Die vorliegende Arbeit beinhaltet die Generierung und Evaluation von Natürlichen Killerzellen, die EGFRvIII-positive und SDF-1alpha sekretierende primäre Glioblastomzellen aufspüren, erkennen und effizient abtöten können. Die Kombination der gelenkten Zytotoxizität mit einer optimierten Migration von Effektorzellen des Immunsystems wird auf Grundlage der in dieser Arbeit gewonnenen Daten als ein vielversprechender Ansatz für eine zukünftige Therapie des primären Glioblastoms vorgeschlagen.

Chemotherapy is still one of the most widely used anticancer therapies. It is mostly about inhibiting the proliferation of rapidly dividing cells, so it is not selective for tumor cells. As a result, many undesirable side effects are associated with chemotherapy. The disadvantageous properties of chemotherapeutics can be largely eliminated by using conjugates of polymers with low molecular weight drugs. An example of such a conjugate is a doxorubicin-linked HPMA polymer. In addition to the properties obtained by polymer binding, such as achieving solubility in aqueous solutions, reducing systemic toxicity, increasing the maximum tolerated dose, or passive targeting by the EPR effect, the fact that doxorubicin induces immunogenic cell death is used in therapy with this drug. It has already been shown that after complete cure of the experimental mice with polymeric conjugates of HPMA with doxorubicin, some mice develop long-term resistance to re-inoculation with a lethal dose of tumor cells. Resistance is specific to the particular line of tumor cells from which the mouse was cured, and CD8+ cytotoxic T cells and IFNγ play an important role. In this work, we monitored changes in the proportion of immune populations and their activation markers after treatment with HPMA-based polymers with doxorubicin...

[ES] Las bacterias resistentes a múltiples antibióticos, como el Enterococo resistente a vancomicina (ERV), son un problema creciente en los pacientes hospitalizados, por lo que se necesita estrategias alternativas para combatir estos patógenos. Las infecciones causadas por ERV suelen comenzar con la colonización del tracto intestinal, un paso crucial que se afectado por la presencia de la microbiota. Sin embargo, los antibióticos alteran la microbiota y esto promueve la colonización de ERV. Una vez que el patógeno ha colonizado el intestino, alcanza niveles muy altos pudiendo diseminar a otros órganos y pacientes. A pesar de su importancia, se sabe muy poco sobre los genes que codifica para colonizar el intestino y sobre el mecanismo por el cual la microbiota suprime su colonización intestinal, siendo los dos objetivos principales. En primer lugar hemos utilizado una metodología previamente descrita (Zhang et al., 2017, BMC Genomics), basada en la generación de una librería de mutantes por transposición junto a secuenciación masiva, con el fin de identificar los genes codificados por ERV necesarios para la colonización del intestino en ratones. Además, hemos realizado análisis metatranscriptómicos para identificar aquellos genes más expresados. El análisis ha identificado genes cuya interrupción reduce significativamente la colonización intestinal en el intestino grueso. Los genes que más afectaron a la colonización codifican proteínas relacionadas con la absorción o el transporte de diversos nutrientes como los carbohidratos (subunidad EIIAB del transportador PTS de manosa, el regulador transcripcional de la familia LacI, ácido N-acetilmurámico 6-fosfato eterasa) o iones (proteína transportadora dependiente de ATP (ABC) y proteínas del grupo [Fe-S]). El papel de estos genes en la colonización se ha confirmado mediante experimentos de mutagénesis directa y de competición con la cepa salvaje. Además, estos genes afectan a la colonización intestinal con diferentes antibióticos (clindamicina y vancomicina). Para identificar el mecanismo molecular por el cual cada gen afecta a la colonización, hemos realizado experimentos in vitro y ex vivo además del análisis transcriptómico. Los experimentos in vitro confirman que las proteínas del grupo [Fe-S] están involucradas en el transporte iones de hierro, principalmente Fe3+. Por otra parte, los genes de la subunidad EIIAB del transportador de manosa y del ácido N-acetilmurámico 6-fosfato eterasa son necesarios para la utilización de la manosa y el ácido N-acetilmurámico, respectivamente, azúcares que suelen estar presentes en el intestino. También confirmamos que el regulador transcripcional de la familia LacI es un represor que afecta a proteínas transportadoras ABC, probablemente implicadas en la absorción de carbohidratos. Además, algunos de estos genes están codificados principalmente por cepas clínicas de E. faecium y en menor medida por cepas comensales. En segundo lugar, estudiamos los mecanismos de protección de un consorcio de cinco bacterias comensales, que anteriormente se había demostrado que disminuían la colonización intestinal por ERV en ratones. Mediante transcriptómica, metabolómica y los ensayos in vivo observamos que el consorcio bacteriano inhibe el crecimiento de ERV mediante la reducción de nutrientes, concretamente fructosa. Por último, el análisis ARN-Seq in vivo de cada aislado en combinación con los ensayos ex vivo e in vivo demostraron que una sola bacteria (Olsenella sp.) proporciona protección. En conjunto, los resultados obtenidos han identificado la función de genes específicos requeridos por ERV para colonizar el intestino. Además, hemos identificado un mecanismo mediante el cual la microbiota confiere protección. Estos resultados podrían conducir a nuevos enfoques terapéuticos para prevenir las infecciones causadas por este patógeno multiresistente a los antibióticos. / [CA] Els bacteris resistents a múltiples antibiòtics, com el Enterococo resistent a vancomicina (ERV), són un problema creixent en els pacients hospitalitzats, que són resistents a la majoria d'antibiòtics disponibles per la qual cosa es necessita estratègies alternatives per a combatre aquests patògens. Les infeccions causades per ERV solen començar amb la colonització del tracte intestinal, un pas crucial que es veu afectat per la presència de la microbiota. No obstant això, els antibiòtics alteren la microbiota i això promou la colonització de ERV. Una vegada que el patogen ha colonitzat l'intestí, aconsegueix nivells molt alts podent disseminar a altres òrgans i pacients. Malgrat la seua importància, se sap molt poc sobre els gens que codifica ERV per a colonitzar l'intestí i sobre el mecanisme pel qual la microbiota suprimeix la seua colonització intestinal. En primer lloc hem utilitzat una metodologia prèviament descrita (Zhang et al., 2017, BMC Genomics), basada en la generació d'una llibreria de mutants per transposició junt amb seqüenciació massiva, amb la finalitat d'identificar els gens codificats per ERV necessaris per a la colonització de l'intestí en ratolins. A més a més, hem realitzat anàlisi metatranscriptòmics per a identificar aquells gens més expressats. L'anàlisi ha identificat gens quina interrupció redueix significativament la colonització intestinal en l'intestí gros. Els gens que més van afectar la colonització codifiquen proteïnes relacionades amb l'absorció o el transport de diversos nutrients com els carbohidrats (subunitat EIIAB del transportador PTS de manosa, el regulador transcripcional de la família LacI, àcid N-acetilmuràmic 6-fosfat eterasa) o ions (proteïna transportadora dependent d'ATP (ABC) i proteïnes del grup [Fe-S]). El paper d'aquests gens en la colonització s'ha confirmat mitjançant experiments de mutagènesis directa i de competició amb el cep salvatge. A més, aquests gens afecten la colonització intestinal amb diferents antibiòtics (clindamicina i vancomicina). Per a identificar el mecanisme molecular pel qual cada gen afecta a la colonització, hem realitzat experiments in vitro i ex viu a més de l'anàlisi transcriptòmic. Els experiments in vitro confirmen que les proteïnes del grup [Fe-S] estan involucrades en el transport d'ions de ferro, principalment Fe3+. D'altra banda, els gens de la subunitat EIIAB del transportador PTS de manosa i de l'àcid N-acetilmuràmic 6-fosfat eterasa són necessaris per a la utilització de la manosa i l'àcid N-acetilmuràmic, respectivament, sucres que solen estar presents en l'intestí. També confirmem que el regulador transcripcional de la família LacI és un repressor que afecta proteïnes transportadores ABC, probablement implicades en l'absorció de carbohidrats. A més a més, alguns d'aquests gens estan codificats principalment per ceps clínics de E. faecium i en menor mesura per ceps comensals. En segon lloc, estudiem els mecanismes de protecció d'un consorci de cinc bacteris comensals, que adès s'havia demostrat que disminuïen la colonització intestinal per ERV en ratolins. Amb l'ús de transcriptòmica, metabolòmica i els assajos in vivo observem que el consorci bacterià inhibeix el creixement de ERV mitjançant la reducció de nutrients, concretament fructosa. Finalment, l'anàlisi ARN-Seq in vivo de cada aïllat en combinació amb els assajos ex viu i in vivo van demostrar que un sol bacteri (Olsenella sp.) proporciona protecció. En conjunt, els resultats obtinguts han identificat la funció de gens específics requerits per ERV per a colonitzar l'intestí. A més, hem identificat un mecanisme mitjançant el qual la microbiota confereix protecció. Aquests resultats podrien conduir a nous enfocaments terapèutics per a previndre les infeccions causades per aquest patogen multiresistent als antibiòtics. / [EN] Multidrug-resistant bacteria, such as vancomycin-resistant-Enterococcus (VRE), are an increasing problem in hospitalized patients. Some VRE strains can be resistant to most available antibiotics, thus, alternative strategies to antibiotics are urgently needed to combat these challenging pathogens. Infections caused by VRE frequently start by colonization of the intestinal tract, a crucial step that is impaired by the presence of the intestinal microbiota. Administration of antibiotics disrupts the microbiota, which promotes VRE intestinal colonization. Once VRE has colonized the gut, it reaches very high levels, which promotes its dissemination to other organs and its transfer to other patients. Despite the relevance of VRE gut colonization, very little is known about the genes encoded by this pathogen to colonize the gut and about the mechanisms by which the microbiota suppresses VRE gut colonization. In this thesis, we have utilized a previously described methodology (Zhang et al., 2017, BMC Genomics), based on the generation of a transposon mutant library coupled with high-throughput sequencing, in order to identify VRE encoded genes required for colonization of the mouse intestinal tract. In addition, we have performed metatranscriptomic analysis in mice to identify VRE genes specifically expressed in the gut. Our analysis has identified genes whose disruption significantly reduces VRE gut colonization in the large intestine. The genes that most affected VRE gut colonization encoded for proteins related to the uptake or transport of diverse nutrients such as carbohydrates (PTS mannose transporter subunit EIIAB, LacI family DNA-binding transcriptional regulator, N-acetylmuramic acid 6-phosphate etherase) or ions (phosphate ABC transporter ATP-binding protein and proteins from [Fe-S] cluster). The role of these genes in gut colonization has been confirmed through targeted mutagenesis and competition experiments against a wild type strain. Moreover, these genes affect gut colonization under different antibiotic treatments (clindamycin and vancomycin). To elucidate the mechanism by which each gene influences gut colonization, we have performed in vitro and ex vivo experiments besides transcriptomic analysis. In vitro experiments confirm that proteins from [Fe-S] cluster are involved in the transport of different forms of iron ions, mostly Fe3+. On the other hand, the PTS mannose transporter subunit EIIAB and N-acetylmuramic acid 6-phosphate etherase genes are required for the utilization of mannose and N-acetyl-muramic acid, respectively, sugars that are usually present in the intestinal environment. We have also confirmed that LacI family DNA-binding transcriptional regulator is a repressor that affects the expression of genes encoding for an ABC transporter probably involved in the uptake of carbohydrates. Furthermore, we have confirmed that some of these genes are encoded mainly by E. faecium clinical strains but not or to a lower extent by commensal strains. Secondly, we studied the mechanisms of protection of a consortium of five commensals bacteria, previously shown to restrict VRE gut colonization in mice. Functional transcriptomics in combination with targeted metabolomics and in vivo assays performed in this thesis indicated that the bacterial consortium inhibits VRE growth through nutrient depletion, specifically by reducing the levels of fructose. Finally, in vivo RNA-Seq analysis of each bacterial isolate of the consortium in combination with ex vivo and in vivo assays demonstrated that a single bacterium (Olsenella sp.) could recapitulate the protective effect. Altogether, the results obtained have identified the function of specific genes required by VRE to colonize the gut. In addition, we have identified a specific mechanism by which the microbiota confers protection against VRE colonization. These results could lead to novel therapeutic approaches to prevent infections caused by this pathogen. / Flor Duro, A. (2021). Characterization of Genes and Functions Required by Multidrug-resistant Enterococci to Colonize the Intestine [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/166494 / TESIS

Mängden datainsamling växer snabbt i dagens informationssamhälle. I takt med attwebbinnehavare samlar in allt mer personlig information om internetanvändare, harkontroverser om integritet och negativa attityder uppkommit. Trots dessa kontroverser hartidigare forskning visat att internetanvändare tenderar att ignorera försiktighetsåtgärder för attskydda deras integritet. Denna skillnad mellan attityd och beteende beskrivs som "the privacyparadox". Syftet med denna studie är att undersöka “the privacy paradox” och de faktorersom påverkar fenomenen med avseende på personligt riktad annonsering. En konceptuellmodell med olika relationer konstruerades, baserat på tidigare forskning. Komponenterna imodellen inkluderade följande faktorer: tillit, upplevd risk, generell integritetsoro, upplevdfördel, avsett beteende och faktiskt beteende. För att utvärdera modellen genomfördes enenkätstudie (N = 107). Den insamlade datans resultat analyserades med hjälp av univariatstatistik, bivariat statistik och i slutändan användes PLS-SEM-metoder för multivariatstatistik. Resultaten bevisade att det finns en påtaglig skillnad mellan internetanvändareuttryckta attityd och beteende, vilket inte kunde förklaras av demografiska variabler.Dessutom visade resultaten att påverkansfaktorerna hade en positiv effekt på attityd ochbeteende. Genom att tolka dessa resultat drog vi slutsatsen att upplevd risk och tillit har enpositiv effekt på generell integritetsoro. Följaktligen har integritetsoro och upplevd fördel enpositiv effekt på avsett beteende, vilket i sin tur har en positiv effekt på faktiskt beteende. / The amount of data collection is growing rapidly in today’s information society. As thecollection of personal information by web holders increases, controversies about privacy andnegative attitudes have occurred among web users. Despite this, previous research has shownthat web users tend to ignore precautions in order to protect their privacy. This differencebetween attitude and behavior is described as “the privacy paradox”. The aim of this study isto investigate the privacy paradox and the influencing factors of the phenomena, with regardsto personally targeted advertisement. A conceptual model with various relationships wasconstructed, based on previous research. Components of the model included the followingfactors: trust, perceived risk, privacy concerns, perceived benefits, behavioral intention andactual behavior. In order to evaluate the model, a survey was conducted (N = 107). Thesurvey’s results were analyzed by using univariate statistics, bivariate statistics and ultimatelyPLS-SEM methods were applied for the multivariate statistics. The results proved that thereis indeed a difference between web user’s expressed attitude and behavior, which could notbe explained by demographic variables. Furthermore, the results indicated that theinfluencing factors had a positive effect on attitude and behavior. By interpreting theseresults, we concluded that perceived risk and trust have a positive effect on privacy concerns.Furthermore, privacy concerns and perceived benefits have a positive effect on behavioralintention, which in turn has a positive effect on actual behavior.

Discovery of new antifungal chemo-therapeutics for humans is limited by the large degree of conservation among eukaryotic organisms. In recent years, the histone acetyl-transferase Rtt109 was identified as the sole enzyme responsible for an abundant and important histone modification, histone H3 lysine 56 (H3K56) acetylation. In the absence of Rtt109, the lack of acetylated H3K56 renders yeast cells extremely sensitive to genotoxic agents. Consequently, the ability to sustain genotoxic stress from the host immune system is crucial for pathogens to perpetuate an infection. Because Rtt109 is conserved only within the fungal kingdom, I reasoned that Rtt109 could be a novel drug target. My dissertation first establishes that genome stability provided by Rtt109 and H3K56 acetylation is required for Candida albicans pathogenesis. I demonstrate that mice infected with rtt109 -/- cells experience a significant reduction in organ pathology and mortality rate. I hypothesized that the avirulent phenotype of rtt109 -/- cells is due to their intrinsic hypersensitivity to the genotoxic effects of reactive oxygen species (ROS), which are utilized by phagocytic cells of the immune system to kill pathogens. Indeed, C. albicans rtt109 -/- cells are more efficiently killed by macrophages in vitro than are wild-type cells. However, inhibition of ROS generation in macrophages renders rtt109 -/- and wild-type yeast cells equally resilient to killing. These findings support the concept that ability to resist genotoxic stress conferred by Rtt109 and H3K56 acetylation is a virulence factor for fungal pathogens and establish Rtt109 as an opportune drug- target for novel antifungal therapeutics. Second, I report the discovery of a specific chemical inhibitor of Rtt109 catalysis as the initial step in the development of a novel antifungal agent. We established a collaboration with the Broad Institute (Cambridge, MA) to perform a high-throughput screen of 300,000 compounds. From these, I identified a single chemical, termed KB7, which specifically inhibits Rtt109 catalysis, with no effect on other HAT enzymes tested. KB7 has an IC50 value of approximately 60 nM and displays noncompetitive inhibition regarding both acetyl-coenzyme A and histone substrates. With the genotoxic agent camptothecin, KB7 causes a synergistic decrease in C. albicans growth rate. However, this effect is only observed in an efflux-pump mutant, suggesting that this compound would be more effective if it were better retained intracellularly. Further studies through structure-activity relationship (SAR) modifications will be conducted on KB7 to improve its effective cellular concentration.

Le cancer du sein triple négatif (CSTN) représente 10-15% des cancers du sein. Son pronostic est sombre en particulier face à la rareté des thérapies ciblées adaptées à ce sous type. Sa complexité de prise en charge est directement liée à sa grande hétérogénéité tant au niveau moléculaire que morphologique.Dans ce contexte, nous avons développés des modèles de Patient Derived Xenograft (PDX) issus de CSTN. Ce modèle, robuste, a la particularité de retenir les caractéristiques (histologiques, génotypiques mais aussi phénotypiques) des tumeurs observées chez les patients.Dans notre cohorte de 61 PDX de CSTN, nous avons confirmé l’hétérogénéité anatomopathologique et génomique de ce sous type. Les différentes anomalies moléculaires mises en évidence sont de faible fréquence (<10%) mais 88% de nos modèles ont une altération potentiellement ciblables et plus de la moitié ont au moins 2 altérations ciblables. Nous nous sommes particulièrement intéressés à 2 sous types de CSTN : (i) le sous -type LAR (Luminal Androgen Receptor) dont nous avons décrit les premiers modèles de PDX : ces modèles présentent des altérations fréquentes de la voie PI3K ainsi que des réponses majeures aux inhibiteurs de cette voie ; (ii) le sous type métaplasique, dont 4 de nos 9 modèles présentent une double altération genomique dans les voies PI3K et RTK-MAPK ainsi que des réponses complètes et durables à la combinaison d’inhibiteurs de PI3K et de MAPK.Dans les autres sous-types de CSTN, nous avons également mis en évidence des taux de réponse importants aux inhibiteurs de la voie PI3K et MAPK. Les biomarqueurs de réponse à ces différentes thérapies ciblées testées sont en cours d’étude en particulier par intégration des données génomique et protéique de nos modèles. / Triple negative breast cancer (TNBC) accounts for 10-15% of breast cancers. Its prognosis is worse, particularly due to the rarity of targeted therapies adapted to this subtype. Its complexity of management is directly related to its high heterogeneity, both at the morphological and genomical levels.In this context, we developed Patient Derived Xenograft (PDX) models from TNBC. This robust model has the specificity of retaining the characteristics (histological, genotypic but also phenotypic) of the tumors observed in patients.In our cohort of 61 PDXs of TNBC, we confirmed the anatomopathological and genomical heterogeneity of this subtype. Majority of targeted alterations are of low frequency (<10%) but 88% of our models harbour a potential targetable alteration and more than half have at least 2 targetable alterations. We were particularly interested in 2 subtypes of TNBC: (i) the LAR subtype for which we have described the first PDX models: these models present frequent alterations of the PI3K pathway as well as major responses to PI3K inhibitors; (ii) the metaplastic subtype, of which 4 of our 9 models show double alterations in the PI3K and RTK-MAPK pathways and complete and durable responses to the combination of PI3K-MAPK inhibitors.In the other CSTN subtypes, we have also demonstrated significant response rates to PI3K and MAPK inhibitors. Biomarkers of response to these various targeted therapies tested are being studied, in particular by integrating the genomic and protein data from a higher number of PDX models.

At Base Elementary School (BES) in the Southwest United States school administrators were concerned that writing proficiency levels for 2014-2015 were below district and state standards and there was not a clear understanding of teachers' perceptions on writing proficiency of military-connected (MC) students at the target site. Therefore, the purpose of this qualitative case study was to explore teachers' perceptions on writing proficiency of MC students at BES. Using Lave and Wenger's communities of practice framework, a qualitative instrumental case study was used to discern perceptions of elementary English Language Arts (ELA) teachers regarding the writing proficiency of MC students. Through a purposeful sample of 12 ELA teachers, telephone interviews were used to explore teachers' writing perceptions. Data from interviews were analyzed using inductive and iterative analysis resulting in identification of key themes. Major themes included the status of existing writing practices, diverse culture of MC students, need for collaborative relationship building among teachers, and the need for targeted writing professional development (PD) focused on connecting evidence-based practices (EBP) to state writing standards using culturally responsive practices (CRP). The resulting project of a white paper, will promote stakeholder awareness of teachers' perceptions, includes themes supporting the findings with recommendations that teachers would benefit from targeted writing PD focused on EBP and CRP using a collaborative model. Teacher use of these recommendations may promote social change by improving writing support for MC students possibly leading to improved performance on state proficiency assessments.

Genom digitalisering av samhället och teknologins utveckling har marknadsföringsstrategier progressivt reformerats, från att uppmärksamma produkter mot konsumenten till att istället sätta konsumenten i fokus. Genom avancerade algoritmer, Business Intelligence och digitala DNA spår har det blivit möjligt att individualisera och rikta marknadsföring mot konsumentens intressen och även förutse individens konsumentbeteende. Samtidigt uttrycker individer ett stort värde för anonymitet och integritet online. Trots detta fortsätter konsumenter att frivilligt att lämna sin persondata, främst via olika kundklubbar, internet och sociala medier. Detta beteende påvisar en så kallad “privacy paradox”. Privacy paradox syftar på medvetenhet och oro kring utgivandet av persondata samtidigt som man agerar annorlunda. Avsikten med denna studie var att utforska om fenomenet privacy paradox existerar inom svenska konsumenters handlingar och konsumentens medvetenhet kring användning av personlig data för riktad marknadsföring online. Det empiriska materialet i denna studie består av semi-strukturerade intervjuer med sju olika respondenter gällande deras medvetenhet, tillit och integritet online. Resultatet analyserades med hjälp av den tematiska strategin för att lättare identifiera beetendemönster som respondenterna utgav. Slutligen besvaras fenomenet privacy paradox hos svenska konsumenter genom tre forskningsfrågor 1.​“Hur medvetna är svenska konsumenter om den information som de delar med sig av, i synnerhet inom riktad marknadsföring?” 2.​“Hur mycket värnar svenska konsumenter om sin integritet?” ​3.​“ Påvisar svenska konsumenter privacy paradox och varför?”. Majoriteten av respondenterna var medvetna om personliga uppgifter online, dock varierade medvetenheten om vad för information som fanns tillgänglig både för privata användare och verksamheter. Man sa sig även värna om sin integritet men ens handlingar stödde inte detta till fullo. Med hjälp av denna studie fann man att fenomenet privacy paradox existerar hos de svenska konsumenter som deltog under denna studie. Anledningar till dessa var bland annat att man inte vill bli exkluderad från samhället och det kognitiva förtroendet till verksamheter. Man litar på att de gör rätt för sig. Värnande om integritet visades då genom att man minskade mängden personinformation som andra privatpersoner kunde komma åt. En annan anledning som uppkom var svårigheten i att bryta vanor och beteendemönster. Därför fortsätter man agera på samma sätt som tidigare, trots ny kunskap samt GDPR. Respondenter hade olika nivåer av förståelse riktad marknadsföring. Det majoriteten inte var medvetna om var mängden av lagrad information samt hur den samlas in t.ex. genom cookies. / Through digitalisation of the society and the technological development, the marketing strategies has progressively been reformed. From mainly giving attention to the product towards the consumers to instead place the consumer in the center of attention. Subsequently advanced algorithms, Business Intelligence and digital DNA tracing has enabled individualisation and target marketing, for the interest of the consumer, this also gave access to predict consumer behaviour. Meanwhile individuals put a big value on anonymity and integrity online. Despite this consumers keep sharing their data voluntary, primarily through customer clubs, the internet and social media. This behaviour demonstrates a so called “privacy paradox”. Privacy paradox refers consumers awareness and concern about sharing personal data, while still sharing their information. The purpose of this study was to examine whether the phenomenon of privacy paradox exists in Swedish consumers actions and the consumer’s awareness of the use of personal data for targeted online marketing. The empirical material in this study exists of semi-structured interviews with 7 different respondents regarding their consciousness, trust and integrity online. The results were analyzed through the thematic strategy to easily identify behavioural patterns that the respondents showed. Lastly, the phenomenon of privacy paradox in Swedish consumers is answered through three research questions 1. ​“How aware are Swedish consumers regarding the information they share, particularly in target marketing? ​2. ​“How much does the Swedish consumer care about their integrity?” ​3. ​“Does the Swedish consumer show privacy paradox and why?”. The majority of the respondents were aware that personal information exists online. The awareness regarding what kind of information that is available for both private users and organisations varied. While respondents mentioned that they want to protect their privacy, their actions proved otherwise. With the help of this study, we could conclude that the phenomenon named privacy paradox exists through the information gathered from the swedish consumers that participated in this study. Reasons being the willingness to not be excluded from society and the cognitive trust towards organizations. You trust that they do the right thing. Respondents protected privacy by reducing the amount of personal information other individuals could access. Another reason that was brought up was the difficulty in changing habits and behaviour. Therefore respondents continued doing the same things as before, despite new knowledge and GDPR. Respondents showed different levels of understanding regarding targeted marketing. However the majority was not aware of the amount of stored information and how it is collected, for example through cookies.

Prostate cancer diagnostic algorithm Aim: The aim of the study is to implement the latest scientific knowledge in the diagnosis of prostate cancer (PC). We focused on tumor markers, imaging methods, prostate biopsy methodology and we created a diagnostic algorithm based on a review of current literature in combination with our own experience. Material and methods: The algorithm is divided into several branches, which have been individually subjected to clinical studies. Due to the low sensitivity and specificity of PSA, prostate health index (PHI) was added to the first line of patient stratification. 787 patients were primarily examined and these subsequently underwent radical prostatectomy. PHI levels were compared with definitive staging and grading. Cut-off values for PC detection and high-risk stratification, including locally advanced PC were determined. Next, 320 patients underwent prostate biopsy followed by radical prostatectomy. The cohort was further divided into two subgroups, patients with GS = 6 and patients with GS > 6. The ability of PHI to distinguish between insignificant and significant prostate cancer was evaluated. In a multicentric study with 395 patients, PHI with additional markers (tPSA, PSAD) and multiparametric magnetic resonance imaging of prostate (mpMRI) was assessed....

No description available.