Quantitative multiparameter assays to measure the effect of adjuvants on human antigen-specific CD8 T-cell responses.

Large numbers and functionally competent T cells are required to protect from diseases for which antibody-based vaccines have consistently failed (1), which is the case for many chronic viral infections and solid tumors. Therefore, therapeutic vaccines aim at the induction of strong antigen-specific T-cell responses. Novel adjuvants have considerably improved the capacity of synthetic vaccines to activate T cells, but more research is necessary to identify optimal compositions of potent vaccine formulations. Consequently, there is a great need to develop accurate methods for the efficient identification of antigen-specific T cells and the assessment of their functional characteristics directly ex vivo. In this regard, hundreds of clinical vaccination trials have been implemented during the last 15 years, and monitoring techniques become more and more standardized.

Can resistance to trastuzumab be reversed by endocrine therapy? Combination of trastuzumab and letrozole after resistance to sequential trastuzumab and aromatase inhibitor monotherapies in patients with ER-positive, HER-2 positive, advanced breast cancer: a proof-of-concept trial (SAKK 23/03)

Introduction: Trastuzumab (T) is a cornerstone in the treatment of patients with HER2-overexpressing advanced breast cancer and development of resistance to T is a major therapeutic problem. HER-2 is part of a highly interactive signaling network that may impair efficacy of endocrine therapy. A sequential treatment design was chosen in this trial to ensure complete resistance to single agent therapy before receiving both a non-steroidal aromatase inhibitor (AI) and T. Any kind of clinical activity with combined treatment of AI and T after progression of single agent treatments could indicate restoration of sensitivity as a consequence of cross-talking and networking between both pathways. Methods: Key eligibility criteria included postmenopausal patients (pts.) with advanced, measurable, HER-2 positive (assessed by FISH, ratio (≥2)), HR positive disease and progression on prior treatment with a non-steroidal AI, e.g. letrozole or anastrozole, either in an adjuvant or advanced setting. Pts. received standard dose T monotherapy either weekly or three-weekly in step 1 and upon disease progression, continued T in combination with letrozole in step 2. The primary endpoint was clinical benefit response (CBR: CR, PR or SD for at least 24 weeks (+/- 1 week) according to RECIST) in step 2. Results: Thirteen pts. were enrolled in five centers in Switzerland. In step 1, six pts. (46%) achieved CBR. Median time to progression (TTP) was 161 days (Range: 50 - 627). Based on data collected until the end of May 2010, CBR was observed in seven out of the eleven evaluable pts. (64%) in step 2, including one pt. with partial response. Four of the seven pts. within step 2 that achieved CBR also had CBR in step 1. Seven out of eleven pts. have documented tumor progression during step 2 treatment. Median TTP for all eleven pts. was 184 days (range 61 - 471). Mean time on study treatment (TTP in step 1 plus TTP in step 2) for pts. reaching step 2 was 380 days (range 174 - 864). Adverse events were generally mild. Conclusion: Results of this proof-of-principle trial suggest that complete resistance to both AI and T can be overcome in a proportion of pts. by combined treatment of AI and T, as all pts. served as their own control. Our results appear promising for a new treatment strategy which offers a chemotherapy-free and well-tolerated option for at least a subset of the pts. with HR positive, HER-2 positive breast cancer. Further trials will need to corroborate this finding.

Rifaximin treatment for the irritable bowel syndrome with a positive lactulose hydrogen breath test improves symptoms for at least 3 months.

BACKGROUND: While rifaximin was able to improve symptoms in patients with irritable bowel syndrome (IBS) in phase III trials, these results are yet to be repeated in phase IV studies. AIM: To evaluate the treatment response to rifaximin in IBS patients in a phase IV trial. METHODS: IBS patients underwent lactulose hydrogen breath testing (LHBT). LHBT-positive patients were treated with rifaximin for 14 days. Prior to treatment as well as at week 4 and 14 following the start of rifaximin treatment, patients completed a questionnaire assessing symptom severity on a Likert scale from 0 to 10. RESULTS: One hundred and six of 150 IBS patients (71%) were LHBT-positive and treated with rifaximin. As assessed at week 4 following commencement of the therapy, rifaximin provided significant improvement of the following IBS-associated symptoms: bloating (5.5±2.6 before the start of the treatment vs. 3.6±2.7 at week 4, P<0.001), flatulence (5.0±2.7 vs. 4.0±2.7, P=0.015), diarrhoea (2.9±2.4 vs. 2.0±2.4, P=0.005) and abdominal pain (4.8±2.7 vs. 3.3±2.5, P<0.001). Overall well-being also significantly improved (3.9 ± 2.4 vs. 2.7 ± 2.3, P < 0.001). Similar improvements in IBS symptoms were obtained at week 14. Eighty-six per cent of patients undergoing repetitive LHBT (55/64) tested negative at week 4. CONCLUSIONS: We found a high percentage of LHBT-positive IBS patients. IBS-associated symptoms (bloating, flatulence, diarrhoea, pain) were improved for a period of 3 months following 2 weeks of treatment with rifaximin. We conclude that rifaximin treatment alleviates symptoms in LHBT-positive IBS patients.

Predicting prognosis using molecular profiling in estrogen receptor-positive breast cancer treated with tamoxifen.

Background: Estrogen receptor positive (ER+) breast cancers (BC) are heterogeneous with regard to their clinical behavior and response to therapies. The ER is currently the best predictor of response to the anti-estrogen agent tamoxifen, yet up to 30-40% of ER+ BC will relapse despite tamoxifen treatment. New prognostic biomarkers and further biological understanding of tamoxifen resistance are required. We used gene expression profiling to develop an outcome-based predictor using a training set of 255 ER+ BC samples from women treated with adjuvant tamoxifen monotherapy. We used clusters of highly correlated genes to develop our predictor to facilitate both signature stability and biological interpretation. Independent validation was performed using 362 tamoxifen-treated ER+ BC samples obtained from multiple institutions and treated with tamoxifen only in the adjuvant and metastatic settings.Results: We developed a gene classifier consisting of 181 genes belonging to 13 biological clusters. In the independent set of adjuvantly-treated samples, it was able to define two distinct prognostic groups (HR 2.01 95% CI: 1.29-3.13; p = 0.002). Six of the 13 gene clusters represented pathways involved in cell cycle and proliferation. In 112 metastatic breast cancer patients treated with tamoxifen, one of the classifier components suggesting a cellular inflammatory mechanism was significantly predictive of response.Conclusion: We have developed a gene classifier that can predict clinical outcome in tamoxifen-treated ER+ BC patients. Whilst our study emphasizes the important role of proliferation genes in prognosis, our approach proposes other genes and pathways that may elucidate further mechanisms that influence clinical outcome and prediction of response to tamoxifen.

The potential of metastatic lymph nodes to predict positive resection margins in patients with resectable pancreatic cancer

Objective: Despite progress during recent decades, long-term outcome¦of patients with pancreatic cancer remains dismal. Since positive resection¦margins and metastatic lymph nodes are known risk factors for early tumor¦recurrence, patients at risk should be identified and could potentially benefit¦from preoperative radio-chemotherapy. This study aimed to assess whether the¦presence of lymph node metastasis could be used to predict positive resection¦margins in patients with pancreatic cancer.¦Methods: A series of 146 patients (82 male, 64 female, median age 68 years)¦underwent pancreatic head resection for various malignant diseases (pancreatic¦ductal adenocarcinoma, biliary cancer, periampullary cancer) at our institution¦from 2000 to 2011. Patients were identified from our prospective database¦that collects more than 60 single items of all patients undergoing pancreatic¦resection. Lymph node metastasis and positive resection margins were all¦confirmed by histological evaluation. Positive predictive value (PPV), negative¦predictive value (NPV), sensitivity and specificity were calculated to assess¦the predictive value of metastatic lymph nodes regarding tumor-free (R0) and¦tumor-involved (R1) resection margins.¦Results: There were 110 specimens (76%) with tumor-positive lymph nodes¦and 36 specimens with tumor-negative lymph nodes. Resection margins were¦positive in 47 specimens (32%) and negative in 99 specimens. Sensitivity of¦tumor-positive lymph nodes to detect positive resection margins was 96%, and¦the NPV was 94%. In contrast, specificity was 34% and the PPV was 41%.¦Conclusion: Patients with resectable pancreatic cancer, who have no lymph¦node metastasis, are at very low risk to have positive resection margins (2 of¦36 patients, NPV 94%). In contrast, more than one third of patients with¦metastatic lymph nodes are at increased risk for an incomplete tumor resection¦(sensitivity 96%). If lymph nodesmetastases are highly suspected at preoperative¦staging, a neoadjuvant treatment strategy should be considered to increase the¦R0 resection rate.

Transnational private authority and the participation of workers' organizations in the regulatory space surrounding the employment relationship

Most corporate codes of conduct and multi-stakeholder sustainability standards guarantee workers' rights to freedom of association and collective bargaining, but many authors are sceptical about the concrete impact of codes and standards of this kind. In this paper we use Hancher and Moran's (1998) concept of 'regulatory space' to assess the potential of private transnational regulation to support the growth of trade union membership and collective bargaining relationships, drawing on some preliminary case study results from a project on the impact of the International Finance Corporation's (IFC) social conditionality on worker organization and social dialogue. One of the major effects of neoliberal economic and industrial policy has been the routine exclusion of workers' organizations from regulatory processes on the grounds that they introduce inappropriate 'political' motives into what ought to be technical decision-making processes. This, rather than any direct attack on their capacity to take action, is what seems best to explain the global decline in union influence (Cradden 2004; Howell 2007; Howe 2012). The evidence we present in the paper suggests that private labour regulation may under certain conditions contribute to a reversal of this tendency, re-establishing the legitimacy of workers' organizations within regulatory processes and by extension the legitimacy of their use of economic and social power. We argue that guarantees of freedom of association and bargaining rights within private regulation schemes are effective to the extent that they can be used by workers' organizations in support of a claim for access to the regulatory space within which the terms and conditions of the employment relationship are determined. Our case study evidence shows that certain trade unions in East Africa have indeed been able to use IFC and other private regulation schemes as levers to win recognition from employers and to establish collective bargaining relationships. Although they did not attempt to use formal procedures to make a claim for the enforcement of freedom of association rights on behalf of their members, the unions did use enterprises' adherence to private regulation schemes as a normative point of reference in argument and political exchange about worker representation. For these unions, the regulation was a useful addition to the range of arguments that they could deploy as means to justify their demand for recognition by employers. By contrast, the private regulation that helps workers' organizations to win access to regulatory processes does little to ensure that they are able to participate meaningfully, whether in terms of technical capacity or of their ability to mobilize social power as a counterweight to the economic power of employers. To the extent that our East African unions were able to make an impact on terms and conditions of employment via their participation in regulatory space it was solely on the basis of their own capacities and resources and the application of national labour law.

Continuous positive airway pressure causes lung injury in a model of sepsis.

Continuous positive airway pressure, aimed at preventing pulmonary atelectasis, has been used for decades to reduce lung injury in critically ill patients. In neonatal practice, it is increasingly used worldwide as a primary form of respiratory support due to its low cost and because it reduces the need for endotracheal intubation and conventional mechanical ventilation. We studied the anesthetized in vivo rat and determined the optimal circuit design for delivery of continuous positive airway pressure. We investigated the effects of continuous positive airway pressure following lipopolysaccharide administration in the anesthetized rat. Whereas neither continuous positive airway pressure nor lipopolysaccharide alone caused lung injury, continuous positive airway pressure applied following intravenous lipopolysaccharide resulted in increased microvascular permeability, elevated cytokine protein and mRNA production, and impaired static compliance. A dose-response relationship was demonstrated whereby higher levels of continuous positive airway pressure (up to 6 cmH(2)O) caused greater lung injury. Lung injury was attenuated by pretreatment with dexamethasone. These data demonstrate that despite optimal circuit design, continuous positive airway pressure causes significant lung injury (proportional to the airway pressure) in the setting of circulating lipopolysaccharide. Although we would currently avoid direct extrapolation of these findings to clinical practice, we believe that in the context of increasing clinical use, these data are grounds for concern and warrant further investigation.

Differentiation of blue ballpoint pen inks by positive and negative mode LDI-MS

Usually, the differentiation of inks on questioned documents is carried out by optical methods and thin layer chromatography (TLC). Therefore, spectrometric methods were also proposed in forensic literature for the analysis of dyes. Between these techniques, laser desorption/ionization mass spectrometry (LDI-MS) has demonstrated a great versatility thanks to its sensitivity to blue ballpoint ink dyes and minimal sample destruction. Previous researches concentrated mostly on the LDI-MS positive mode and have shown that this analytical tool offers higher discrimination power than high performance TLC (HPTLC) for the differentiation of blue ballpoint inks. Although LDI-MS negative mode has already been applied in numerous forensic domains like the studies of works of art, automotive paints or rollerball pens, its potential for the discrimination of ballpoint pens was never studied before. The aim of the present paper is therefore to evaluate its potential for the discrimination of blue ballpoint inks. After optimization of the method, ink entries from 33 blue ballpoint pens were analyzed directly on paper in both positive and negative modes by LDI-MS. Several cationic and anionic ink components were identified in inks; therefore, pens were classified and compared according to their formulations. Results show that additional information provided by anionic dyes and pigments significantly increases the discrimination power of positive mode. In fact, it was demonstrated that classifications obtained by the two modes were, to some extent, complementary (i.e., inks with specific cationic dyes not necessarily contained the same anionic components).

Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons.

BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection. METHODS: In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort. RESULTS: A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9 × 10(-4)). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05-2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06-1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16-1.96), diabetes (OR = 1.66; 95% CI, 1.10-2.49), ≥ 1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06-1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17-2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD. CONCLUSIONS: In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD.

Suorituskyvyn menestyksellinen ohjaaminen organisaatiossa

Henkilöstö on yrityksen yksi tärkeimmistä menestystekijöistä ja siksi on tärkeää, että työntekijät ovat sitoutuneita, motivoituneita ja toimivat tehokkaasti. Työn tavoitteena on kehittää organisaatioiden käyttöön suorituskyvyn menestyksellisen ohjaamisen työkalu, jolla voidaan mitata työmotivaation ja toiminnan tehokkuuden taustalla olevia tekijöitä. Kirjallisuudesta, aiemmista tutkimuksista ja haastatteluista selvisi viisi osa-aluetta, jotka vaikuttavat positiivisesti henkilöstön toiminnan tehokkuuteen, työmotivaation ja sitoutumiseen. Osa-alueet ovat tavoitteiden asettaminen, viestintä, henkilöstön vaikutusmahdollisuudet, palkitseminen ja motivointi sekä koulutukseen ja työympäristöön liittyvät tekijät. Jokaisen osa-alueen alle on kerätty kysymyksiä, jotka ovat jaettu kahteen osaan: avainkysymykset ja omavalinnaiset kysymykset. Avainkysymykset ovat sellaisia, joita suositellaan otettavaksi mukaan mittaukseen ja omavalinnaisten kysymysten valinta jää organisaation itsensä päätettäväksi. Näin saadaan organisaatioille mahdollisuus räätälöidä työkalu tarpeisiinsa ja strategiaan sopiviksi. Tutkimukseen empiirinen aineisto kerättiin haastattelemalla. Osallistuneista organisaatioista kaksi oli julkiselta sektorilta ja kuusi yksityiseltä sektorilta. Yksityisen sektorin yritykset koostuvat pienistä, keskisuurista ja suurista yrityksistä. Haastatteluilla kerättiin tietoa työkalun toteutusta ja sisältöä varten. SUMO-kartoituksesta saatuja mittaustuloksia organisaatio voi hyödyntää monella eri tavalla. Esimerkiksi organisaatio voi nähdä osa-alueiden ja toiminnan tehokkuuden kehitystarpeita sekä kuinka henkilöstön toimintaa voidaan tehostaa. Suorituskyvyn mittausjärjestelmän käytöllä on myös positiivisia vaikutuksia mittausosa-alueisiin.

Introducing Basic Systematic Requirements Engineering Practices in Small Organizations with an Easy to Adopt Method

Requirements-relatedissues have been found the third most important risk factor in software projects and as the biggest reason for software project failures. This is not a surprise since; requirements engineering (RE) practices have been reported deficient inmore than 75% of all; enterprises. A problem analysis on small and low maturitysoftware organizations revealed two; central reasons for not starting process improvement efforts: lack of resources and uncertainty; about process improvementeffort paybacks.; In the constructive part of the study a basic RE method, BaRE, was developed to provide an; easy to adopt way to introduce basic systematic RE practices in small and low maturity; organizations. Based on diffusion of innovations literature, thirteen desirable characteristics; were identified for the solution and the method was implemented in five key components:; requirements document template, requirements development practices, requirements; management practices, tool support for requirements management, and training.; The empirical evaluation of the BaRE method was conducted in three industrial case studies. In; this evaluation, two companies established a completely new RE infrastructure following the; suggested practices while the third company conducted continued requirements document; template development based on the provided template and used it extensively in practice. The; real benefits of the adoption of the method were visible in the companies in four to six months; from the start of the evaluation project, and the two small companies in the project completed; their improvement efforts with an input equal to about one person month. The collected dataon; the case studies indicates that the companies implemented new practices with little adaptations; and little effort. Thus it can be concluded that the constructed BaRE method is indeed easy to; adopt and it can help introduce basic systematic RE practices in small organizations.

Laadun kehittäminen suomalaisissa yrityksissä

Laadun ja sen kehittämisen sisältö on ollut jatkuvassa muutostilassa. Laatuajattelu on laajentunut käsittämään yhä suuremman osan organisaatioiden toiminnasta. Laadun kehittämisessä on jatkuvasti otettu käyttöön uusi kehittämiskeinoja. Laaja-alaisesti organisaation toimintaan kytkeytyvistä keinoista tunnetuimpia ovat erilaiset laadunhallintajärjestelmät ja itsearviointi eri kriteeristöjen avulla. Tämän tutkimuksen tavoitteina olivat: a) etsiä motiiveja, minkä vuoksi yritykset ovat alkaneet kehittää laatuaan, b) tutkia total quality management (TQM) -ajattelun soveltamisen syvällisyyden vaikutuksia, c) selvittää laadunkehittämistyön ajallisen keston vaikutuksia, ja d) saada kokonaiskuva keskeisimpien laadun kehittämiskeinojen toteutuksesta ja menestyksellisyydestä. Työn teoriaosassa paneuduttiin laatu-käsitteeseen yritystoiminnassa, laatu- ja TQM-ajattelun sisältöön sekä laadun kehittämisen johtamiseen. Lisäksi tutkittiin keskeisimpiä laadun kehittämisen keinoja, joita olivat mm. ihmisten toiminta, laadunhallintajärjestelmät, itsearvioinnit, toimintaprosessien kehittäminen, asiakas- ja toimittajayhteistyö. Tutkimuksen empiirisessä osassa tutkittiinem. laadun kehittämiseen liittyviä asioita suomalaisissa yrityksissä. Aineisto kerättiin haastattelemalla yritysten laadun kehittämisestä vastaavia henkilöitä 24 yrityksessä. Tulosten esittämisessä hyödynnettiin tilastollisia tutkimusmenetelmiä kvalitatiivisten menetelmien ohella. Tässä aineistossa asiakasvaatimukset ja oma kehityshalu nousivat yleisimmiksi tärkeimmistä laadun kehittämisen aloitusmotiiveista. Mikään tärkeimmistä aloitusmotiiveista ei ollutkuitenkaan johtanut selkeästi ylivoimaisimpaan menestymiseen myöhemmin. TQM-ajattelun laaja-alainen soveltaminen johti laadun kehittämisen kannalta positiiviseen suuntaan. Pisimpään laatuaan kehittäneet yritykset olivat suuria ja kansainvälisesti suuntautuneita. Pelkkä kehitystyön ajallinen kesto näkyi vain vähän kehittämisen eri osa-alueilla. Laadun kehittämistyön menetyksellisyyden kannalta positiivia asioita olivat: henkilöstön aktiivisuus, itsearviointien hyödyntäminen, toimintaprosessien kuvaaminen ja kehittäminen, sekä asiakas- ja toimittajayhteistyö. Laadun kehittämiseen kannattaa ottaa aktiivisesti mukaankoko organisaation henkilöstö. Itsearviointien käytöllä on mahdollista kehittääorganisaatiota laaja-alaisesti. Niin asiakkaat kuin toimittajat kannattaa ottaaaktiivisesti mukaan kehittämistoimintaan. Se on kaikkien osapuolien yhteinen etu.

Value Processingin Organizations - Individual Perceptions in Three Case Companies

Values and value processes are said to be needed in every organization nowadays, as the world is changing and companies have to have something to "keep it together". Organizational values, which are approvedand used by the personnel, could be the key. Every organization has values. But what is the real value of values? The greatest and most crucial challenge is the feasibility of the value process. The main point in this thesis is tostudy how organizational members at different hierarchical levels perceive values and value processes in their organizations. This includes themes such as how values are disseminated, the targets of value processing, factors that affect the process, problems that occur during the value implementation and improvements that could be made when organizational values are implemented. These subjects are studied from the perspective of organizational members (both managers and employees); individuals in the organizations. The aim is to get the insider-perspective on value processing, from multiple hierarchical levels. In this research I study three different organizations (forest industry, bank and retail cooperative) and their value processes. The data is gathered from companies interviewing personnel in the head office and at the local level. The individuals areseen as members of organizations, and the cultural aspect is topical throughout the whole study. Values and cultures are seen as the 'actuality of reality' of organizations, interpreted by organizational members. The three case companies were chosen because they represented different lines of business and they all implemented value processing differently. Sincethe emphasis in this study is at the local level, the similar size of the local units was also an important factor. Values are in 'fashion' -but what does the fashion tell us about the real corporate practices? In annual reports companies emphasize the importance and power of official values. But what is the real 'point' of values? Values are publicly respected and advertised, but still it seems that the words do not meet the deeds. There is a clear conflict between theoretical, official and substantive organizational values: in the value processing from words to real action. This contradiction in value processing is studied through individual perceptions in this study. I study the kinds of perceptions organizationalmembers have when values are processed from the head office to the local level: the official value process is studied from the individual's perspective. Value management has been studied more during the 1990's. The emphasis has usually been on managers: how they consider the values in organizations and what effects it has on the management. Recent literature has emphasized values as tools for improving company performance. The value implementation as a process has been studied through 'good' and 'bad' examples, as if one successful value process could be copied to all organizations. Each company is different with different cultures and personnel, so no all-powerful way of processing values exists. In this study, the organizational members' perceptions at different hierarchical levels are emphasized. Still, managers are also interviewed; this is done since managerial roles in value dissemination are crucial. Organizational values cannot be well disseminated without management; this has been proved in several earlier studies (e.g. Kunda 1992, Martin 1992, Parker 2000). Recent literature has not sufficiently emphasized the individual's (organizational member's) role in value processing. Organizations consist of differentindividuals with personal values, at all hierarchical levels. The aim in this study is to let the individual take the floor. Very often the value process is described starting from the value definition and ending at dissemination, and the real results are left without attention. I wish to contribute to this area. Values are published officially in annual reports etc. as a 'goal' just like profits. Still, the results/implementationof value processing is rarely followed, at least in official reports. This is a very interesting point: why do companies espouse values, if there is no real control or feedback after the processing? In this study, the personnel in three different companies is asked to give an answer. In the empirical findings, there are several results which bring new aspects to the research area of organizational values. The targets of value processing, factors effecting value processing, the management's roles and the problems in value implementation are presented through the individual's perspective. The individual's perceptions in value processing are a recurring theme throughout the whole study. A comparison between the three companies with diverse value processes makes the research complete