Potential of Microneedles in Enhancing Delivery of Photosensitising Agents for Photodynamic Therapy

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.

Associations between Achievement Goal Orientations and Academic Performance Among Students at a UK Pharmacy School

Objective. To ascertain goal orientations of pharmacy students and establish whether associations exist between academic performance, gender, or year of study. Methods. Goal orientations were assessed using a validated questionnaire. Respondents were categorized as high or low performers based on university grades. Associations and statistical significance were ascertained using parametric and nonparametric tests and linear regression, as appropriate. Results. A response rate of 60.7% was obtained. High performers were more likely to be female than male. The highest mean score was for mastery approach; the lowest for work avoidance. The mean score for work avoidance was significantly greater for low performers than for high performers and for males than for females. First-year students were most likely to have top scores in mastery and performance approaches. Conclusion. It is encouraging that the highest mean score was for mastery approach orientation, as goal orientation may play a role in academic performance of pharmacy students.

Applying imagined contact to improve physiological responses in anticipation of intergroup interactions and the perceived quality of these interactions

This experiment (N 5 49) is the first to show that imagined contact can bufferanticipatory physiological responses to future interactions, and improve the qualityof these interactions. Participants imagined a positive interaction with a person withschizophrenia, or in a control condition, a person who did not have schizophrenia. They then interacted with a confederate whom they believed had schizophrenia. Participants in the imagined contact condition reported more positive attitudes andless avoidance of people with schizophrenia, displayed smaller anticipatory physio-logical responses, specifically smaller changes in interbeat interval and skin conduct-ance responses, and had a more positive interaction according to the confederate.These findings support applying imagined contact to improve interactions with people with severe mental illnesses.

Defining and assessing animal pain

The detection and assessment of pain in animals is crucial to improving their welfare in a variety of contexts in which humans are ethically or legally bound to do so. Thus clear standards to judge whether pain is likely to occur in any animal species is vital to inform whether to alleviate pain or to drive the refinement of procedures to reduce invasiveness, thereby minimizing pain. We define two key concepts that can be used to evaluate the potential for pain in both invertebrate and vertebrate taxa. First, responses to noxious, potentially painful events should affect neurobiology, physiology and behaviour in a different manner to innocuous stimuli and subsequent behaviour should be modified including avoidance learning and protective responses. Second, animals should show a change in motivational state after experiencing a painful event such that future behavioural decision making is altered and can be measured as a change in conditioned place preference, self-administration of analgesia, paying a cost to access analgesia or avoidance of painful stimuli and reduced performance in concurrent events. The extent to which vertebrate and selected invertebrate groups fulfil these criteria is discussed in light of the empirical evidence and where there are gaps in our knowledge we propose future studies are vital to improve our assessment of pain. This review highlights arguments regarding animal pain and defines criteria that demonstrate, beyond a reasonable doubt, whether animals of a given species experience pain.

Arts Council Ballet Policy Review

In May 2006 the Arts Council commissioned an independent review of the context and issues affecting professional ballet in Ireland. The findings were subsequently collated in a policy paper entitled Towards a Strategy of Support for Professional Ballet in Ireland, which was published in 2007 and adopted by the Council in the same year. The report acknowledged ballet as an integral part of cultural life and its importance to the development of many forms of professional dance. The document set forth a number of recommendations that have since formed the basis of art-form policy and funding relationships with ballet organisations.
In parallel since then, a number of important changes have taken place within the ballet sector. Some of these changes are the inevitable consequences of these difficult financial times. However, despite these funding challenges, the sector has managed to retain its vibrancy and popularity with national audiences. While the sector continues to evolve, the limited financial resources available to the Council have become an obstacle to implementing the road map envisioned in 2007. Given its significance and popularity, ballet remains an extraordinarily underdeveloped art form in Ireland. A key weakness of the sector is that future development of ballet provision remains fundamentally uncertain and is still overly dependent on the personal and professional commitment of a few individuals.
This review aims to analyse the current situation, discuss and consider how matters might be progressed and to propose a comprehensive framework for the development of ballet in Ireland. The purpose of the review is to provide an objective point of reference for the Arts Council‘s medium- term ballet policy and to inform and guide future public investment in the art form. The review also intends to progress the work undertaken since 2007 in response to the document Towards a Strategy of Support for Professional Ballet in Ireland.
Within a wider perspective, the review is expected to provide compelling evidence of ballet's relevance to Irish cultural life. It will also create an opportunity for the Council to engage with relevant stakeholders with a view to addressing the challenge of how best to provide for ballet on a sustainable basis within the context of a changed financial environment and an evolving professional sector. There is reason to expect this review will also assist the sector in giving voice to its aspirations and needs. This would certainly assist the Council in garnering support for a blueprint for the consolidation of professional ballet practice and education in Ireland.
It is envisioned the ballet policy review will be closely aligned to the Arts Council‘s own high-level objectives and will take account of developments that may arise from the broader process of strategic review the Council will undertake in 2014.

Supervised walking in comparison with fitness training for chronic back pain in physiotherapy: results of the SWIFT single-blinded randomized controlled trial (ISRCTN17592092)

Effectiveness of brief/minimal contact self-activation interventions that encourage participation in physical activity (PA) for chronic low back pain (CLBP >12 weeks) is unproven. The primary objective of this assessor-blinded randomized controlled trial was to investigate the difference between an individualized walking programme (WP), group exercise class (EC), and usual physiotherapy (UP, control) in mean change in functional disability at 6 months. A sample of 246 participants with CLBP aged 18 to 65 years (79 men and 167 women; mean age ± SD: 45.4 ± 11.4 years) were recruited from 5 outpatient physiotherapy departments in Dublin, Ireland. Consenting participants completed self-report measures of functional disability, pain, quality of life, psychosocial beliefs, and PA were randomly allocated to the WP (n = 82), EC (n = 83), or UP (n = 81) and followed up at 3 (81%; n = 200), 6 (80.1%; n = 197), and 12 months (76.4%; n = 188). Cost diaries were completed at all follow-ups. An intention-to-treat analysis using a mixed between-within repeated-measures analysis of covariance found significant improvements over time on the Oswestry Disability Index (Primary Outcome), the Numerical Rating Scale, Fear Avoidance-PA scale, and the EuroQol EQ-5D-3L Weighted Health Index (P < 0.05), but no significant between-group differences and small between-group effect sizes (WP: mean difference at 6 months, 6.89 Oswestry Disability Index points, 95% confidence interval [CI] -3.64 to -10.15; EC: -5.91, CI: -2.68 to -9.15; UP: -5.09, CI: -1.93 to -8.24). The WP had the lowest mean costs and the highest level of adherence. Supervised walking provides an effective alternative to current forms of CLBP management.

Stress in parents of children born very preterm is predicted by child externalising behaviour and parent coping at age 7 years

Objective: To examine factors which predict parenting stress in a longitudinal cohort of children born very preterm seen at age seven years.
Methods: We recruited 100 very preterm (< 32 weeks GA) child-parent dyads and a control group of 50 term-born dyads born between 2001 and 2004 with follow-up at seven years. Parents completed the Parenting Stress Index, Ways of Coping Questionnaire, Child Behavior Check List, Beck Depression Inventory and the State Trait Anxiety Inventory questionnaires. Child IQ was assessed using the Wechsler Intelligence Scale-IV.
Results: After controlling for maternal education, parents of preterm children (95% CI, 111.1 to 121.4) scored higher (p = .027) on the Parenting Stress Index than term born controls (95% CI, 97.8 to 113.2). Regression analyses showed that child externalising behaviour, sex and parent escape/avoidance coping style, predicted higher parenting stress in the preterm group. Parents of preterm girls expressed higher levels of stress than those of boys. 
Conclusions: Maladaptive coping strategies contribute to greater stress in parents of very preterm children. Our findings suggest that these parents need support for many years after birth of a very preterm infant.

Activity and coke formation of nickel and nickel carbide in dry reforming: A deactivation scheme from density functional theory

Dry reforming is a promising reaction to utilise the greenhouse gases CO2 and CH4. Nickel-based catalysts are the most popular catalysts for the reaction, and the coke formation on the catalysts is the main obstacle to the commercialisation of dry reforming. In this study, the whole reaction network of dry reformation on both flat and stepped nickel catalysts (Ni(111) and Ni(211)) as well as nickel carbide (flat: Ni3C(001); stepped: Ni3C(111)) is investigated using density functional theory calculations. The overall reaction energy profiles in the free energy landscape are obtained, and kinetic analyses are utilised to evaluate the activity of the four surfaces. By careful examination of our results, we find the following regarding the activity: (i) flat surfaces are more active than stepped surfaces for the dry reforming and (ii) metallic nickel catalysts are more active than those of nickel carbide, and therefore, the phase transformation from nickel to nickel carbide will reduce the activity. With respect to the coke formation, the following is found: (i) the coke formation probability can be measured by the rate ratio of CH oxidation pathway to C oxidation pathway (r(CH)/r(C)) and the barrier of CO dissociation, (ii) on Ni(111), the coke is unlikely to form, and (iii) the coke formations on the stepped surfaces of both nickel and nickel carbide can readily occur. A deactivation scheme, using which experimental results can be rationalised, is proposed. 

Modeling Klebsiella pneumoniae pathogenesis by infection of the wax moth Galleria mellonella

The implementation of infection models that approximate human disease is essential for understanding pathogenesis at the molecular level and for testing new therapies before they are entered into clinical stages. Insects are increasingly being used as surrogate hosts because they share, with mammals, essential aspects of the innate immune response to infections. We examined whether the larva of the wax moth Galleria mellonella could be used as a host model to conceptually approximate Klebsiella pneumoniae-triggered pneumonia. We report that the G. mellonella model is capable of distinguishing between pathogenic and nonpathogenic Klebsiella strains. Moreover, K. pneumoniae infection of G. mellonella models some of the known features of Klebsiella-induced pneumonia, i.e., cell death associated with bacterial replication, avoidance of phagocytosis by phagocytes, and the attenuation of host defense responses, chiefly the production of antimicrobial factors. Similar to the case for the mouse pneumonia model, activation of innate responses improved G. mellonella survival against subsequent Klebsiella challenge. Virulence factors necessary in the mouse pneumonia model were also implicated in the Galleria model. We found that mutants lacking capsule polysaccharide, lipid A decorations, or the outer membrane proteins OmpA and OmpK36 were attenuated in Galleria. All mutants activated G. mellonella defensive responses. The Galleria model also allowed us to monitor Klebsiella gene expression. The expression levels of cps and the loci implicated in lipid A remodeling peaked during the first hours postinfection, in a PhoPQ- and PmrAB-governed process. Taken together, these results support the utility of G. mellonella as a surrogate host for assessing infections with K. pneumoniae.

The role of microneedles for drug and vaccine delivery

INTRODUCTION: Transdermal drug delivery offers a number of advantages for the patient, not only due to its non-invasive and convenient nature, but also due to factors such as avoidance of first-pass metabolism and prevention of gastrointestinal degradation. It has been demonstrated that microneedles (MNs) can increase the number of compounds amenable to transdermal delivery by penetrating the skin's protective barrier, the stratum corneum, and creating a pathway for drug permeation to the dermal tissue below.

AREAS COVERED: MNs have been extensively investigated for drug and vaccine delivery. The different types of MN arrays and their delivery capabilities are discussed in terms of drugs, including biopharmaceutics and vaccines. Patient usage and effects on the skin are also considered.

EXPERT OPINION: MN research and development is now at the stage where commercialisation is a viable possibility. There are a number of long-term safety questions relating to patient usage which will need to be addressed moving forward. Regulatory guidance is awaited to direct the scale-up of the manufacturing process alongside provision of clearer patient instruction for safe and effective use of MN devices.

Bringing sounds into use: Thinking of sounds as materials and a sketch of auditory affordances

We live in a richly structured auditory environment. From the sounds of cars charging towards us on the street to the sounds of music filling a dancehall, sounds like these are generally seen as being instances of things we hear but can also be understood as opportunities for action. In some circumstances, the sound of a car approaching towards us can provide critical information for the avoidance of harm. In the context of a concert venue, sociocultural practices like music can equally afford coordinated activities of movement, such as dancing or music making. Despite how evident the behavioral effects of sound are in our everyday experience, they have been sparsely accounted for within the field of psychology. Instead, most theories of auditory perception have been more concerned with understanding how sounds are passively processed and represented or how they convey information of world, neglecting how this information can be used for anything. Here, we argue against these previous rationalizations, suggesting instead that information is instantiated through use and, therefore, is an emergent effect of a perceiver’s interaction with their environment. Drawing on theory from psychology, philosophy and anthropology, we contend that by thinking of sounds as materials, theorists and researchers alike can get to grips with the vast array of auditory affordances that we purposefully bring into use when interacting with the environment.

'Talk to me': a mixed methods study on preferred physician behaviours during end-of-life communication from the patient perspective

Background
Despite the recognized importance of end-of-life (EOL) communication between patients and physicians, the extent and quality of such communication is lacking.

Objective
We sought to understand patient perspectives on physician behaviours during EOL communication.

Design
In this mixed methods study, we conducted quantitative and qualitative strands and then merged data sets during a mixed methods analysis phase. In the quantitative strand, we used the quality of communication tool (QOC) to measure physician behaviours that predict global rating of satisfaction in EOL communication skills, while in the qualitative strand we conducted semi-structured interviews. During the mixed methods analysis, we compared and contrasted qualitative and quantitative data.

Setting and Participants
Seriously ill inpatients at three tertiary care hospitals in Canada.

Results
We found convergence between qualitative and quantitative strands: patients desire candid information from their physician and a sense of familiarity. The quantitative results (n = 132) suggest a paucity of certain EOL communication behaviours in this seriously ill population with a limited prognosis. The qualitative findings (n = 16) suggest that at times, physicians did not engage in EOL communication despite patient readiness, while sometimes this may represent an appropriate deferral after assessment of a patient's lack of readiness.

Conclusions
Avoidance of certain EOL topics may not always be a failure if it is a result of an assessment of lack of patient readiness. This has implications for future tool development: a measure could be built in to assess whether physician behaviours align with patient readiness.

Joining together or pushing apart? Building relations and exploring difference through shared education in Northern Ireland

In divided societies, the promotion of cross-cultural contact through the education system has been central to efforts to improve intergroup relations. This approach is informed by an understanding of the contact hypothesis, which suggests that positive contact with a member of a different group should contribute to improvements in attitudes towards the group as a whole. While a substantial body of research provides support for contact theory, critics have argued that its emphasis on harmonious encounters can result in the neglect of group differences and associated issues of conflict and discrimination during contact. The research discussed in this article explores this tension with reference to two shared education projects in Northern Ireland. Research data, gathered primarily through interviews with pupils, confirms that divisive issues are rarely addressed during contact and explores several influences on this: the nature of pupils’ relationships, the programme structure, and the prevailing social norms of avoidance.

Survival and behaviour of the earthworms Lumbricus rubellus and Dendrodrilus rubidus from arsenate-contaminated and non-contaminated sites

Two arsenic- and heavy metal-contaminated mine-spoil sites, at Carrock Fell, Cumbria and Devon Great Consols Mine, Devon, were found to support populations of the earthworms Lumbricus rubellus Hoffmeister and Dendrodrilus rubidus (Savigny). L. rubellus and D. rubidus collected from the Devon site and an uncontaminated site were kept for 28 days in uncontaminated soil and in soil containing sodium arsenate (494 mg As kg^-1). The state of the specimens was recorded every 7 days using a semi-quantitative assessment of earthworm health (condition index, C. I.). The C. I. remained high for all specimens except those of L. rubellus and D. rubidus from uncontaminated sites, which displayed 60 and 10% mortality, respectively. L. rubellus collected from the Carrock Fell site, and L. rubellus and D. rubidus from an uncontaminated site, burrowed as rapidly into soil containing up to 1235 mg As kg^-1 in the form of sodium arsenate as into uncontaminated soil when placed on the soil surface. When earthworms were allowed a choice between uncontaminated soil and soil contaminated with sodium arsenate in concentrations of up to 1235 mg As kg^-1, the threshold concentration for avoidance of contaminated soil was lower for L. rubellus and D. rubidus from uncontaminated soil than for specimens from contaminated soil. There was no significant effect of pH on soil discrimination. The LC₅₀ concentration of As for L. rubellus from Devon Great Consols was significantly higher (P < 0.001) than for L. rubellus from the uncontaminated site: 1510 and 96 mg As kg^-1, respectively. © 2001 Elsevier Science Ltd. All rights reserved.

Perceptions of therapist responses to shame disclosures by clients: A quasi-experimental investigation with non-clinical participants

Background
Therapist responses to initial shame disclosure in therapy have received little empirical attention.

Aim
This study explored different therapeutic responses to shame disclosures in terms of their perceived helpfulness. Responses ranged from complete withdrawal from the feeling (withdrawal) to completely tuning into it (non-withdrawal). Given the tendency of shame to evoke avoidance, participants higher on shame-proneness (as measured by The Experience of Shame Scale) were expected to perceive withdrawal responses to shame as more helpful than non-withdrawal responses.

Methodology
Fifty-five non-clinical participants were assessed for shame-proneness before viewing videos of mock therapy sessions showing clients either disclosing shame (two videos) or shock (control condition). Participants then rated the helpfulness of different therapist responses. The responses differed in the degree they allowed the client to withdraw from their emotions.

Results
High shame proneness was associated with rating withdrawal responses to shame as least helpful. Overall, neither the withdrawal response nor the non-withdrawal response were rated as particularly helpful. The therapeutic response which addressed management strategies when shame is initially experienced in therapy was deemed most helpful.

Conclusion
Despite the tendency to withdraw from shame feelings, this response is not deemed helpful in therapy.