The Effect of nutritional supplementation on subjective and objective measures of visual and retinal function:a random controlled trial

In industrialised countries age-related macular disease (ARMD) is the leading cause of visual loss in older people. Because oxidative stress is purported to be associated with an increased risk of disease development the role of antioxidant supplementation is of interest. Lutein is a carotenoid antioxidant that accumulates within the retina and is thought to filter blue light. Increased levels of lutein have been associated with reduced risk of developing ARMD and improvements in visual and retinal function in eyes with ARMD. The aim of this randomised controlled trial (RCT) was to investigate the effect of a lutein-based nutritional supplement on subjective and objective measures of visual function in healthy eyes and in eyes with age-related maculopathy (ARM) – an early form of ARMD. Supplement withdrawal effects were also investigated. A sample size of 66 healthy older (HO), healthy younger (HY), and ARM eyes were randomly allocated to receive a lutein-based supplement or no treatment for 40 weeks. The supplemented group then stopped supplementation to look at the effects of withdrawal over a further 20 weeks. The primary outcome measure was multifocal electroretinogram (mfERG) N1P1 amplitude. Secondary outcome measures were mfERG N1, P1 and N2 latency, contrast sensitivity (CS), Visual acuity (VA) and macular pigment optical density (MPOD). Sample sizes were sufficient for the RCT to have an 80% power to detect a significant clinical effect at the 5% significance level for all outcome measures when the healthy eye groups were combined, and CS, VA and mfERG in the ARM group. This RCT demonstrates significant improvements in MPOD in HY and HO supplemented eyes. When HY and HO supplemented groups were combined, MPOD improvements were maintained, and mfERG ring 2 P1 latency became shorter. On withdrawal of the supplement mfERG ring 1 N1P1 amplitude reduced in HO eyes. When HO and HY groups were combined, mfERG ring 1 and ring 2 N1P1 amplitudes were reduced. In ARM eyes, ring 3 N2 latency and ring 4 P1 latency became longer. These statistically significant changes may not be clinically significant. The finding that a lutein-based supplement increases MPOD in healthy eyes, but does not increase mfERG amplitudes contrasts with the CARMIS study and contributes to the debate on the use of nutritional supplementation in ARM.

The best days of your life? Youth, policy and Blair's New Labour

Since the election of New Labour in 1997, young people's relationship to work and to the labour market has been the subject of intense scrutiny and policy activity. By equipping young workers with the qualifications and skills they are held to need in the knowledge economy, the government hopes to reconcile its quest for economic progress with the commitment to social justice for young people. However, as this article argues, the importance invested in this area of 'youth policy' overlays a more fundamental process of disengagement in which New Labour is presiding over the withdrawal of those traditional sources of support it has held out to the young. For this reason, the article concludes by suggesting that the importance that New Labour attaches to policy for young workers tells us more about the needs of government than it does about the needs of young people.

Sub-types of nonbelieved memories reveal differential outcomes of challenges to memories

Nonbelieved memories (NBMs) highlight the independence between metamemorial judgments that contribute to the experience of remembering. Initial definitions of NBMs portrayed them as involving the withdrawal of autobiographical belief despite sustained recollection. While people rate belief for their NBMs as weaker than recollection, the average difference is too small to support the idea that belief is completely withdrawn in all cases. Furthermore, ratings vary considerably across NBMs. In two studies, we reanalyzed reports from prior studies to examine whether NBM reports reflect a single category or multiple sub-categories using cluster analytic methods. In Study 1, we identified three sub-types of NBMs. In Study 2 we incorporated the concept of belief in accuracy, and found that two of the clusters from Study 1 split into two clusters apiece. Higher ratings of recollection than belief in occurrence characterized all clusters, which were differentiated by the degree of difference between these variables. In both studies the clusters were differentiated by a number of memory characteristic ratings and by reasons reported as leading to the alteration of belief. Implications for understanding the remembering of past events and predicting the creation of NBMs are discussed.

Diabetic patient education and motivation. Available in 2 volumes.

Diabetes mellitus is a condition which requires a high degree of patient cooperation in self-management to achieve optimal glycaemic control. The concept of patient education, to enhance the treatment and management of diabetes, is well recognised. Several diabetes education programmes have already been described, but increased knowledge of diabetes did not necessarily result in improved self-mangement or glycaemic control. Other factors, such as attitudes and motivations, may therefore be particuarly important. The aims of the present study were to investigate the influence of patients' attitudes to diabetes, and to develop motivational aspects which enable the application of knowledge to enhance self-management and compliance with treatment. Thirty-one insulin-dependent diabetic (IDD) patients entered into a 12 month educational programme, particularly designed to increase motivation. Patients' attitudes to diabetes, their knowledge and self-management skills were assessed using questionnaires and practical tests, and parameters of glycaemic control were measured. The progress of these patients was compared at intervals with a close matched group of 25 control IFF patients who continued to receive routine clinic care. Patients completing the educational programme achieved better glycaemic control (p< 0.05), greater knowledge (p< 0.001), more favourable attitudes (p< 0.03) and increased competence in management skills (p< 0.02) compared with the control group. Evaluation procedures indicated that the programme was acceptable to the patients, and was successful in terms of increasing patient motivation. Six months after completion of the programme, glycaemic control deteriorated, although knowledge, attitudes and management skills were unchanged. This might reflect the withdrawal of extrinsic motivation, attention and supervision provided during the programme. It is recommended that consideration be given to the development of patients' intrinsic motivation to achieve maximum benefit from diabetes education programmes.

Drug repurposing screen identifies Foxo1-dependent angiopoietin-2 regulation in sepsis

Objective: The recent withdrawal of a targeted sepsis therapy has diminished pharmaceutical enthusiasm for developing novel drugs for the treatment of sepsis. Angiopoietin-2 is an endothelial-derived protein that potentiates vascular inflammation and leakage and may be involved in sepsis pathogenesis. We screened approved compounds for putative inhibitors of angiopoietin-2 production and investigated underlying molecular mechanisms. Design: Laboratory and animal research plus prospective placebo-controlled randomized controlled trial (NCT00529139) and retrospective analysis (NCT00676897). Setting: Research laboratories of Hannover Medical School and Harvard Medical School. Patients: Septic patients/C57Bl/6 mice and human endothelial cells. Interventions: Food and Drug Administration-approved library screening. Measurements and Main Results: In a cell-based screen of more than 650 Food and Drug Administration-approved compounds, we identified multiple members of the 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor drug class (referred to as statins) that suppressed angiopoietin-2. Simvastatin inhibited 3-hydroxy-3-methyl-glutaryl-CoA reductase, which in turn activated PI3K-kinase. Downstream of this signaling, PI3K-dependent phosphorylation of the transcription factor Foxo1 at key amino acids inhibited its ability to shuttle to the nucleus and bind cis-elements in the angiopoietin-2 promoter. In septic mice, transient inhibition of angiopoietin-2 expression by liposomal siRNA in vivo improved absolute survival by 50%. Simvastatin had a similar effect, but the combination of angiopoietin-2 siRNA and simvastatin showed no additive benefit. To verify the link between statins and angiopoietin-2 in humans, we performed a pilot matched case-control study and a small randomized placebo-controlled trial demonstrating beneficial effects on angiopoietin-2. Conclusions: 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors may operate through a novel Foxo1-angiopoietin-2 mechanism to suppress de novo production of angiopoietin-2 and thereby ameliorate manifestations of sepsis. Given angiopoietin-2's dual role as a biomarker and candidate disease mediator, early serum angiopoietin-2 measurement may serve as a stratification tool for future trials of drugs targeting vascular leakage.

Doing the right thing or doing the thing right:implications of participant withdrawal

This article discusses implications of participant withdrawal for inductive research. I describe and analyze how a third of my participants withdrew from a grounded theory study. I position my example, ensuing issues, and potential solutions as reflective of inductive methodologies as a whole. The crux of the problem is the disruption inflicted by withdrawal on inductive processes of generating knowledge. I examine the subsequent methodological and ethical issues in trying to determine the best course of action following withdrawal. I suggest three potential options for researchers: Continuing the study with partial data, continuing the study with all data, and discontinuing the study. Motivated by my experience, and wider theoretical considerations, I present several suggestions and questions, with the aim of supporting researchers in determining the best course of action for their individual field circumstances.

Leader-member exchange in a Chinese context:antecedents, outcomes and mediating role of psychological empowerment

This study examines organizational antecedents of LMX and the mediating influence of empowerment on the relationships between LMX and the work outcomes of job satisfaction, task performance and psychological withdrawal behavior. Data were obtained from employees of a listed Chinese company in Guangdong Province, People's Republic of China. The results revealed that: (a) supervisor control of rewards and work unit climate were related to LMX and (b) empowerment fully mediated the relationship between LMX and the work outcomes as hypothesized.

International retail restructuring and divestment: the experience of Tesco

A key purpose of this study is to explore the lessons learned from international retail divestment and market withdrawal experiences. Drawing on 33 in-depth interviews with leading investment banks and key retail executives at Tesco, the study investigates the company's international restructuring and divestment activities in Ireland and France during the mid -1980s and 1990s. It has been demonstrated that, despite the progressive merger and acquisition wave sweeping through the corporate retail landscape recently, international retail divestment is quite widespread. The main conclusion from this study is that Tesco originally did not envisage divestment or de-internationalisation as part of the original internationalisation strategy process in either the acquisition of Three Guys in Ireland or Catteau in France. There was no appreciation from Tesco during their early period of expansion of the fact that exit pressures might arise during the course of market entry. In this regard, the case study provides insights into the relationship between investment and divestment within the context of international retail restructuring. The case evidence also demonstrates the positive impact of the Three Guys and Catteau divestments which helped management to refocus and rejuvenate the company's internationalisation process.

Economic aspects of safety in the Greek construction industry

The thesis addresses the economic impacts of construction safety in Greece. The research involved the development of a methodology for determining the overall costs of safety, namely the sum of the costs of accidents and the costs of safety management failures (with or without accident) including image cost. Hitherto, very little work has been published on the cost of accidents in practical case studies. Moreover, to the author’s belief, no research has been published that seeks to determine in real cases the costs of prevention. The methodology developed is new, transparent, and capable of being replicated and adapted to other employment sectors and to other countries. The methodology was applied to three construction projects in Greece to test the safety costing methodology and to offer some preliminary evidence on the business case for safety. The survey work took place between 1999 and 2001 and involved 27 months of costing work on site. The study focuses on the overall costs of safety that apply to the main (principal) contractor. The methodology is supported by 120 discrete cost categories, and systematic criteria for determining which costs are included (counted) in the overall cost of safety. A quality system (in compliance with ISO9000 series) was developed to support the work and ensure accuracy of data gathering. The results of the study offer some support for the business case for safety. Though they offer good support for the economics of safety as they demonstrate need for cost effectiveness. Subject to important caveats, those projects that appeared to manage safety more cost-effectively achieved the lowest overall safety cost. Nevertheless, results are significantly lower than of other published works for two main reasons; first costs due to damages with no potential to injury were not included and second only costs to main constructor were considered. Study’s results are discussed and compared with other publish works.

The design of novel antifolates against pneumocystis carinii

The pneumonia caused by Pneumocystis carinii is ultimately responsible for the death of many acquired immunodeficiency syndrome (AIDS) patients. Large doses of trimethoprim and pyrimethamine in combination with a sulphonamide and/or pentamidine suppress the infection but produce serious side-effects and seldom prevent recurrence after treatment withdrawal. However, the partial success of the aforementioned antifolates, and also trimetrexate used alone, does suggest dihydrofolate reductase (DHFR) as a target for the development of antipneumocystis agents. From the DHFR inhibitory activities of 3'-substituted pyrimethamine analogues it was suggested that the 3'-(3'',3''-dimethyltriazen-1''-yl) substituent may be responsible for the greater activity for the P.carinii over the mammalian enzyme. Crystallographic and molecular modeling studies revealed considerable geometrical and electronic differences between the triazene and the chemically related formamidine functions that may account for the differences in DHFR inhibitory profiles. Structural and electronic parameters calculated for a series of 3'-(3'',3''-disubstitutedtriazen-1''-yl) pyrimethamine analogues did not correlate with the DHFR inhibitory activities. However, the in vitro screening against P.carinii DHFR revealed that the 3''-hydroxyethyl-3''-benzyl analogue was the most active and selective. Models of the active sites of human and P.carinii DHFRs were constructed using DHFR sequence and structural homology data which had identified key residues involved in substrate and cofactor binding. Low energy conformations of the 3'',3''-dimethyl and 3''-hydroxyethyl-3''-benzyle analogues, determined from nuclear magnetic resonance studies and theoretical calculations, were docked by superimposing the diaminopyrimidine fragment onto a previously docked pyrimethamine analogue. Enzyme kinetic data supported the 3''-hydroxyethyl-3''-benzyl moiety being located in the NADPH binding groove. The 3''-benzyl substituent was able to locate to within 3 AA of a valine residue in the active site of P.carinii DHFR thereby producing a hydrophobic contact. The equivalent residue in human DHFR is threonine, more hydrophilic and less likely to be involved in such a contact. This difference may account for the greater inhibitory activity this analogue has for P.carinii DHFR and provide a basis for future drug design. From an in vivo model of PCP in immunosuppressed rats it was established that the 3"-hydroxyethyl-3"-benzyl analogue was able to reduce the.P.carinii burden more effectively with increasing doses, without causmg any visible signs of toxicity. However, equivalent doses were not as effective as pentamidine, a current treatment of choice for Pneumocystis carinii pneumonia.

The effects of a lutein-based supplement on objective and subjective measures of retinal and visual function in eyes with age-related maculopathy - a randomised controlled trial

Lutein and zeaxanthin are lipid-soluble antioxidants found within the macula region of the retina. Links have been suggested between increased levels of these carotenoids and reduced risk for age-related macular disease (ARMD). Therefore, the effect of lutein-based supplementation on retinal and visual function in people with early stages of ARMD (age-related maculopathy, ARM) was assessed using multi-focal electroretinography (mfERG), contrast sensitivity and distance visual acuity. A total of fourteen participants were randomly allocated to either receive a lutein-based oral supplement (treated group) or no supplement (non-treated group). There were eight participants aged between 56 and 81 years (65·50 (sd 9·27) years) in the treated group and six participants aged between 61 and 83 years (69·67 (sd 7·52) years) in the non-treated group. Sample sizes provided 80 % power at the 5 % significance level. Participants attended for three visits (0, 20 and 40 weeks). At 60 weeks, the treated group attended a fourth visit following 20 weeks of supplement withdrawal. No changes were seen between the treated and non-treated groups during supplementation. Although not clinically significant, mfERG ring 3 N2 latency (P= 0·041) and ring 4 P1 latency (P= 0·016) increased, and a trend for reduction of mfERG amplitudes was observed in rings 1, 3 and 4 on supplement withdrawal. The statistically significant increase in mfERG latencies and the trend for reduced mfERG amplitudes on withdrawal are encouraging and may suggest a potentially beneficial effect of lutein-based supplementation in ARM-affected eyes. Copyright © 2012 The Authors.

The mediating role of discrete emotions in the relationship between injustice and counterproductive work behaviors:a study in Pakistan

Purpose: Our study explores the mediating role of discrete emotions in the relationships between employee perceptions of distributive and procedural injustice, regarding an annual salary raise, and counterproductive work behaviors (CWBs). Design/Methodology/Approach: Survey data were provided by 508 individuals from telecom and IT companies in Pakistan. Confirmatory factor analysis, structural equation modeling, and bootstrapping were used to test our hypothesized model. Findings: We found a good fit between the data and our tested model. As predicted, anger (and not sadness) was positively related to aggressive CWBs (abuse against others and production deviance) and fully mediated the relationship between perceived distributive injustice and these CWBs. Against predictions, however, neither sadness nor anger was significantly related to employee withdrawal. Implications: Our findings provide organizations with an insight into the emotional consequences of unfair HR policies, and the potential implications for CWBs. Such knowledge may help employers to develop training and counseling interventions that support the effective management of emotions at work. Our findings are particularly salient for national and multinational organizations in Pakistan. Originality/Value: This is one of the first studies to provide empirical support for the relationships between in/justice, discrete emotions and CWBs in a non-Western (Pakistani) context. Our study also provides new evidence for the differential effects of outward/inward emotions on aggressive/passive CWBs. © 2012 Springer Science+Business Media, LLC.

Family-supportive work environment and employee work behaviors:an investigation of mediating mechanisms

This study examined psychological mechanisms that underpin the relationships between perceived organizational family support (POFS) and a family-supportive supervisor (FSS) on employee work behaviors. Based on data from employed parents and their supervisors (N = 230) in 12 South Korean organizations, structural equation modeling results revealed three salient findings: (1) POFS and FSS are indirectly related to contextual performance through control over work time, (2) FSS is indirectly related to both contextual performance and work withdrawal through organization-based self-esteem (OBSE), and (3) control over work time is indirectly related to the two work outcomes through OBSE. The authors interpret these findings as indicating support for the focus on informal workplace family support and the need for research to examine the psychological resources they engender if we are to understand why these forms of support have their demonstrated outcomes. © The Author(s) 2012.

Redefining neuromarketing as an integrated science of influence

Multiple transformative forces target marketing, many of which derive from new technologies that allow us to sample thinking in real time (i.e., brain imaging), or to look at large aggregations of decisions (i.e., big data). There has been an inclination to refer to the intersection of these technologies with the general topic of marketing as “neuromarketing”. There has not been a serious effort to frame neuromarketing, which is the goal of this paper. Neuromarketing can be compared to neuroeconomics, wherein neuroeconomics is generally focused on how individuals make “choices”, and represent distributions of choices. Neuromarketing, in contrast, focuses on how a distribution of choices can be shifted or “influenced”, which can occur at multiple “scales” of behavior (e.g., individual, group, or market/society). Given influence can affect choice through many cognitive modalities, and not just that of valuation of choice options, a science of influence also implies a need to develop a model of cognitive function integrating attention, memory, and reward/aversion function. The paper concludes with a brief description of three domains of neuromarketing application for studying influence, and their caveats.

Gravimetric and density profiling using the combination of surface acoustic waves and neutron reflectivity

A new approach is described herein, where neutron reflectivity measurements that probe changes in the density profile of thin films as they absorb material from the gas phase have been combined with a Love wave based gravimetric assay that measures the mass of absorbed material. This combination of techniques not only determines the spatial distribution of absorbed molecules, but also reveals the amount of void space within the thin film (a quantity that can be difficult to assess using neutron reflectivity measurements alone). The uptake of organic solvent vapours into spun cast films of polystyrene has been used as a model system with a view to this method having the potential for extension to the study of other systems. These could include, for example, humidity sensors, hydrogel swelling, biomolecule adsorption or transformations of electroactive and chemically reactive thin films. This is the first ever demonstration of combined neutron reflectivity and Love wave-based gravimetry and the experimental caveats, limitations and scope of the method are explored and discussed in detail.