Development of liposome gel based formulations for intravaginal delivery of the recombinant HIV-1 envelope protein CN54gp140

Mucosally-administered vaccine strategies are widely investigated as a promising means of preventing HIV infection. This study describes the development of liposomal gel formulations, and novel lyophilised variants, comprising HIV-1 envelope glycoprotein, CN54gp140, encapsulated within neutral, positively charged or negatively charged liposomes. The CN54gp140 liposomes were evaluated for mean vesicle diameter, polydispersity, morphology, zeta potential and antigen encapsulation efficiency before being incorporated into hydroxyethyl cellulose (HEC) aqueous gel and subsequently lyophilised to produce a rod-shaped solid dosage form for practical vaginal application. The lyophilised liposome-HEC rods were evaluated for moisture content and redispersibility in simulated vaginal fluid. Since these rods are designed to revert to gel form following intravaginal application, mucoadhesive, mechanical (compressibility and hardness) and rheological properties of the reformed gels were evaluated. The liposomes exhibited good encapsulation efficiency and the gels demonstrated suitable mucoadhesive strength. The freeze-dried liposome-HEC formulations represent a novel formulation strategy that could offer potential as stable and practical dosage form.

The Development of Corporate Identity: A Political Perspective

A corporate identity denotes a set of attributes that senior managers ascribe to their organization. It is therefore an organizational identity articulated by a powerful interest group. It can constitute a claim which serves inter alia to justify the authority vested in top managers and to further their interests. The academic literature on organizational identity, and on corporate identity in particular, pays little attention to these political considerations. It focuses in an apolitical manner on shared meanings when corporate identity works, or on cognitive dissonance when it breaks down. In response to this analytical void, we develop a political analysis of corporate identity and its development, using as illustration a longitudinal study of successive changes in the corporate identity of a Brazilian telecommunications company. This suggests a cyclical model in which corporate identity definition and redefinition involve power relations, resource mobilization and struggles for legitimacy. © Blackwell Publishing Ltd 2007.

Strategic development in exact calculation: Group and individual differences in four achievement subtypes

This longitudinal study sought to identify developmental changes
in strategy use between 5 and 7 years of age when solving exact
calculation problems. Four mathematics and reading achievement
subtypes were examined at four time points. Five strategies were
considered: finger counting, verbal counting, delayed retrieval,
automatic retrieval, and derived fact retrieval. Results provided
unique insights into children’s strategic development in exact calculation
at this early stage. Group analysis revealed relationships
between mathematical and/or reading difficulties and strategy
choice, shift, and adaptiveness. Use of derived fact retrieval by
7 years of age distinguished children with mathematical difficulties
from other achievement subtypes. Analysis of individual differences
revealed marked heterogeneity within all subtypes,
suggesting (inter alia) no marked qualitative distinction between
our two mathematical difficulty subtypes.

Novel hapten synthesis for antibody production and development of an enzyme-linked immunosorbent assay for determination of furaltadone metabolite 3-amino-5-morpholinomethyl-2-oxazolidinone (AMOZ)

A heterologous competitive indirect enzyme-linked immunosorbent assay (ciELISA) for the determination of the furaltadone metabolite 3-amino-5-morpholinomethyl-2-oxazolidinone (AMOZ) was developed. AMOZ was derivatised with 2-(4-formylphenoxy) acetic acid or 2-(3-formylphenoxy) acetic acid to obtain two novel immunizing haptens. The ability of these haptens in producing specific polyclonal antibodies against the nitrophenyl derivative of AMOZ (NPAMOZ) was compared with that of traditional immunizing haptens (derivatised AMOZ with 3-carboxybenzaldehyle or 4-carboxybenzaldehyle). The results indicated that the novel immunizing haptens were able to produce antibodies with almost a two-fold improvement in sensitivity of the ciELISA for NPAMOZ in comparison with the existing antibody based ELISAs. The differences in sensitivity were explained by the molecular modeling of the lowest energy conformations of NPAMOZ and the haptens. Another novel hapten, derivatised AMOZ with 2-oxoacetic acid, was synthesized and used as a heterologous coating hapten. The results showed that this strategy of using only a partial structure of the target molecule as the coating hapten was able to obtain a two to three-fold improvement in sensitivity. This study provided a modern approach for the development of an immunoassay with improved sensitivity for the metabolites of nitrofuran antibiotics. © 2012 Elsevier B.V. All rights reserved.

A pseudo-transient solution strategy for the analysis of delamination by means of interface elements

Recent efforts in the finite element modelling of delamination have concentrated on the development of cohesive interface elements. These are characterised by a bilinear constitutive law, where there is an initial high positive stiffness until a threshold stress level is reached, followed by a negative tangent stiffness representing softening (or damage evolution). Complete decohesion occurs when the amount of work done per unit area of crack surface is equal to a critical strain energy release rate. It is difficult to achieve a stable, oscillation-free solution beyond the onset of damage, using standard implicit quasi-static methods, unless a very refined mesh is used. In the present paper, a new solution strategy is proposed based on a pseudo-transient formulation and demonstrated through the modelling of a double cantilever beam undergoing Mode I delamination. A detailed analysis into the sensitivity of the user-defined parameters is also presented. Comparisons with other published solutions using a quasi-static formulation show that the pseudo-transient formulation gives improved accuracy and oscillation-free results with coarser meshes

Home-based child development interventions for preschool children from socially disadvantaged families

BACKGROUND
Social disadvantage can have a significant impact on early child development, health and wellbeing. What happens during this critical period is important for all aspects of development. Caregiving competence and the quality of the environment play an important role in supporting development in young children and parents have an important role to play in optimising child development and mitigating the negative effects of social disadvantage. Home-based child development programmes aim to optimise children's developmental outcomes through educating, training and supporting parents in their own home to provide a more nurturing and stimulating environment for their child.

OBJECTIVES
To determine the effects of home-based programmes aimed specifically at improving developmental outcomes for preschool children from socially disadvantaged families.

SEARCH STRATEGY
We searched the following databases between 7 October and 12 October 2010: Cochrane Central Register of Controlled Trials (CENTRAL) (2010, Issue 4), MEDLINE (1950 to week 4, September 2010), EMBASE (1980 to Week 39, 2010), CINAHL (1937 to current), PsycINFO (1887 to current), ERIC (1966 to current), ASSIA (1987 to current), Sociological Abstracts (1952 to current), Social Science Citation Index (1970 to current). We also searched reference lists of articles.

SELECTION CRITERIA
Randomised controlled trials comparing home-based preschool child development interventions with a 'standard care' control. Participants were parents with children up to the age of school entry who were socially disadvantaged in respect of poverty, lone parenthood or ethnic minority status.

DATA COLLECTION AND ANALYSIS
Two authors independently selected studies, assessed the trials' risk of bias and extracted data.

RESULTS
We included seven studies, which involved 723 participants. We assessed four of the seven studies as being at high risk of bias and three had an unclear risk of bias; the quality of the evidence was difficult to assess as there was often insufficient detail reported to enable any conclusions to be drawn about the methodological rigour of the studies. Four trials involving 285 participants measured cognitive development and we synthesised these data in a meta-analysis. Compared to the control group, there was no statistically significant impact of the intervention on cognitive development (standardised mean difference (SMD) 0.30; 95% confidence interval -0.18 to 0.78). Only three studies reported socioemotional outcomes and there was insufficient data to combine into a meta-analysis. No study reported on adverse effects.

AUTHORS’ CONCLUSIONS
This review does not provide evidence of the effectiveness of home-based interventions that are specifically targeted at improving developmental outcomes for preschool children from socially disadvantaged families. Future studies should endeavour to better document and report their methodological processes.

Testing a model for developing, implementing and evaluating a strategy to improve the quality of nursing and midwifery care in an acute hospital trust.

Abstract:
Background: Health care organisations
worldwide are faced with the need to develop
and implement strategic organisational plans
to meet the challenges of modern health care.
There is a need for models for developing, implementing and evaluating strategic plans that engage practitioners, and make a measurable difference to the patients that they serve. These presentations describe the development, implementation and evaluation of such a model by a team of senior nurses and practice developers, to underpin a strategy for nursing and midwifery in an acute hospital trust. Developing a Strategy The PARIHS (Promoting Action on Research Implementation in Health Services) conceptual framework (Kitson et al, 1998) proposes that successful implementation of change in practice is a function of the interplay of three core elements: the level of evidence supporting the proposed change; the context or environment in which the change takes place, and the way in which change is facilitated. We chose to draw on this framework to develop our strategy and implementation plan (O’Halloran, Martin and Connolly, 2005). At the centre of the plan are ward managers. These professionals provide leadership for the majority of staff in the trust and so were seen to be a key group in the implementation process.

Food web indicators under the Marine Strategy Framework Directive: From complexity to simplicity?

The Marine Strategy Framework Directive (MSFD) requires that European Union Member States achieve "Good Environmental Status" (GES) in respect of 11 Descriptors of the marine environment by 2020. Of those, Descriptor 4, which focuses on marine food webs, is perhaps the most challenging to implement since the identification of simple indicators able to assess the health of highly dynamic and complex interactions is difficult. Here, we present the proposed food web criteria/indicators and analyse their theoretical background and applicability in order to highlight both the current knowledge gaps and the difficulties associated with the assessment of GES. We conclude that the existing suite of indicators gives variable focus to the three important food web properties: structure, functioning and dynamics, and more emphasis should be given to the latter two and the general principles that relate these three properties. The development of food web indicators should be directed towards more integrative and process-based indicators with an emphasis on their responsiveness to multiple anthropogenic pressures. (C) 2013 Elsevier Ltd. All rights reserved.

Lovastatin biosynthesis depends on the carbon-nitrogen proportion: model development and controller design

Lovastatin biosynthesis depends on the relative concentrations of dissolved oxygen and the carbon and nitrogen resources. An elucidation of the underlying relationship would facilitate the derivation of a controller for the improvement of lovastatin yield in bioprocesses. To achieve this goal, batch submerged cultivation experiments of lovastatin production by Aspergillus flavipus BICC 5174, using both lactose and glucose as carbon sources, were performed in a 7 liter bioreactor and the data used to determine how the relative concentrations of lactose, glucose, glutamine and oxygen affected lovastatin yield. A model was developed based on these results and its prediction was validated using an independent set of batch data obtained from a 15-liter bioreactor using five statistical measures, including the Willmott index of agreement. A nonlinear controller was designed considering that dissolved oxygen and lactose concentrations could be measured online, and using the lactose feed rate and airflow rate as process inputs. Simulation experiments were performed to demonstrate that a practical implementation of the nonlinear controller would result in satisfactory outcomes. This is the first model that correlates lovastatin biosynthesis to carbon-nitrogen proportion and possesses a structure suitable for implementing a strategy for controlling lovastatin production.

A study to evaluate the introduction of simulation as a teaching strategy for the mental health and learning disability fields of nursing, in an undergraduate nursing curriculum within one higher education institution

High Fidelity Simulation or Human Patient Simulation is an educational strategy embedded within nursing curricula throughout many healthcare educational institutions. This paper reports on an evaluative study that investigated the views of a group of Year 2 undergraduate nursing students from the mental health and the learning disability fields of nursing (n = 75) in relation to simulation as a teaching pedagogy. The study took place in the simulation suite within a School of Nursing and Midwifery in the UK. Two patient scenarios were used for the session and participants completed a 22-item questionnaire consisting of three biographical information questions and a 19-item Likert scale. Descriptive statistics were employed to illustrate the data and non-parametric testing (Mann-Whitney U test) was employed to test a number of hypotheses. Overall students were positive about the introduction of patient scenarios using the human patient simulator into the undergraduate nursing curriculum. This study used a small, convenience sample in one institution and therefore the results obtained cannot be generalised to nursing education before further research can be conducted with larger samples and a mixed-method research approach. However these results provide encouraging evidence to support the use of simulation within the mental health and the learning disability fields of nursing, and the development and implementation of further simulations to complement the students’ practicum.

Establishing a nurse practitioner collaborative: evolution, development, and outcomes

The first Australian palliative care nurse practitioner (NP) was endorsed in 2003. In 2009 the Victoria Department of Health funded the development of the Victorian Palliative Care Nurse Practitioner Collaborative (VPCNPC). Its aim was to promote the NP role, develop resources, and provide education and mentorship to NPs, nurse practitioner candidates (NPCs), and health service managers. Four key objectives were developed: identify the demographic profile of palliative care NPCs in Victoria; develop an education curriculum and practical resources to support the training and education of palliative care NPCs and NPs; provide mentorship to NPs, NPCs, and service managers; and ensure effective communication with all key stakeholders. An NPC survey was also conducted to explore NPC demographics, models of care, the hours of study required for the role, the mentoring process, and education needs. This paper reports on the establishment of the VPCNPC, the steps taken to achieve its objectives, and the results of the survey. The NP role in palliative care in Australia continues to evolve, and the VPCNPC provides a structure and resources to clearly articulate the benefits of the role to nursing and clinical services. The advanced clinical practice role of the nurse practitioner (NP) has been well established in North America for several decades and across a range of specialties (Ryan-Woolley et al, 2007; Poghosyan et al, 2012). The NP role in Australia and the UK is a relatively new initiative that commenced in the early 2000s (Gardner et al, 2009). There are over 1000 NPs across all states and territories of Australia, of whom approximately 130 work in the state of Victoria (Victorian Government Health Information, 2012). Australian NPs work across a range of specialties, including palliative, emergency, older person, renal, cardiac, respiratory, and mental health care. There has been increasing focus nationally and internationally on developing academic programmes specifically for nurses working toward NP status (Gardner et al, 2006). There has been less emphasis on identifying the comprehensive clinical support requirements for NPs and NP candidates (NPCs) to ensure they meet all registration requirements to achieve and/or maintain endorsement, or on articulating the ongoing requirements for NPs once endorsed. Historically in Australia there has been a lack of clarity and limited published evidence on the benefits of the NP role for patients, carers, and health services (Quaglietti et al, 2004; Gardner and Gardner, 2005; Bookbinder et al, 2011; Dyar et al, 2012). An NP is considered to be at the apex of clinical nursing practice. The NP role typically entails comprehensively assessing and managing patients, prescribing medicines, making direct referrals to other specialists and services, and ordering diagnostic investigations (Australian Nursing and Midwifery Council, 2009). All NPs in Australia are required to meet the following generic criteria: be a registered nurse, have completed a Nursing and Midwifery Board of Australia approved postgraduate university Master's (nurse practitioner) degree programme, and be able to demonstrate a minimum of 3 years' experience in an advanced practice role (Nursing and Midwifery Board of Australia, 2011). An NPC in Victoria is a registered nurse employed by a service or organisation to work toward meeting the academic and clinical requirements for national endorsement as an NP. During the period of candidacy, which is of variable duration, NPCs consolidate their competence to work at the advanced practice level of an NP. The candidacy period is a process of learning the new role while engaging with mentors (medical and nursing) and accessing other learning opportunities both within and outside one's organisation to meet the educational requirements. Integral to the NP role is the development of a model of care that is responsive to identified service delivery gaps that can be addressed by the skills, knowledge, and expertise of an NP. These are unique to each individual service. The practice of an Australian NP is guided by national standards (Nursing and Midwifery Board of Australia 2014). It is defined by four overarching standards: clinical, education, research, and leadership. Following the initial endorsement of four Victorian palliative care NPs in 2005, there was a lull in recruitment. The Victoria Department of Health (DH) recognised the potential benefits of NPs for health services, and in 2008 it provided funding for Victorian public health services to scope palliative care NP models of care that could enhance service delivery and patient outcomes. The scoping strategy was effective and led to the appointment of 16 palliative care nurses to NPC positions over the ensuing 3 years. The NPCs work across a broad range of care settings, including inpatient, community, and outpatient in metropolitan, regional, and rural areas of Victoria. At the same time, the DH also funded the Centre for Palliative Care to establish the Victorian Palliative Care Nurse Practitioner Collaborative (VPCNPC) to support the NPs and NPCs. The Centre is a state-wide service that is part of St Vincent's Hospital Melbourne and a collaborative Centre of the University of Melbourne. Its primary function is to provide training and conduct research in palliative care. The purpose of the VPCNPC was to provide support and mentorship and develop resources targeted at palliative care NPs, NPCs, and health service managers. Membership of the VPCNPC is open to all NPs, NPCs, health service managers, and nurses interested in the NP role. The aim of this paper is to describe the development of the VPCNPC, its actions, and the outcomes of these actions.

Development of Novel Activity-Based Probes for the Detection of Serine Proteases

Cystic Fibrosis (CF) is a genetic disease featuring a chronic cycle of inflammation and infection in the airways of sufferers. Mutations lead to altered ion transport, which in turn causes dehydrated airways and reduced mucociliary clearance which predisposes the patient to infection, resulting in a severe immune response and tissue destruction (1). Airway dehydration is primarily caused by the hyperabsorption of sodium by the epithelial sodium channel (ENaC) (2). ENaC is activated by the action of a number of predominantly trypsin-like Channel Activating Proteases (CAPs) including prostasin, matriptase and furin (3). Additional proteases known to activate ENaC include human airway trypsin (3), plasmin, neutrophil elastase and chymotrypsin (4).

Activity profiling is a valuable technique which involves the use of small inhibitory molecules called Activity-Based Probes (ABPs) which can be used to covalently label the active site of proteases and provide a range of information regarding its structure, catalytic mechanism, location and function within biological systems. The development of novel ABPs for CAPs, would enhance understanding of the role of these proteases in CF airways disease and in particular their role in ENaC activation and airway dehydration. This project investigates the application of a range of novel broad-spectrum ABPs targeting the various subclasses of serine proteases, to include those proteases involved in ENaC activation. Additionally, the application of more selective ABPs in detecting specific serine proteases is investigated.

Compounds were synthesised by Solid-Phase Peptide Synthesis (SPPS) using a standard Fmoc/tBu strategy. Kinetic evaluation of synthesised ABPs against various serine proteases was determined by fluorogenic steady-state enzyme assays. Furthermore, application of ABPs and confirmation of irreversible nature of the compounds was carried out through SDS-PAGE and electroblotting techniques.

Synthesised compounds showed potent irreversible inhibition of serine proteases within their respective targeting class (NAP855 vs Trypsin k3/Ki = 2.60 x 106 M-1 min-1, NFP849 vs Chymotrypsin k3/Ki = 1.28 x 106 M-1 min-1 and NVP800 vs Neutrophil Elastase k3/Ki = 6.41 x 104 M-1 min-1). Furthermore ABPs showed little to no cross-reactivity between classes and so display selectivity between classes. The irreversible nature of compounds was further demonstrated through labelling of proteases, followed by separation and detection via SDS-PAGE and electroblotting techniques. Targeted labelling of active proteases only, was demonstrated by failure of ABPs to detect previously inactivated proteases. Extension of the substrate recognition site within probes resulted in an increased potency and selectivity in the detection of the target proteases. Successful detection of neutrophil elastase from CF sputum samples by NVP800, demonstrated the application of compounds within biological samples and their potential use in identifying further proteases involved in ENaC activation and airway dehydration in CF patients.

A strategy towards professionalism in the dissecting room

The teaching and cultivation of professionalism is an integral part of medical education as professionalism is central to maintaining the public’s trust in the medical profession. Traditionally professional values would have been acquired through an informal process of socialisation and observation of role models. Recently, however, medical educators have accepted the responsibility to explicitly teach and effectively evaluate professionalism. A comprehensive working definition of the term professionalism and a universally agreed list of the constituent elements of professionalism are currently debated. The School of Medicine and Dentistry of The Queen’s University of Belfast uses an approach of self-directed learning for teaching anatomy, and students are given the opportunity to learn anatomy from human dissection. Self-directed learning teams have been found to be underutilised as educational strategies and presented an opportunity to utilise the first year dissection room teaching environment to nurture the development of the attributes of professionalism. An educational strategy based on role-playing was developed to engage all students around the dissection table. Students received comprehensive background reviews on professionalism, its attributes and the identification of such attributes in the context of the dissection room. Roles, with specific duties attached, were allocated to each team member. Circulating academic staff members directly observed student participation and gave formative feedback. Students were given the opportunity to reflect on their ability to identify the attributes and reflect on their own and their peer’s ability to develop and practise these attributes. This strategy indicated that small group learning teams in the dissection room utilise widely accepted principles of adult learning and offer an opportunity to create learning activities that will instil in students the knowledge, values, attitudes and behaviours that characterise medical professionalism. Anatomy faculty have a responsibility to nurture and exemplify professionalism and play a significant role in the early promotion and inculcation of professionalism. It remains imperative not only to assess this strategy but also to create opportunities for critical reflection and evaluation within the strategy. Key words: Medical Education – Professionalism – Anatomy - Reflective Practise – Role-play

Environmental and social supply chain management sustainability practices: construct development and measurement

The purpose of this paper is to conceptualise and operationalise the concept of supply chain management sustainability practices. Based on a multi-stage procedure involving a literature review, expert Q-sort and pre-test process, pilot test and survey of 156 supply chain directors and managers in Ireland, we develop a multidimensional conceptualisation and measure of social and environmental supply chain management sustainability practices. The research findings show theoretically sound constructs based on four underlying sustainable supply chain management practices: monitoring, implementing systems, new product and process development and strategy redefinition. A two-factor model is then identified as the most reliable: comprising process-based and market-based practices.