The Temporal Focus Scale:Factor structure and association with alcohol use in a sample of Northern Irish school children

The Temporal Focus Scale (TFS) is a 12-item self-report measure of cognitive engagement with the temporal domains of past, present and future. Developed in college student samples, a three-factor structure with adequate reliability and validity was documented in a series of independent studies. We tested the factor structure of the scale in a sample of Northern Irish adolescents and found that our data supported a three factor structure, although there were problems with item 10. Because time perspective measures have been found to relate differentially to various health behaviours, we tested the relations between scores on the TFS and self-reported alcohol use. Results showed that scores on the TFS were not consistent statistical predictors of drinking category in a logistic regression. Results are discussed in terms of scale development, future scale use and the assessment of health-compromising behaviours such as adolescent alcohol consumption. © 2012 The Foundation for Professionals in Services for Adolescents.

VEIDase is a principal caspase-like activity involved in plant programmed cell death and essential for embryonic pattern formation

Plant embryogenesis is intimately associated with programmed cell death. The mechanisms of initiation and control of programmed cell death during plant embryo development are not known. Proteolytic activity associated with caspase-like proteins is paramount for control of programmed cell death in animals and yeasts. Caspase family of proteases has unique strong preference for cleavage of the target proteins next to asparagine residue. In this work, we have used synthetic peptide substrates containing caspase recognition sites and corresponding specific inhibitors to analyse the role of caspase-like activity in the regulation of programmed cell death during plant embryogenesis. We demonstrate that VEIDase is a principal caspase-like activity implicated in plant embryogenesis. This activity increases at the early stages of embryo development that coincide with massive cell death during shape remodeling. The VEIDase activity exhibits high sensitivity to pH, ionic strength and Zn2+ concentration. Altogether, biochemical assays show that VEIDase plant caspase-like activity resembles that of both mammalian caspase-6 and yeast metacaspase, YCA1. In vivo, VEIDase activity is localised specifically in the embryonic cells during both the commitment and in the beginning of the execution phase of programmed cell death. Inhibition of VEIDase prevents normal embryo development via blocking the embryo-suspensor differentiation. Our data indicate that the VEIDase activity is an integral part in the control of plant developmental cell death programme, and that this activity is essential for the embryo pattern formation.

A phase II study of vorinostat (MK-0683) in patients with polycythaemia vera and essential thrombocythaemia

Inhibition of histone deacetylases may be an important target in patients with myeloproliferative neoplasms. This investigator-initiated, non-randomized, open-label phase II multi-centre study included 63 patients (19 essential thrombocythaemia, 44 polycythaemia vera) from 15 centres. The primary objective was to evaluate if vorinostat was followed by a decline in clonal myeloproliferation as defined by European Leukaemia Net. Thirty patients (48%) completed the intervention period (24 weeks of therapy). An intention-to-treat response rate of 35% was identified. Pruritus was resolved [19% to 0% (P = 0·06)] and the prevalence of splenomegaly was lowered from 50% to 27% (P = 0·03). Sixty-five per cent of the patients experienced a decrease in JAK2 V617F allele burden (P = 0·006). Thirty-three patients (52% of patients) discontinued study drug before end of intervention due to adverse events (28 patients) or lack of response (5 patients). In conclusion, vorinostat showed effectiveness by normalizing elevated leucocyte and platelet counts, resolving pruritus and significantly reducing splenomegaly. However, vorinostat was associated with significant side effects resulting in a high discontinuation rate. A lower dose of vorinostat in combination with conventional and/or novel targeted therapies may be warranted in future studies.

A highly potent and specific MET therapeutic protein antagonist with both ligand-dependent and ligand-independent activity

Activation of the MET oncogenic pathway has been implicated in the development of aggressive cancers that are difficult to treat with current chemotherapies. This has led to an increased interest in developing novel therapies that target the MET pathway. However, most existing drug modalities are confounded by their inability to specifically target and/or antagonize this pathway. Anticalins, a novel class of monovalent small biologics, are hypothesized to be "fit for purpose" for developing highly specific and potent antagonists of cancer pathways. Here, we describe a monovalent full MET antagonist, PRS-110, displaying efficacy in both ligand-dependent and ligand-independent cancer models. PRS-110 specifically binds to MET with high affinity and blocks hepatocyte growth factor (HGF) interaction. Phosphorylation assays show that PRS-110 efficiently inhibits HGF-mediated signaling of MET receptor and has no agonistic activity. Confocal microscopy shows that PRS-110 results in the trafficking of MET to late endosomal/lysosomal compartments in the absence of HGF. In vivo administration of PRS-110 resulted in significant, dose-dependent tumor growth inhibition in ligand-dependent (U87-MG) and ligand-independent (Caki-1) xenograft models. Analysis of MET protein levels on xenograft biopsy samples show a significant reduction in total MET following therapy with PRS-110 supporting its ligand-independent mechanism of action. Taken together, these data indicate that the MET inhibitor PRS-110 has potentially broad anticancer activity that warrants evaluation in patients.

Towards an understanding of bacterial metabolites prodigiosin and violacein and their potential for use in commercial sunscreens

Synopsis
Objectives

To exploit the microbial ecology of bacterial metabolite production and, specifically, to: (i) evaluate the potential use of the pigments prodigiosin and violacein as additives to commercial sunscreens for protection of human skin, and (ii) determine antioxidant and antimicrobial activities (against pathogenic bacteria) for these two pigments.

Methods
Prodigiosin and violacein were used to supplement extracts of Aloe vera leaf and Cucumis sativus (cucumber) fruit which are known to have photoprotective activity, as well as some commercial sunscreen preparations. For each, sunscreen protection factors (SPFs) were determined spectrophotometrically. Assays for antimicrobial activity were carried out using 96-well plates to quantify growth inhibition of Staphylococcus aureus and Escherichia coli.
Results
For the plant extracts, SPFs were increased by an order of magnitude (i.e. up to ~3.5) and those for the commercial sunscreens increased by 10–22% (for 4% w/w violacein) and 20–65% (for 4% w/w prodigiosin). The antioxidant activities of prodigiosin and violacein were approximately 30% and 20% those of ascorbic acid (a well-characterized, potent antioxidant). Violacein inhibited S. aureus (IC_{506.99 ± 0.146 μM) but not E. coli, whereas prodigiosin was effective against both of these bacteria (IC50 values were 0.68 ± 0.06 μM and 0.53 ± 0.03 μM, respectively).}

Conclusion
The bacterial pigments prodigiosin and violacein exhibited antioxidant and antimicrobial activities and were able to increase the SPF of commercial sunscreens as well as the extracts of the two plant species tested. These pigments have potential as ingredients for a new product range of and, indeed, represent a new paradigm for sunscreens that utilize substances of biological origin. We discussed the biotechnological potential of these bacterial metabolites for use in commercial sunscreens, and the need for studies of mammalian cells to determine safety.

Choline Kinase Alpha as an Androgen Receptor Chaperone and Prostate Cancer Therapeutic Target

BACKGROUND: The androgen receptor (AR) is a major drug target in prostate cancer (PCa). We profiled the AR-regulated kinome to identify clinically relevant and druggable effectors of AR signaling.

METHODS: Using genome-wide approaches, we interrogated all AR regulated kinases. Among these, choline kinase alpha (CHKA) expression was evaluated in benign (n = 195), prostatic intraepithelial neoplasia (PIN) (n = 153) and prostate cancer (PCa) lesions (n = 359). We interrogated how CHKA regulates AR signaling using biochemical assays and investigated androgen regulation of CHKA expression in men with PCa, both untreated (n = 20) and treated with an androgen biosynthesis inhibitor degarelix (n = 27). We studied the effect of CHKA inhibition on the PCa transcriptome using RNA sequencing and tested the effect of CHKA inhibition on cell growth, clonogenic survival and invasion. Tumor xenografts (n = 6 per group) were generated in mice using genetically engineered prostate cancer cells with inducible CHKA knockdown. Data were analyzed with χ(2) tests, Cox regression analysis, and Kaplan-Meier methods. All statistical tests were two-sided.

RESULTS: CHKA expression was shown to be androgen regulated in cell lines, xenografts, and human tissue (log fold change from 6.75 to 6.59, P = .002) and was positively associated with tumor stage. CHKA binds directly to the ligand-binding domain (LBD) of AR, enhancing its stability. As such, CHKA is the first kinase identified as an AR chaperone. Inhibition of CHKA repressed the AR transcriptional program including pathways enriched for regulation of protein folding, decreased AR protein levels, and inhibited the growth of PCa cell lines, human PCa explants, and tumor xenografts.

CONCLUSIONS: CHKA can act as an AR chaperone, providing, to our knowledge, the first evidence for kinases as molecular chaperones, making CHKA both a marker of tumor progression and a potential therapeutic target for PCa.

Attitudes of students, parents, and teachers toward glasses use in rural China.

OBJECTIVE:

To use focus groups to understand barriers to glasses use among children in rural China.

METHODS:

Separate focus groups were conducted between December 17, 2007, and August 5, 2008, for the following 3 groups at each of 3 schools in rural China: children aged 14 to 18 years with myopia of less than -0.5 diopters in both eyes, those children's parents, and those children's teachers. Participants were also asked to rank their responses to questions about glasses use. The focus group transcripts were coded independently by 2 investigators using qualitative data management software.

RESULTS:

Respondents of all 3 types indicated that glasses purchase and wear should be delayed in children with early myopia and might be harmful to the eyes. Parents and students reported being uncertain about children's actual myopia status and whether glasses should be worn. Parents ranked their most common reason for not buying glasses as being "too busy with work," whereas "too expensive" ranked low. Inconvenience was ranked as an important reason for not wearing glasses among all 3 student groups. "Accuracy of lens power" was the first-ranked requirement for glasses among all student groups, whereas "new and attractive styles" was ranked last by all. All 3 types of respondents believed that wearing glasses or failing to wear them might worsen myopia.

CONCLUSIONS:

Educational programs are needed to address significant knowledge gaps in families and schools about glasses use in rural China. Cost and the need for attractive styles may not be significant barriers to use in this setting, raising the possibility of paying for such programs through cost recovery.

An evaluation of portion size estimation aids precision, ease of use and likelihood of future use

OBJECTIVE: The present study aimed to evaluate the precision, ease of use and likelihood of future use of portion size estimation aids (PSEA).

DESIGN: A range of PSEA were used to estimate the serving sizes of a range of commonly eaten foods and rated for ease of use and likelihood of future usage.

SETTING: For each food, participants selected their preferred PSEA from a range of options including: quantities and measures; reference objects; measuring; and indicators on food packets. These PSEA were used to serve out various foods (e.g. liquid, amorphous, and composite dishes). Ease of use and likelihood of future use were noted. The foods were weighed to determine the precision of each PSEA.

SUBJECTS: Males and females aged 18-64 years (n 120).

RESULTS: The quantities and measures were the most precise PSEA (lowest range of weights for estimated portion sizes). However, participants preferred household measures (e.g. 200 ml disposable cup) - deemed easy to use (median rating of 5), likely to use again in future (all scored either 4 or 5 on a scale from 1='not very likely' to 5='very likely to use again') and precise (narrow range of weights for estimated portion sizes). The majority indicated they would most likely use the PSEA preparing a meal (94 %), particularly dinner (86 %) in the home (89 %; all P<0·001) for amorphous grain foods.

CONCLUSIONS: Household measures may be precise, easy to use and acceptable aids for estimating the appropriate portion size of amorphous grain foods.

Substance Use and Misuse : Adolescent Substance Use in the context of the family ; a qualitative study of young people's views on parent child attachments , parenting style and parental substance use

Introduction and Aims. While the role of the family in adolescent substance use has been well documented, few studies have attempted to explore in-depth youth perceptions of how these familial processes/dynamics influence teenage substance use. This paper reports the findings from a study exploring risk and protective factors for teenage substance use within the context of the family as perceived by young people with a view to informing current and future family based prevention and education interventions.
Design and Methods. Data collection took place in nine post-primary schools across Northern Ireland. Nine focus groups using participatory techniques were facilitated with a purposive sample of sixty-two young people (age 13-17 years). Data were transcribed verbatim and analysed using a content/thematic analysis.
Results. Three broad themes/aspects of the family emerged from the data, which may serve to protect or attenuate the risk of substance use among young people. Parent-child attachment was a major theme identified in protecting adolescents from substance use in addition to effective parenting particularly an authoritative style of parenting supplemented by parental monitoring and good parent-child communication to encourage child disclosure. Family substance use was deemed to impact on children’s substance use if exposed at an early age and the harms associated with PSM were discussed in detail.
Discussion and Conclusions. The qualitative approach provides insight into current understanding of youth perceptions of substance use in the context of family dynamics. A number of recommendations are outlined. Family based (preventive) interventions/parenting programmes may benefit from components on effective parenting including authoritative styles, parental monitoring, effective communication, spending time together (building attachments), parent-child conflict, adolescent development and factors which impact on parenting. Parenting programmes tailored to mothers and fathers may be beneficial. School based interventions targeting children/adolescents may be best placed to target children living with parental substance misuse.
Keywords: substance/substance related disorders, focus groups, young people/adolescent,

Natural substances and high pressure processing to preserve sea bass

Esta tese teve como objectivo estudar estratégias de conservação de pescado fresco, recorrendo ao uso de extractos e óleos essenciais de plantas e do processamento por alta pressão (HPP), usando filetes de robalo como um caso de estudo modelo. Relativamente aos extractos e óleos essenciais, avaliaram-se as suas propriedades antibacterianas e antioxidantes. Os extractos aquosos quente de poejo e de orégão e o óleo essencial de cravinho apresentaram a maior actividade antioxidante. Os óleos essenciais foram mais eficientes do que os extractos para inibir o crescimento das estirpes bacterianas testadas, tendo-se observado os menores valores de concentração mínima inibitória nos óleos essenciais de orégão, citronela, alho e orégão Espanhol. De seguida, estudou-se o efeito dos óleos essenciais de orégão Espanhol e de limão na conservação de filetes de robalo fresco tendo em conta critérios microbiológicos, químicos, físicos e sensoriais. A aplicação do óleo essencial de orégão Espanhol aumentou o tempo de vida útil dos filetes sob o ponto de vista bacteriano, mas não em termos sensoriais. A combinação dos óleos essenciais de orégão Espanhol e de limão melhorou o efeito antioxidante e reduziu a intensidade do odor e a sua eficácia em relação às Enterobacteriaceae, comparando com o tratamento com óleo essencial de orégão Espanhol per se. No sentido de reduzir o odor conferido pelos óleos essenciais realizou-se um estudo de conservação para avaliar o efeito de películas com óleos essenciais (citronela, alho e tomilho) em filetes de robalo, recorrendo a uma teste de desafio bacteriano. As películas sem óleos essenciais aumentaram o tempo de vida útil sob o ponto de vista bacteriano, mas este efeito não foi observado com a incorporação dos óleos essenciais nas películas. Em relação ao HPP, testaram-se diversas condições (nível de pressão, tempo de pressurização e taxa de pressurização) e avaliaram-se os efeitos na actividade enzimática, na qualidade global e na conservação de filetes de robalo fresco. Em geral, o aumento do nível de pressão e do tempo de pressurização diminuiu a actividade da fosfatase ácida e das enzimas proteolíticas, a carga bacteriana e a capacidade de retenção de água, enquanto que os filetes ficaram mais brancos. O HPP revelou potencial para o desenvolvimento de novos produtos: mais brancos, não translúcidos, mais firmes e com maior tempo de frescura e estabilidade microbiológica. Em conclusão, os óleos essenciais e o HPP têm potencial para conservar pescado fresco, devido aos seus efeitos na qualidade bacteriana. Ainda assim, mais esforços devem ser feitos no sentido de reduzir a transferência de odor dos óleos essenciais para o pescado e os efeitos do HPP no aspecto do pescado e na oxidação lipídica.

Heterotopias of mental health care: The role of space in experiences of distress, madness and mental health service use.

The change from an institutional to community care model of mental health services can be seen as a fundamental spatial change in the lives of service users (Payne, 1999; Symonds & Kelly, 1998; Wolch & Philo, 2000). It has been argued that little attention has been paid to the experience of the specific sites of mental health care, due to a utopic (idealised and placeless) idea of ‘community’ present in ‘community care’ (Symonds, 1998). This project hence explored the role of space in service users’ experiences, both of mental health care, and community living. Seventeen ‘spatial interviews’ with service users, utilising participatory mapping techniques (Gould & White, 1974; Herlihy & Knapp, 2003; Pain & Francis, 2003), plus seven, already published first person narratives of distress (Hornstein, 2009), were analysed using thematic analysis (Braun & Clarke, 2006). Mental health service sites are argued to have been described as heterotopias (Foucault, 1986a) of a ‘control society’ (Deleuze, 1992), dominated by observation and the administration of risk (Rose, 1998a), which can in turn be seen to make visible (Hetherington, 2011) to service users a passive and stigmatised subject position (Scheff, 1974; 1999). Such visible positioning can be seen to ‘modulate’ (Deleuze, 1992) participants’ experiences in mainstream space. The management of space has hence been argued to be a central issue in the production and management of distress and madness in the community, both in terms of a differential experience of spaces as ‘concordant’ or ‘discordant’ with distress, and with movement through space being described as a key mediator of experiences of distress. It is argued that this consideration of space has profound implications for the ‘social inclusion’ agenda (Spandler, 2007; Wallcraft, 2001).

Leading as designing: how educational developers in leadership and management studies can use architectural design to facilitate student learning about delivering innovation

This paper describes a qualitative observational study of how a work based learning masters leadership development programme for middle managers in health and social care in the UK introduced students to key aspects of delivering innovation, through a formative assignment on contemporary architectural design. Action learning and activity theoretical approaches were used to enable students to explore common principles of leading the delivery of innovation. Between 2001 and 2013 a total of 89 students in 7 cohorts completed the assignment. Evaluation lent support for the view that the assignment provided a powerful learning experience for many. Several students found the creativity, determination and dedication of architects, designers and structural engineers inspirational in their ability to translate a creative idea into a completed artefact, deploy resources and negotiate complex demands of stakeholders. Others expressed varying levels of self-empowerment as regards their capacity for fostering an equivalent creativity in self and others. Theoretical approaches in addition to activity theory, including Engeström’s concepts of stabilisation knowledge and possibility knowledge, are discussed to explain these differing outcomes and to clarify the challenges and opportunities for educational developers seeking to utilise cross-disciplinary, creative approaches in curriculum design.

Film thickness in a ball-on-disc contact lubricated with greases, bleed oils and base oils

Three different lubricating greases and their bleed and base oils were compared in terms of film thickness in a ball-on-disc test rig through optical interferometry. The theoretical values calculated according to Hamrock's equation are in close agreement with the base oil film thickness measurements, which validates the selected experimental methodology. The grease and bleed oil film thickness under fully flooded lubrication conditions presented quite similar behaviour and levels. Therefore, the grease film thickness under full film conditions might be predicted using their bleed oil properties, namely the viscosity and pressure-viscosity coefficient. The base and bleed oil lubricant parameter LP are proportional to the measured film thickness. A relationship between grease and the corresponding bleed oil film thickness was evidenced.