Methodology for development of a physiological model incorporating CYP3A and P-glycoprotein for the prediction of intestinal drug absorption

The small intestine poses a major barrier to the efficient absorption of orally administered therapeutics. Intestinal epithelial cells are an extremely important site for extrahepatic clearance, primarily due to prominent P-glycoprotein-mediated active efflux and the presence of cytochrome P450s. We describe a physiologically based pharmacokinetic model which incorporates geometric variations, pH alterations and descriptions of the abundance and distribution of cytochrome 3A and P-glycoprotein along the length of the small intestine. Simulations using preclinical in vitro data for model drugs were performed to establish the influence of P-glycoprotein efflux, cytochrome 3A metabolism and passive permeability on drug available for absorption within the enterocytes. The fraction of drug escaping the enterocyte (F(G)) for 10 cytochrome 3A substrates with a range of intrinsic metabolic clearances were simulated. Following incorporation of P-glycoprotein in vitro efflux ratios all predicted F(G) values were within 20% of observed in vivo F(G). The presence of P-glycoprotein increased the level of cytochrome 3A drug metabolism by up to 12-fold in the distal intestine. F(G) was highly sensitive to changes in intrinsic metabolic clearance but less sensitive to changes in intestinal drug permeability. The model will be valuable for quantifying aspects of intestinal drug absorption and distribution.

TiN-based coatings on fuel cladding tubes for advanced nuclear reactors

Titanium nitride (TiN) thin films are coated on HT-9 and MA957 fuel cladding tubes and bars to explore their mechanical strength, thermal stability, diffusion barrier properties, and thermal conductivity properties. The ultimate goal is to implement TiN as an effective diffusion barrier to prevent the inter-diffusion between the nuclear fuel and the cladding material, and thus lead to a longer lifetime of the cladding tubes. Mechanical tests including hardness and scratch tests for the samples before and after thermal cycle tests show that the films have a high hardness of 28GPa and excellent adhesion properties despite the thermal treatment. Thermal conductivity measurements demonstrate that the thin TiN films have very minimal impact on the overall thermal conductivity of the MA957 and HT-9 substrates, i.e., the thermal conductivity of the uncoated HT-9 and MA957 substrates was 26.25 and 28.44 W m-1 K-1, and that of the coated ones was 26.21 and 28.38W m-1 K-1, respectively. A preliminary Ce diffusion test on the couple of Ce/TiN/HT-9 suggests that TiN has excellent material compatibility and good diffusion barrier properties.

Energy efficient radio access architectures for green radio:large versus small cell size deployment

In this paper new architectural approaches that improve the energy efficiency of a cellular radio access network (RAN) are investigated. The aim of the paper is to characterize both the energy consumption ratio (ECR) and the energy consumption gain (ECG) of a cellular RAN when the cell size is reduced for a given user density and service area. The paper affirms that reducing the cell size reduces the cell ECR as desired while increasing the capacity density but the overall RAN energy consumption remains unchanged. In order to trade the increase in capacity density with RAN energy consumption, without degrading the cell capacity provision, a sleep mode is introduced. In sleep mode, cells without active users are powered-off, thereby saving energy. By combining a sleep mode with a small-cell deployment architecture, the paper shows that the ECG can be increased by the factor n = (R/R) while the cell ECR continues to decrease with decreasing cell size.

Salmonella in companion animals

In an increasingly hygiene concerned society, a major barrier to pet ownership is the perceived role of companion animals in contributing to the risk of exposure to zoonotic bacterial pathogens, such as Salmonella. Manifestations of Salmonella can range from acute gastroenteritis to perfuse enteric fever, in both humans and dogs. Dogs are heavily associated with asymptomatic carriage of Salmonella as the microorganism can persist in the lower intestines of this host which can be then excreted into the environment. Studies in to the asymptomatic carriage of Salmonella in dogs are somewhat dated and there is limited UK data. The current UK carriage rate in dogs was investigated in a randomised dog population and it was revealed that the carriage rate in this population was very low with only one household dog positive for the carriage of Salmonella enterica arizonae (0.2%), out of 490 dogs sampled. Salmonella serotypes share phenotypic and genotypic similarities which are captured in epidemiological typing methods. Therefore, in parallel to the epidemiological investigations, a panel of clinical canine (VLA, UK) and human (Aston University, UK) Salmonella isolates were profiled based on their phenotypic and genotypic characteristics; using API 20E, Biolog Microbial ID System, antibiotic sensitivity testing and PFGE, respectively. Antibiotic sensitivity testing revealed a significant difference between the canine and human isolates with the canine group demonstrating a higher resistance to the panel of antibiotics tested. Further metabolic capabilities of the strains were tested using the Biolog Microbial ID System, which reveal no clear association between the two host groups. However, coupled with Principle Component Analysis two canine isolates were discriminated from the entire population on the basis of a high up-regulation of two carbohydrates. API 20E testing revealed no association between the two host groups. A PFGE harmonised protocol was used to genotypically profile the strains. A dendrogram depicting PFGE profiles of the panel of Salmonella isolates was performed where similarities were calculated by Dice coefficient and represented by UPGMA clustering. Clustering of the profiles from canine isolates and human isolates (HPA, UK) was diverse representing a natural heterogeneity of the genus, additionally, no clear clustering of the isolates was observed between host groups. Clustering was observed with isolates from the same serotype, independent of host origin. Host adaption is a common phenomenon in certain Salmonella serotypes, for example S. Typhi in humans and S. Dublin in cattle. It was of interest to investigate potential host adaptive or restricted strains for canine host by performing adhesion and invasion assays on Dog Intestinal Epithelial Cells (DIECs) (WALTHAM®, UK) and human CaCo-2 (HPA, UK) cell lines. Salmonella arizonae and Enteritidis from an asymptomatic dog and clinical isolate, respectively, demonstrated a significantly high proportion of invasion in DIEC in comparison to human CaCo-2 cells and other tested Salmonella serotypes. This may be suggestive of a potential host restrictive strain as their ability to invade the CaCo-2 cell line was significantly lower than the other serotypes. In conclusion to this thesis the investigations carried out suggest that asymptomatic carriage of Salmonella in UK dogs is low however the microorganism remains as a zoonotic and anthroponotic pathogen based on phenotypic and genotypic characterisation however there may be potential for particular serotype to become host restricted as observed in invasion assays

Specialist contact lens fitting

What is meant by the term ‘specialist contact lens fitting’? Or put another way, what would be considered non-specialist contact lens fitting? Is there such a thing as routine contact lens fitting? Soft or silicone hydrogel fitting for daily wear would probably be considered as routine contact lens fitting, but would extended or flexible wear remain in the same category or would they be considered a specialist fit? Different eras will classify different products as being ‘specialist’. Certainly twenty years ago soft toric contact lenses were considered as being speciality lenses but today would be thought of as routine lenses. Conversely, gas permeable lenses were thought of as mainstream twenty years ago but now are considered as speciality lenses. Although this would not be the same globally, as in some countries (such as Netherlands, France and Japan) gas permeable lens fitting remains popular and is not on the decline as in other countries (Canada, Australia and Sweden) [1]. Bandage soft lenses applied after surface laser refractive procedures would be considered as therapeutic lenses but in reality they are just plano thin hydrogel lenses worn constantly for 3–4 days to allow the underlying epithelium to convalesce and are then removed [2]. Some patients find that wearing hydrogel lenses during periods when they suffer from seasonal allergies actually improves their ocular comfort as the contact lens acts as a barrier to the allergen [3] and [4]. Scleral lenses have long been considered speciality lenses, apart from a time when they were the only lenses available but at that time all contact lens work would have been considered speciality practice! Nowadays we see the advent of mini-scleral designs and we see large diameter gas permeable lenses too. It is possible that these lenses increase the popularity of gas permeable lenses again and they become more main stream. So it would seem that the lines between routine and speciality contact lens fitting are not clear. Whether a lens is classed a specialist fit or not would depend on the lens type, why it was fitted, where in the world the fitting was being done and even the era in which it was fitted. This begs the question as to what would be considered entry level knowledge in contact lens fitting. This may not be an issue for most BCLA members or CLAE readers but certainly would be for bodies such as the College of Optometrists (UK) or the Association of British Dispensing Opticians when they are planning the final registration examinations for budding practitioners or when planning the level of higher level qualifications such as College Certificates or Diplomas. Similarly for training institutions when they are planning their course content. This becomes even trickier when trying to devise a qualification that spans across many countries, like the European Diploma in Optometry and Optics. How do we know if the training and examination level is correct? One way would be to analyse things when they go wrong and if patterns of malpractice are seen then maybe that could be used as an indicator to more training being needed. There were 162 Fitness to Practice Hearing at the General Optical Council between 2001 and 2010. Forty-seven of these were clinically related case, 39 fraud related, and 76 others. Of the clinical ones only 3 were contact lens related. So it would appear that as whole, in the profession, contact lens clinical skills are not being questioned too often (although it seems a few of us can’t keep our hands out the cookie jar!).

Developing a decision framework for the strategic sourcing of biomass

The deployment of bioenergy technologies is a key part of UK and European renewable energy policy. A key barrier to the deployment of bioenergy technologies is the management of biomass supply chains including the evaluation of suppliers and the contracting of biomass. In the undeveloped biomass for energy market buyers of biomass are faced with three major challenges during the development of new bioenergy projects. What characteristics will a certain supply of biomass have, how to evaluate biomass suppliers and which suppliers to contract with in order to provide a portfolio of suppliers that best satisfies the needs of the project and its stakeholder group whilst also satisfying crisp and non-crisp technological constraints. The problem description is taken from the situation faced by the industrial partner in this research, Express Energy Ltd. This research tackles these three areas separately then combines them to form a decision framework to assist biomass buyers with the strategic sourcing of biomass. The BioSS framework. The BioSS framework consists of three modes which mirror the development stages of bioenergy projects. BioSS.2 mode for early stage development, BioSS.3 mode for financial close stage and BioSS.Op for the operational phase of the project. BioSS is formed of a fuels library, a supplier evaluation module and an order allocation module, a Monte-Carlo analysis module is also included to evaluate the accuracy of the recommended portfolios. In each mode BioSS can recommend which suppliers should be contracted with and how much material should be purchased from each. The recommended blend should have chemical characteristics within the technological constraints of the conversion technology and also best satisfy the stakeholder group. The fuels library is made up from a wide variety of sources and contains around 100 unique descriptions of potential biomass sources that a developer may encounter. The library takes a wide data collection approach and has the aim of allowing for estimates to be made of biomass characteristics without expensive and time consuming testing. The supplier evaluation part of BioSS uses a QFD-AHP method to give importance weightings to 27 different evaluating criteria. The evaluating criteria have been compiled from interviews with stakeholders and policy and position documents and the weightings have been assigned using a mixture of workshops and expert interview. The weighted importance scores allow potential suppliers to better tailor their business offering and provides a robust framework for decision makers to better understand the requirements of the bioenergy project stakeholder groups. The order allocation part of BioSS uses a chance-constrained programming approach to assign orders of material between potential suppliers based on the chemical characteristics of those suppliers and the preference score of those suppliers. The optimisation program finds the portfolio of orders to allocate to suppliers to give the highest performance portfolio in the eyes of the stakeholder group whilst also complying with technological constraints. The technological constraints can be breached if the decision maker requires by setting the constraint as a chance-constraint. This allows a wider range of biomass sources to be procured and allows a greater overall performance to be realised than considering crisp constraints or using deterministic programming approaches. BioSS is demonstrated against two scenarios faced by UK bioenergy developers. The first is a large scale combustion power project, the second a small scale gasification project. The Bioss is applied in each mode for both scenarios and is shown to adapt the solution to the stakeholder group importance and the different constraints of the different conversion technologies whilst finding a globally optimal portfolio for stakeholder satisfaction.

Extra compensation for inventive employees:is our system equitable, unbiased and motivating?

There is a presumption that invention is good. It provides us with innovative goods, services and ways of doing things leading to greater employment, wealth and health. This article looks at the two recent UK cases regarding statutory extra compensation that may be awarded to employee inventors under the Patents Act 1977. Most universities worldwide and many companies have individual inventor reward schemes. Researchers now work in teams made up of both industry and academic researchers who are often based in different countries where different legal regimes apply. Is leaving the decision to award employees extra financial compensation up to individual companies unfair, unequal and de-motivating? Is having differing legislative systems in different European countries counter productive and a barrier to economic growth? There must be a balance between the inventor and the innovator. Do we have it right and if not what should it be? Legislation: Patents Act 1977 s.39 , s.40 , s.41 Cases: Kelly v GE Healthcare Ltd [2009] EWHC 181 (Pat); [2009] R.P.C. 12 (Ch D (Patents Ct)) Shanks v Unilever Plc [2010] EWCA Civ 1283; [2011] R.P.C. 12 (CA (Civ Div))

Plasminogen activator inhibitor-1 supports IL-8-mediated neutrophil transendothelial migration by inhibition of the constitutive shedding of endothelial IL-8/heparan sulfate/syndecan-1 complexes

The endothelium is the primary barrier to leukocyte recruitment at sites of inflammation. Neutrophil recruitment is directed by transendothelial gradients of IL-8 that, in vivo, are bound to the endothelial cell surface. We have investigated the identity and function of the binding site(s) in an in vitro model of neutrophil transendothelial migration. In endothelial culture supernatants, IL-8 was detected in a trimolecular complex with heparan sulfate and syndecan-1. Constitutive shedding of IL-8 in this form was increased in the presence of a neutralizing Ab to plasminogen activator inhibitor-1 (PAI-1), indicating a role for endothelial plasminogen activator in the shedding of IL-8. Increased shedding of IL-8/heparan sulfate/syndecan-1 complexes was accompanied by inhibition of neutrophil transendothelial migration, and aprotinin, a potent plasmin inhibitor, reversed this inhibition. Platelets, added as an exogenous source of PAI-1, had no effect on shedding of the complexes or neutrophil migration. Our results indicate that IL-8 is immobilized on the endothelial cell surface through binding to syndecan-1 ectodomains, and that plasmin, generated by endothelial plasminogen activator, induces the shedding of this form of IL-8. PAI-1 appears to stabilize the chemoattractant form of IL-8 at the cell surface and may represent a therapeutic target for novel anti-inflammatory strategies.

International session at the BCLA conference

Full text: It seems a long time ago now since we were at the BCLA conference. The excellent FIFA World Cup in Brazil kept us occupied over the summer as well as Formula 1, Wimbledon, Tour de France, Commonwealth Games and of course exam paper marking! The BCLA conference this year was held in Birmingham at the International Convention Centre which again proved to be a great venue. The number of attendees overall was up on previous years, and at a record high of 1500 people. Amongst the highlights at this year's annual conference was the live surgery link where Professor Sunil Shah demonstrated the differences in technique between traditional phacoemulsification cataract surgery and femtosecond assisted phacoemulsification cataract surgery. Dr. Raquel Gil Cazorla, a research optometrist at Aston University, assisted in the procedure including calibrating the femtosecond laser. Another highlight for me was the session that I chaired, which was the international session organised by IACLE (International Association of CL Educators). There was a talk by Mirjam van Tilborg about dry eye prevalence in the Netherlands and how it was managed by medical general practitioners (GPs) or optometrists. It was interesting to know that there are only 2 schools of optometry there and currently under 1000 registered optometrists there. It also seems that GPs were more likely to blame CL as the cause for dry eye whereas optometrists who had a fuller range of tests were better at solving the issue. The next part of the session included the presentation of 5 selected posters from around the world. The posters were also displayed in the main poster area but were selected to be presented here as they had international relevance. The posters were: 1. Motivators and Barriers for Contact Lens Recommendation and Wear by Nilesh Thite (India) 2. Contact lens hygiene among Saudi wearers by Dr. Ali Masmaly (Saudi) 3. Trends of contact lens prescribing and patterns of contact lens practice in Jordan by Dr. Mera Haddad (Jordan) 4. Contact Lens Behaviour in Greece by Dr. Dimitra Makrynioti (Greece) 5. How practitioners inform ametropes about the benefits of contact lenses and overcome the potential barriers: an Italian survey, by Dr. Fabrizio Zeri (Italy) It was interesting to learn about CL practice in different parts, for example the CL wearing population ration in Saudi Arabia is around 1:2 Male:Female (similar to other parts of the world) and although the sale of CL is restricted to registered practitioners there are many unregistered outlets, like clothing stores, that flout the rules. In Jordan some older practitioners will still advise patients to use tap water or even saliva! But thankfully the newer generation of practitioners have been educated not to advise this. In Greece one of the concerns was that some practitioners may advise patients to use disposable lenses for longer than they should and again it seems to be the practitioners with inadequate education that would do this. In India it was found that cost was one barrier to using contact lenses but also some practitioners felt that they shouldn’t offer CLs due to cost too. In Italy sensitive eyes and CL care and maintenance were the barriers to CL wear but the motivators were vision and comfort and aesthetics. Finally the international session ended with the IACLE travel award and educator awards presented by IACLE president Shehzad Naroo and BCLA President Andrew Yorke. The travel award went to Wang Ling, Jinling Institute of Technology, Nanjing, China. There were 3 regional Contact Lens Educator of the Year Awards sponsored by Coopervision and presented by Dr. J.C. Aragorn of Coopervision. 1. Asia Pacific Region – Dr. Rajeswari Mahadevan of Sankara Nethralaya Medical Research Foundation, Chennai, India 2. Americas Region – Dr. Sergio Garcia of University of La Salle, Bogotá and the University Santo Tomás, Bucaramanga, Colombia 3. Europe/Africa – Middle East Region: Dr. Eef van der Worp, affiliated with the University of Maastricht, the Netherlands The posters above were just a small selection of those displayed at this year's BCLA conference. If you missed the BCLA conference then you can see the abstracts for all posters and talks in a virtual issue of CLAE very soon. The poster competition was kindly sponsored by Elsevier. The poster winner this year was: Joan Gispets – Corneal and Anterior Chamber Parameters in Keratoconus The 3 runners up were: Debby Yeung – Scleral Lens Central Corneal Clearance Assessment with Biomicroscopy Sarah L. Smith – Subjective Grading of Lid Margin Staining Heiko Pult – Impact of Soft Contact Lenses on Lid Parallel Conjunctival Folds My final two highlights are a little more personal. Firstly, I was awarded Honorary Life Fellowship of the BCLA for my work with the Journal, and I would like to thank the BCLA, Elsevier, the editorial board of CLAE, the reviewers and the authors for their support of my role. My final highlight from the BCLA conference this year was the final presentation of the conference – the BCLA Gold Medal award. The recipient this year was Professor Philip Morgan with his talk ‘Changing the world with contact lenses’. Phil was the person who advised me to go to my first BCLA conference in 1994 (funnily he didn’t attend himself as he was busy getting married!) and now 20 years later he was being honoured with the accolade of being the BCLA Gold Medallist. The date of his BCLA medal addressed was shared with his father's birthday so a double celebration for Phil. Well done to outgoing BCLA President Andy Yorke and his team at the BCLA (including Nick Rumney, Cheryl Donnelly, Sarah Greenwood and Amir Khan) on an excellent conference. And finally welcome to new President Susan Bowers. Copyright © 2014 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Medical students' personal experience of high-stakes failure:case studies using interpretative phenomenological analysis

Abstract (provisional): Background Failing a high-stakes assessment at medical school is a major event for those who go through the experience. Students who fail at medical school may be more likely to struggle in professional practice, therefore helping individuals overcome problems and respond appropriately is important. There is little understanding about what factors influence how individuals experience failure or make sense of the failing experience in remediation. The aim of this study was to investigate the complexity surrounding the failure experience from the student’s perspective using interpretative phenomenological analysis (IPA). Methods The accounts of 3 medical students who had failed final re-sit exams, were subjected to in-depth analysis using IPA methodology. IPA was used to analyse each transcript case-by-case allowing the researcher to make sense of the participant’s subjective world. The analysis process allowed the complexity surrounding the failure to be highlighted, alongside a narrative describing how students made sense of the experience. Results The circumstances surrounding students as they approached assessment and experienced failure at finals were a complex interaction between academic problems, personal problems (specifically finance and relationships), strained relationships with friends, family or faculty, and various mental health problems. Each student experienced multi-dimensional issues, each with their own individual combination of problems, but experienced remediation as a one-dimensional intervention with focus only on improving performance in written exams. What these students needed to be included was help with clinical skills, plus social and emotional support. Fear of termination of the their course was a barrier to open communication with staff. Conclusions These students’ experience of failure was complex. The experience of remediation is influenced by the way in which students make sense of failing. Generic remediation programmes may fail to meet the needs of students for whom personal, social and mental health issues are a part of the picture.

Cellular impermeability and uptake of biocides and antibiotics in Gram-positive bacteria and mycobacteria

Gram-positive bacteria possess a permeable cell wall that usually does not restrict the penetration of antimicrobials. However, resistance due to restricted penetration can occur, as illustrated by vancomycin-intermediate resistant Staphylococcus aureus strains (VISA) which produce a markedly thickened cell wall. Alterations in these strains include increased amounts of nonamidated glutamine residues in the peptidoglycan and it is suggested that the resistance mechanism involves 'affinity trapping' of vancomycin in the thickened cell wall. VISA strains have reduced doubling times, lower sensitivity to lysostaphin and reduced autolytic activity, which may reflect changes in the D-alanyl ester content of the wall and membrane teichoic acids. Mycobacterial cell walls have a high lipid content, which is assumed to act as a major barrier to the penetration of antimicrobial agents. Relatively hydrophobic antibiotics such as rifampicin and fluoroquinolones may be able to cross the cell wall by diffusion through the hydrophobic bilayer composed of long chain length mycolic acids and glycolipids. Hydrophilic antibiotics and nutrients cannot diffuse across this layer and are thought to use porin channels which have been reported in many species of mycobacteria. The occurrence of porins in a lipid bilayer supports the view that the mycobacterial wall has an outer membrane analogous to that of gram-negative bacteria. However, mycobacterial porins are much less abundant than in the gram-negative outer membrane and allow only low rates of uptake for small hydrophilic nutrients and antibiotics.

Significant quantum effects in hydrogen activation

Dissociation of molecular hydrogen is an important step in a wide variety of chemical, biological, and physical processes. Due to the light mass of hydrogen, it is recognized that quantum effects are often important to its reactivity. However, understanding how quantum effects impact the reactivity of hydrogen is still in its infancy. Here, we examine this issue using a well-defined Pd/Cu(111) alloy that allows the activation of hydrogen and deuterium molecules to be examined at individual Pd atom surface sites over a wide range of temperatures. Experiments comparing the uptake of hydrogen and deuterium as a function of temperature reveal completely different behavior of the two species. The rate of hydrogen activation increases at lower sample temperature, whereas deuterium activation slows as the temperature is lowered. Density functional theory simulations in which quantum nuclear effects are accounted for reveal that tunneling through the dissociation barrier is prevalent for H2 up to ∼190 K and for D2 up to ∼140 K. Kinetic Monte Carlo simulations indicate that the effective barrier to H2 dissociation is so low that hydrogen uptake on the surface is limited merely by thermodynamics, whereas the D2 dissociation process is controlled by kinetics. These data illustrate the complexity and inherent quantum nature of this ubiquitous and seemingly simple chemical process. Examining these effects in other systems with a similar range of approaches may uncover temperature regimes where quantum effects can be harnessed, yielding greater control of bond-breaking processes at surfaces and uncovering useful chemistries such as selective bond activation or isotope separation.

Learning from a deceptively spacious policy discourse

In this chapter, the way in which varied terms such as Networked learning, e-learning and Technology Enhanced Learning (TEL) have each become colonised to support a dominant, economically-based world view of educational technology is discussed. Critical social theory about technology, language and learning is brought into dialogue with examples from a corpus-based Critical Discourse Analysis (CDA) of UK policy texts for educational technology between1997 and 2012. Though these policy documents offer much promise for enhancement of people’s performance via technology, the human presence to enact such innovation is missing. Given that ‘academic workload’ is a ‘silent barrier’ to the implementation of TEL strategies (Gregory and Lodge, 2015), analysis further exposes, through empirical examples, that the academic labour of both staff and students appears to be unacknowledged. Global neoliberal capitalist values have strongly territorialised the contemporary university (Hayes & Jandric, 2014), utilising existing naïve, utopian arguments about what technology alone achieves. Whilst the chapter reveals how humans are easily ‘evicted’, even from discourse about their own learning (Hayes, 2015), it also challenges staff and students to seek to re-occupy the important territory of policy to subvert the established order. We can use the very political discourse that has disguised our networked learning practices, in new explicit ways, to restore our human visibility.

On the adoption of privacy-enhancing technologies

We propose a model, based on the work of Brock and Durlauf, which looks at how agents make choices between competing technologies, as a framework for exploring aspects of the economics of the adoption of privacy-enhancing technologies. In order to formulate a model of decision-making among choices of technologies by these agents, we consider the following: context, the setting in which and the purpose for which a given technology is used; requirement, the level of privacy that the technology must provide for an agent to be willing to use the technology in a given context; belief, an agent’s perception of the level of privacy provided by a given technology in a given context; and the relative value of privacy, how much an agent cares about privacy in this context and how willing an agent is to trade off privacy for other attributes. We introduce these concepts into the model, admitting heterogeneity among agents in order to capture variations in requirement, belief, and relative value in the population. We illustrate the model with two examples: the possible effects on the adoption of iOS devices being caused by the recent Apple–FBI case; and the recent revelations about the non-deletion of images on the adoption of Snapchat.