Physical enhancement of transdermal drug application: is delivery technology keeping up with pharmaceutical development?

Advances in molecular biology have given us a wide range of protein and peptide-based drugs that are unsuitable for oral delivery because of their high degree of first-pass metabolism. Though parenteral delivery is the obvious answer, for the successful development of commercial chronic and self-administration usage formulations it is not the ideal choice. Transdermal delivery is emerging as the biggest application target for these agents, however, the skin is extremely efficient at keeping out such large molecular weight compounds and therapeutic levels are never going to be realistically achieved by passive absorption. Physical enhancement mechanisms including: iontophoresis, electroporation, ultrasound, photomechanical waves, microneedles and jet-propelled particles are emerging as solutions to this topical delivery dilemma. Adding proteins and peptides to the list of other large molecular weight drugs with insufficient passive transdermal fluxes to be therapeutically useful, we have a collection of pharmacological agents waiting for efficient delivery methods to be introduced. This article reviews the current state of physical transdermal delivery technology, assesses the pros and cons of each technique and summarises the evidence-base of their drug delivery capabilities.

Subordinate-manager gender combination and perceived leadership style influence on emotions, self-esteem and organizational commitment

A theoretical model was developed to investigate the relationships among subordinate-manager gender combinations, perceived leadership style, experienced frustration and optimism, organization-based self-esteem and organizational commitment. The model was tested within the context of a probabilistic structural model, a discrete Bayesian network, using cross-sectional data from a global pharmaceutical company. The Bayesian network allowed forward inference to assess the relative influence of gender combination and leadership style on the emotions, self-esteem and commitment consequence variables. Further, diagnostics from backward inference were used to assess the relative influence of variables antecedent to organizational commitment. The results showed that gender combination was independent of leadership style and had a direct impact on subordinates' levels of frustration and optimism. Female manager-female subordinate had the largest probability of optimism, while male manager teamed with a male subordinate had the largest probability of frustration. Furthermore, having a female manager teamed up with a male subordinate resulted in the lowest possibility of frustration. However, the findings show that the gender issue is not simply female managers versus male managers, but is concerned with the interaction of the subordinate-manager gender combination and leadership style in a nonlinear manner. (C) 2003 Elsevier Inc. All rights reserved.

Pretend play, mirror self-recognition and imitation: A longitudinal investigation through the second year

The aim in the current study was to investigate the emergence of pretend play, mirror self-recognition, synchronic imitation and deferred imitation in normally developing human infants. A longitudinal study was conducted with 98 infants seen at three-monthly intervals from 12 through to 24 months of age. At each session the infants were tested on a range of tasks assessing the four target skills. Deferred imitation was found to emerge prior to synchronic imitation, pretend play and mirror self-recognition. In contrast, the latter three skills emerged between 18 and 21 months and followed similar developmental trajectories. Deferred imitation was found to hold a prerequisite relation with these three skills. Synchronic imitation, pretend play and mirror self-recognition were not closely associated and no prerequisite relations were found between these skills. These findings are discussed in the context of current theories regarding the development of pretend play, mirror self-recognition, synchronic imitation and deferred imitation in the second year. (C) 2004 Elsevier Inc. All rights reserved.

Origins and early development of human body knowledge

As a knowable object, the human body is highly complex. Evidence from several converging lines of research, including psychological studies, neuroimaging and clinical neuropsychology, indicates that human body knowledge is widely distributed in the adult brain, and is instantiated in at least three partially independent levels of representation. Sensori-motor body knowledge is responsible for on-line control and movement of one's own body and may also contribute to the perception of others' moving bodies; visuo-spatial body knowledge specifies detailed structural descriptions of the spatial attributes of the human body; and lexical-semantic body knowledge contains language-based knowledge about the human body. In the first chapter of this Monograph, we outline the evidence for these three hypothesized levels of human body knowledge, then review relevant literature on infants' and young children's human body knowledge in terms of the three-level framework. In Chapters II and III, we report two complimentary series of studies that specifically investigate the emergence of visuospatial body knowledge in infancy. Our technique is to compare infants' responses to typical and scrambled human bodies, in order to evaluate when and how infants acquire knowledge about the canonical spatial layout of the human body. Data from a series of visual habituation studies indicate that infants first discriminate scrambled from typical human body pictures at 15 to 18 months of age. Data from object examination studies similarly indicate that infants are sensitive to violations of three-dimensional human body stimuli starting at 15-18 months of age. The overall pattern of data supports several conclusions about the early development of human body knowledge: (a) detailed visuo-spatial knowledge about the human body is first evident in the second year of life, (b) visuo-spatial knowledge of human faces and human bodies are at least partially independent in infancy and (c) infants' initial visuo-spatial human body representations appear to be highly schematic, becoming more detailed and specific with development. In the final chapter, we explore these conclusions and discuss how levels of body knowledge may interact in early development.

Parenting and adolescent self-regulation

This study examined the relationship between adolescents' academic and non-academic self-regulation (SR), authoritative parenting (as demonstrated by high levels of Involvement, Strictness, and Autonomy Granting), and parent self-efficacy in four areas. Participants were 214 Australian high school students and their parents. There was a moderate correlation (r = 0.63) between academic and non-academic SR. Adolescents and their parents differed significantly in their perceptions of parenting behaviours, with parents rating themselves higher than their children on Involvement, Autonomy Granting, and Strictness behaviours. A model of the relationships between the constructs was developed showing a strong path from parent self-efficacy to both academic and non-academic SR via high parental Involvement (as perceived by adolescents). Strict parenting and the granting by parents of psychological autonomy to their adolescent children did not appear to be important in the development of young people's self-regulatory behaviours. (C) 2004 The Association for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

The social identity perspective - Intergroup relations, self-conception, and small groups

The historical development, metatheoretical background, and current state of the social identity perspective in social psychology are described. Although originally, an analysis mainly of intergroup relations between large-scale social categories, and more recently an analysis with a strong social cognitive emphasis, this article shows that the social identity perspective is intended to be a general analysis of group membership and group processes. It focuses on the generative relationship between collective self-conception and group phenomena. To demonstrate the relevance of the social identity perspective to small groups, the article describes social identity research in a number of areas: differentiation within groups; leadership; deviance; group decision making; organizations; computer mediated communication; mobilization, collective action, and social loafing; and group culture. These art the areas in which most work has been done and which arc therefore best placed for further developments in the near future.

Leadership, self, and identity: A review and research agenda

This article reviews empirical research on the role of follower self-conception in leader-ship effectiveness. and specifies an agenda for future research in this area. The review shows that several aspects of follower self-conception (i.e., self-construal, self-efficacy, self-esteem, and self-consistency) may be affected by leadership. and may mediate the effects of leadership on follower behavior. There also is consistent evidence that follower self-construal moderates the impact of leadership on follower attitudes and behavior. Two key themes for future research are defined. First, future research should focus on the development of theory about the role of relational self-construal in the leadership process. Second, it seems particularly valuable to develop theory about the interplay of different aspects of follower self-conception in leadership effectiveness. including the interactive effects of these aspects of self Working backwards from these theoretical models of follower self-conception, specific leader behavior relevant to these aspects of self should then be identified. (C) 2004 Elsevier Inc. All rights reserved.

Group A streptococcal vaccine delivery by immunization with a self-adjuvanting M protein-based lipid core peptide construct

Background & objectives: To develop a broad strain coverage GAS vaccine, several strategies have been investigated which included multi-epitope approaches as well as targeting the M protein conserved C-region. These approaches, however, have relied on the use of adjuvants that are toxic for human application. The development of safe and effective adjuvants for human use is a key issue in the development of effective vaccines. In this study, we investigated the lipid polylysine core peptide (LCP) system as a self-adjuvanting GAS vaccine delivery approach. Methods: An LCP-GAS construct was synthesised incorporating multiple copies of a protective peptide epitope (J8) from the conserved carboxy terminal C-repeat region of the M protein. B10.BR mice were immunized parenterally with the LCP-J8 construct, with or without conventional adjuvant, prior to the assessment of immunogenicity and the induction of serum opsonic antibodies. Results: Our data demonstrated immunogenicity of LCP-J8 when coadministered in complete Freund's adjuvant (CFA), or administered in the absence of conventional adjuvant. In both cases, immunization led to the induction of high-titre J8 peptide-specific serum IgG antibody responses, and the induction of heterologous opsonic antibodies that did not cross-react with human heart tissue proteins. Interpretation & conclusion: These data indicated the potential of a novel self-adjuvanting LCP vaccine delivery system incorporating a synthetic GAS M protein C-region peptide immunogen in the induction of broadly protective immune responses, and pointed to the potential application of this system in human vaccine development against infectious diseases.

The gambling related cognitions scale (GRCS): development, confirmatory factor validation and psychometric properties

Aims The aims of this study are to develop and validate a measure to screen for a range of gambling-related cognitions (GRC) in gamblers. Design and participants A total of 968 volunteers were recruited from a community-based population. They were divided randomly into two groups. Principal axis factoring with varimax rotation was performed on group one and confirmatory factor analysis (CFA) was used on group two to confirm the best-fitted solution. Measurements The Gambling Related Cognition Scale (GRCS) was developed for this study and the South Oaks Gambling Screen (SOGS), the Motivation Towards Gambling Scale (MTGS) and the Depression Anxiety Stress Scale (DASS-2 1) were used for validation. Findings Exploratory factor analysis performed using half the sample indicated five factors, which included interpretative control/bias (GRCS-IB), illusion of control (GRCS-IC), predictive control (GRCS-PC), gambling-related expectancies (GRCS-GE) and a perceived inability to stop gambling (GRCS-IS). These accounted for 70% of the total variance. Using the other half of the sample, CFA confirmed that the five-factor solution fitted the data most effectively. Cronbach's alpha coefficients for the factors ranged from 0.77 to 0.91, and 0.93 for the overall scale. Conclusions This paper demonstrated that the 23-item GRCS has good psychometric properties and thus is a useful instrument for identifying GRC among non-clinical gamblers. It provides the first step towards devising/adapting similar tools for problem gamblers as well as developing more specialized instruments to assess particular domains of GRC.

The role of psychological climate in facilitating employee adjustment during organizational change

The current research tested a theoretical model of employee adjustment during organizational change based on Lazarus and Folkman's (1984) cognitive-phenomenological framework. The model hypothesized that psychological climate variables would act as coping resources and predict improved adjustment during change. Two variations of this model were tested using survey data from two different organizational samples: 779 public hospital employees and 877 public sector employees. Confirmatory factor analyses and structural equation analyses were conducted in order to evaluate the models. Results showed that employees whose perceptions of the organization and environment in which they were working (that is, psychological climate) were more positive, were more likely to appraise change favourably and report better adjustment in terms of higher job satisfaction, psychological well-being, and organizational commitment, and lower absenteeism and turnover intentions.

The WOMAC knee and hip osteoarthritis indices: Development, validation, globafization and influence on the development of the AUSCAN hand osteoarthritis indices

Clinical measurement in both clinical research and clinical practice requires tools and techniques that are valid, reliable and responsive. Patient-centred self-reported measures provide opportunity to evaluate consequences of osteoarthritis, that are important and relevant to patients with the condition. The WOMAC and AUSCAN Indices are health status measurement questionnaires that are valid, reliable and responsive, easy to complete, simple to score and available in multiple language forms and scaling formats. They provide opportunities to capture patient relevant information, relating to the impact of interventions, in clinical research and clinical practice environments. WOMAC data have also contributed to the development of proposed definitions for responder criteria and state-attainment criteria in osteoarthritis.

Protection against group A streptococcal infection by vaccination with self-adjuvanting lipid core M protein peptides

We have investigated the lipid polylysine core peptide (LCP) system as a self-adjuvanting group A streptococcal (GAS) vaccine delivery approach. LCP constructs were synthesised incorporating peptides from the M protein conserved carboxy terminal C-repeat region, the amino terminal type-specific region and from both of these regions. Immunisation with the constructs without adjuvant led to the induction of peptide-specific serum IgG antibody responses, heterologous opsonic antibodies, and complete protection from GAS infection. These data indicate that protective immunity to GAS infection can be evoked using the self-adjuvanting LCP system, and point to the potential application of this system in human mucosal GAS vaccine development. (c) 2005 Elsevier Ltd. All rights reserved.

Self-determination theory: A case study of evidence-based coaching

The coach is central to the development of expertise in sport (Bloom, 1985) and is subsequently key to facilitating adaptive forms of motivation to enhance the quality of sport performance (Mallett & Hanrahan, 2004). In designing optimal training environments that are sensitive to the underlying motives of athletes, the coach requires an in-depth understanding of motivation. This paper reports on the application of self-determination theory (SDT; Deci & Ryan, 1985; Ryan & Deci, 2000) to coaching elite athletes. Specifically, the application of SDT to designing an autonomy-supportive motivational climate is outlined, which was used in preparing Australia's two men's relay teams for the 2004 Olympic Games in Athens.

Interventions for improving self-awareness following acquired brain injury

Accurate self-awareness in clients who have had an acquired brain injury (ABI) has been associated with positive outcomes. However, providing intervention that improves clients' self-awareness is a challenging task for occupational therapists. The present paper provides an overview of the literature regarding models to guide intervention, intervention considerations, descriptions of interventions, and research evidence for interventions. Professionals can draw upon cognitive rehabilitation models and specific models of self-awareness. Facilitatory interventions, such as education, feedback, behaviour therapy and psychotherapy have been recommended to a greater extent than compensatory interventions. The development of interventions for improving self-awareness is at an early stage, and research on the effectiveness of interventions is limited. Future research is required into the effectiveness of interventions to improve clients' self-awareness before structured intervention guidelines can be developed.