tool to evaluate lung fibrosis progression and antifibrotic efficacy in a refined Bleomycin mouse model

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with no curative pharmacological treatment. Animal models play an essential role in revealing molecular mechanisms involved in the pathogenesis of the disease. Bleomycin (BLM)-induced lung fibrosis is the most widely used and characterized model for anti-fibrotic drugs screening. However, several issues have been reported, such as the identification of an optimal BLM dose and administration scheme as well as gender-specificity. Moreover, the balance between disease resolution, an appropriate time window for therapeutic intervention and animal welfare remains critical aspects yet to be fully elucidated. In this thesis, Micro CT imaging has been used as a tool to identify the ideal BLM dose regimen to induce sustained lung fibrosis in mice as well as to assess the anti-fibrotic effect of Nintedanib (NINT) treatment upon this BLM administration regimen. In order to select the optimal BLM dose scheme, C57bl/6 male mice were treated with BLM via oropharyngeal aspiration (OA), following either double or triple BLM administration. The triple BLM administration resulted in the most promising scheme, able to balance disease resolution, appropriate time-window for therapeutic intervention and animal welfare. The fibrosis progression was longitudinally assessed by micro-CT every 7 days for 5 weeks after BLM administration and 5 animals were sacrificed at each timepoint for the BALF and histological evaluation. The antifibrotic effect of NINT was assessed following different treatment regimens in this model. Herein, we have developed an optimized mouse model of pulmonary fibrosis, enabling three weeks of the therapeutic window to screen putative anti-fibrotic drugs. micro-CT scanning, allowed us to monitor the progression of lung fibrosis and the therapeutical response longitudinally in the same subject, drastically reducing the number of animals involved in the experiment.

Pharmacological targeting of P-selectin to halt the progression of myelofibrosis in the Gata1low mouse model

Primary myelofibrosis is a clonal hematopoietic disorder characterized by marked degrees of systemic inflammation. The release of pro-inflammatory factors by clonal hematopoietic cell populations cause the remodeling of a specialized microenvironment, defined niche, in which the hematopoietic stem cells reside. The main source of pro-inflammatory cytokines is represented by malignant megakaryocytes. The bone marrow and spleen from myelofibrosis patients, as well as those from the Gata1low mouse model of the disease, contain increased number of abnormal megakaryocytes. These cells express on their surface high levels of the adhesion receptor P-selectin that, by triggering a pathological megakaryocyte-neutrophil emperipolesis, lead to increased bioavailability of TGF-β1 in the microenvironment and disease progression. Gata1low mice develop with age a phenotype similar to that of patients with myelofibrosis. We previously demonstrated that deletion of the P-selectin gene in Gata1low mice prevented the development of the myelofibrotic phenotype in these mice. In the current study, we tested the hypothesis that pharmacological inhibition of P-selectin may rescue the fibrotic phenotype of Gata1low mice. To test this hypothesis, we have investigated the phenotype expressed by old Gata1low mice treated with the anti-mouse monoclonal antibody against P-selectin RB40.34, alone or in combination with the JAK2 inhibitor Ruxolitinib. The results showed that the combined therapy normalized the phenotype of Gata1low mice with limited toxicity by reducing fibrosis, TGF-β1 and CXCL1 content in the BM and spleen and by restoring hematopoiesis in the bone marrow and the normal architecture of the spleen. In conclusion, pharmacological inhibition of P-selectin was effective in targeting malignant megakaryocytes and the microenvironmental abnormalities that affect the hematopoietic stem cell compartment in this model. These results suggest that P-selectin and JAK1/2 inhibitors in combination may represent a valid therapeutic option for patients with myelofibrosis.