Translational models of coronary artery disease, myocardial infarction and heart failure. Development, validation and in vivo imaging studies using positron emission tomography

Coronary artery disease is an atherosclerotic disease, which leads to narrowing of coronary arteries, deteriorated myocardial blood flow and myocardial ischaemia. In acute myocardial infarction, a prolonged period of myocardial ischaemia leads to myocardial necrosis. Necrotic myocardium is replaced with scar tissue. Myocardial infarction results in various changes in cardiac structure and function over time that results in “adverse remodelling”. This remodelling may result in a progressive worsening of cardiac function and development of chronic heart failure. In this thesis, we developed and validated three different large animal models of coronary artery disease, myocardial ischaemia and infarction for translational studies. In the first study the coronary artery disease model had both induced diabetes and hypercholesterolemia. In the second study myocardial ischaemia and infarction were caused by a surgical method and in the third study by catheterisation. For model characterisation, we used non-invasive positron emission tomography (PET) methods for measurement of myocardial perfusion, oxidative metabolism and glucose utilisation. Additionally, cardiac function was measured by echocardiography and computed tomography. To study the metabolic changes that occur during atherosclerosis, a hypercholesterolemic and diabetic model was used with [18F] fluorodeoxyglucose ([18F]FDG) PET-imaging technology. Coronary occlusion models were used to evaluate metabolic and structural changes in the heart and the cardioprotective effects of levosimendan during post-infarction cardiac remodelling. Large animal models were used in testing of novel radiopharmaceuticals for myocardial perfusion imaging. In the coronary artery disease model, we observed atherosclerotic lesions that were associated with focally increased [18F]FDG uptake. In heart failure models, chronic myocardial infarction led to the worsening of systolic function, cardiac remodelling and decreased efficiency of cardiac pumping function. Levosimendan therapy reduced post-infarction myocardial infarct size and improved cardiac function. The novel 68Ga-labeled radiopharmaceuticals tested in this study were not successful for the determination of myocardial blood flow. In conclusion, diabetes and hypercholesterolemia lead to the development of early phase atherosclerotic lesions. Coronary artery occlusion produced considerable myocardial ischaemia and later infarction following myocardial remodelling. The experimental models evaluated in these studies will enable further studies concerning disease mechanisms, new radiopharmaceuticals and interventions in coronary artery disease and heart failure.

Severity score system for progressive myelopathy: development and validation of a new clinical scale

Progressive myelopathies can be secondary to inborn errors of metabolism (IEM) such as mucopolysaccharidosis, mucolipidosis, and adrenomyeloneuropathy. The available scale, Japanese Orthopaedic Association (JOA) score, was validated only for degenerative vertebral diseases. Our objective is to propose and validate a new scale addressing progressive myelopathies and to present validating data for JOA in these diseases. A new scale, Severity Score System for Progressive Myelopathy (SSPROM), covering motor disability, sphincter dysfunction, spasticity, and sensory losses. Inter- and intra-rater reliabilities were measured. External validation was tested by applying JOA, the Expanded Disability Status Scale (EDSS), the Barthel index, and the Osame Motor Disability Score. Thirty-eight patients, 17 with adrenomyeloneuropathy, 3 with mucopolysaccharidosis I, 3 with mucopolysaccharidosis IV, 2 with mucopolysaccharidosis VI, 2 with mucolipidosis, and 11 with human T-cell lymphotropic virus type-1 (HTLV-1)-associated myelopathy participated in the study. The mean ± SD SSPROM and JOA scores were 74.6 ± 11.4 and 12.4 ± 2.3, respectively. Construct validity for SSPROM (JOA: r = 0.84, P < 0.0001; EDSS: r = -0.83, P < 0.0001; Barthel: r = 0.56, P < 0.002; Osame: r = -0.94, P < 0.0001) and reliability (intra-rater: r = 0.83, P < 0.0001; inter-rater: r = 0.94, P < 0.0001) were demonstrated. The metric properties of JOA were similar to those found in SSPROM. Several clinimetric requirements were met for both SSPROM and JOA scales. Since SSPROM has a wider range, it should be useful for follow-up studies on IEM myelopathies.

Development and validation of a genotype 3 recombinant protein-based immunoassay for hepatitis E virus serology in swine

Hepatitis E virus (HEV) is classified within the family Hepeviridae, genus Hepevirus. HEV genotype 3 (Gt3) infections are endemic in pigs in Western Europe and in North and South America and cause zoonotic infections in humans. Several serological assays to detect HEV antibodies in pigs have been developed, at first mainly based on HEV genotype 1 (Gt1) antigens. To develop a sensitive HEV Gt3 ELISA, a recombinant baculovirus expression product of HEV Gt3 open reading frame-2 was produced and coated onto polystyrene ELISA plates. After incubation of porcine sera, bound HEV antibodies were detected with anti-porcine anti-IgG and anti-IgM conjugates. For primary estimation of sensitivity and specificity of the assay, sets of sera were used from pigs experimentally infected with HEV Gt3. For further validation of the assay and to set the cutoff value, a batch of 1100 pig sera was used. All pig sera were tested using the developed HEV Gt3 assay and two other serologic assays based on HEV Gt1 antigens. Since there is no gold standard available for HEV antibody testing, further validation and a definite setting of the cutoff of the developed HEV Gt3 assay were performed using a statistical approach based on Bayes' theorem. The developed and validated HEV antibody assay showed effective detection of HEV-specific antibodies. This assay can contribute to an improved detection of HEV antibodies and enable more reliable estimates of the prevalence of HEV Gt3 in swine in different regions.

Capillary electrophoresis: Applicability and method validation for biorefinery analytics

Wood-based bioprocesses present one of the fields of interest with the most potential in the circular economy. Expanding the use of wood raw material in sustainable industrial processes is acknowledged on both a global and a regional scale. This thesis concerns the application of a capillary zone electrophoresis (CZE) method with the aim of monitoring wood-based bioprocesses. The range of detectable carbohydrate compounds is expanded to furfural and polydatin in aquatic matrices. The experimental portion has been conducted on a laboratory scale with samples imitating process samples. This thesis presents a novel strategy for the uncertainty evaluation via in-house validation. The focus of the work is on the uncertainty factors of the CZE method. The CZE equipment is sensitive to ambient conditions. Therefore, a proper validation is essential for robust application. This thesis introduces a tool for process monitoring of modern bioprocesses. As a result, it is concluded that the applied CZE method provides additional results to the analysed samples and that the profiling approach is suitable for detecting changes in process samples. The CZE method shows significant potential in process monitoring because of the capability of simultaneously detecting carbohydrate-related compound clusters. The clusters can be used as summary terms, indicating process variation and drift.

Optimization and validation of a methodology to determine total arsenic, As(III) and As(V), in water samples, through graphite furnace atomic absorption spectrometry

The Graphite furnace atomic absorption spectrometry (GF AAS) was the technique chosen by the inorganic contamination laboratory (INCQ/ FIOCRUZ) to be validated and applied in routine analysis for arsenic detection and quantification. The selectivity, linearity, sensibility, detection, and quantification limits besides accuracy and precision parameters were studied and optimized under Stabilized Temperature Platform Furnace (STPF) conditions. The limit of detection obtained was 0.13 µg.L-1 and the limit of quantification was 1.04 µg.L-1, with an average precision, for total arsenic, less than 15% and an accuracy of 96%. To quantify the chemical species As(III) and As(V), an ion-exchange resin (Dowex 1X8, Cl- form) was used and the physical-chemical parameters were optimized resulting in a recuperation of 98% of As(III) and of 90% of As(V). The method was applied to groundwater, mineral water, and hemodialysis purified water samples. All results obtained were lower than the maximum limit values established by the legal Brazilian regulations, in effect, 50, 10, and 5 µg.L-1 para As total, As(III) e As(V), respectively. All results were statistically evaluated.

Development and validation of a method for detection and quantification of ochratoxin A in green coffee using liquid chromatography coupled to mass spectrometry

A method using Liquid Chromatography Tanden Mass Spectrometry (LC-MS/MS) with matrix-matched calibration curve was developed and validated for determining ochratoxin A (OTA) in green coffee. Linearity was found between 3.0 and 23.0 ng.g-1. Mean recoveries ranged between 90.45% and 108.81%; the relative standard deviation under repeatability and intermediate precision conditions ranged from 5.39% to 9.94% and from 2.20% to 14.34%, respectively. The limits of detection and quantification were 1.2 ng.g-1 and 3.0 ng.g-¹, respectively. The method developed was suitable and contributed to the field of mycotoxin analysis, and it will be used for future production of the Certified Reference Material (CRM) for OTA in coffee.

In-house method validation and occurrence of alpha-, beta-endosulfan, endosulfan sulphate, lambda-cyhalothrin, procymidone and trifluralin residues in strawberry

A method for determination of organohalogen pesticides in strawberry by gas chromatography with electron capture detection was validated and applied in a monitoring program. Linearity, matrix effects, and day effect were evaluated for the analytes alpha-endosulfan, beta-endosulfan, endosulfan sulphate, lambda-cyhalothrin, procymidone, and trifluralin. The linear range varied according to the chromatographic response of the analyte. Significant matrix effects were observed. The mean recoveries ranged from 74.6 to 115.4%, with repeatability standard deviations between 1.6 and 21.0% and intermediate precision between 5.9 and 21.0%. Detection, quantification and decision limit, and detection capacity ranged from 0.003 to 0.007 mg/kg, 0.005 to 0.013 mg/kg; 0.003 to 3.128 mg/kg; and 0.005 to 3.266 mg/kg, respectively. The method was fit for the purpose of monitoring organohalogen residues in strawberries. Residues of these pesticides were detected in 124 of the 186 samples analyzed between 2009 and 2011 in the state of Minas Gerais. Nine of them did not comply with the current legislation requirements; among them, seven (3.8%) had residues of unauthorized pesticide for the culture of strawberry, one (0.5%) had residues above the maximum residue limit, and another one (0.5%) exhibited both non-conformities.

Construction of a supercritical fluid extraction (SFE) equipment: validation using annatto and fennel and extract analysis by thin layer chromatography coupled to image

Abstract The present work describes setting up a laboratory unit for supercritical fluid extraction. In addition to its construction, a survey of cost was done to compare the cost of the homemade unit with that of commercial units. The equipment was validated using an extraction of annatto seeds’ oil, and the extraction and fractionation of fennel oil were used to validate the two separators; for both systems, the solvent was carbon dioxide. The chemical profiles of annatto and fennel extracts were assessed using thin layer chromatography; the images of the chromatographic plates were processed using the free ImageJ software. The cost survey showed that the homemade equipment has a very low cost (~US$ 16,000) compared to commercial equipment. The extraction curves of annatto were similar to those obtained in the literature (yield of 3.8% oil). The separators were validated, producing both a 2.5% fraction of fennel seed extract rich in essential oils and another extract fraction composed mainly of oleoresins. The ImageJ software proved to be a low-cost tool for obtaining an initial evaluation of the chemical profile of the extracts.

Future operational-tactical level warfare : challenges and opportunities for the defence of Finland

Finnish Defence Studies is published under the auspices of the National Defence College, and the contributions reflect the fields of research and teaching of the College. Finnish Defence Studies will occasionally feature documentation on Finnish Security Policy. Views expressed are those of the authors and do not necessarily imply endorsement by the National Defence College.

Individual Crimes or a Sociological Phenomenon: A Critical discourse analysis of the 2014 Royal Canadian Mounted Police National Operational Overview on missing and murdered Indigenous women in Canada

Pro gradu -tutkielma käsittelee Kanadan poliisivoimien, Royal Canadian Mounted Police (RCMP), vuoden 2014 operationaalista raporttia Kanadan kadonneista ja murhatuista alkuperäiskansojen naisista. Heitä katoaa ja murhataan Kanadassa suhteessa huomattavasti enemmän kuin muita naisia. Aihe on hyvin ajankohtainen sekä kriittinen ja siihen on paikallisten organisaatioiden lisäksi kiinnittänyt huomiota mm. Amnesty International ja Yhdistyneet Kansakunnat. Tilannetta pidetään jo ihmisoikeuskriisinä ja sen puolesta puhuminen voidaan nähdä osana laajempaa kansannousua alkuperäiskansojen oikeuksien puolesta. Kanadan hallitusta sekä poliisivoimia on syytetty välinpitämättömyydestä ja rasismista, poliiseja jopa väkivallasta alkuperäiskansojen naisia kohtaan. Kanadan hallitus ei myönnä ongelman olevan sosiologinen ilmiö, vaan pääministerin mukaan naisten katoamiset ja murhat ovat yksittäisiä rikoksia. Tilanteen taustalla on laajempi ongelma, joka juontaa juurensa kolonialismista, alkuperäiskansojen pakkokoulutuksesta ja heidän kulttuurinsa sekä identiteettinsä tuhoamisesta. Ennakkoluulot ja stereotypiat elävät yhä vahvana luoden heikon aseman alkuperäiskansojen edustajille ja tässä tapauksessa erityisesti naisille, joita myös usein syytetään omista ongelmistaan. Tutkielma selvittää, onko tämä operationaalinen raportti eriarvoisuutta, stereotypioita sekä ennakkoluuloja ylläpitävä ja tukeeko se näkemystä sosiologisesta ilmiöstä. Poliisivoimat ovat yhteiskunnassa vaikutusvaltaisessa asemassa ja voivat edesauttaa, jatkaa ja voimistaa syrjivää ajattelua, käytöstä ja viestintää. Vaikka he myös ajavat alkuperäiskansojen etuja, tulee heidän toimintaansa ja täten tätä kyseistä raporttia tarkastella kriittisesti. Tutkielma keskittyy kriittiseen diskurssianalyysiin (Fairclough 1995, Wodak & Meyer 2009). Raportin teksti ei ole avoimesti diskriminoivaa ja keskittyy tilastojen ja lukujen raportointiin sekä vertailuun, luoden samalla kuvan asianomaisista sekä tilanteesta yleisesti. Makroanalyysi (van Dijk 1977, 1980) mahdollistaa korkeamman tason ajatusten ja ideoiden esille tuonnin paljastaen ns. rivien välistä löytyvän viestinnän. Näistä makroanalyysin tuloksista etsitään erilaisia diskurssistrategioita (Reisigl & Wodak 2001), joiden avulla luodaan mm. kuva positiivisesta itsestä ja negatiivisesta toisesta. Näitä tuloksia tuetaan lyhyellä multimodaalisella analyysillä, joka keskittyy lähinnä raportin kahteen kuvaan (Kress & van Leeuwen 2006). Lopuksi tuloksista keskustellaan suhteessa yhteiskunnan valtasuhteisiin (Foucault 1976), rasismiin ja seksismiin. Analyysin perusteella raportti on selkeästi diskriminoiva. Se tuo esiin vanhoja stereotypioita ja ennakkoluuloja, esittää tilanteen alkuperäiskansojen sisäisenä ongelmana, jättää mainitsematta tilanteen taustat ja luo hyvin positiivisen kuvan poliisivoimista (RCMP). Tällä tavoin se ylläpitää yhteiskunnan epätasapainoisia valtasuhteita ja alkuperäiskansojen naisten heikompaa ja marginalisoitua asemaa. Raportti todistaa kuinka syvällä Kanadan yhteiskunnassa jopa institutionaalisella tasolla nämä ajatukset piilevät, sillä diskriminaatio ulottuu tapausten syistä niiden käsittelyyn ja raportointiin. Tilanne on huolestuttava ja voidaan nähdä sosiologisena ilmiönä. Poliisivoimien tulisi lisätä sisäistä koulutusta asian suhteen sekä hallituksen tutkia tätä ilmiönä ja paneutua sen selvittämiseen laaja-alaisesti ja läpinäkyvästi.

Individual Crimes or a Sociological Phenomenon: A Critical discourse analysis of the 2014 Royal Canadian Mounted Police National Operational Overview on missing and murdered Indigenous women in Canada

Pro gradu -tutkielma käsittelee Kanadan poliisivoimien, Royal Canadian Mounted Police (RCMP), vuoden 2014 operationaalista raporttia Kanadan kadonneista ja murhatuista alkuperäiskansojen naisista. Heitä katoaa ja murhataan Kanadassa suhteessa huomattavasti enemmän kuin muita naisia. Aihe on hyvin ajankohtainen sekä kriittinen ja siihen on paikallisten organisaatioiden lisäksi kiinnittänyt huomiota mm. Amnesty International ja Yhdistyneet Kansakunnat. Tilannetta pidetään jo ihmisoikeuskriisinä ja sen puolesta puhuminen voidaan nähdä osana laajempaa kansannousua alkuperäiskansojen oikeuksien puolesta. Kanadan hallitusta sekä poliisivoimia on syytetty välinpitämättömyydestä ja rasismista, poliiseja jopa väkivallasta alkuperäiskansojen naisia kohtaan. Kanadan hallitus ei myönnä ongelman olevan sosiologinen ilmiö, vaan pääministerin mukaan naisten katoamiset ja murhat ovat yksittäisiä rikoksia. Tilanteen taustalla on laajempi ongelma, joka juontaa juurensa kolonialismista, alkuperäiskansojen pakkokoulutuksesta ja heidän kulttuurinsa sekä identiteettinsä tuhoamisesta. Ennakkoluulot ja stereotypiat elävät yhä vahvana luoden heikon aseman alkuperäiskansojen edustajille ja tässä tapauksessa erityisesti naisille, joita myös usein syytetään omista ongelmistaan. Tutkielma selvittää, onko tämä operationaalinen raportti eriarvoisuutta, stereotypioita sekä ennakkoluuloja ylläpitävä ja tukeeko se näkemystä sosiologisesta ilmiöstä. Poliisivoimat ovat yhteiskunnassa vaikutusvaltaisessa asemassa ja voivat edesauttaa, jatkaa ja voimistaa syrjivää ajattelua, käytöstä ja viestintää. Vaikka he myös ajavat alkuperäiskansojen etuja, tulee heidän toimintaansa ja täten tätä kyseistä raporttia tarkastella kriittisesti. Tutkielma keskittyy kriittiseen diskurssianalyysiin (Fairclough 1995, Wodak & Meyer 2009). Raportin teksti ei ole avoimesti diskriminoivaa ja keskittyy tilastojen ja lukujen raportointiin sekä vertailuun, luoden samalla kuvan asianomaisista sekä tilanteesta yleisesti. Makroanalyysi (van Dijk 1977, 1980) mahdollistaa korkeamman tason ajatusten ja ideoiden esille tuonnin paljastaen ns. rivien välistä löytyvän viestinnän. Näistä makroanalyysin tuloksista etsitään erilaisia diskurssistrategioita (Reisigl & Wodak 2001), joiden avulla luodaan mm. kuva positiivisesta itsestä ja negatiivisesta toisesta. Näitä tuloksia tuetaan lyhyellä multimodaalisella analyysillä, joka keskittyy lähinnä raportin kahteen kuvaan (Kress & van Leeuwen 2006). Lopuksi tuloksista keskustellaan suhteessa yhteiskunnan valtasuhteisiin (Foucault 1976), rasismiin ja seksismiin. Analyysin perusteella raportti on selkeästi diskriminoiva. Se tuo esiin vanhoja stereotypioita ja ennakkoluuloja, esittää tilanteen alkuperäiskansojen sisäisenä ongelmana, jättää mainitsematta tilanteen taustat ja luo hyvin positiivisen kuvan poliisivoimista (RCMP). Tällä tavoin se ylläpitää yhteiskunnan epätasapainoisia valtasuhteita ja alkuperäiskansojen naisten heikompaa ja marginalisoitua asemaa. Raportti todistaa kuinka syvällä Kanadan yhteiskunnassa jopa institutionaalisella tasolla nämä ajatukset piilevät, sillä diskriminaatio ulottuu tapausten syistä niiden käsittelyyn ja raportointiin. Tilanne on huolestuttava ja voidaan nähdä sosiologisena ilmiönä. Poliisivoimien tulisi lisätä sisäistä koulutusta asian suhteen sekä hallituksen tutkia tätä ilmiönä ja paneutua sen selvittämiseen laaja-alaisesti ja läpinäkyvästi.

Identification and validation of novel prostate cancer biomarkers

Prostate cancer (PCa) has emerged as the most commonly diagnosed lethal cancer in European men. PCa is a heterogeneous cancer that in the majority of the cases is slow growing: consequently, these patients would not need any medical treatment. Currently, the measurement of prostate-specific antigen (PSA) from blood by immunoassay followed by digital rectal examination and a pathological examination of prostate tissue biopsies are the most widely used methods in the diagnosis of PCa. These methods suffer from a lack of sensitivity and specificity that may cause either missed cancers or overtreatment as a consequence of over-diagnosis. Therefore, more reliable biomarkers are needed for a better discrimination between indolent and potentially aggressive cancers. The aim of this thesis was the identification and validation of novel biomarkers for PCa. The mRNA expression level of 14 genes including AMACR, AR, PCA3, SPINK1, TMPRSS2-ERG, KLK3, ACSM1, CACNA1D, DLX1, LMNB1, PLA2G7, RHOU, SPON2, and TDRD1 was measured by a truly quantitative reverse transcription PCR in different prostate tissue samples from men with and without PCa. For the last eight genes the function of the genes in PCa progression was studied by a specific siRNA knockdown in PC-3 and VCaP cells. The results from radical prostatectomy and cystoprostatectomy samples showed statistically significant overexpression for all the target genes, except for KLK3 in men with PCa compared with men without PCa. Statistically significant difference was also observed in low versus high Gleason grade tumors (for PLA2G7), PSA relapse versus no relapse (for SPON2), and low versus high TNM stages (for CACNA1D and DLX1). Functional studies and siRNA silencing results revealed a cytotoxicity effect for the knock-down of DLX1, PLA2G7, and RHOU, and altered tumor cell invasion for PLA2G7, RHOU, ACSM1, and CACNA1D knock-down in 3D conditions. In addition, effects on tumor cell motility were observed after silencing PLA2G7 and RHOU in 2D monolayer cultures. Altogether, these findings indicate the possibility of utilizing these new markers as diagnostic and prognostic markers, and they may also represent therapeutic targets for PCa.

Customer Discovery and Customer Validation in Lean Software Startups

The traditional business models and the traditionally successful development methods that have been distinctive to the industrial era, do not satisfy the needs of modern IT companies. Due to the rapid nature of IT markets, the uncertainty of new innovations‟ success and the overwhelming competition with established companies, startups need to make quick decisions and eliminate wasted resources more effectively than ever before. There is a need for an empirical basis on which to build business models, as well as evaluate the presumptions regarding value and profit. Less than ten years ago, the Lean software development principles and practices became widely well-known in the academic circles. Those practices help startup entrepreneurs to validate their learning, test their assumptions and be more and more dynamical and flexible. What is special about today‟s software startups is that they are increasingly individual. There are quantitative research studies available regarding the details of Lean startups. Broad research with hundreds of companies presented in a few charts is informative, but a detailed study of fewer examples gives an insight to the way software entrepreneurs see Lean startup philosophy and how they describe it in their own words. This thesis focuses on Lean software startups‟ early phases, namely Customer Discovery (discovering a valuable solution to a real problem) and Customer Validation (being in a good market with a product which satisfies that market). The thesis first offers a sufficiently compact insight into the Lean software startup concept to a reader who is not previously familiar with the term. The Lean startup philosophy is then put into a real-life test, based on interviews with four Finnish Lean software startup entrepreneurs. The interviews reveal 1) whether the Lean startup philosophy is actually valuable for them, 2) how can the theory be practically implemented in real life and 3) does theoretical Lean startup knowledge compensate a lack of entrepreneurship experience. A reader gets familiar with the key elements and tools of Lean startups, as well as their mutual connections. The thesis explains why Lean startups waste less time and money than many other startups. The thesis, especially its research sections, aims at providing data and analysis simultaneously.

Customer Discovery and Customer Validation in Lean Software Startups

The traditional business models and the traditionally successful development methods that have been distinctive to the industrial era, do not satisfy the needs of modern IT companies. Due to the rapid nature of IT markets, the uncertainty of new innovations‟ success and the overwhelming competition with established companies, startups need to make quick decisions and eliminate wasted resources more effectively than ever before. There is a need for an empirical basis on which to build business models, as well as evaluate the presumptions regarding value and profit. Less than ten years ago, the Lean software development principles and practices became widely well-known in the academic circles. Those practices help startup entrepreneurs to validate their learning, test their assumptions and be more and more dynamical and flexible. What is special about today‟s software startups is that they are increasingly individual. There are quantitative research studies available regarding the details of Lean startups. Broad research with hundreds of companies presented in a few charts is informative, but a detailed study of fewer examples gives an insight to the way software entrepreneurs see Lean startup philosophy and how they describe it in their own words. This thesis focuses on Lean software startups‟ early phases, namely Customer Discovery (discovering a valuable solution to a real problem) and Customer Validation (being in a good market with a product which satisfies that market). The thesis first offers a sufficiently compact insight into the Lean software startup concept to a reader who is not previously familiar with the term. The Lean startup philosophy is then put into a real-life test, based on interviews with four Finnish Lean software startup entrepreneurs. The interviews reveal 1) whether the Lean startup philosophy is actually valuable for them, 2) how can the theory be practically implemented in real life and 3) does theoretical Lean startup knowledge compensate a lack of entrepreneurship experience. A reader gets familiar with the key elements and tools of Lean startups, as well as their mutual connections. The thesis explains why Lean startups waste less time and money than many other startups. The thesis, especially its research sections, aims at providing data and analysis simultaneously.