The human factors of computer input using a mouse device

This thesis investigates how people select items from a computer display using the mouse input device. The term computer mouse refers to a class of input devices which share certain features, but these may have different characteristics which influence the ways in which people use the device. Although task completion time is one of the most commonly used performance measures for input device evaluation, there is no consensus as to its definition. Furthermore most mouse studies fail to provide adequate assurances regarding its correct measurement.Therefore precise and accurate timing software were developed which permitted the recording of movement data which by means of automated analysis yielded the device movements made. Input system gain, an important task parameter, has been poorly defined and misconceptualized in most previous studies. The issue of gain has been clarified and investigated within this thesis. Movement characteristics varied between users and within users, even for the same task conditions. The variables of target size, movement amplitude, and experience exerted significant effects on performance. Subjects consistently undershot the target area. This may be a consequence of the particular task demands. Although task completion times indicated that mouse performance had stabilized after 132 trials the movement traces, even of very experienced users, indicated that there was still considerable room for improvement in performance, as indicated by the proportion of poorly made movements. The mouse input device was suitable for older novice device users, but they took longer to complete the experimental trials. Given the diversity and inconsistency of device movements, even for the same task conditions, caution is urged when interpreting averaged grouped data. Performance was found to be sensitive to; task conditions, device implementations, and experience in ways which are problematic for the theoretical descriptions of device movement, and limit the generalizability of such findings within this thesis.

Amino acid, peptide and drug transport across monolayers of human intestinal (CAC0-2) cells in vitro

The properties of Caco-2 monolayers were compared on aluminium oxide and nitrocellulose permeable-supports. On nitrocellulose, Caco-2 cells displayed a higher rate of taurocholic acid transport than those cultured on aluminium oxide inserts. In addition, Caco-2 cells grown on these two inserts were not comparable with respect to cell morphology, cell numbers and transepithelial electrical resistance. The low adsorption potential of the aluminium oxide inserts, particularly for high molecular weight or lipophilic ligands, offers a distinct advantage over nitrocellulose inserts for drug transport studies. The carrier-mediated uptake and transport of the imino acid (L-proline) and the acidic amino acids (L-aspartate and L-glutamate) have been studied. At pH7.4, L-proline uptake is mediated via an A-system carrier. Elevated uptake and transport under acidic conditions occurs by activation of a distinct carrier population. Acidic amino acid transport is mediated via a X-AG system. The flux of baclofen, CGP40116 andCGP40117 across Caco-2 monolayers was described by passive transport. The transport of three peptides, thyrotrophin-releasing hormone, SQ29852 and cyclosporin were investigated. Thyrotrophin-releasing hormone transport acrossCaco-2 monolayers was characterised by a minor saturable (carrier-mediated,approximately 25%) pathway, superimposed onto a major non-saturable (diffusional)pathway. SQ29852 uptake into Caco-2 monolayers is described by a major saturable mechanism (Km = 0.91 mM) superimposed onto a minor passive component.However, the initial-rate of SQ29852 transport is consistent with a passive transepithelial transport mechanism. These data highlight the possibility that itsbasolateral efflux is severely retarded such that the passive paracellular transportdictates the overall transepithelial transport characteristics. In addition, modelsuitable for investigating the transepithelial transport of cyclosporin A has been developed. A modification of the conventional Caco-2 model has been developed which has a calcium-free Ap donor-solution and a Bl receiver-solution containing the minimumcalcium concentration required to maintain monolayer integrity (100 μM). The influence of calcium and magnesium on the absorption of [14C]pamidronate was evaluated by comparing its transport across the conventional and minimum calciumCaco-2 models. Ap calcium and magnesium ions retard the Ap-to-Bl flux of pamidronate across Caco-2 monolayers. The effect of self-emulsifying oleic acid-Tween 80 formulations on Caco-2monolayer integrity has been investigated. Oleic acid-Tween 80 (1 0:1) formulations produced a dose-dependent disruption of Caco-2 monolayer integrity. This disruption was related to the oleic acid content of the formulation.

Neuromagnetic investigations of functional organisation within human visual cortex

This thesis describes a series of experimental investigations into the functional organisation of human visual cortex using neuromagnetometry.This technique combines good spatial and temporal resolution enabling identification of the location and temporal response characteristics of cortical neurones within alert humans. To activate different neuronal populations and cortical areas a range of stimuli were used, the parameters of which were selected to match the known physiological properties of primate cortical neurones. In one series of experiments the evoked magnetic response was recorded to isoluminant red/green gratings. Co-registration of signal and magnetic resonance image data indicated a contribution to the response from visual areas V1, V2 and V4. To investigate the spatio-temporal characteristics of neurones within area V1 the evoked response was recorded for a range of stimulus spatial and temporal frequencies. The response to isoluminant red/green gratings was dominated by a major component which was found to have bandpass spatial frequency tuning with a peak at 1-2 cycles/degree, falling to the level of the noise at 6-8 cycles/degree. The temporal frequency tuning characteristics of the response showed bimodal sensitivity with peaks at 0-1Hz and 4Hz. In a further series of experiments the luminance evoked response was recorded to red/black, yellow/black and achromatic gratings and in all cases was found to be more complex than the isoluminant chromatic response, comprising up to three distinct components. The major response peak showed bandpass spatial frequency tuning characteristics, peaking at 6-8 cycles/degree, falling to the level of the noise at 12-16 cycles/degree. The results provide evidence to suggest that within area V1 the same neuronal population encodes both chromatic and luminance information and has spatial frequency tuning properties consistent with single-opponent cells. Furthermore, the results indicate that cells within area V1 encode chromatic motion information over a wide range of temporal frequencies with temporal response characteristics suggestive of the existence of a sub-population of cells sensitive to high temporal frequencies.

Biometric and physiological factors in human ocular perfusion

By addressing the vascular features that characterise myopia, this thesis aims to provide an understanding of the early structural changes associated with human myopia and the progression to co-morbidity with age. This thesis addresses three main areas of study: 1. Ocular perfusion features and autoregulatory mechanisms in human myopia; 2. Choroidal thickness at the macular area of myopic eyes; 3. Effect of chronic smoking on the ocular haemodynamics and autoregulation. This thesis demonstrated a reduced resting ocular pulse amplitude and retrobulbar blood flow in human myopia, associated with an apparent oversensitivity to the vasodilatory effects of hypercapnia, which may be due to anatomical differences in the volume of the vessel beds. In young smokers, normal resting state vascular characteristics were present; however there also appeared to be increased reactivity to hypercapnia, possibly due to relative chronic hypoxia. The systemic circulation in myopes and smokers over-reacted similarly to hypercapnia suggesting that physiologic differences are not confined to the eye. Age also showed a negative effect on autoregulatory capacity in otherwise normal eyes. Collectively, these findings suggest that myopes and smokers require greater autoregulatory capacity to maintain appropriate oxygenation of retinal tissue, and since the capacity for such regulation reduces with age, these groups are at greater risk of insufficient autoregulation and relative hypoxia with age.

A smart sensing platform for the discrimination of human movement

This thesis documents the design, implementation and testing of a smart sensing platform that is able to discriminate between differences or small changes in a persons walking. The distributive tactile sensing method is used to monitor the deflection of the platform surface using just a small number of sensors and, through the use of neural networks, infer the characteristics of the object in contact with the surface. The thesis first describes the development of a mathematical model which uses a novel method to track the position of a moving load as it passes over the smart sensing surface. Experimental methods are then described for using the platform to track the position of swinging pendulum in three dimensions. It is demonstrated that the method can be extended to that of real-time measurement of balance and sway of a person during quiet standing. Current classification methods are then investigated for use in the classification of different gait patterns, in particular to identify individuals by their unique gait pattern. Based on these observations, a novel algorithm is developed that is able to discriminate between abnormal and affected gait. This algorithm, using the distributive tactile sensing method, was found to have greater accuracy than other methods investigated and was designed to be able to cope with any type of gait variation. The system developed in this thesis has applications in the area of medical diagnostics, either as an initial screening tool for detecting walking disorders or to be able to automatically detect changes in gait over time. The system could also be used as a discrete biometric identification method, for example identifying office workers as they pass over the surface.

Ocular biometric correlates of ciliary muscle thickness in human myopia

Purpose - Anterior segment optical coherent tomography (AS-OCT) is used to further examine previous reports that ciliary muscle thickness (CMT) is increased in myopic eyes. With reference to temporal and nasal CMT, interrelationships between biometric and morphological characteristics of anterior and posterior segments are analysed for British-White and British-South-Asian adults with and without myopia. Methods - Data are presented for the right eyes of 62 subjects (British-White n = 39, British-South-Asian n = 23, aged 18–40 years) with a range of refractive error (mean spherical error (MSE (D)) -1.74 ± 3.26; range -10.06 to +4.38) and separated into myopes (MSE (D) <-0.50, range -10.06 to -0.56; n = 30) and non-myopes (MSE (D) =-0.50, -0.50 to +4.38; n = 32). Temporal and nasal ciliary muscle cross-sections were imaged using a Visante AS-OCT. Using Visante software, manual measures of nasal and temporal CMT (NCMT and TCMT respectively) were taken in successive posterior 1 mm steps from the scleral spur over a 3 mm distance (designated NCMT1, TCMT1 et seq). Measures of axial length and anterior chamber depth were taken with an IOLMaster biometer. MSE and corneal curvature (CC) measurements were taken with a Shin-Nippon auto-refractor. Magnetic resonance imaging was used to determine total ocular volume (OV) for 31 of the original subject group. Statistical comparisons and analyses were made using mixed repeated measures anovas, Pearson's correlation coefficient and stepwise forward multiple linear regression. Results - MSE was significantly associated with CMT, with thicker CMT2 and CMT3 being found in the myopic eyes (p = 0.002). In non-myopic eyes TCMT1, TCMT2, NCMT1 and NCMT2 correlated significantly with MSE, AL and OV (p < 0.05). In contrast, myopic eyes failed generally to exhibit a significant correlation between CMT, MSE and axial length but notably retained a significant correlation between OV, TCMT2, TCMT3, NCMT2 and NCMT3 (p < 0.05). OV was found to be a significantly better predictor of TCMT2 and TCMT3 than AL by approximately a factor of two (p < 0.001). Anterior chamber depth was significantly associated with both temporal and nasal CMT2 and CMT3; TCMT1 correlated positively with CC. Ethnicity had no significant effect on differences in CMT. Conclusions - Increased CMT is associated with myopia. We speculate that the lack of correlation in myopic subjects between CMT and axial length, but not between CMT and OV, is evidence that disrupted feedback between the fovea and ciliary apparatus occurs in myopia development.

Human single-donor composite skin substitutes based on collagen and polycaprolactone copolymer

The development and characterization of an enhanced composite skin substitute based on collagen and poly(e-caprolactone) are reported. Considering the features of excellent biocompatibility, easy-manipulated property and exempt from cross-linking related toxicity observed in the 1:20 biocomposites, skin substitutes were developed by seeding human single-donor keratinocytes and fibroblasts alone on both sides of the 1:20 biocomposite to allow for separation of two cell types and preserving cell signals transmission via micro-pores with a porosity of 28.8 ± 16.1 µm. The bi-layered skin substitute exhibited both differentiated epidermis and fibrous dermis in vitro. Less Keratinocyte Growth Factor production was measured in the co-cultured skin model compared to fibroblast alone condition indicating a favorable microenvironment for epidermal homeostasis. Moreover, fast wound closure, epidermal differentiation, and abundant dermal collagen deposition were observed in composite skin in vivo. In summary, the beneficial characteristics of the new skin substitutes exploited the potential for pharmaceutical screening and clinical application.

A case-study investigating the physicochemical characteristics that dictate the function of a liposomal adjuvant

A range of particulate delivery systems have been considered as vaccine adjuvants. Of these systems, liposomes offer a range of advantages including versatility and flexibility in design format and their ability to incorporate a range of immunomodulators and antigens. Here we briefly outline research, from within our laboratories, which focused on the systematic evaluation of cationic liposomes as vaccines adjuvants. Our aim was to identify physicochemical characteristics that correlate with vaccine efficacy, with particular consideration of the interlink between depot-forming action and immune responses. A variety of parameters were investigated and over a range of studies we have confirmed that cationic liposomes, based on dimethyldioctadecylammonium bromide and trehalose 6,6'-dibehenate formed a depot at the injection site, which stimulates recruitment of antigen presenting cells to the injection site and promotes strong humoral and cell-mediated immune responses. Physicochemical factors which promote a strong vaccine depot include the combination of a high cationic charge and electrostatic binding of the antigen to the liposome system and the use of lipids with high transition temperatures, which form rigid bilayer vesicles. Reduction in vesicle size of cationic vesicles did not promote enhanced drainage from the injection site. However, reducing the cationic nature through substitution of the cationic lipid for a neutral lipid, or by masking of the charge using PEGylation, resulted in a reduced depot formation and reduced Th1-type immune responses, while Th2-type responses were less influenced. These studies confirm that the physicochemical characteristics of particulate-based adjuvants play a key role in the modulation of immune responses.

Directly unproductive schooling:how country characteristics affect the impact of schooling on growth

The rapid rise in schooling in developing countries in recent decades has been dramatic. However, many cross-country regression analyses of the impact of schooling on economic growth find low and insignificant coefficients. This empirical 'puzzle' contrasts with theoretical arguments that schooling, through raising human capital, should raise income levels. This paper argues that poor results are to be expected when regression samples include countries that vary greatly in their ability to use schooling productively. Data on corruption, the black market premium on foreign exchange and the extent of the brain drain for developing countries are used as indicators of an economy's productive use of schooling. Regression analysis shows that the impact of secondary schooling on economic growth is substantially higher in countries that are adjudged to use schooling productivity.

Changes in ocular physiology, tear film characteristics, and symptomatology with 18 months silicone hydrogel contact lens wear

Purpose. The purpose of this study was to evaluate the longitudinal changes in ocular physiology, tear film characteristics, and symptomatology experienced by neophyte silicone hydrogel (SiH) contact lens wearers in a daily-wear compared with a continuous-wear modality and with the different commercially available lenses over an 18-month period. Methods. Forty-five neophyte subjects were enrolled in the study and randomly assigned to wear one of two SiH materials: lotrafilcon A or balafilcon A lenses on either a daily- (LDW; BDW) or continuous-wear (LCW; BCW) basis. Additionally, a group of noncontact lens-wearing subjects (control group) was also recruited and followed over the same study period. Objective and subjective grading of ocular physiology were carried out together with tear meniscus height (TMH) and noninvasive tear breakup time (NITBUT). Subjects also subjectively rated symptoms and judgments with lens wear. After initial screening, subsequent measurements were taken after 1, 3, 6, 12, and 18 months. Results. Subjective and objective grading of ocular physiology revealed a small increase in bulbar, limbal, and palpebral hyperemia as well as corneal staining over time with both lens materials and regimes of wear (p < 0.05). No significant changes in NITBUT or TMH were found (p > 0.05). Subjective symptoms and judgment were not material- or modality-specific. Conclusions. Daily and continuous wear of SiH contact lenses induced small but statistically significant changes in ocular physiology and symptomatology. Clinical measures of tear film characteristics were unaffected by lens wear. Both materials and regimes of wear showed similar clinical performance. Long-term SiH contact lens wear is shown to be a successful option for patients. Copyright © 2006 American Academy of Optometry.

Measuring the impact of innovative human capital on small firms' propensity to innovate

The ability to identify and evaluate the competitive advantage of employees' transferable and innovative characteristics is of importance to firms and policymakers. This research extends the standard measure of human capital by developing a unique and far reaching concept of Innovative Human Capital and emphasises its effect on small firm innovation and hence growth (jobs, sales and productivity). This new Innovative Human Capital concept encapsulates four elements: education, training, willingness to change in the workplace and job satisfaction to overcome the limitations of measurements used previously. An augmented innovation production function is used to test the hypothesis that small firms who employ managers with Innovative Human Capital are more likely to innovate. There is evidence from the results that Innovative Human Capital may be more valuable to small firms (i.e. less than 50 employees) than larger-sized firms (i.e. more than 50 employees). The research expands innovation theory to include the concept of Innovative Human Capital as a competitive advantage and determinant of small firm innovation; and distinguishes Innovative Human Capital as a significant concept to consider when creating public support programmes for small firms.

Acoustic source characteristics, across-formant integration, and speech intelligibility under competitive conditions

An important aspect of speech perception is the ability to group or select formants using cues in the acoustic source characteristics-for example, fundamental frequency (F0) differences between formants promote their segregation. This study explored the role of more radical differences in source characteristics. Three-formant (F1+F2+F3) synthetic speech analogues were derived from natural sentences. In Experiment 1, F1+F3 were generated by passing a harmonic glottal source (F0 = 140 Hz) through second-order resonators (H1+H3); in Experiment 2, F1+F3 were tonal (sine-wave) analogues (T1+T3). F2 could take either form (H2 or T2). In some conditions, the target formants were presented alone, either monaurally or dichotically (left ear = F1+F3; right ear = F2). In others, they were accompanied by a competitor for F2 (F1+F2C+F3; F2), which listeners must reject to optimize recognition. Competitors (H2C or T2C) were created using the time-reversed frequency and amplitude contours of F2. Dichotic presentation of F2 and F2C ensured that the impact of the competitor arose primarily through informational masking. In the absence of F2C, the effect of a source mismatch between F1+F3 and F2 was relatively modest. When F2C was present, intelligibility was lowest when F2 was tonal and F2C was harmonic, irrespective of which type matched F1+F3. This finding suggests that source type and context, rather than similarity, govern the phonetic contribution of a formant. It is proposed that wideband harmonic analogues are more effective informational maskers than narrowband tonal analogues, and so become dominant in across-frequency integration of phonetic information when placed in competition.

Serum-free process development:improving the yield and consistency of human mesenchymal stromal cell production

Background aims: The cost-effective production of human mesenchymal stromal cells (hMSCs) for off-the-shelf and patient specific therapies will require an increasing focus on improving product yield and driving manufacturing consistency. Methods: Bone marrow-derived hMSCs (BM-hMSCs) from two donors were expanded for 36 days in monolayer with medium supplemented with either fetal bovine serum (FBS) or PRIME-XV serum-free medium (SFM). Cells were assessed throughout culture for proliferation, mean cell diameter, colony-forming potential, osteogenic potential, gene expression and metabolites. Results: Expansion of BM-hMSCs in PRIME-XV SFM resulted in a significantly higher growth rate (P < 0.001) and increased consistency between donors compared with FBS-based culture. FBS-based culture showed an inter-batch production range of 0.9 and 5 days per dose compared with 0.5 and 0.6 days in SFM for each BM-hMSC donor line. The consistency between donors was also improved by the use of PRIME-XV SFM, with a production range of 0.9 days compared with 19.4 days in FBS-based culture. Mean cell diameter has also been demonstrated as a process metric for BM-hMSC growth rate and senescence through a correlation (R² = 0.8705) across all conditions. PRIME-XV SFM has also shown increased consistency in BM-hMSC characteristics such as per cell metabolite utilization, in vitro colony-forming potential and osteogenic potential despite the higher number of population doublings. Conclusions: We have increased the yield and consistency of BM-hMSC expansion between donors, demonstrating a level of control over the product, which has the potential to increase the cost-effectiveness and reduce the risk in these manufacturing processes.

Human capital:theoretical and empirical insights

There is nothing more difficult to plan, more Doubtful of success, nor more dangerous to manage Than the creation of a new system. For the initiator has the enmity of all who would Profit by the preservation of the old system, and Merely lukewarm defenders in those who should gain By the new one. N. Machiavelli (1513) Abstract: The purpose of this paper is twofold. First, we want to challenge the notion of "human capital" as "education, training and work experience" and suggest that it is the "quality of the workforce" that matters, here defined as the set of characteristics that allow workers to function in a specific institutional and historical context. Our main conclusion is that the quality of the workforce is affected by the institutional environment where the workers live and that therefore it can vary across countries and institutional contexts. Second, we want to show the empirical relevance of this last point by testing the extent to which the quality of institutions (here proxied by the governance indicators of Kaufmann etal. (2007)) can affect the quality of the workforce (proxied by the percentage of the working age population registered in a lifelong learning program). Our empirical analysis is conducted on a data-set of 11 European countries observed over the period 1996-2006. The results indicate that countries with better governance indicators are also endowed with a more qualified workforce. © 2011 American Journal of Economics and Sociology, Inc.

Scalability and process transfer of mesenchymal stromal cell production from monolayer to microcarrier culture using human platelet lysate

Background aims: The selection of medium and associated reagents for human mesenchymal stromal cell (hMSC) culture forms an integral part of manufacturing process development and must be suitable for multiple process scales and expansion technologies. Methods: In this work, we have expanded BM-hMSCs in fetal bovine serum (FBS)- and human platelet lysate (HPL)-containing media in both a monolayer and a suspension-based microcarrier process. Results: The introduction of HPL into the monolayer process increased the BM-hMSC growth rate at the first experimental passage by 0.049 day and 0.127/day for the two BM-hMSC donors compared with the FBS-based monolayer process. This increase in growth rate in HPL-containing medium was associated with an increase in the inter-donor consistency, with an inter-donor range of 0.406 cumulative population doublings after 18 days compared with 2.013 in FBS-containing medium. Identity and quality characteristics of the BM-hMSCs are also comparable between conditions in terms of colony-forming potential, osteogenic potential and expression of key genes during monolayer and post-harvest from microcarrier expansion. BM-hMSCs cultured on microcarriers in HPL-containing medium demonstrated a reduction in the initial lag phase for both BM-hMSC donors and an increased BM-hMSC yield after 6 days of culture to 1.20 ± 0.17 × 105 and 1.02 ± 0.005 × 105 cells/mL compared with 0.79 ± 0.05 × 105 and 0.36 ± 0.04 × 105 cells/mL in FBS-containing medium. Conclusions: This study has demonstrated that HPL, compared with FBS-containing medium, delivers increased growth and comparability across two BM-hMSC donors between monolayer and microcarrier culture, which will have key implications for process transfer during scale-up.