Fecal water as a non-invasive biomarker in nutritional intervention: comparison of preparation methods and refinement of different endpoints

The assessment of cellular effects by the aqueous phase of human feces (fecal water, FW) is a useful biomarker approach to study cancer risks and protective activities of food. In order to refine and develop the biomarker, different protocols of preparing FW were compared. Fecal waters were prepared by 3 methods: (A) direct centrifugation; (B) extraction of feces in PBS before centrifugation; and (C) centrifugation of lyophilized and reconstituted feces. Genotoxicity was determined in colon cells using the Comet assay. Selected samples were investigated for additional parameters related to carcinogenesis. Two of 7 FWs obtained by methods A and B were similarly genotoxic. Method B, however, yielded higher volumes of FW, allowing sterile filtration for long-term culture experiments. Four of 7 samples were non-genotoxic when prepared according to all 3 methods. FW from lyophilized feces and from fresh samples were equally genotoxic. FWs modulated cytotoxicity, paracellular permeability, and invasion, independent of their genotoxicity. All 3 methods of FW preparation can be used to assess genotoxicity. The higher volumes of FWobtained by preparation method B greatly enhance the perspectives of measuring different types of biological parameters and using these to disclose activities related to cancer development.

A novel technique for differentiation of proteins in the development of acid gel structure from control and heat treated milk using confocal scanning laser microscopy

The incorporation of caseins and whey proteins into acid gels produced from unheated and heat treated skimmed milk was studied by confocal scanning laser microscopy (CSLM) using fluorescent labelled proteins. Bovine casein micelles were labelled using Alexa Fluor 594, while whey proteins were labelled using Alexa Fluor 488. Samples of the labelled protein solutions were introduced into aliquots of pasteurised skim milk, and skim milk heated to 90 degrees C for 2 min and 95 degrees C for 8 min. The milk was acidified at 40 degrees C to a final pH of 4.4 using 20 g gluconodelta-lactone/l (GDL). The formation of gels was observed with CSLM at two wavelengths (488 nm and 594 nm), and also by visual and rheological methods. In the control milk, as pH decreased distinct casein aggregates appeared, and as further pH reduction occurred, the whey proteins could be seen to coat the casein aggregates. With the heated milks, the gel structure was formed of continuous strands consisting of both casein and whey protein. The formation of the gel network was correlated with an increase in the elastic modulus for all three treatments, in relation to the severity of heat treatment. This model system allows the separate observation of the caseins and whey proteins, and the study of the interactions between the two protein fractions during the formation of the acid gel structure, on a real-time basis. The system could therefore be a valuable tool in the study of structure formation in yoghurt and other dairy protein systems.

The development of convergence and accommodation

Aim: To review current literature on the development of convergence and accommodation. The accommodation and vergence systems provide the foundation upon which bifoveal binocular single vision develops. Deviations from their normal development not only are implicated in the aetiology of convergence anomalies, accommodative anomalies and strabismus, but may also be implicated in failure of the emmetropisation process. Method: This review considers the problems of researching the development of accommodation and vergence in infants and how infant research has had to differ from adult methods. It then reviews and discusses the implications of current research into the development of both systems and their linkages. Results: Vergence and accommodation develop rapidly in the first months of life, with accommodation changing from relatively fixed myopic focus in the neonatal period to adult-like responses by 4 months of age. Vergence develops gradually and becomes more accurate after 4 months of age, but has been demonstrated in infants well before the age that binocular disparity detection mechanisms are thought to develop. Hypotheses for this early vergence mechanism are discussed. The relationship between accommodation and vergence shows much more variability in infants than adult literature has found, but this apparent adult/infant difference may be partly attributed to methodological differences rather than maturational change alone. Conclusions: Variability and flexibility characterise infant responses. This variability may enable infants to develop a flexible and robust binocular system for later life. Studies of infant visual cue use may give clues to the aetiology of strabismus and refractive error.

Development of multi-electrode array screening for anticonvulsants in acute rat brain slices

The acute hippocampal brain slice preparation is an important in vitro screening tool for potential anticonvulsants. Application of 4-aminopyridine (4-AP) or removal of external Mg2+ ions induces epileptiform bursting in slices which is analogous to electrical brain activity seen in status epilepticus states. We have developed these epileptiform models for use with multi-electrode arrays (MEAs), allowing recording across the hippocampal slice surface from 59 points. We present validation of this novel approach and analyses using two anticonvulsants, felbamate and phenobarbital, the effects of which have already been assessed in these models using conventional extracellular recordings. In addition to assessing drug effects on commonly described parameters (duration, amplitude and frequency), we describe novel methods using the MEA to assess burst propagation speeds and the underlying frequencies that contribute to the epileptiform activity seen. Contour plots are also used as a method of illustrating burst activity. Finally, we describe hitherto unreported properties of epileptiform, bursting induced by 100 mu M 4-AP or removal of external Mg2+ ions. Specifically, we observed decreases over time in burst amplitude and increase over time in burst frequency in the absence of additional pharmacological interventions. These MEA methods enhance the depth, quality and range of data that can be derived from the hippocampal slice preparation compared to conventional extracellular recordings. it may also uncover additional modes of action that contribute to anti-epileptiform drug effects. (C) 2009 Elsevier B.V. All rights reserved.

A decade of research and development in disability, virtual reality and associated technologies: review of ICDVRAT 1996−2006

The International Conference (series) on Disability, Virtual Reality and Associated Technologies (ICDVRAT) this year held its sixth biennial conference, celebrating ten years of research and development in this field. A total of 220 papers have been presented at the first six conferences, addressing potential, development, exploration and examination of how these technologies can be applied in disabilities research and practice. The research community is broad and multi-disciplined, comprising a variety of scientific and medical researchers, rehabilitation therapists, educators and practitioners. Likewise, technologies, their applications and target user populations are also broad, ranging from sensors positioned on real world objects to fully immersive interactive simulated environments. A common factor is the desire to identify what the technologies have to offer and how they can provide added value to existing methods of assessment, rehabilitation and support for individuals with disabilities. This paper presents a brief review of the first decade of research and development in the ICDVRAT community, defining technologies, applications and target user populations served.

Development and experimental identification of a biomechanical model of the trunk for functional electrical stimulation control in paraplegia

Objectives. Theoretic modeling and experimental studies suggest that functional electrical stimulation (FES) can improve trunk balance in spinal cord injured subjects. This can have a positive impact on daily life, increasing the volume of bimanual workspace, improving sitting posture, and wheelchair propulsion. A closed loop controller for the stimulation is desirable, as it can potentially decrease muscle fatigue and offer better rejection to disturbances. This paper proposes a biomechanical model of the human trunk, and a procedure for its identification, to be used for the future development of FES controllers. The advantage over previous models resides in the simplicity of the solution proposed, which makes it possible to identify the model just before a stimulation session ( taking into account the variability of the muscle response to the FES). Materials and Methods. The structure of the model is based on previous research on FES and muscle physiology. Some details could not be inferred from previous studies, and were determined from experimental data. Experiments with a paraplegic volunteer were conducted in order to measure the moments exerted by the trunk-passive tissues and artificially stimulated muscles. Data for model identification and validation also were collected. Results. Using the proposed structure and identification procedure, the model could adequately reproduce the moments exerted during the experiments. The study reveals that the stimulated trunk extensors can exert maximal moment when the trunk is in the upright position. In contrast, previous studies show that able-bodied subjects can exert maximal trunk extension when flexed forward. Conclusions. The proposed model and identification procedure are a successful first step toward the development of a model-based controller for trunk FES. The model also gives information on the trunk in unique conditions, normally not observable in able-bodied subjects (ie, subject only to extensor muscles contraction).

Comparison of bottom-up protein identification methods

With the rapid development of proteomics, a number of different methods appeared for the basic task of protein identification. We made a simple comparison between a common liquid chromatography-tandem mass spectrometry (LC-MS/MS) workflow using an ion trap mass spectrometer and a combined LC-MS and LC-MS/MS method using Fourier transform ion cyclotron resonance (FTICR) mass spectrometry and accurate peptide masses. To compare the two methods for protein identification, we grew and extracted proteins from E. coli using established protocols. Cystines were reduced and alkylated, and proteins digested by trypsin. The resulting peptide mixtures were separated by reversed-phase liquid chromatography using a 4 h gradient from 0 to 50% acetonitrile over a C18 reversed-phase column. The LC separation was coupled on-line to either a Bruker Esquire HCT ion trap or a Bruker 7 tesla APEX-Qe Qh-FTICR hybrid mass spectrometer. Data-dependent Qh-FTICR-MS/MS spectra were acquired using the quadrupole mass filter and collisionally induced dissociation into the external hexapole trap. Proteins were in both schemes identified by Mascot MS/MS ion searches and the peptides identified from these proteins in the FTICR MS/MS data were used for automatic internal calibration of the FTICR-MS data, together with ambient polydimethylcyclosiloxane ions.

Refinement of the Clinical Scenario Evaluation Framework for Assessment of Competing Development Strategies with an Application to Multiple Sclerosis

When competing strategies for development programs, clinical trial designs, or data analysis methods exist, the alternatives need to be evaluated in a systematic way to facilitate informed decision making. Here we describe a refinement of the recently proposed clinical scenario evaluation framework for the assessment of competing strategies. The refinement is achieved by subdividing key elements previously proposed into new categories, distinguishing between quantities that can be estimated from preexisting data and those that cannot and between aspects under the control of the decision maker from those that are determined by external constraints. The refined framework is illustrated by an application to a design project for an adaptive seamless design for a clinical trial in progressive multiple sclerosis.

Loss of language in early development of autism and specific language impairment

Background:  Several authors have highlighted areas of overlap in symptoms and impairment among children with autism spectrum disorder (ASD) and children with specific language impairment (SLI). By contrast, loss of language and broadly defined regression have been reported as relatively specific to autism. We compare the incidence of language loss and language progression of children with autism and SLI. Methods:  We used two complementary studies: the Special Needs and Autism Project (SNAP) and the Manchester Language Study (MLS) involving children with SLI. This yielded a combined sample of 368 children (305 males and 63 females) assessed in late childhood for autism, history of language loss, epilepsy, language abilities and nonverbal IQ. Results:  language loss occurred in just 1% of children with SLI but in 15% of children classified as having autism or autism spectrum disorder. Loss was more common among children with autism rather than milder ASD and is much less frequently reported when language development is delayed. For children who lost language skills before their first phrases, the phrased speech milestone was postponed but long-term language skills were not significantly lower than children with autism but without loss. For the few who experienced language loss after acquiring phrased speech, subsequent cognitive performance is more uncertain. Conclusions:  Language loss is highly specific to ASD. The underlying developmental abnormality may be more prevalent than raw data might suggest, its possible presence being hidden for children whose language development is delayed.

Real option pricing in mixed-use development projects

The application of real options theory to commercial real estate has developed rapidly during the last 15 Years. In particular, several pricing models have been applied to value real options embedded in development projects. In this study we use a case study of a mixed use development scheme and identify the major implied and explicit real options available to the developer. We offer the perspective of a real market application by exploring different binomial models and the associated methods of estimating the crucial parameter of volatility. We include simple binomial lattices, quadranomial lattices and demonstrate the sensitivity of the results to the choice of inputs and method.

A prospective longitudinal study of the impact of early postnatal vs. chronic maternal depressive symptoms on child development

Background Few studies of the effects of postnatal depression on child development have considered the chronicity of depressive symptoms. We investigated whether early postnatal depressive symptoms (PNDS) predicted child developmental outcome independently of later maternal depressive symptoms. Methods In a prospective, longitudinal study, mothers and children were followed-up from birth to 2 years; repeated measures of PNDS were made using the Edinburgh Postnatal Depression Scale (EPDS); child development was assessed using the Bayley Scales II. Multilevel modelling techniques were used to examine the association between 6 week PNDS, and child development, taking subsequent depressive symptoms into account. Results Children of mothers with 6 week PNDS were significantly more likely than children of non-symptomatic mothers to have poor cognitive outcome; however, this association was reduced to trend level when adjusted for later maternal depressive symptoms. Conclusion Effects of early PNDS on infant development may be partly explained by subsequent depressive symptoms.

British pharmacy professionals’ beliefs and participation in continuing professional development: a review of the literature.

Objectives Continuing professional development (CPD) has potential to be useful in pharmacy revalidation but past uptake and attitudes to CPD in Great Britain (GB) need to be mapped. This review examines published literature to chart the participation and beliefs of pharmacy professionals towards CPD in GB in a decade that had seen a formal transition from continuing education to CPD. Methods A comprehensive review of the published literature was conducted to identify studies of the uptake of, or attitudes towards, CPD cross different sectors of pharmacy in GB from 2000 to 2010. Key findings Twenty-two studies were included and analysed, including 13 research papers, six conference papers, two news items reporting survey outcomes and one commissioned study. Eight barriers to CPD were identified as: time, financial costs and resource issues, understanding of CPD, facilitation and support for CPD, motivation and interest in CPD, attitudes towards compulsory CPD, system constraints, and technical problems. Pharmacy professionals on the whole agreed with the principle of engaging with CPD but there was little evidence to suggest widespread and wholehearted acceptance and uptake of CPD, essential for revalidation. Conclusions If CPD is to succeed, people's beliefs and attitudes must be addressed by recognising and modifying perceived barriers through a combination of regulatory, professional, work-related and personal channels. A number of recommendations are made. Direct experience of effective CPD in the absence of perceived barriers could impact on personal development, career development and patient benefit thus strengthening personal beliefs in the value of CPD in an iterative manner.

British pharmacy professionals' beliefs and participation in continuing professional development: a review of the literature

Objectives:  Continuing professional development (CPD) has potential to be useful in pharmacy revalidation but past uptake and attitudes to CPD in Great Britain (GB) need to be mapped. This review examines published literature to chart the participation and beliefs of pharmacy professionals towards CPD in GB in a decade that had seen a formal transition from continuing education to CPD. Methods:  A comprehensive review of the published literature was conducted to identify studies of the uptake of, or attitudes towards, CPD cross different sectors of pharmacy in GB from 2000 to 2010. Key findings:  Twenty-two studies were included and analysed, including 13 research papers, six conference papers, two news items reporting survey outcomes and one commissioned study. Eight barriers to CPD were identified as: time, financial costs and resource issues, understanding of CPD, facilitation and support for CPD, motivation and interest in CPD, attitudes towards compulsory CPD, system constraints, and technical problems. Pharmacy professionals on the whole agreed with the principle of engaging with CPD but there was little evidence to suggest widespread and wholehearted acceptance and uptake of CPD, essential for revalidation. Conclusions:  If CPD is to succeed, people's beliefs and attitudes must be addressed by recognising and modifying perceived barriers through a combination of regulatory, professional, work-related and personal channels. A number of recommendations are made. Direct experience of effective CPD in the absence of perceived barriers could impact on personal development, career development and patient benefit thus strengthening personal beliefs in the value of CPD in an iterative manner.

Fit for planning? An evaluation of the application of development viability appraisal models in the UK planning system

The aim of this paper is to critically examine the application of development appraisal to viability assessment in the planning system. This evaluation is of development appraisal models in general and also their use in particular applications associated with estimating planning obligation capacity. The paper is organised into four themes: · The context and conceptual basis for development viability appraisal · A review of development viability appraisal methods · A discussion of selected key inputs into a development viability appraisal · A discussion of the applications of development viability appraisals in the planning system It is assumed that readers are familiar with the basic models and information needs of development viability appraisal rather than at the cutting edge of practice and/or academe

Urban conservation areas and sustainable development: exploring the relationship

With increasing emphasis being placed on concentrating development in urban areas and improving the quality of life in British cities and towns, the importance of accommodating necessary development without compromising the valued heritage and architectural quality of urban areas is now becoming central to sustainable urban development. Urban conservation policy and practice has the potential to contribute to this and other aspects of sustainability. This paper explores this contribution and develops an analytical framework which draws out the key linkages between conservation area policy and sustainable development. The framework is then used to research the potential and actual contribution of urban conservation policy and practice in England, using a selective survey and two case studies (i.e. Winchester and Basingstoke). The main conclusions from the research are that: Conservation area policy can make a significant contribution to the principles of sustainable development; Most local planning authorities in England have not fully woken-up to this potential and have not developed policies or practices to address it; and Urban conservation policy needs to develop a more proactive approach in which local planning authorities actively guide and encourage new development with regard to use, design, layout, methods of construction, materials and energy efficiency.