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This master’s thesis studies engagement and player retention in a free-to-play mobile game. The research design of this study was causal comparative. The study was based on statistical analysis of 5,000 first time players of a mobile game. These players’ behaviour on their first day of playing was analysed. Game engagement was defined by combining views of prior research of school engagement and game engagement. Game engagement was defined as players’ involvement, interest, and connection to a game. Game engagement was further defined as a four-dimensional concept consisting of behavioural, cognitive, affective, and agentic engagement. This study focused on studying behavioural and agentic game engagement. This study focused on examining how different engaged player behaviours on the first day of gameplay were connected to whether players continue playing the game. Continued play was examined through player retention at two points in time: after the first day and after the first week of gameplay. The research questions of this study examined how behavioural and agentic game engagement on the first day of gameplay were connected to whether players continued playing the game after the first day and first week of playing. The results of this study showed that behavioural and agentic game engagement factors on the first day of playing were important predictors in player retention both after the first day and after the first week of playing. The variables of first day gameplay had different effects after the first day and first week of gameplay. The most influential first day variables predicting continued gameplay both after a day and after a week were customising the game and gathering game rewards. Social interaction and time spent playing also impacted player retention after the first day. After the first week, influential factors were time spent playing, gathering rewards and skill level on the first day. The results of this study can be applied in developing different game-based solutions.Sitoutumisen rooli pelaamisen jatkamisessa ilmaisessa mobiilipelissä. Tiivistelmä. Tämä pro gradu -tutkielma tarkastelee pelaajien sitoutumista ja pelaamisen jatkamista ilmaisessa mobiilipelissä. Tutkimuksessa tarkastellaan tilastollisen analyysin avulla 5,000 ensikertalaispelaajaa mobiilipelissä ensimmäisen pelipäivänsä aikana. Peliin sitoutuminen määritellään yhdistelemällä aiemman tutkimuksen näkökulmia. Pohjana määrittelylle toimivat kouluoppimiseen sitoutumisen ja peleihin sitoutumisen teoriat. Peliin sitoutuminen määritellään pelaajan osallistumisena, kiinnostuksena ja suhteena peliin. Tarkemmin peliin sitoutuminen määritellään neljästä osasta koostuvana käsitteenä. Nämä osat ovat behaviouraalinen, kognitiivinen, affektiivinen ja toimijuudellinen sitoutuminen. Tässä tutkimuksessa tutkitaan behavioraalista ja toimijuudellista peliin sitoutumista. Tutkimuksessa tarkastellaan sitä, onko pelaajien ensimmäisen pelipäivän toiminnalla yhteyttä siihen, jatkaako pelaaja pelaamista. Pelaamisen jatkamista tarkastellaan kahtena ajankohtana: ensimmäisen pelipäivän ja ensimmäisen peliviikon jälkeen. Tutkimuskysymykset tarkastelevat sitä, miten behavioraalinen ja toimijuudellinen peliin sitoutuminen ensimmäisenä päivänä ennustaa pelaamisen jatkamista ensimmäisen pelipäivän ja ensimmäisen peliviikon jälkeen. Tutkimuksen tulokset osoittavat, että behavioraalinen ja toimijuudellinen peliin sitoutuminen ensimmäisenä pelipäivänä ennustavat tilastollisesti merkittävästi pelaamisen jatkamista. Ensimmäisen päivän pelitoiminnoilla oli erilaisia yhteyksiä yhden päivän ja yhden viikon pelaamisen jälkeen. Merkitsevimmät ensipäivän pelitoiminnot, jotka ennustivat pelaamisen jatkamista sekä ensimmäisen päivän jälkeen että ensimmäisen viikon jälkeen olivat pelin kustomointi sekä palkintojen kerääminen. Myös sosiaalisella vuorovaikutuksella ja pelissä käytetyllä ajalla oli vaikutusta ensimmäisen päivän jälkeen pelaamisen jatkamiseen. Ensimmäisen viikon jälkeen ensipäivän toiminnasta vaikuttavia olivat myös pelissä käytetty aika, palkintojen kerääminen sekä taitotaso. Tutkimuksen tuloksia voi hyödyntää erilaisten pelipohjaisten ratkaisujen suunnittelussa.

Background: Autologous stem cell transplantation (auto-SCT) is a widely used treatment option in multiple myeloma (MM) patients. The optimal graft cellular composition is not known. Study design and methods: Autograft cellular composition was analyzed after freezing by flow cytometry in 127 MM patients participating in a prospective multicenter study. The impact of graft cellular composition on hematologic recovery and outcome after auto-SCT was evaluated. Results: A higher graft CD34⁺ cell content predicted faster platelet recovery after auto-SCT in both the short and long term. In patients with standard-risk cytogenetics, a higher graft CD34⁺ count (0.065 × 10⁶/kg, p = 0.009) and NK cell count (%gt;2.5 × 10⁶/kg, p = 0.026), lenalidomide maintenance and standard-risk cytogenetics predicted better PFS. In contrast, a higher CD34+ count (>2.5 × 10⁶/kg, p = 0.015) predicted worse PFS. A very low CD3⁺ cell count (≤20 × 10⁶/kg, p = 0.001) in the infused graft and high-risk cytogenetics remained predictive of worse OS. Conclusions: Autograft cellular composition may impact outcome in MM patients after auto-SCT. More studies are needed to define optimal graft composition.

Background: Autologous stem cell transplantation is an established treatment option for patients with multiple myeloma (MM) or non‐Hodgkinʼs lymphoma (NHL). Study design and methods: In this prospective multicenter study, 147 patients with MM were compared with 136 patients with NHL regarding the mobilization and apheresis of blood CD34+ cells, cellular composition of infused blood grafts, posttransplant recovery, and outcome. Results: Multiple myeloma patients mobilized CD34+ cells more effectively (6.3 × 10⁶/kg vs. 3.9 × 10⁶/kg, p = 0.001). The proportion of poor mobilizers (peak blood CD34+ cell count 100 days) nonrelapse mortality (NRM; 6% vs. 0%, p = 0.003). Conclusions: Non‐Hodgkinʼs lymphoma and MM patients differ in terms of mobilization of CD34+ cells, graft cellular composition, and posttransplant recovery. Thus, the optimal graft characteristics may also be different.

Tiivistelmä. Tarkastelen kandidaatintutkielmassani dissosiaatiota mielenterveyden häiriöiden oireena ja dissosiaatiohäiriöissä. Tutkimuskysymykseni ovat miten dissosiaatio voidaan määritellä, miten dissosiaatiohäiriöt kehittyvät, millaisia erityispiirteitä liittyy lapsuuden dissosiaatioon, miten dissosiaatiohäiriöitä voidaan diagnosoida sekä miten dissosiaatiota voidaan hoitaa. Tutkielmani on systemaattinen kirjallisuuskatsaus, jonka perustana on aiempi aiheeseen liittyvä tutkimuskirjallisuus. Dissosiaatio voidaan määritellä persoonallisuuden integraation puutteeksi, joka on seurausta traumasta. Etenkin lapsuuden trauma voi olla liikaa psyyken käsittelykyvylle, josta seuraa trauman eriyttäminen muusta persoonallisuudesta. Ei ole olemassa selkeää selitystä sille, miksi eri dissosiaatiohäiriöt kehittyvät, mutta niiden oireet vaikuttavat laajasti yksilön toimintakykyyn ja kykyyn jäsentää ympäröivää todellisuutta ja omaa identiteettiä. Lapsuuden dissosiaatio kehittyy trauman seurauksena adaptiivisena toimintona, joka mahdollistaa lapsen selviämisen. Silloin kun lapsi ei voi välttyä traumaattiselta kokemukselta ja koska hän ei välttämättä osaa käsitellä sellaista sen kohdatessaan, dissosiaatio mahdollistaa traumaattisen kokemuksen unohtamisen tai eriyttämisen muista psyyken toiminnoista. Dissosiaatiohäiriöiden diagnosoimisessa tulee ottaa huomioon samankaltaisuudet monien eri mielenterveyden häiriöiden kanssa. Esimerkiksi epävakaan persoonallisuushäiriön, masennuksen ja skitsofrenian oireet ovat usein yhteneviä dissosiaatiohäiriöiden kanssa. Dissosiaatiohäiriöistä kärsivillä on suuri riski saada väärä diagnoosi. Dissosiaatiohäiriön oikea diagnoosi on kuitenkin erittäin tärkeä tekijä oikean hoidon saamisessa. Diagnosointimenetelminä toimivat kliininen haastattelu ja erilaiset seulontamenetelmät, joista yleisimpiä ovat itsearviointikyselyt. Dissosiaatiohäiriöt ovat yhteydessä itsetuhoiseen käyttäytymiseen ja korkeaan terveydenhuoltopalveluiden käyttöasteeseen. Dissosiaatiohäiriöistä kärsivät hyötyvät dissosiaatioon ja traumaan keskittyvästä psykoterapiasta, joka etenee vaiheittain turvallisuuden luomisesta ja oireiden vähentämisestä traumaattisten muistojen kohtaamiseen ja käsittelyyn ja lopulta keskittyen identiteetin integroimiseen sekä tulevaisuuteen suuntaamiseen.

Tiivistelmä Myeloomassa luuytimen pahanlaatuiset plasmasolut syövyttävät luustoa ja tuottavat poikkeavaa valkuaista, paraproteiinia. Myelooman hoito aloitetaan, mikäli potilaalla todetaan hyperkalsemia, munuaisvaurio, anemia tai lyyttisiä luustopesäkkeitä. Näiden kohde-elinvaurioiden lisäksi tietyt laboratorio- ja luuston kuvantamislöydökset ovat nykyään hoidon aloittamisen aihe. Kliininen taudinkuva vaihtelee paljon ja määräytyy pitkälti tautisolukon geneettisten muutosten mukaan. Vaikka laajasti käytetty autologinen kantasolusiirtohoito ja 15 viime vuoden aikana käyttöön saadut myelooman patofysiologisiin avainkohtiin vaikuttavat lääkkeet ovat parantaneet erityisesti nuorempien potilaiden ennustetta. Yksittäisten potilaiden ennuste on hyvin vaihteleva. Erityisesti suuren riskin potilaille tarvittaisiin nykyistä tehokkaampia hoitoja. Abstract Multiple myeloma is characterized by proliferation of malignant plasma cells in the bone marrow with monoclonal protein in the serum and/or urine. Active treatment of the disease is initiated when associated with specific biomarkers or end-organ damage, i.e. anemia, renal insufficiency, lytic bone lesions or hypercalcemia. Genetic background of the disease has a substantial impact on the clinical course. Although overall survival of younger patients has increased with the wide use of autologous stem cell transplantation and the introduction of novel drugs, new therapeutic strategies are needed for patients with high-risk disease.

Background: Large randomized clinical trials (RCT) are the foundation of the registration of newly developed drugs. A potential problem with RCTs is that the inclusion/exclusion criteria will make the population different from the actual population treated in real life. Hence, it is important to understand how the results from the RCT can be generalized to a general population. Aims: The primary aim of the present study was to assess the generalizability of the large 1st line RCTs in Multiple Myeloma (MM) to the Nordic setting and to understand potential difference and magnitude in outcomes between RCTs and patients treated in standard care in the Nordics. Methods: A retrospective analysis was performed on an incident cohort of 2960 MM-patients from 24 hospitals in Denmark, Finland, Norway and Sweden. The database contained information on patient baseline characteristics, treatments and outcomes. Data from relevant 1st line MM RCTs was selected from the treatment MP (Waage, A., et al., Blood. 2010], MPT (Waage, A., et al., Blood. 2010) and VMP (San Miguel, J.F., et al., N Engl J Med, 2008) and baseline characteristics were compared to newly diagnosed Nordic MM treated patients. Potential difference in response and overall survival (OS) was estimated by adjusting the RWE population to the RCT population using matching adjusted indirect comparisons. Patients were matched on age (median approximated to mean), gender, calcium, beta2-microglobulin and ISS score 3. These variables were selected because they were reported in all trials and have previously been identified as having prognostic value. Results: Patients in the Nordic database treated with MP (n=880) had a response rate of (PD, NR, PR, VGPR, ≥nCR) of (13%, 39%, 38%, 6%, 4%). After matching (n=347), the response rate was slightly worse (12%, 43%, 36%, 6%, 3%). This can be compared to the response rate from the RCT of (7%, 53%, 33%, 3%, 4%). OS for Nordic MP treated patients was 2.67 years (2.25-3.17). After matching the OS was 3.37 years (2.86-3.96) and this can be compared to the trial with OS 2.40 years (2.23-2.66). Patients treated with MPT (n=283) in the Nordic countries had a response rate of (5%, 14%, 52%, 20%, 9%). After matching (n=179) the response rate was slightly changed to (6%, 20%, 50%, 13% 11%). The corresponding RCT response results were 14%, 29%, 34%, 10%, and 13% respectively. OS for Nordic MPT treated patients was 4.15 years (3.73- 4.74). After matching the OS was 4.28 years (3.98-NA) years and compared to 2.42 years (2.08-3.17) OS observed in the corresponding trial. Patients treated with VMP (n=59) in the Nordic countries had a response rate of (4%, 5%, 40%, 18%, 33%). After matching (n=31) the response rate was improved to (8%, 11%, 28%, 8%, 45%). This corresponding response rates shown in the trial are 1%, 23%, 33%, 8%, and 33% respectively. OS for Nordic MP treated patients was 4.86 years (3.79-NA). After matching the OS was 4.86 years (4.86-NA) and this can be compared to the trial with OS 4.70 years. Summary and Conclusions: Surprisingly Nordic treated MM patients do very well compared to, and even better than, patients treated in RCTs. Since the OS for all tested treatments improves after matching to the RCT baseline characteristics, patients recruited to the RCTs seems to be a bit better than ordinary Nordic patents. The database used in the present study, and the used method, can be valuable for generalizing the results to the Nordic setting and estimating potential difference for future RCTs and Nordic MM treated patients. Future research should include different data cuts to see whether the analyses are biased by differences subsequent treatments applied in RCTs and clinical practice.

Background: Several authors have highlighted the importance of a deep response to chemotherapy in multiple myeloma (MM), especially in first line. Aims: The objective was to assess which patient/treatment/disease characteristics are prognostic for a deep response. Also, to assess whether the deep response is prognostic for overall survival (OS) independent of treatment, treatment line and patient/disease characteristics. Methods: A retrospective analysis was performed on 2960 MM-patients from 24 hospitals in Denmark, Finland, Norway and Sweden. The database contained information on patient baseline characteristics such as age, gender, ISS stage, albumin, creatine, and MM type, which were recorded at start of first line therapy. The following outcomes were considered; response, time to next line of treatment (TTNT) and OS. The following categories of response were differentiated: progressive disease (PD), no response (NR), partial response (PR), very good PR (VGPR) and equal or better than near complete response (>=nCR). To identify prognostic factors for response, univariate and multivariate multinomial regression were conducted with response as dependent and patient baseline characteristics and type of treatment as independent variables. To assess whether response is an independent predictor of OS, multivariate cox-proportional hazard models were run for the first four lines of treatment. Results: Patients in the dataset were on average 67 years old, 48% were male, 28%, 41% and 31% in ISS stages I, II and III, respectively. Multinomial regression showed that type of treatment, age, ISS type and MM type were significant prognostic factors for response in first line. In second line, first line response, type of treatment and age were significant prognostic factors for response in second line. Multivariate cox-regression showed that in first line patients with NR, PR, VGPR and >=nCR had significant lower hazard ratio's (HRs) 0.61 (0.43-0.85), 0.56 (0.41-0.78), 0.34 (0.22-0.51) and 0.36 (0.24-0.54) respectively compared to PD. Age, Albumin, Calcium and Beta-2-microglobulin levels were also significant prognostic factors for OS with HRs of 1.03 (1.01- 1.04), 0.98 (0.96-0.99), 1.41 (1.11-1.79) and 1.02 (1.01-1.03) respectively. The following categorical variables also were significant prognostic factors for first line OS; type of treatment, ISS-stage and MM type. For second line OS multivariate cox-regression showed that patients with PR, VGPR and >=nCR had significant lower HR's 0.58 (0.46-0.73), 0.42 (0.3-0.58), 0.4 (0.27-0.6) compared to PD respectively. Age also had a significant HR of 1.02 (1.01-1.03). For third line OS multivariate cox-regression showed that patients with NR, PR, VGPR and >=nCR had significant lower HR's 0.67 (0.5-0.89), 0.37 (0.27-0.51), 0.32 (0.21-0.5), 0.18 (0.1-0.34) compared to PD respectively. Age also had a significant HR of 1.01 (1.00-1.02). For fourth line OS multivariate cox-regression showed that patients with PR, VGPR and >=nCR had significant lower HR's 0.45 (0.31-0.64), 0.31 (0.19-0.52) and 0.39 (0.21-0.73) compared to PD respectively. Age was also identified as a significant prognostic factor. Summary and Conclusions: Type of treatment, age, ISS type and MM type were significant prognostic factors for response in first line. For second line response, the significant prognostic factors were response in first line, type of treatment and age. Moreover, multivariate cox-regressions shows that in the first four lines of treatment, response is an independent prognostic factor for OS. Future research should include genetic prognostic factors, which were not collected in our dataset and could therefore not be assessed.

Background: The ongoing introduction of novel therapies for MM provides clinicians and patients various treatment options in numerous lines of treatment. Understanding the current treatment practices and the outcomes in different age groups is of vital importance to understand whether these new treatment should be used in patients from all age groups and where options for treatment optimization exist. Aims: (i) To describe treatment patterns and corresponding outcomes in terms of response, time to next therapy (TTNT) and overall survival (OS) of Nordic Multiple Myeloma (MM) patients with a focus on age. (ii) To investigate whether age affected the patients' probability of being treated with a conventional (e.g. melphelan prednisone) or a novel treatment (bortezomib, thalidomide or lenalidomide) and whether this treatment choice affected OS in the elderly. Methods: A retrospective analysis was performed on incident 2960 MMpatients from 24 hospitals in Denmark, Finland, Norway and Sweden. The database contained information on patient baseline characteristics such as age, gender, international staging system (ISS) stage, albumin, creatine, MM type and response, TTNT and OS over eight lines of treatment. The patients were stratified over three age groups (