Time and Location as Customer Perceived Value Drivers

Since the emergence of service marketing, the focus of service research has evolved. Currently the focus of research is shifting towards value co-created by the customer. Consequently, value creation is increasingly less fixed to a specific time or location controlled by the service provider. However, present service management models, although acknowledging customer participation and accessibility, have not considered the role of the empowered customer who may perform the service at various locations and time frames. The present study expands this scope and provides a framework for exploring customer perceived value from a temporal and spatial perspective. The framework is used to understand and analyse customer perceived value and to explore customer value profiles. It is proposed that customer perceived value can be conceptualised as a function of technical, functional, temporal and spatial value dimensions. These dimensions are suggested to have value-increasing and value-decreasing facets. This conceptualisation is empirically explored in an online banking context and it is shown that time and location are more important value dimensions relative to the technical and functional dimensions. The findings demonstrate that time and location are important not only in terms of having the possibility to choose when and where the service is performed. Customers also value an efficient and optimised use of time and a private and customised service location. The study demonstrates that time and location are not external elements that form the service context, but service value dimensions, in addition to the technical and functional dimensions. This thesis contributes to existing service management research through its framework for understanding temporal and spatial dimensions of perceived value. Practical implications of the study are that time and location need to be considered as service design elements in order to differentiate the service from other services and create additional value for customers. Also, because of increased customer control and the importance of time and location, it is increasingly relevant for service providers to provide a facilitating arena for customers to create value, rather than trying to control the value creation process. Kristina Heinonen is associated with CERS, the Center for Relationship Marketing and Service Management at the Swedish School of Economics and Business Administration

Understanding Customer Loyalty and Disloyalty The Effect of Loyalty-Supporting and -Repressing Factors (first edition sold out, 'print on demand' 60 €)

Customer loyalty has been a central topic of both marketing theory and practice for several decades. Customer disloyalty, or relationship ending, has received much less attention. Despite the close relation between customer loyalty and disloyalty, they have rarely been addressed in the same study. The thesis bridges this gap by focusing on both loyal and disloyal customers and the factors characterising them. Based on a qualitative study of loyal and disloyal bank customers in the Finnish retail banking market, both factors that are common to the groups and factors that differentiate between them are identified. A conceptual framework of factors that affect customer loyalty or disloyalty is developed and used to analyse the empirical data. According to the framework, customers’ loyalty status (behavioural and attitudinal loyalty) is influenced by positive, loyalty-supporting, and negative, loyalty-repressing factors. Loyalty-supporting factors either promote customer dedication, making the customer want to remain loyal, or act as constraints, hindering the customer from switching. Among the loyalty-repressing factors it is especially important to identify those that act as triggers of disloyal behaviour, making customers switch service providers. The framework further suggests that by identifying the sources of loyalty-supporting and -repressing factors (the environment, the provider, the customer, the provider-customer interaction, or the core service) one can determine which factors are within the control of the service provider. Attitudinal loyalty is approached through a customer’s “feeling of loyalty”, as described by customers both orally and graphically. By combining the graphs with behavioural loyalty, seven customer groups are identified: Stable Loyals, Rescued Loyals, Loyals at Risk, Positive Disloyals, Healing Disloyals, Fading Disloyals, and Abrupt Disloyals. The framework and models of the thesis can be used to analyse factors that affect customer loyalty and disloyalty in different service contexts. Since the empirical study was carried out in a retail bank setting, the thesis has managerial relevance especially for banks. Christina Nordman is associated with CERS, Center for Relationship Marketing and Service Management at the Swedish School of Economics and Business Administration. The doctoral thesis is part of the Göran Collert Research Project in Customer Relationships and Retail Banking and has been funded by The Göran Collert Foundation.

What is A Virtual Service?- Broadening the Perspective on Technology-Based Services

This article expands the discussion of the impact of technology on services and contributes to a broader comprehension of the nature of virtual services. This is done by discovering dimensions that distinguish physical services from virtual services, i.e. services that are distributed by electronic means and where the customer has no direct human interaction with the service provider. Differences in the core characteristics of services, servicescape and service delivery are discussed. Moreover, dimensions that differentiate between virtual services are analysed. A classification scheme for virtual services is proposed, including the origin of the service, the element of the service offering, the customisation process, stage of the service process performed, and the degree of mobility of the service.

T-type calcium channel:from physiological function to therapeutical targeting – Exploring neuronal development

Tämän tutkimuksen tarkoitus oli tutkia T-tyypin kalsiumkanavan toimintaa ja sen mahdollista roolia neuronaalisten kantasolujen migraatiossa. T-tyypin kalsiumkanavan tehtävän kehittyneissä aivoissa tiedetään olevan elektroenkefalografisten oskillaatioiden tuottaminen. Nämä taas ovat eräiden fysiologisten ja patofysiologisten tapahtumien säätelyssä avainasemassa. Tällaisia tapahtumia ovat uni, muisti, oppiminen ja epileptiset poissaolokohtaukset. Näiden lisäksi T-tyypin kalsiumkanavalla on myös periferaalisia vaikutuksia, mutta tämä tutkielma keskittyy sen neuronaalisiin toimintoihin. Tämän matalan jännitteen säätelemän kanavan toiminta neurogeneesin aikana on vähemmän tutkittua ja tunnettua kuin sen vaikutukset kehittyneissä aivoissa. T-tyypin kalsiumkanavan tiedetään edistävän kantasolujen proliferaatiota ja erilaistumista neurogeneesiksen aikana, mutta vaikutukset niiden migraatioon ovat vähemmän tunnetut. Tämä tutkimus näyttää T-tyypin kalsiumkanavan todennäköisesti osallistuvan neuronaaliseen migraatioon hiiren alkion subventrikkeli alueelta eristetyillä kanta- tai progeniittorisoluilla tehdyissä kokeissa. Selektiiviset T-tyypin kalsiumkanavan antagonistit, etosuksimidi, nikkeli ja skorpionitoksiini, kurtoxin hidastivat migraatiota erilaistuvissa progeniittorisoluissa. Tämä tutkimus koostuu kirjallisuuskatsauksesta ja kokeellisesta osasta. Tämän tutkimuksen toinen tarkoitus oli esitellä vaihtoehtoinen lähestymistapa invasiiviselle kantasoluterapialle, joka vaatii kantasolujen viljelyä ja siirtämistä ihmiseen. Tämä toinen tapa on endogeenisten kantasolujen eiinvasiivinen stimulointi, jolla ne saadaan migratoitumaan kohdekudokseen, erilaistumaan siellä ja tehtävänsä suoritettuaan lopettamaan jakaantumisen. Non-invasiivinen kantasoluterapia on vasta tiensä alussa, ja tarvitsee farmakologista osaamista kehittyäkseen. Joitain onnistuneita ei-invasiivisia hoitoja on jo tehty selkärangan vaurioiden korjaamisessa. Vastaavanlaisia menetelmiä voitaisiin käyttää myös keskushermoston vaurioiden ja neurodegeneratiivisten sairauksien hoidossa. Näiden menetelmien kehittäminen vaatii endogeenisten kantasoluja inhiboivien ja indusoivien mekanismien tuntemista. Yksi tärkeä kantasolujen erilaistumista stimuloiva tekijä on kalsiumioni. Jänniteherkät kalsiumkanavat osallistuvat kaikkiin neurogeneesiksen eri vaiheisiin. T-tyypin kalsiumkanava, joka ekspressoituu suuressa määrin keskushermoston kehityksen alkuvaiheessa ja vähenee neuronaalisen kehityksen edetessä, saattaa olla oleellisessa asemassa progeniittorisolujen ohjaamisessa.

Genome-wide expression profiling identifies deregulated miRNAs in malignant astrocytoma

Malignant astrocytoma includes anaplastic astrocytoma (grade III) and glioblastoma (grade IV). Among them, glioblastoma is the most common primary brain tumor with dismal responses to all therapeutic modalities. We performed a large-scale, genome-wide microRNA (miRNA) (n=756) expression profiling of 26 glioblastoma, 13 anaplastic astrocytoma and 7 normal brain samples with an aim to find deregulated miRNA in malignant astrocytoma. We identified several differentially regulated miRNAs between these groups, which could differentiate glioma grades and normal brain as recognized by PCA. More importantly, we identified a most discriminatory 23-miRNA expression signature, by using PAM, which precisely distinguished glioblastoma from anaplastic astrocytoma with an accuracy of 95%. The differential expression pattern of nine miRNAs was further validated by real-time RT-PCR on an independent set of malignant astrocytomas (n-72) and normal samples (n=7). Inhibition of two glioblastoma-upregulated miRNAs (miR-21 and miR-23a) and exogenous overexpression of two glioblastoma-downregulated miRNAs (miR-218 and miR-219-5p) resulted in reduced soft agar colony formation but showed varying effects on cell proliferation and chemosensitivity. Thus we have identified the miRNA expression signature for malignant astrocytoma, in particular glioblastoma, and showed the miRNA involvement and their importance in astrocytoma development. Modern Pathology (2010) 23, 1404-1417; doi:10.1038/modpathol.2010.135; published online 13 August 2010

How to write a passable technical paper

In my job I see many students who have not learned to write a technical paper. When they do competent work, I want them to be able to write passable reports. This article is for them. There are well established principles for citing the relevant work of others; for not copying things without giving credit; for not stealing. If a reader feels you have copied anything, a figure, even a phrase, from elsewhere without citing its source, then you are guilty of plagiarism in the eyes of that reader. Committing plagiarism is so bad that I cannot do justice to it here. So I merely say: never do it. On, then, to writing your own honest and original material. Art requires talent. In contrast, through discipline and persistence alone, you can learn how to differentiate functions and ride bicycles. Similarly, you can write a passable technical paper. You just have to realize that your job does not end with research. Writing a passable paper involves extra work.

Regulation and Function of GATA Transcription Factors in Adrenocortical Tumors and Granulosa Cells

Transcription factors play a key role in tumor development, in which dysfunction of genes regulating tissue growth and differentiation is a central phenomenon. The GATA family of transcription factors consists of six members that bind to a consensus DNA sequence (A/T)GATA(A/G) in gene promoters and enhancers. The two GATA factors expressed in the adrenal cortex are GATA-4 and GATA-6. In both mice and humans, GATA-4 can be detected only during the fetal period, whereas GATA-6 expression is abundant both throughout development and in the adult. It is already established that GATA factors are important in both normal development and tumorigenesis of several endocrine organs, and expression of GATA-4 and GATA-6 is detected in adrenocortical tumors. The aim of this study was to elucidate the function of these factors in adrenocortical tumor growth. In embryonal development, the adrenocortical cells arise and differentiate from a common pool with gonadal steroidogenic cells, the urogenital ridge. As the adult adrenal cortex undergoes constant renewal, it is hypothesized that undifferentiated adrenocortical progenitor cells reside adjacent to the adrenal capsule and give rise to daughter cells that differentiate and migrate centripetally. A diverse array of hormones controls the differentiation, growth and survival of steroidogenic cells in the adrenal gland and the gonads. Factors such as luteinizing hormone and inhibins, traditionally associated with gonadal steroidogenic cells, can also influence the function of adrenocortical cells in physiological and pathophysiological states. Certain inbred strains of mice develop subcapsular adrenocortical tumors in response to gonadectomy. In this study, we found that these tumors express GATA-4, normally absent from the adult adrenal cortex, while GATA-6 expression is downregulated. Gonadal markers such as luteinizing hormone receptor, anti-Müllerian hormone and P450c17 are also expressed in the neoplastic cells, and the tumors produce gonadal hormones. The tumor cells have lost the expression of melanocortin-2 receptor and the CYP enzymes necessary for the synthesis of corticosterone and aldosterone. By way of xenograft studies utilizing NU/J nude mice, we confirmed that chronic gonadotropin elevation is sufficient to induce adrenocortical tumorigenesis in susceptible inbred strains. Collectively, these studies suggest that subcapsular adrenocortical progenitor cells can, under certain conditions, adopt a gonadal fate. We studied the molecular mechanisms involved in gene regulation in endocrine cells in order to elucidate the role of GATA factors in endocrine tissues. Ovarian granulosa cells express both GATA-4 and GATA-6, and the TGF-β signaling pathway is active in these cells. Inhibin-α is both a target gene for, and an atypical or antagonistic member of the TGF-β growth factor superfamily. In this study, we show that GATA-4 is required for TGF-β-mediated inhibin-α promoter activation in granulosa cells, and that GATA-4 physically interacts with Smad3, a TGF-β downstream protein. Apart from the regulation of steroidogenesis and other events in normal tissues, TGF-β signaling is implicated in tumors of multiple organs, including the adrenal cortex. Another signaling pathway found often to be aberrantly active in adrenocortical tumors is the Wnt pathway. As both of these pathways regulate the expression of inhibin-α, a transcriptional target for GATA-4 and GATA-6, we wanted to investigate whether GATA factors are associated with the components of these signaling cascades in human adrenocortical tumors. We found that the expression of Wnt co-receptors LRP5 and LRP6, Smad3, GATA-6 and SF-1 was diminished in adrenocortical carcinomas with poor outcome. All of these factors drive inhibin-α expression, and their expression in adrenocortical tumors correlated with that of inhibin-α. The results support a tumor suppressor role previously suggested for inhibin-α in the mouse adrenal cortex, and offer putative pathways associated with adrenocortical tumor aggressiveness. Unraveling the role of GATA factors and associated molecules in human and mouse adrenocortical tumors could ultimately contribute to the development of diagnostic tools and future therapies for these diseases.

Quasicrystals and their crystalline homologues in the Al-Mn-Cu ternary alloys

Electron diffraction and high-resolution electron microscopy have been employed to differentiate among icosahedral, decagonal and crystalline particles that occur in as-cast and rapidly solidified Al-Mn-Cu alloys. The resemblance between decagonal quasicrystals and crystals in their electron diffraction patterns is striking. The crystalline structure is based on the orthorhombic 'Al3Mn' structure, but also a new monoclinic phase called 'X' has been discovered and described here. The present observations are also closely related to the orthorhombic structures in Al60Mn11Ni4. The occurrence of fine-scale twinning and fragmentation into domains explains the complex diffraction effects.

”Ihanan överi ja juhlallinen jakku olisi kyllä kiva lisä vaatekaappiin” – tutkimus kuluttamisesta ja professionalisoitumisesta elämäntyyliblogeissa

Tarkastelen tutkimuksessani muotibloggaajien kulutuspuhetta. Tutkimuksen tarkoituksena on selvittää, millaista kuluttajuutta muotiblogeissa ilmaistaan ja millainen kehityskaari muotiblogeissa on tapahtunut vuodesta 2007 tämän tutkimuksen tekemiseen asti tutkimusaineiston sekä tekemieni havaintojen perusteella. Tutkimus on toteutettu laadullisia tutkimusmenetelmiä käyttämällä. Olen kerännyt aineistoni kymmenestä naisten kirjoittamasta muotiblogista kahtena eri ajanjaksona vuonna 2009. Lisäksi tutkimuksessa on sekä etnografisen että netnografisen havainnoinnin piirteitä. Aineiston analysoinnin apuna olen käyttänyt teemoittelua sekä tyypittelyä. Tutkimuksesta selvisi, että muotibloggaajien näkeminen identiteettiään etsivänä liittyy oman tyylin etsimiseen ja erottautumisen haluun. Perinteinen näkemys kuluttajasta valitsijana ja passiivisena markkinoilla toimijana on väistymässä, sillä muotibloggaajat näyttäytyvät tutkimuksessa aktiivisina toimijoina ja tuottajina. Muotibloggaajat hakevat myös jatkuvasti uusia kulutuselämyksiä ja kommunikoivat toistensa kanssa välittämällä merkityksiä kuluttamisensa kautta. Muotibloggaajien kulutuspuheet näyttäytyvät tutkimuksessa ekonomistisen kulutuseetoksen ja perinteisen suomalaisen kulutuspuheen mukaisesti järkevinä. Säästäväisyyttä pidetään hyveellisenä ja tuotteiden hinnat vaikuttavat ostopäätösten tekemiseen. Muotibloggaajat osaavat kuitenkin kontrolloidusti nauttia kuluttamisesta. Kulutuspuheet noudattavat myös ekologis-eettisen kulutuseetoksen perinnettä, mikä ilmenee fanaattisuuden välttämisenä sekä perinteisten että sosiaalisen median kirpputorien suosimisena. Lisäksi muotibloggaajien kulutuspuheet käyvät ilmi sosiaalisena pakkona, sillä muotiblogin pitäminen mielenkiintoisena vaatii jatkuvaa himoa uusia kulutustuotteita kohtaan. Tutkimuksen perusteella muotiblogeissa korostuu yhteisöllisyys ja kuluttaminen on hyvin naisellista. Tutkimusaineistosta sekä havainnoista tekemieni päätelmien mukaan muotiblogit ovat muuttumassa elämäntyyliblogeiksi, sillä niissä kerrotaan yhä enemmän myös muista kuin kuluttamiseen liittyvistä aiheista. Samalla muotibloggaajat ovat kehittymässä tavallisesta kuluttajasta kohti asiantuntijuutta eli professionalisoitumassa. Professionalisoitumisen myötä muotibloggaajat toimivat uuden ajan kuluttajavalistajina ja muotiblogeissa syntyy uusia sanoja ja merkityksiä. Lisäksi muotibloggaajille on kehittynyt sellaisia tietoja ja taitoja, joita voi myydä. Muotibloggaajista onkin tulossa muodin ammattilaisia, joille maksetaan tulevaisuudessa bloggaamisesta myös palkkaa.

Interfacial Phenomena in Pharmaceutical Low Moisture Content Powder Processing

Powders are essential materials in the pharmaceutical industry, being involved in majority of all drug manufacturing. Powder flow and particle size are central particle properties addressed by means of particle engineering. The aim of the thesis was to gain knowledge on powder processing with restricted liquid addition, with a primary focus on particle coating and early granule growth. Furthermore, characterisation of this kind of processes was performed. A thin coating layer of hydroxypropyl methylcellulose was applied on individual particles of ibuprofen in a fluidised bed top-spray process. The polymeric coating improved the flow properties of the powder. The improvement was strongly related to relative humidity, which can be seen as an indicator of a change in surface hydrophilicity caused by the coating. The ibuprofen used in the present study had a d50 of 40 μm and thus belongs to the Geldart group C powders, which can be considered as challenging materials in top-spray coating processes. Ibuprofen was similarly coated using a novel ultrasound-assisted coating method. The results were in line with those obtained from powders coated in the fluidised bed process mentioned above. It was found that the ultrasound-assisted method was capable of coating single particles with a simple and robust setup. Granule growth in a fluidised bed process was inhibited by feeding the liquid in pulses. The results showed that the length of the pulsing cycles is of importance, and can be used to adjust granule growth. Moreover, pulsed liquid feed was found to be of greater significance to granule growth in high inlet air relative humidity. Liquid feed pulsing can thus be used as a tool in particle size targeting in fluidised bed processes and in compensating for changes in relative humidity of the inlet air. The nozzle function of a two-fluid external mixing pneumatic nozzle, typical for small scale pharmaceutical fluidised bed processes, was studied in situ in an ongoing fluidised bed process with particle tracking velocimetry. It was found that the liquid droplets undergo coalescence as they proceed away from the nozzle head. The coalescence was expected to increase droplet speed, which was confirmed in the study. The spray turbulence was studied, and the results showed turbulence caused by the event of atomisation and by the oppositely directed fluidising air. It was concluded that particle tracking velocimetry is a suitable tool for in situ spray characterisation. The light transmission through dense particulate systems was found to carry information on particle size and packing density as expected based on the theory of light scattering by solids. It was possible to differentiate binary blends consisting of components with differences in optical properties. Light transmission showed potential as a rapid, simple and inexpensive tool in characterisation of particulate systems giving information on changes in particle systems, which could be utilised in basic process diagnostics.

Morphogenesis and plant regeneration from cotyledonary cultures of Eucalyptus

Callus cultures were established from hypocotyls and cotyledons derived from young seedlings of Eucalyptus citriodora. Successful plantlet production from cotyledonary callus was achieved within 6 weeks on Murashige and Skoog's basal medium supplemented with zeatin (1 mg/l) and indoleacetic acid (0.2 mg/l). Leaf and shoot callus obtained from one-year-old plants did not differentiate. Results reported contribute to defining optimal conditions for callus growth and plantlet formation

Ekotuotteet kuluttajan arjessa – vastuullisuutta, puhtautta ja arjen luksusta

Tutkielmassa tarkastellaan kuluttajien näkemyksiä ekotuotteiden valintaan vaikuttavista tekijöistä. Analysoin ekotuotteiden hankintaa kolmen teeman kautta. Ne ovat vihreys ja vastuullisuus, puhtaus tuotevalinnoissa sekä niin sanottu arjen luksus. Tutkimukseni empiirinen osa koostuu 10 teemahaastattelusta. Tutkimuskohteena on ekokauppa Ruohonjuuressa ostoksiaan tekevät kuluttajat. Haastateltavia etsin ilmoituksella ekokauppa Ruohonjuuresta sekä kaupan Facebook-sivuilta. Lisäksi oma haastattelupäivä Ruohonjuuren myymälässä tuotti haastateltavia mukaan tutkimukseen. Kirjoitin haastatteluista yhteenvedon ja analysoin aineistoa teemoittelun avulla. Nykyiset ympäristöongelmat vaikuttavat siihen, millaisena koemme arjen tulevaisuudessa. Vihreä ja vastuulllinen kuluttaja ottaa huomioon kulutuspäätöksiensä vaikutukset ympäristöön. Vihreät kulutuspäätökset tarkoittavat kestäviä kulutustapoja kuten jätteiden lajittelua, kirpputorikierrättämistä ja ympäristöä säästävien ekotuotteiden valintaa. Aineiston perusteella voi todeta, että ekotuotteiden ympäristömyönteisyyteen liitetään läheisesti luomutuotanto ja luomutuotteet. Ekotuotteet nähdään myös eettisinä ja moraalisina valintoina, joiden avulla halutaan vaikuttaa myös muiden hyvinvointiin. Ekotuotteisiin kohdistuu siten monenlaisia odotuksia, mutta myös epäilyjä. Aineistoni perusteella tuotetta ei välttämättä koettu ekotuotteeksi, jos sen valmistamiseen on käytetty paljon resursseja. Kuluttajat ovat kiinnostuneita ruoan alkuperästä ja sen aitoudesta. Ekotuotteet koetaan muita tuotteita päinvastoin puhtaiksi vaihtoehdoiksi. Puhtaus ekotuotteissa mielletään laadultaan turvallisiksi ja terveellisiksi tuotteiksi, jotka maistuvat hyvältä. Haastatteluaineiston perusteella voi todeta, että ekotuotteet koettiin myös arjen ostosten erikoisuudeksi. Arjen luksus lisää käyttäjälleen mielihyvän elämyksiä. Ekotuotteita ostamalla rakennetaan myös omaa elämäntyyliä ja erottaudutaan muista. Aineiston perusteella ekokauppaan mennään kiertelemään, tekemään heräteostoksia ja etsimään uutuuksia. Shoppailu ekokaupassa voi olla nautinnollista ja miellyttävää toimintaa, vaikka ostamista vain harkitaan. Ekotuote lahjana kertoo lahjan antajasta ja tuo lahjan saajalle palan luksusta vaikkapa luomusuklaan muodossa.

HELANAL: A program to characterise helix geometry in proteins,

A detailed analysis of structural and position dependent characteristic features of helices will give a better understanding of the secondary structure formation in globular proteins. Here we describe an algorithm that quantifies the geometry of helices in proteins on the basis of their C-alpha atoms alone. The Fortran program HELANAL can extract the helices from the PDB files and then characterises the overall geometry of each helix as being linear, curved or kinked, in terms of its local structural features, viz. local helical twist and rise, virtual torsion angle, local helix origins and bending angles between successive local helix axes. Even helices with large radius of curvature are unambiguously identified as being linear or curved. The program can also be used to differentiate a kinked helix and other motifs, such as helix-loop-helix or a helix-turn-helix (with a single residue linker) with the help of local bending angles. In addition to these, the program can also be used to characterise the helix start and end as well as other types of secondary structures.

Noninvasive biomarkers for early smoking related lung disease

Chronic obstructive pulmonary disease (COPD) is a slowly progressive disease characterized by airway inflammation and largely irreversible airflow limitation. One major risk factor for COPD is cigarette smoking. Since the inflammatory process starts many years prior to the onset of clinical symptoms and still continues after smoking cessation, there is an urgent need to find simple non-invasive biomarkers that can be used in the early diagnosis of COPD and which could help in predicting the disease progression. The first aim of the present study was to evaluate the involvement of different oxidative/nitrosative stress markers, matrix metalloproteinases (MMPs) and their tissue inhibitor-1 (TIMP-1) in smokers and in COPD. Elevated numbers of inducible nitric oxide synthase (iNOS), nitrotyrosine, myeloperoxidase (MPO) and 4-hydroxy-2-nonenal (4-HNE) positive cells and increased levels of 8-isoprostane and lactoferrin were found in sputum of non-symptomatic smokers compared to non-smokers, and especially in subjects with stable mild to moderate COPD, and they correlated with the severity of airway obstruction. This suggests that an increased oxidant burden exists already in the airways of smokers with normal lung function values. However, none of these markers could differentiate healthy smokers from symptomatic smokers with normal lung function values i.e. those individuals who are at risk of developing COPD. In contrast what is known about asthma exhaled nitric oxide (FENO) was lower in smokers than in non-smokers, the reduced FENO value was significantly associated with neutrophilic inflammation and the elevated oxidant burden (positive cells for iNOS, nitrotyrosine and MPO). The levels of sputum MMP-8 and plasma MMP-12 appeared to differentiate subjects who have a risk for COPD development but these finding require further investigations. The levels of all studied MMPs correlated with the numbers of neutrophils, and MMP-8 and MMP-9 with markers of neutrophil activation (MPO, lactoferrin) suggesting that especially neutrophil derived oxidants may stimulate the tissue destructive MMPs already in lungs of smokers who are not yet experiencing any airflow limitation. When investigating the role of neutrophil proteases (neutrophil elastase, MMP-8, MMP-9) during COPD exacerbation and its recovery period, we found that levels of all these proteases were increased in sputum of patients with COPD exacerbation as compared to stable COPD and controls, and decreased during the one-month recovery period, giving evidence for a role of these enzymes in COPD exacerbations. In the last study, the effects of subject`s age and smoking habits were evaluated on the plasma levels of surfactant protein A (SP-A), SP-D, MMP-9 and TIMP-1. Long-term smoking increased the levels of all of these proteins. SP-A most clearly correlated with age, pack years and lung function decline (FEV1/FVC), and based on the receiver operating characteristic curve analysis, SP-A was the best marker for discriminating subjects with COPD from controls. In conclusion, these findings support the hypothesis that especially neutrophil derived oxidants may activate MMPs and induce an active remodeling process already in the lungs of smokers with normal lung function values. The marked increase of sputum levels of neutrophil proteases in smokers, stable COPD and/or during its exacerbations suggest that these enzymes play a role in the development and progression of COPD. Based on the comparison of various biomarkers, SP-A can be proposed to serve as sensitive biomarker in COPD development.

Migration-Development Nexus in the Malawian Health Sector: European Union Blue Card – circular migration for development?

The European Union has agreed on implementing the Policy Coherence for Development (PCD) principle in all policy sectors that are likely to have a direct impact on developing countries. This is in order to take account of and support the EU development cooperation objectives and the achievement of the internationally agreed Millennium Development Goals. The common EU migration policy and the newly introduced EU Blue Card directive present an example of the implementation of the principle in practice: the directive is not only designed to respond to the occurring EU labour demand by attracting highly skilled third-country professionals, but is also intended to contribute to the development objectives of the migrant-sending developing countries, primarily through the tool of circular migration and the consequent skills transfers. My objective in this study is to assess such twofold role of the EU Blue Card and to explore the idea that migration could be harnessed for the benefit of development in conformity with the notion that the two form a positive nexus. Seeing that the EU Blue Card fails to differentiate the most vulnerable countries and sectors from those that are in a better position to take advantage of the global migration flows, the developmental consequences of the directive must be accounted for even in the most severe settings. Accordingly, my intention is to question whether circular migration, as claimed, could address the problem of brain drain in the Malawian health sector, which has witnessed an excessive outflow of its professionals to the UK during the past decade. In order to assess the applicability, likelihood and relevance of circular migration and consequent skills transfers for development in the Malawian context, a field study of a total of 23 interviews with local health professionals was carried out in autumn 2010. The selected approach not only allows me to introduce a developing country perspective to the on-going discussion at the EU level, but also enables me to assess the development dimension of the EU Blue Card and the intended PCD principle through a local lens. Thus these interviews and local viewpoints are at the very heart of this study. Based on my findings from the field, the propensity of the EU Blue Card to result in circular migration and to address the persisting South-North migratory flows as well as the relevance of skills transfers can be called to question. This is as due to the bias in its twofold role the directive overlooks the importance of the sending country circumstances, which are known to determine any developmental outcomes of migration, and assumes that circular migration alone could bring about immediate benefits. Without initial emphasis on local conditions, however, positive outcomes for vulnerable countries such as Malawi are ever more distant. Indeed it seems as if the EU internal interests in migration policy forbid the fulfilment of the PCD principle and diminish the attempt to harness migration for development to bare rhetoric.