968 resultados para Pardoski, Ryan
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Objectives: To explore children's views on microneedle use for this population, particularly as an alternative approach to blood sampling, in monitoring applications, and so, examine the acceptability of this approach to children.
Methods: Focus groups were conducted with children (aged 10-14 years) in a range of schools across Northern Ireland. Convenience sampling was employed, i.e. children involved in a university-directed community-outreach project (Pharmacists in Schools) were recruited.
Key findings: A total of 86 children participated in 13 focus groups across seven schools in Northern Ireland. A widespread disapproval for blood sampling was evident, with pain, blood and traditional needle visualisation particularly unpopular aspects. In general, microneedles had greater visual acceptability and caused less fear. A patch-based design enabled minimal patient awareness of the monitoring procedure, with personalised designs, e.g. cartoon themes, favoured. Children's concerns included possible allergy and potential inaccuracies with this novel approach; however, many had confidence in the judgement of healthcare professionals if deeming this technique appropriate. They considered paediatric patient education critical for acceptance of this new approach and called for an alternative name, without any reference to 'needles'.
Conclusions: The findings presented here support the development of blood-free, minimally invasive techniques and provide an initial indication of microneedle acceptability in children, particularly for monitoring purposes. A proactive response to these unique insights should enable microneedle array design to better meet the needs of this end-user group. Further work in this area is recommended to ascertain the perspectives of a purposive sample of children with chronic conditions who require regular monitoring. © 2013 Royal Pharmaceutical Society.
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Purpose: To investigate, for the first time, the influence of pharmacist intervention and the use of a patient information leaflet on self-application of hydrogel-forming microneedle arrays by human volunteers without the aid of an applicator device.
Methods: A patient information leaflet was drafted and pharmacist counselling strategy devised. Twenty human volunteers applied 11 × 11 arrays of 400 μm hydrogel-forming microneedle arrays to their own skin following the instructions provided. Skin barrier function disruption was assessed using transepidermal water loss measurements and optical coherence tomography and results compared to those obtained when more experienced researchers applied the microneedles to the volunteers or themselves.
Results: Volunteer self-application of the 400 μm microneedle design resulted in an approximately 30% increase in skin transepidermal water loss, which was not significantly different from that seen with self-application by the more experienced researchers or application to the volunteers. Use of optical coherence tomography showed that self-application of microneedles of the same density (400 μm, 600 μm and 900 μm) led to percentage penetration depths of approximately 75%, 70% and 60%, respectively, though the diameter of the micropores created remained quite constant at approximately 200 μm. Transepidermal water loss progressively increased with increasing height of the applied microneedles and this data, like that for penetration depth, was consistent, regardless of applicant.
Conclusion: We have shown that hydrogel-forming microneedle arrays can be successfully and reproducibly applied by human volunteers given appropriate instruction. If these outcomes were able to be extrapolated to the general patient population, then use of bespoke MN applicator devices may not be necessary, thus possibly enhancing patient compliance.
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We describe the Pan-STARRS Moving Object Processing System (MOPS), a modern software package that produces automatic asteroid discoveries and identifications from catalogs of transient detections from next-generation astronomical survey telescopes. MOPS achieves >99.5% efficiency in producing orbits from a synthetic but realistic population of asteroids whose measurements were simulated for a Pan-STARRS4-class telescope. Additionally, using a nonphysical grid population, we demonstrate that MOPS can detect populations of currently unknown objects such as interstellar asteroids. MOPS has been adapted successfully to the prototype Pan-STARRS1 telescope despite differences in expected false detection rates, fill-factor loss, and relatively sparse observing cadence compared to a hypothetical Pan-STARRS4 telescope and survey. MOPS remains highly efficient at detecting objects but drops to 80% efficiency at producing orbits. This loss is primarily due to configurable MOPS processing limits that are not yet tuned for the Pan-STARRS1 mission. The core MOPS software package is the product of more than 15 person-years of software development and incorporates countless additional years of effort in third-party software to perform lower-level functions such as spatial searching or orbit determination. We describe the high-level design of MOPS and essential subcomponents, the suitability of MOPS for other survey programs, and suggest a road map for future MOPS development.
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The design of a non-viral gene delivery vehicle capable of delivering and releasing a functional nucleic acid cargo intracellularly remains a formidable challenge. For systemic gene therapy to be successful a delivery vehicle is required that protects the nucleic acid cargo from enzymatic degradation, extravasates from the vasculature, traverses the cell membrane, disrupts the endosomal vesicles and unloads the cargo at its destination site, namely the nucleus for the purposes of gene delivery. This manuscript reports the extensive investigation of a novel amphipathic peptide composed of repeating RALA units capable of overcoming the biological barriers to gene delivery both in vitro and in vivo. Our data demonstrates the spontaneous self-assembly of cationic DNA-loaded nanoparticles when the peptide is complexed with pDNA. Nanoparticles were < 100 nm, were stable in the presence of serum and were fusogenic in nature, with increased peptide α-helicity at a lower pH. Nanoparticles proved to be non-cytotoxic, readily traversed the plasma membrane of both cancer and fibroblast cell lines and elicited reporter-gene expression following intravenous delivery in vivo. The results of this study indicate that RALA presents an exciting delivery platform for the systemic delivery of nucleic acid therapeutics.
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Dendritic cells (DCs) of the skin play an important role in skin-mediated immunity capable of promoting potent immune responses. We availed of polymeric dissolving microneedle (MN) arrays laden with nano-encapsulated antigen to specifically target skin DC networks. This modality of immunization represents an economic, efficient and potent means of antigen delivery directly to skin DCs, which are inefficiently targeted by more conventional immunization routes. Following MN immunization, Langerhans cells (LCs) constituted the major skin DC subset capable of cross-priming antigen-specific CD8(+) T cells ex-vivo. While all DC subsets were equally efficient in priming CD4(+) T cells, LCs were largely responsible for orchestrating the differentiation of CD4(+) IFN-γ and IL-17 producing effectors. Importantly, depletion of LCs prior to immunization had a profound effect on CD8(+) CTL responses in vivo, and vaccinated animals displayed reduced protective anti-tumour and viral immunity. Interestingly, this cross-priming bias was lost following MN immunization with soluble antigen, suggesting that processing and cross-presentation of nano-particulate antigen is favoured by LCs. Therefore, these studies highlight the importance of LCs in skin immunization strategies and that targeting of nano-particulate immunogens through dissolvable polymeric MNs potentially provides a promising technological platform for improved vaccination strategies.Journal of Investigative Dermatology accepted article preview online, 22 September 2014. doi:10.1038/jid.2014.415.
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Photodynamic therapy can be used in the treatment of pre-malignant and malignant diseases. It offers advantages over other therapies currently used in the treatment of skin lesions including avoidance of damage to surrounding tissue and minimal or no scarring. Unfortunately, systemic delivery of photosensitising agents can result in adverse effects, such as prolonged cutaneous photosensitivity; while topical administration lacks efficacy in the clearance of deeper skin lesions and those with a thick overlying keratotic layer. Therefore, enhancement of conventional photosensitiser delivery is desired. However, the physicochemical properties of photosensitising agents, such as extreme hydrophilicity or lipophilicity and large molecular weights make this challenging. This paper reviews the potential of microneedles as a viable method to overcome these delivery-limiting physicochemical characteristics and discusses the current benefits and limitations of solid, dissolving and hydrogel-forming microneedles. Clinical studies in which microneedles have successfully improved photodynamic therapy are also discussed, along with benefits which microneedles offer, such as precise photosensitiser localisation, painless application and reduction in waiting times between photosensitiser administration and irradiation highlighted.
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BACKGROUND: Whilst multimorbidity is more prevalent with increasing age, approximately 30% of middle-aged adults (45-64 years) are also affected. Several prescribing criteria have been developed to optimise medication use in older people (≥65 years) with little focus on potentially inappropriate prescribing (PIP) in middle-aged adults. We have developed a set of explicit prescribing criteria called PROMPT (PRescribing Optimally in Middle-aged People's Treatments) which may be applied to prescribing datasets to determine the prevalence of PIP in this age-group.
METHODS: A literature search was conducted to identify published prescribing criteria for all age groups, with the Project Steering Group (convened for this study) adding further criteria for consideration, all of which were reviewed for relevance to middle-aged adults. These criteria underwent a two-round Delphi process, using an expert panel consisting of general practitioners, pharmacists and clinical pharmacologists from the United Kingdom and Republic of Ireland. Using web-based questionnaires, 17 panellists were asked to indicate their level of agreement with each criterion via a 5-point Likert scale (1 = Strongly Disagree, 5 = Strongly Agree) to assess the applicability to middle-aged adults in the absence of clinical information. Criteria were accepted/rejected/revised dependent on the panel's level of agreement using the median response/interquartile range and additional comments.
RESULTS: Thirty-four criteria were rated in the first round of this exercise and consensus was achieved on 17 criteria which were accepted into the PROMPT criteria. Consensus was not reached on the remaining 17, and six criteria were removed following a review of the additional comments. The second round of this exercise focused on the remaining 11 criteria, some of which were revised following the first exercise. Five criteria were accepted from the second round, providing a final list of 22 criteria [gastro-intestinal system (n = 3), cardiovascular system (n = 4), respiratory system (n = 4), central nervous system (n = 6), infections (n = 1), endocrine system (n = 1), musculoskeletal system (n = 2), duplicates (n = 1)].
CONCLUSIONS: PROMPT is the first set of prescribing criteria developed for use in middle-aged adults. The utility of these criteria will be tested in future studies using prescribing datasets.
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PURPOSE: screening tool of older people's prescriptions (STOPP) and screening tool to alert to right treatment (START) criteria were first published in 2008. Due to an expanding therapeutics evidence base, updating of the criteria was required.
METHODS: we reviewed the 2008 STOPP/START criteria to add new evidence-based criteria and remove any obsolete criteria. A thorough literature review was performed to reassess the evidence base of the 2008 criteria and the proposed new criteria. Nineteen experts from 13 European countries reviewed a new draft of STOPP & START criteria including proposed new criteria. These experts were also asked to propose additional criteria they considered important to include in the revised STOPP & START criteria and to highlight any criteria from the 2008 list they considered less important or lacking an evidence base. The revised list of criteria was then validated using the Delphi consensus methodology.
RESULTS: the expert panel agreed a final list of 114 criteria after two Delphi validation rounds, i.e. 80 STOPP criteria and 34 START criteria. This represents an overall 31% increase in STOPP/START criteria compared with version 1. Several new STOPP categories were created in version 2, namely antiplatelet/anticoagulant drugs, drugs affecting, or affected by, renal function and drugs that increase anticholinergic burden; new START categories include urogenital system drugs, analgesics and vaccines.
CONCLUSION: STOPP/START version 2 criteria have been expanded and updated for the purpose of minimizing inappropriate prescribing in older people. These criteria are based on an up-to-date literature review and consensus validation among a European panel of experts.
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The determination of the efflux velocity is key to the process of calculating the subsequent value of velocity at any other location within a propeller jet. This paper reports on the findings of an experimental investigation into the magnitude of the efflux velocities within the jets produced by four differing propellers. Measurements of velocity have been made using a 3D LDA system with the test propellers operating at a range of rotational speeds which bound typical operational values. Comparisons are made with existing predictive theories and to aid design engineers, methods are presented by which the 3D efflux velocity components, as well as the resultant efflux value, can be determined.
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The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5) proposing a common simulation tool to assist physicians; and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies. AIRWAYSICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers).
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As a consequence of climate change there is now a more frequent occurrence of extreme rainfall events where, with higher rates of urbanisation, the built environment has become increasingly affected by flooding.. This is of particular importance in relation to the stability of bridge structures that span rivers and canals etc. In November 2009, the UK and Ireland were subjected to extraordinarily severe weather conditions for several days. The rainfall was logged as the highest level of rainfall ever recorded within the UK, and as a direct consequence, unprecedented flooding occurred in Cumbria. This flooding led to the collapse of three road bridges which were generally 19th century masonry arch bridges, with relatively shallow foundations. In the UK, knowledge of the combined effect of bridge scouring and inundation has been not been particularly widely studied. Research carried out by Hamill et al [1] considered the hydraulic analysis of single arch bridges under flood conditions, but no consideration was given towards the likely damage to these structures due to scouring. Prior to this, Bierry and Delleur [2] produced a classic paper in predicting the discharge downstream of an inundated arch, focussing on predicting afflux as opposed to bridge scour. Further work on backwater effects was carried out by Martin-Vide & Prio [3] in semi-circular arch bridges. Both pressurized and free-surface flows at the bridge were investigated. Flows on a mobile bed in clear-water conditions were compared to those with a rigid bed, but no predictive equation for scour under pressurised conditions was considered. This paper will present initial findings from an experimental investigation into the effects of surcharged flow and subsequent scour within the vicinity of single span arch bridges. Velocities profiles will be shown within the vicinity of the arch, in addition to the depth of clear water scour, for a series of flows and model spans. The data will be presented, where results will be correlated to the most recent predictive equations that are proposed.
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No abstract available
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Animals frequently engage in mutual displays that may allow or at least help decisions about the outcome of agonistic encounters with mutual benefit to the opponents. In fish these often involve lateral displays, with previous studies finding evidence of population-level lateralization with a marked preference for showing the right side and using the right eye. Because both opponents tend to show this preference a head to tail configuration is formed and is used extensively during the display phase. Here we tested the significance of these lateral displays by comparing displays to a mirror with those to a real opponent behind a transparent barrier. The frequency of displays was lower to a mirror but the individual displays were of greater duration indicating a slower pace of the interaction with a mirror. This suggests that fish respond to initiatives of real opponents but as mirror images do not initiate moves the focal fish only moves when it is ready to change position. However, lateralization was still found with mirrors, indicating that the right-side bias is a feature of the individual and not of the interaction between opponents. We discuss implications for ideas about the evolution of mutual cooperation and information exchange in contests, as well as the utility of the use of mirrors in the study of aggression in fish.
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Objective: To systematically review the evidence examining effects of walking interventions on pain and self-reported function in individuals with chronic musculoskeletal pain.
Data Sources: Six electronic databases (Medline, CINAHL, PsychINFO, PEDro, Sport Discus and the Cochrane Central Register of Controlled Trials) were searched from January 1980 up to March 2014.
Study Selection: Randomized and quasi-randomized controlled trials in adults with chronic low back pain, osteoarthritis or fibromyalgia comparing walking interventions to a non-exercise or non-walking exercise control group.
Data Extraction: Data were independently extracted using a standardized form. Methodological quality was assessed using the United States Preventative Services Task Force (USPSTF) system.
Data Synthesis: Twenty-six studies (2384 participants) were included and suitable data from 17 were pooled for meta-analysis with a random effects model used to calculate between group mean differences and 95% confidence intervals. Data were analyzed according to length of follow-up (short-term: ≤8 weeks post randomization; medium-term: >2 months - 12 months; long-term: > 12 months). Interventions were associated with small to moderate improvements in pain at short (mean difference (MD) -5.31, 95% confidence interval (95% CI) -8.06 to -2.56) and medium-term follow-up (MD -7.92, 95% CI -12.37 to -3.48). Improvements in function were observed at short (MD -6.47, 95% CI -12.00 to -0.95), medium (MD -9.31, 95% CI -14.00 to -4.61) and long-term follow-up (MD -5.22, 95% CI 7.21 to -3.23).
Conclusions: Evidence of fair methodological quality suggests that walking is associated with significant improvements in outcome compared to control interventions but longer-term effectiveness is uncertain. Using the USPSTF system, walking can be recommended as an effective form of exercise or activity for individuals with chronic musculoskeletal pain but should be supplemented with strategies aimed at maintaining participation. Further work is also required examining effects on important health related outcomes in this population in robustly designed studies.