Analysis of nocturnal oxygen saturation recordings using kernel entropy to assist in sleep apnea-hypopnea diagnosis

In this study, a new entropy measure known as kernel entropy (KerEnt), which quantifies the irregularity in a series, was applied to nocturnal oxygen saturation (SaO 2) recordings. A total of 96 subjects suspected of suffering from sleep apnea-hypopnea syndrome (SAHS) took part in the study: 32 SAHS-negative and 64 SAHS-positive subjects. Their SaO 2 signals were separately processed by means of KerEnt. Our results show that a higher degree of irregularity is associated to SAHS-positive subjects. Statistical analysis revealed significant differences between the KerEnt values of SAHS-negative and SAHS-positive groups. The diagnostic utility of this parameter was studied by means of receiver operating characteristic (ROC) analysis. A classification accuracy of 81.25% (81.25% sensitivity and 81.25% specificity) was achieved. Repeated apneas during sleep increase irregularity in SaO 2 data. This effect can be measured by KerEnt in order to detect SAHS. This non-linear measure can provide useful information for the development of alternative diagnostic techniques in order to reduce the demand for conventional polysomnography (PSG). © 2011 IEEE.

A cationic vaccine adjuvant based on a saturated quaternary ammonium lipid have different in vivo distribution kinetics and display a distinct CD4 T cell-inducing capacity compared to its unsaturated analog

Adjuvants are often composed of different constituents that can be divided into two groups based on their primary activity: the delivery system which carries and presents the vaccine antigen to antigen-presenting cells, and the immunostimulator that activates and modulates the ensuing immune response. Herein, we have investigated the importance of the delivery system and in particular its physical characteristics by comparing the delivery properties of two lipids which differ only in the degree of saturation of the acyl chains, rendering the liposomes either rigid (DDA, dimethyldioctadecylammonium) or highly fluid (DODA, dimethyldioleoylammonium) at physiological temperature. We show that these delivery systems are remarkably different in their ability to prime a Th1-directed immune response with the rigid DDA-based liposomes inducing a response more than 100 times higher compared to that obtained with the fluid DODA-based liposomes. Upon injection with a vaccine antigen, DDA-based liposomes form a vaccine depot that results in a continuous attraction of antigen-presenting cells that engulf a high amount of adjuvant and are subsequently efficiently activated as measured by an elevated expression of the co-stimulatory molecules CD40 and CD86. In contrast, the fluid DODA-based liposomes are more rapidly removed from the site of injection resulting in a lower up-regulation of co-stimulatory CD40 and CD86 molecules on adjuvant-positive antigen-presenting cells. Additionally, the vaccine antigen is readily dissociated from the DODA-based liposomes leading to a population of antigen-presenting cells that are antigen-positive but adjuvant-negative and consequently are not activated. These studies demonstrate the importance of studying in vivo characteristics of the vaccine components and furthermore show that physicochemical properties of the delivery system have a major impact on the vaccine-induced immune response. © 2012 Elsevier B.V. All rights reserved.

I don't see me like you see me, but is that a problem? Cultural influences on rating discrepancy in 360-degree feedback instruments

360-degree feedback from a variety of rater sources yields important information about leaders' styles, strengths and weaknesses for development. Results where observer ratings are discrepant (i.e., different) from self-ratings are often seen as indicators of problematic leadership relationships, skills, or lack of self-awareness. Yet research into the antecedents of such self-observer rating discrepancy suggests the presence of systematic influences, such as cultural values. The present study investigates the variation of rating discrepancies on three leadership skills (decision making, leading employees, and composure) in dependence of one exemplary culture dimension (power distance) on data from 31 countries using multilevel structural equation modelling. Results show that cultural values indeed predict self-observer rating discrepancies. Thus, systemic and contextual influences such as culture need to be taken into consideration when interpreting the importance and meaning of self-observer rating discrepancies in 360-degree instruments.

Science or practice? UK undergraduate experiences and attitudes to the MPharm degree

Objective: The debate surrounding the science/practice balance in the teaching of undergraduate pharmacy has been played out in the professional literature for years. The objective of this work was to explore the attitudes of pharmacy undergraduates on the practice-science debate. Setting: The study was undertaken as part of a national study of teaching, learning and assessment methods in United Kingdom (UK) schools of pharmacy. Method: Six focus groups were carried out. The sample was 44 volunteer students from nine UK schools of pharmacy, representing all 4 years of the MPharm programme. Groups were tape recorded and transcribed. Analysis of the transcripts was theme based by topic. Main Outcome Measure: Qualitative data on student attitudes and experiences. Results: Most students thought that there was too strong an emphasis placed on the science components of the course in the early part of their studies. Later in the course they realised that the majority of the science was necessary; it just had not been apparent to them at the time. There were strongly held attitudes across all 4 years that it would be beneficial to include more practice-related material at the beginning of their studies. This would be beneficial for three reasons: to make the course more interesting, to aid in the contextualisation of the science component and to assist the students in any early placement or vacational work. Conclusion: Internationally, changes to the role of the pharmacist from a traditional supply function to a more clinical role has resulted in differing educational needs for the pharmacist of the future. Pharmacy will remain a degree built on a strong scientific background, but students advise that the contextualisation and sequencing of material within the degree could make a considerable improvement to their learning. Consulting students helps us to understand the teaching, learning and assessment experience better by giving insights into ways of improving the delivery. In the case of the UK, there are legislative changes impending which may provide an opportunity to review the balance of practice-and science in the curriculum. © 2006 Springer Science+Business Media B.V.

Measuring the degree of spatial correlation between histological features in thin sections of brain tissue

Histological features visible in thin sections of brain tissue, such as neuronal perikarya, blood vessels, or pathological lesions may exhibit a degree of spatial association or correlation. In neurodegenerative disorders such as AD, Pick's disease, and CJD, information on whether different types of pathological lesion are spatially correlated may be useful in elucidating disease pathogenesis. In the present article the statistical methods available for studying spatial association in histological sections are reviewed. These include tests of interspecific association between two or more histological features using χ2 contingency tables, measurement of 'complete' and 'absolute' association, and more complex methods that use grids of contiguous samples. In addition, the use of correlation matrices and stepwise multiple regression methods are described. The advantages and limitations of each method are reviewed and possible future developments discussed.

Motion, flash, and flicker:A unified spatiotemporal model of perceived edge sharpening

Blurred edges appear sharper in motion than when they are stationary. We proposed a model of this motion sharpening that invokes a local, nonlinear contrast transducer function (Hammett et al, 1998 Vision Research 38 2099-2108). Response saturation in the transducer compresses or 'clips' the input spatial waveform, rendering the edges as sharper. To explain the increasing distortion of drifting edges at higher speeds, the degree of nonlinearity must increase with speed or temporal frequency. A dynamic contrast gain control before the transducer can account for both the speed dependence and approximate contrast invariance of motion sharpening (Hammett et al, 2003 Vision Research, in press). We show here that this model also predicts perceived sharpening of briefly flashed and flickering edges, and we show that the model can account fairly well for experimental data from all three modes of presentation (motion, flash, and flicker). At moderate durations and lower temporal frequencies the gain control attenuates the input signal, thus protecting it from later compression by the transducer. The gain control is somewhat sluggish, and so it suffers both a slow onset, and loss of power at high temporal frequencies. Consequently, brief presentations and high temporal frequencies of drift and flicker are less protected from distortion, and show greater perceptual sharpening.

Carrier lifetime and exciton saturation in a strain-balanced InGaAs/InAsP multiple-quantum-well

The bleaching of the n = 1 heavy-hole and light-hole exciton absorption has been studied at room temperature and zero bias in a strain-balanced InGaAs/InAsP multiple quantum well. Pump-probe spectroscopy was used to measure the decay of the light-hole absorption saturation, giving a hole lifetime of only 280 ps. As only 16 meV separates the light- and heavy-hole bands, the short escape time can be explained by thermalization between these bands followed by thermionic emission over the heavy-hole barrier. The saturation density was estimated to be 1 × 1016 cm-3; this is much lower than expected for tensile-strained wells where both heavy and light holes have large in-plane masses. © 1998 American Institute of Physics.

Measuring the degree of spatial correlation between pathological lesions in Alzheimer's disease

The pathological lesions characteristic of Alzheimer's disease (AD), viz., senile plaques (SP) and neurofibrillary tangles (NFT) may not be randomly distributed with reference to each other but exhibit a degree of sptial association or correlation, information on the degree of association between SP and NFT or between the lesions and normal histological features, such as neuronal perikarya and blood vessels, may be valuable in elucidating the pathogenesis of AD. This article reviews the statistical methods available for studying the degree of spatial association in histological sections of AD tissue. These include tests of interspecific association between two or more histological features using chi-square contingency tables, measurement of 'complete' and 'absolute' association, and more complex methods that use grids of contiguous samples. In addition, analyses of association using correlation matrices and stepwise multiple regression methods are described. The advantages and limitations of each method are reviewed and possible future developments discussed.

Learning with other health professions in the United Kingdom MPharm degree:Multidisciplinary and placement education

This paper reviews the approach to multidisciplinary and placement education in UK schools of pharmacy. The methodology involved triangulation of course documentation, staff interviews and a final year student survey. Staff members were supportive of multidisciplinary learning. The advantages were development of a wider appreciation of the students? future professional role and better understanding of the roles of other professional groups. The barriers were logistics (student numbers; multiple sites; different timetables), the achievement of balanced numbers between disciplines and engagement of students from all participating disciplines. Placement education was offered by all schools, predominantly in hospital settings. Key problems were funding and the lack of staff resources. Currently, multidisciplinary learning within the UK for pharmacy students is inadequate and is coupled with relatively low levels of placement education. In order for things to change, there should be a review of funding and support from government and the private sector employers.

Submission for the degree of Doctor of Philosophy by published work at Aston University

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Chemical and physical methods of enhancing the percutaneous absorption of antimicrobial agents

Contrary to previously held beliefs, it is now known that bacteria exist not only on the surface of the skin but they are also distributed at varying depths beneath the skin surface. Hence, in order to sterilise the skin, antimicrobial agents are required to penetrate across the skin and eliminate the bacteria residing at all depths. Chlorhexidine is an antimicrobial agent with the widest use for skin sterilisation. However, due to its poor permeation rate across the skin, sterilisation of the skin cannot be achieved and, therefore, the remaining bacteria can act as a source of infection during an operation or insertion of catheters. The underlying theme of this study is to enhance the permeation of this antimicrobial agent in the skin by employing chemical (enhancers and supersaturated systems) or physical (iontophoresis) techniques. The hydrochloride salt of chlorhexidine (CHX), a poorly soluble salt, was used throughout this study. The effect of ionisation on in vitro permeation rate across the excised human epidennis was investigated using Franz-type diffusion cells. Saturated solutions of CHX were used as donor and the variable studied was vehicle pH. Permeation rate was increased with increasing vehicle pH. The pH effect was not related to the level of ionisation of the drug. The effect of donor vehicle was also studied using saturated solutions of CHX in 10% and 20% ethanol as the donor solutions. Permeation of CHX was enhanced by increasing the concentration of ethanol which could be due to the higher concentration of CHX in the donor phase and the effect of ethanol itself on the membrane. The interplay between drug diffusion and enhancer pretreatment of the epidennis was studied. Pretreatment of the membrane with 10% Azone/PG demonstrated the highest diffusion rate followed by 10% olcic acid/PG pretreatment compared to other pretreatment regimens (ethanol, dimethyl sulfoxide (DMSO), propylene glycol (PG), sodium dodecyl sulphate (SDS) and dodecyl trimethyl ammonium bromide (DT AB). Differential Scanning Calorimetry (DSC) was also employed to study the mode of action of these enhancers. The potential of supersaturated solutions in enhancing percutaneous absorption of CHX was investigated. Various anti-nucleating polymers were screened in order to establish the most effective agent. Polyvinylpyrrolidone (PVP, K30) was found to be a better candidate than its lower molecular weight counterpart (K25) and hydroxypropyl methyleellulose (HPMC). The permeation studies showed an increase in diffusion rate by increasing the degree of saturation. Iontophoresis is a physical means of transdemal drug delivery enhancement that causes an increased penetration of molecules into or through the skin by the application of an electric field. This technique was employed in conjunction with chemical enhancers to assess the effect on CHX permeation across the human epidermis. An improved transport of CHX, which was pH dependant was observed upon application of the current. Combined use of iontophoresis and chemical enhancers further increased the CHX transport indicating a synergistic effect. Pretreatment of the membrane with 10% Azone/PG demonstrated the greatest effect.

The percutaneous absorption of ionisable compounds

The effects of ionisation on transdermal drug delivery using excised human epidermis (HS) and silastic rubber (SR) as model permeation barriers were investigated in vitro using Franz-type absorption cells. Suspensions and solutions of salicylic acid (SA), the model ionogenic permeant, were used as donors and the variables studied were vehicle pH and trans-membrane pH-gradients. For solutions, the pH effect was related to the level of ionisation of the drug and the degree of saturation of the solution. With suspensions, the observed permeation rate was unaffected by pH. The penetration profiles through HS and SR were similar, although the overall flux through HS was about 70% of that observed through SR. Pretreatment of the membranes with various enhancer regimens, including oleic acid, Azone and N, N-dimethylamides in propylene glycol (PG) and isopropyl myristate (IPM) promoted the penetration of SA. SR was not a suitable model for enhancer pretreatment using IPM as a vehicle as the membrane was significantly disrupted by this vehicle. The results from comparable experiments with and without a trans-membrane pH-gradient did not have a significant effect upon flux or flux enhancement after pretreatment with the above enhancers. A theoretical model for the extraction coefficients of weak acids was derived using the partition coefficients of the ionised and unionised species, pH and pKa. This model was shown to account for the variation in overall partition of salicylic acid dependent upon pH and pKa. This model was shown to account for the variation in overall partition of salicylic acid dependent upon pH and pKa. The distribution of this solute between aqueous and oily phases, with and without added enhancer, was measured as a function of pH. The extraction coefficients determined were consistent with the model and showed that the behaviour of the system can be explained without referral to ion-pair mechanisms. Phosphonoacetate is an effective antiviral agent. However, as it is charged at physiological pH, its permeation across cell membranes is limited. To assess the improvement of the transport properties of this molecule, mono-, di- and tri-ester prodrugs were examined. These were assessed for stability and subsequent breakdown with respect to pH by HPLC. In vitro percutaneous absorption was observed using the triester, but not the ionic mono- or di-esters. The triester absorption could be potentiated using a range of enhancers with oleic acid being the most effective. Cyclodextrins (CD) have a role as absorption enhancers for peptide compounds across nasal epithelium. One potential mode of action is that CDs include these compounds, protect them from enzymic attack and thereby increase their residence time in the nasal epithelium. This study investigated the potential of CDs to protect ester prodrugs from enzymatic breakdown and prevent production of poorly transportable ionic species. Using a range of CD to ester molar ratios (10:1 to 2500:1) a small, but measurable, protection for the model esters (parabens) against esterase attack was observed. Possible mechanisms for this phenomenon are that CDs include the ester, making it unavailable for hydrolysis, the CDs may also affect the esterase in some way preventing access for the ester into the active site.

A re-evaluation of the use of glyceryl trinitrate to assess the degree of adrenergic beta receptor blockade

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Regional differences in oxygen saturation in retinal arterioles and venules

BACKGROUND: Retinal vessel oxygenation saturation measurements have been the focus of much attention in recent years as a potential diagnostic parameter in a number of ocular and systemic pathologies. This interest has been heightened by the ability to measure oxygen saturation in vivo using a photographic technique. METHODS: Retinal vessel oxygenation in venules and arterioles of 279 retinal vessels of 12 healthy Caucasian participants (mean age: 30 SD (+/- 6) years) were measured consecutively three times to evaluate short-term variation in oxygen saturation and regional variability of retinal vessel oxygen saturation using dual-wavelength technology (Oxymetry Modul, Imedos, Germany). All subjects underwent standard optometric assessment including non-contact intra-ocular pressure assessment as well as having their systemic blood pressure measured. RESULTS: Vessels were grouped as either near-macula or peripheral, depending on their location. Peripheral arterioles and venules exhibited significantly lower oxygen saturation compared to their near-macula counterparts (arterioles: 94.7% (SD 3.9) vs. 99.7% (SD 3.2); venules: 65.1% (SD 7.2) vs. 90.3% (SD 6.7)). Both arterioles and venules, main branches, and those feeding and draining the retina near the macula and periphery showed low short-term variability of oxygen saturation (arterioles: COV 1.2-1.8%; venules: COV 2.9-4.9%). CONCLUSIONS: Retinal arterioles and venules exhibit low short-term variation of oxygen saturation in healthy subjects. Regional differences in oxygen saturation could be a potential useful marker for risk stratification and diagnostic purposes of area-specific retinal pathology such as age-related macula degeneration and diabetic maculopathy.