Matrix-free mass spectrometric imaging using laser desorption ionisation Fourier transform ion cyclotron resonance mass spectrometry

Mass spectrometry imaging (MSI) is a powerful tool in metabolomics and proteomics for the spatial localization and identification of pharmaceuticals, metabolites, lipids, peptides and proteins in biological tissues. However, sample preparation remains a crucial variable in obtaining the most accurate distributions. Common washing steps used to remove salts, and solvent-based matrix application, allow analyte spreading to occur. Solvent-free matrix applications can reduce this risk, but increase the possibility of ionisation bias due to matrix adhesion to tissue sections. We report here the use of matrix-free MSI using laser desorption ionisation performed on a 12 T Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. We used unprocessed tissue with no post-processing following thaw-mounting on matrix-assisted laser desorption ionisation (MALDI) indium-tin oxide (ITO) target plates. The identification and distribution of a range of phospholipids in mouse brain and kidney sections are presented and compared with previously published MALDI time-of-flight (TOF) MSI distributions.

A profile of low vision services in England the Low Vision Service Model Evaluation (LOVSME) project

In the UK, low vision rehabilitation is delivered by a wide variety of providers with different strategies being used to integrate services from health, social care and the voluntary sector. In order to capture the current diversity of service provision the Low vision Service Model Evaluation (LOVSME) project aimed to profile selected low vision services using published standards for service delivery as a guide. Seven geographically and organizationally varied low-vision services across England were chosen for their diversity and all agreed to participate. A series of questionnaires and follow-up visits were undertaken to obtain a comprehensive description of each service, including the staff workloads and the cost of providing the service. In this paper the strengths of each model of delivery are discussed, and examples of good practice identified. As a result of the project, an Assessment Framework tool has been developed that aims to help other service providers evaluate different aspects of their own service to identify any gaps in existing service provision, and will act as a benchmark for future service development.

Microarray-formatted clinical biomarker assay development using peptide aptamers to anterior gradient-2

Anterior gradient-2 protein was identified using proteomic technologies as a p53 inhibitor which is overexpressed in human cancers, and this protein presents a novel pro-oncogenic target with which to develop diagnostic assays for biomarker detection in clinical tissue. Combinatorial phage-peptide libraries were used to select 12 amino acid polypeptide aptamers toward anterior gradient-2 to determine whether methods can be developed to affinity purify the protein from clinical biopsies. Selecting phage aptamers through four rounds of screening on recombinant human anterior gradient-2 protein identified two classes of peptide ligand that bind to distinct epitopes on anterior gradient-2 protein in an immunoblot. Synthetic biotinylated peptide aptamers bound in an ELISA format to anterior gradient-2, and substitution mutagenesis further minimized one polypeptide aptamer to a hexapeptide core. Aptamers containing this latter consensus sequence could be used to affinity purify to homogeneity human anterior gradient-2 protein from a single clinical biopsy. The spotting of a panel of peptide aptamers onto a protein microarray matrix could be used to quantify anterior gradient-2 protein from crude clinical biopsy lysates, providing a format for quantitative screening. These data highlight the utility of peptide combinatorial libraries to acquire rapidly a high-affinity ligand that can selectively bind a target protein from a clinical biopsy and provide a technological approach for clinical biomarker assay development in an aptamer microarray format.

Extra compensation for inventive employees:is our system equitable, unbiased and motivating?

There is a presumption that invention is good. It provides us with innovative goods, services and ways of doing things leading to greater employment, wealth and health. This article looks at the two recent UK cases regarding statutory extra compensation that may be awarded to employee inventors under the Patents Act 1977. Most universities worldwide and many companies have individual inventor reward schemes. Researchers now work in teams made up of both industry and academic researchers who are often based in different countries where different legal regimes apply. Is leaving the decision to award employees extra financial compensation up to individual companies unfair, unequal and de-motivating? Is having differing legislative systems in different European countries counter productive and a barrier to economic growth? There must be a balance between the inventor and the innovator. Do we have it right and if not what should it be? Legislation: Patents Act 1977 s.39 , s.40 , s.41 Cases: Kelly v GE Healthcare Ltd [2009] EWHC 181 (Pat); [2009] R.P.C. 12 (Ch D (Patents Ct)) Shanks v Unilever Plc [2010] EWCA Civ 1283; [2011] R.P.C. 12 (CA (Civ Div))

Trade marks, registered designs and the monopolisation of functional shapes:a consideration of Lego and Dyson

Legislation: Regulation 6/2002 on Community designs art.3(3)(e) Directive 98/71 on the legal protection of designs art.7(1) Cases: Dyson Ltd v Vax Ltd [2010] EWHC 1923 (Pat); [2011] Bus. L.R. 232 (Ch D (Patents Ct)) Lego Juris A/S v Office for Harmonisation in the Internal Market (Trade Marks and Designs) (OHIM) (C-48/09 P) Unreported September 14, 2010 (ECJ) *E.I.P.R. 60 In Lego, the Court of Justice of the European Union denied registration for an exclusively functional shape mark despite the availability of other shapes capable of fulfilling the same function and in Dyson v Vax Mr Justice Arnold established that a design can not be registered for a purely functional shape even though another shape could fulfil the same required function.

Divided care and the Third Way:user involvement in statutory and voluntary sector cancer services

In health care, as in much of the public sphere, the voluntary sector is playing an increasingly large role in the funding, provision and delivery of services and nowhere is this more apparent than in cancer care. Simultaneously the growth of privatisation, marketisation and consumerism has engendered a rise in the promotion of 'user involvement' in health care. These changes in the organisation and delivery of health care, in part inspired by the 'Third Way' and the promotion of public and citizen participation, are particularly apparent in the British National Health Service. This paper presents initial findings from a three-year study of user involvement in cancer services. Using both case study and survey data, we explore the variation in the definition, aims, usefulness and mechanisms for involving users in the evaluation and development of cancer services across three Health Authorities in South West England. The findings have important implications for understanding shifts in power, autonomy and responsibility between patients, carers, clinicians and health service managers. The absence of any common definition of user involvement or its purpose underlines the limited trust between the different actors in the system and highlights the potentially negative impact of a Third Way health service.

Discovering biomarkers for antidepressant response:protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort

Background: Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers ("biomarkers") of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. Methods: CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10-20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2-10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. Discussion: From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research. Trial registration: ClinicalTrials.gov identifier NCT01655706. Registered July 27, 2012.

A European competence framework for industrial pharmacy practice in biotechnology

Project Report: The PHAR-IN ("Competences for industrial pharmacy practice in biotechnology") looked at whether there is a difference in how industrial employees and academics rank competences for practice in the biotechnological industry. A small expert panel consisting of the authors of this paper produced a biotechnology competence framework by drawing up an initial list of competences then ranking them in importance using a three-stage Delphi process. The framework was next evaluated and validated by a large expert panel of academics (n = 37) and industrial employees (n = 154). Results show that priorities for industrial employees and academics were similar. The competences for biotechnology practice that received the highest scores were mainly in: . "Research and Development", . "Upstream" and "Downstream" Processing', " . "Product development and formulation", " . "Aseptic processing", ."Analytical methodology", . "Product stability", and . "Regulation". The main area of disagreement was in the category "Ethics and drug safety" where academics ranked competences higher than did industrial employees.

Geotermikus villamosenergia-termelés lehetőségei Magyarországon

A tanulmány célja kettős. Egyrészt bemutatja a geotermikus energia villamosenergia-termelési célú hasznosításának technológiai lehetőségeit, másrészt szakmai becslések alapján elemzi a Magyarország geotermikus potenciálján megvalósítható jellegzetes projekt gazdaságossági mutatóit. A tanulmány első részében bemutatjuk a geotermikus alapfogalmakat és a geotermikus alapú villamosenergia-termelés jelenlegi helyzetét. Ezek után tárgyaljuk a különböző ipari méretekben használt technológiák jellemzőit, illetve a geotermikus erőforrások felhasználási lehetőségeit nagyságrendileg bővítő, de ma még csak kísérleti léptékben alkalmazott EGS technológiát. A tanulmány második felében értékeljük a magyarországi geotermikus potenciált, illetve 4 különböző kapacitás esetén becsüljük egy Magyarországon megvalósítható geotermikus erőmű gazdaságossági paramétereit. Érzékenységvizsgálatoknak vetjük alá a kapott eredményeket a nagyobb megbízhatóság érdekében.

Gázforrás- és kitermelési szerződés árverési programok hatása a gázpiacok fejlődésére Magyarországon

A Versenykultúra Központ támogatásával 2007-ben elkészítettük az európai gas release programok áttekintését. A mostani tanulmány a magyar gas és contract release programok tapasztalatait tekinti át. Mindkét program az E.ON-Mol felvásárlás jóváhagyásának Európai Bizottság által támasztott feltétele volt, és a végrehajtásuk az idén a harmadik évbe lépett. Tanulmányunkban a hazai program elemzésénél a szokásos piacelemzés részt kiegészítettük egy átfogó interjúsorozattal, melynek során a kiíróval, a szabályozó hatósággal, az EU megbízottjával és a piaci szereplőkkel is beszéltünk.

Hajózni muszáj! - A GDP, az ökológiai lábnyom és a szubjektív jóllét stratégiai összefüggései ("Navigare necesse est." The connections between GDP, ecological footprint, and subjective welfare)

A tanulmányban országok környezetterhelését és jóllétét vizsgáljuk. A környezetterhelést vizsgáló klasszikus I = PAT azonosság célszerű átrendezésével és továbbgondolásával két térképet szerkesztünk, amelyek egy véges, korlátozott erőforrású világban segítik a stratégiai döntéshozatalt. A térképek adatait a bruttó hazai termék, az ökológiai lábnyom, illetve a szubjektív jóllét mutatói szolgáltatják, ezek az információk a világ országaira ma már széles körben rendelkezésre állnak. Bemutatjuk a gazdasági tevékenység és a szubjektív jóllét kapcsolatát, s az erre épülő 12 stratégiát, majd a szűkös természeti erőforrásokkal számot vető újabb 12 stratégialehetőséget tárgyaljuk. A gazdasági tevékenységet, a környezeti korlátokat és az emberi boldogságot egyszerre szem előtt tartó modell alapján nyilvánvaló a makroszintű következtetés: napjainkban a gazdasági tevékenység, illetve az emberi jóllét dematerializációja szükséges és kívánatos célkitűzés /===/ The study examines countries' ecological footprint and welfare. Rearranging and developing the classic I = PAT equation, the author has devised two maps to assist strategic decision-making in a world of finite, limited resources. The data on the maps – GDP, ecological footprint, and subjective welfare indices – are all widely available all over the world. The relation between economic activity and subjective welfare is presented and twelve strategies built upon them, before discussing twelve further strategies based on scarce natural resources. Using a model that considers economic activity, environmental constraints and human happiness concurrently, it becomes obvious that dematerialization of economic activity and human welfare are a necessary and desirable objective.

The Engaged University: Providing a Platform for Research That Transforms Society

Despite a growing recognition that the solutions to current environmental problems will be developed through collaborations between scientists and stakeholders, substantial challenges stifle such cooperation and slow the transfer of knowledge. Challenges occur at several levels, including individual, disciplinary, and institutional. All of these have implications for scholars working at academic and research institutions. Fortunately, creative ideas and tested models exist that provide opportunities for conversation and serious consideration about how such institutions can facilitate the dialogue between scientists and society

Avaliação da efetividade do Programa de Alimentação do Trabalhador

This study analyzed the Worker’s Healthy Eating Program in Rio Grande do Norte state (RN) to assess its possible impact on the nutritional status of the workers benefitted. To that end, we conducted a cross-sectional observational prospective study based on a multistage stratified random sample comparing 26 small and medium-sized companies from the Manufacturing Sector (textiles, food and beverages, and nonmetallic minerals) of RN, divided into two equal groups (WFP and Non WFP). Interviews were conducted at each company by trained interviewers from Tuesday to Saturday between September and December 2014. Data were collected on the company (characterization and information regarding the program’s desired results) and workers (personal and professional information, anthropometrics, health, lifestyle and food consumed the previous day). Population estimates were calculated for RN on the characteristics of workers and the study variables. The main variable was BMI. The secondary variables were waist circumference (WC), nutritional diagnosis, calorie intake, blood pressure, metabolic variables and lifestyle indicators. The statistical method used was hierarchical mixed effects linear regression for interval variables and hierarchical mixed effects logistic regression for binary variables. The variables measured in ordinal scales were analyzed by ordinal logistic regression adjusted for correlated variables, adopting robust standard errors. The results for interval variables are presented as point estimates and their 95% confidence intervals; and as odds-ratios and their 95% confidence intervals for binary variables. The Fisher’s exact and Student’s t-tests were used for simple comparisons between proportions and means, respectively. Differences were considered statistically significant at p<0.05. A total of 1069 workers were interviewed, of which 541 were from the WFP group and 528 from the Non WFP group. Subjects were predominantly males and average age was 34.5 years. Significant intergroup differences were observed for schooling level, income above 1 MW (minimum wage) and specific training for their position at the company. The results indicated a significant difference between the BMI of workers benefitted, which was on average 0.989 kg/m2 higher than the BMI of workers from the Non WFP group (p=0.002); and between the WC, with the waist circumference of WFP group workers an average of 1.528 cm larger (p<0.05). Higher prevalence of overweight and obesity (p<0.001) and cardiovascular risk (p=0.038) were recorded in the WFP group. Tests on the possible effect of the WFP on health (blood pressure and metabolic indicators) and lifestyle indicators (smoking, alcohol consumption and exercise) were not significant. With respect to worker’s diets, differences were significant for consumption of saturated fat (lunch and daily intake), salt (lunch, other meals and daily intake) and proteins (other meals and daily intake), with higher consumption of these nutrients in the WFP group. The study showed a possible positive impact of the WFP on nutritional status (BMI and WC) among the workers benefitted. No possible effects of the program were observed for the lifestyle indicators studied. Workers benefitted consumed less salt, saturated fat and protein. The relevance of the WFP is recognized for this portion of society and it is understood that, if the program can reach and impact those involved, the development of educational initiatives aimed at nutritional and food safety may also exert a positive influence.

Should weight loss and maintenance programmes be designed differently for men? : A systematic review of long-term randomised controlled trials presenting data for men and women: The ROMEO project

Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved. Acknowledgements This review is one of a series of systematic reviews for the ROMEO project (Review Of MEn and Obesity), funded by the National Institute for Health Research, Health Technology Assessment Programme (NIHR HTA Project 09/127/01; Systematic reviews and integrated report on the quantitative and qualitative evidence base for the management of obesity in men http://www.hta.ac.uk/2545). The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Department of Health. HERU, HSRU and NMAHP are funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. The authors accept full responsibility for this publication. We would also like to thank the Men's Health Forums of Scotland, Ireland, England and Wales: Tim Street, Paula Carroll, Colin Fowler and David Wilkins. We also thank Kate Jolly for further information about the Lighten Up trial.