Challenges and potential of the Semantic Web for tourism

The paper explores tourism challenges and potential of the Semantic Web from a theoretical and industry perspective. It first examines tourism business networks and explores a main theme of network interoperability - data standards- followed by technology deficiencies of Web 1.0 and 2.0 and Semantic Web solutions. It then explicates Semantic opportunities and challenges for tourism, including an industry perspective through a qualitative approach. Industry leaders considered that the new Web era was imminent and heralded benefits for supply and demand side interoperability, although management and technical challenges could impede progress and delay realisation

Future eDestination Marketing: Perspective of an Australian Tourism Stakeholder Network.

Tourism destinations are difficult to manage because of the complex relationships of their diverse public and private stakeholders. At the same time, strategic marketing efforts are important for destinations to foster positive consequences of tourism, particularly given the range of opportunities and challenges created by the emergence of social media that destinations can use advantageously. This article aims to explore future eDestination marketing from Australian tourism stakeholder network perspectives. Workshops were convened in July 2012 in Melbourne, Australia, for select stakeholders invited to contribute to the futures national tourism technology strategy. They presented a stakeholder network approach to futures strategy development that aims to contribute to that used in recent national tourism plans and strategies for Australia developed by the government. Building on theories of stakeholder networks and futures, the article demonstrates the value of a futures stakeholder network method compared to traditional government approaches by critically analyzing outcomes of both

GAMBLING WITH OUR TOURISM FUTURE: THE ROLE OF RESEARCH IN DESTINATION AND ENTERPRISE STRATEGIES TO AVOID STRATEGIC DRIFT

The coming decade and a half should see major shifts in the leisure and tourism environment reflecting economic dynamics, changing consumer values, political forces, environmental changes and the explosive growth of information technology. This paper explores the way in which some key drivers could affect the global tourism industry to the year 2020. An exploration of these trends allows important change agents, on both the supply side and the demand side of tourism, to be highlighted and discussed. In response, strategies can be formulated by destination managers and tourism operators to avoid strategic drift for their organisations and to develop tourism in a sustainable way

Development and Evaluation of Dissolving Microarray Patches for Co-administered and Repeated Intradermal Delivery of Long-acting Rilpivirine and Cabotegravir Nanosuspensions for Paediatric HIV Antiretroviral Therapy

Purpose Whilst signifcant progress has been made to defeat HIV infection, the efcacy of antiretroviral (ARV) therapyin the paediatric population is often hindered by poor adherence. Currently, two long-acting (LA) intramuscular injectablenanosuspensions of rilpivirine (RPV) and cabotegravir (CAB) are in clinical development for paediatric populations. However, administration requires access to healthcare resources, is painful, and can result in needle-stick injuries to the end user.To overcome these barriers, this proof-of-concept study was developed to evaluate the intradermal delivery of RPV LA andCAB LA via self-disabling dissolving microarray patches (MAPs).Methods Dissolving MAPs of two conformations, a conventional pyramidal and a bilayer design, were formulated, withvarious nanosuspensions of RPV and CAB incorporated within the respective MAP matrix. MAPs were mechanically robustand were capable of penetrating ex vivo skin with intradermal ARV deposition.Results In a single-dose in vivo study in rats, all ARV MAPs demonstrated sustained release profles, with therapeuticallyrelevant plasma concentrations of RPV and CAB detected to at least 63 and 28 d, respectively. In a multi-dose in vivo study,repeated MAP applications at 14-d intervals maintained therapeutically relevant plasma concentrations throughout theduration of the study.Conclusions These results illustrate the potential of the platform to repeatedly maintain plasma concentrations for RPVand CAB. As such, these MAPs could represent a viable option to improve adherence in the paediatric population, one thatis capable of being painlessly administered in the comfort of the patient’s own home on a biweekly or less frequent basis

Evaluating Islatravir Administered Via Microneedle Array Patch for Long-Acting HIV Pre-exposure Prophylaxis Using Physiologically Based Pharmacokinetic Modelling

Background and objectivesTechnologies for long-acting administration of antiretrovirals (ARVs) for the prevention and treatment of HIV are at the forefront of research initiatives aiming to tackle issues surrounding drug adherence with the current standard of once-daily oral administration. Islatravir (ISL) is an emerging ARV that shows promising characteristics for long-acting prevention and treatment both orally as well as through alternative routes of administration. Microneedle array patches (MAPs) are a pain-free and discreet transdermal delivery technology that offer extended-release administration of nanoparticulate drugs. This study aimed to utilise physiologically based pharmacokinetic (PBPK) modelling to predict the pharmacokinetics resulting from ISL administered via MAP and to identify key MAP characteristics required to sustain effective concentrations over extended dosing intervals.MethodsA PBPK model describing the conversion of ISL to ISL-triphosphate (ISL-TP) and its whole-body disposition was developed and verified against observed clinical data for orally administered ISL in healthy adults. An intradermal PBPK model was integrated with the ISL PBPK model to predict the dose and nanoparticle release rate required for MAP administration strategies capable of achieving a minimum ISL-TP target concentration of 0.05 pmol/106 PBMCs over extended dosing intervals. MAP design was limited to a maximum therapeutic area of 20 cm2 with a dose loading of 4.09 mg/cm2 and a minimum duration of 3 months. Due to the lack of available clinical data, a range of nanoparticle release rates and MAP bioavailability scenarios were simulated to provide an overview of potential clinical outcomes.ResultsThe ISL PBPK model was successfully verified, with predicted vs observed ratios falling within 0.5-2-fold. ISL MAP doses ranging from 15 to 80 mg were predicted to sustain ISL-TP concentrations above the minimum target concentration at 3, 6 and 12 months after administration. Nanoparticle release rate and MAP bioavailability were found to have a major impact on whether dosing strategies achieved the criteria. Minimum doses of 15 mg and 60 mg with a nanoparticle release rate of 0.0005 h-1 and bioavailability ranging from 25 to 100% were predicted to achieve effective ISL-TP concentrations up to 3 and 6 months, respectively. Doses of 15 mg and 30 mg with a nanoparticle release rate of 0.0005 h-1 were also able to attain the target concentration up to 6 months after MAP administration, albeit with a minimum bioavailability of 75% and 50%, respectively. Furthermore, when simulating a bioavailability of 100%, an 80 mg ISL MAP was predicted to sustain ISL-TP concentrations above the minimum target concentration up to 12 months after administration.ConclusionsThe ISL PBPK model successfully predicted ISL and ISL-TP pharmacokinetics across a range of orally administered regimens. The integrated intradermal PBPK model outlined optimal MAP dose and nanoparticle release rates for effective ISL-TP concentrations up to 12 months, providing justification for further investigation of ISL as a candidate for MAP administration

White paper: Understanding, informing and defining the regulatory science of microneedle-based dosage forms that are applied to the skin

The COVID-19 pandemic has accelerated pre-clinical and clinical development of microneedle-based drug delivery technology. However the regulatory science of this emerging dosage form is immature and explicit regulatory guidance is limited. A group of international stakeholders has formed to identify and address key issues for the regulatory science of future products that combine a microneedle device and active pharmaceutical ingredient (in solid or semi-solid state) in a single entity that is designed for application to the skin. Guided by the principles of Quality by Design (QbD) and informed by consultation with wider stakeholders, this ‘White Paper’ describes fundamental elements of the work in an effort to harmonise understanding, stimulate discussion and guide innovation. The paper discusses classification of the dosage form (combination/medicinal product), the regulatory nomenclature that is likely to be adopted and the technical vocabulary that best describes its form and function. More than twenty potential critical quality attributes (CQAs) are identified for the dosage form, and a prioritisation exercise identifies those CQAs that are most pertinent to the dosage form and that will likely require bespoke test methods (delivered dose, puncture performance) or major adaptions to established compendial test methods (dissolution). Hopefully the work will provide a platform for the development of dosage form specific guidance (from regulatory authorities and/or international pharmacopoeias), that expedites clinical translation of safe and effective microneedle-based products

Primary intestinal lymphangiectasia (Waldmann's disease)

Primary intestinal lymphangiectasia (PIL) is a rare disorder characterized by dilated intestinal lacteals resulting in lymph leakage into the small bowel lumen and responsible for protein-losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. PIL is generally diagnosed before 3 years of age but may be diagnosed in older patients. Prevalence is unknown. The main symptom is predominantly bilateral lower limb edema. Edema may be moderate to severe with anasarca and includes pleural effusion, pericarditis or chylous ascites. Fatigue, abdominal pain, weight loss, inability to gain weight, moderate diarrhea or fat-soluble vitamin deficiencies due to malabsorption may also be present. In some patients, limb lymphedema is associated with PIL and is difficult to distinguish lymphedema from edema. Exsudative enteropathy is confirmed by the elevated 24-h stool α1-antitrypsin clearance. Etiology remains unknown. Very rare familial cases of PIL have been reported. Diagnosis is confirmed by endoscopic observation of intestinal lymphangiectasia with the corresponding histology of intestinal biopsy specimens. Videocapsule endoscopy may be useful when endoscopic findings are not contributive. Differential diagnosis includes constrictive pericarditis, intestinal lymphoma, Whipple's disease, Crohn's disease, intestinal tuberculosis, sarcoidosis or systemic sclerosis. Several B-cell lymphomas confined to the gastrointestinal tract (stomach, jejunum, midgut, ileum) or with extra-intestinal localizations were reported in PIL patients. A low-fat diet associated with medium-chain triglyceride supplementation is the cornerstone of PIL medical management. The absence of fat in the diet prevents chyle engorgement of the intestinal lymphatic vessels thereby preventing their rupture with its ensuing lymph loss. Medium-chain triglycerides are absorbed directly into the portal venous circulation and avoid lacteal overloading. Other inconsistently effective treatments have been proposed for PIL patients, such as antiplasmin, octreotide or corticosteroids. Surgical small-bowel resection is useful in the rare cases with segmental and localized intestinal lymphangiectasia. The need for dietary control appears to be permanent, because clinical and biochemical findings reappear after low-fat diet withdrawal. PIL outcome may be severe even life-threatening when malignant complications or serous effusion(s) occur

An Application of an Initial Full Value of Vaccine Assessment Methodology to Measles-Rubella MAPs for Use in Low- and Middle-Income Countries.

Measles and rubella micro-array patches (MR-MAPs) are a promising innovation to address limitations of the current needle and syringe (N&S) presentation due to their single-dose presentation, ease of use, and improved thermostability. To direct and accelerate further research and interventions, an initial full value vaccine assessment (iFVVA) was initiated prior to MR-MAPs entering phase I trials to quantify their value and identify key data gaps and challenges. The iFVVA utilized a mixed-methods approach with rapid assessment of literature, stakeholder interviews and surveys, and quantitative data analyses to (i) assess global need for improved MR vaccines and how MR-MAPs could address MR problem statements; (ii) estimate costs and benefits of MR-MAPs; (iii) identify the best pathway from development to delivery; and (iv) identify outstanding areas of need where stakeholder intervention can be helpful. These analyses found that if MR-MAPs are broadly deployed, they can potentially reach an additional 80 million children compared to the N&S presentation between 2030-2040. MR-MAPs can avert up to 37 million measles cases, 400,000 measles deaths, and 26 million disability-adjusted life years (DALYs). MR-MAPs with the most optimal product characteristics of low price, controlled temperature chain (CTC) properties, and small cold chain volumes were shown to be cost saving for routine immunization (RI) in low- and middle-income countries (LMICs) compared to N&S. Uncertainties about price and future vaccine coverage impact the potential cost-effectiveness of introducing MR-MAPs in LMICs, indicating that it could be cost-effective in 16-81% of LMICs. Furthermore, this iFVVA highlighted the importance of upfront donor investment in manufacturing set-up and clinical studies and the critical influence of an appropriate price to ensure country and manufacturer financial sustainability. To ensure that MR-MAPs achieve the greatest public health benefit, MAP developers, vaccine manufacturers, donors, financiers, and policy- and decision-makers will need close collaboration and open communications

Measles–Rubella Microarray Patches Phase III Clinical Trial Framework: Proposal and considerations

Background: The Measles–Rubella Microarray Patch (MR-MAP) is an important technology that is expected to reduce coverage and equity gaps for measles-containing vaccines (MCVs), reach zero-dose children, and contribute to elimination of measles and rubella. MR-MAPs are anticipated to be easier to deploy programmatically and could be delivered by lesser-trained health workers, thereby increasing immunization coverage. The most advanced MR-MAP has reached clinical proof-of-concept through a Phase I/II trial in the target population of infants and young children. The World Health Organization (WHO) and partners have developed the Phase III clinical trial framework for MR-MAPs presented in this article. Objectives and Methods: The purpose of such framework is to inform the considerations, design and approach for the pivotal clinical trial design, while considering the anticipated data requirements to inform regulatory approval, WHO prequalification, and policy decision. Results: The proposed Phase III trial would compare the immunogenicity and safety of an MR-MAP with MR vaccine delivered subcutaneously in 9- to 10-month-old infants. An analysis of non-inferiority (NI) of immunogenicity would occur six weeks after the first dose. Should regulatory agencies or policy makers require, a proportion of infants could receive a second dose of either the same or alternate MR vaccine presentation six months after the first dose, with those children returning six weeks after the second dose for a descriptive assessment of immunogenicity, and then followed up six months after the second dose for evaluation of safety and immunogenicity. It is anticipated that this proposed pivotal Phase III trial framework would generate the required clinical data for regulatory licensure and WHO prequalification (PQ) of MR-MAPs. However, the trial design would need to be reviewed and confirmed by a national regulatory authority (NRA) that will assess the product for regulatory licensure and the WHO PQ team. Additional research will likely be required to generate data on concomitant vaccine delivery, the safety and immunogenicity of MR-MAPs in other age groups such as children 1–5 years and infants younger than 9 months of age, and the impact of MR-MAPs on coverage and equity. Such studies could be conducted during or after clinical MR-MAP development