Teknoyhteisöä uudistamassa : verkkoyhteisöllisyyden toteutuminen ylläpitäjän näkökulmasta

Opinnäytetyöni käsittelee verkkoyhteisöllisyyttä ja verkkosivun uudistamisen vaikutuksia yhteisöllisyyteen. Käsiteltävää aihetta lähestytään verkkosivun ylläpitäjän näkökulmasta. Työn tapausesimerkkinä on elektronisen musiikin harrastajille suunnattu verkkoyhteisö Platinum, jonka yhtenä ylläpitäjänä toimin. Platinumin yhteisöllisyys on pitkälti rakentunut käyttäjien käymän keskustelun varaan. Platinum on perustettu vuonna 2000 ja siihen kohdistetut uudistukset ovat olleet pitkälti pintapuolisia. Keskeisin syy uudistamiselle oli kuitenkin se, että Platinumin suosio elektronisen musiikin harrastajien keskuudessa alkoi vähentyä. Platinumin näkyvyyttä ja yhteisöllisyyttä haluttiin tukea uudistuksella, jossa Platinumia lähdettiin rakentamaan verkkolehdeksi. Uudistusprosessi tarjosi mielenkiintoisen tilaisuuden tarkastella verkkoyhteisöllisyyttä. Verkkoyhteisöllisyyttä tarkastellaan pääasiallisesti Platinumin kannalta, mutta vertailukohteena yhteisöllisyydestä käytetään toista vastaavaa verkkoyhteisöä, Klubitusta. Vertailukohteena Klubitus oli hyödyllinen, koska se on pääpiirteiltään samankaltainen kuin Platinum. Näiden sivujen keskustelut sekä niille teettämäni kyselyt tukivat ja vahvistivat havaintojani verkkoyhteisöllisyydestä. Käyttäjien näkökulmat ja käyttötottumukset ovat oleellinen alue verkkoyhteisöllisyydessä ja etenkin sivun uudistamisen yhteydessä nämä ovat erittäin tärkeitä. Opinnäytetyö keskittyy tarkastelemaan uudistusprosessin ensimmäistä vaihetta, jossa vasta osa uudistuksista on julkaistu. Kun otetaan huomioon uudistusten saama huomio ja vaikutus, voidaan väittää, että verkkoyhteisöllisyyttä on mahdollista tukea verkkosivun uudistuksilla. Nämä keinot on kuitenkin oltava tarkkaan suunniteltu ottaen huomioon kohderyhmä sekä yhteisön tarpeet. Platinumin kohdalla muutokset kohti verkkolehteä ovat olleet onnistuneita sekä tarpeellisia, koska vastaavanlaista palvelua ei ole ollut tarjolla. Käyttäjät ovat odottaneet muutoksia sivulla ja kaikenlaiset uudistukset ja parannukset on koettu onnistuneiksi. Konseptin muuttaminen Platinumin kohdalla on johtanut positiivisiin tuloksiin, kuten yhteisöllisyyden parantumiseen.

Artifact-free coronary magnetic resonance angiography and coronary vessel wall imaging in the presence of a new, metallic, coronary magnetic resonance imaging stent.

BACKGROUND: Coronary in-stent restenosis cannot be directly assessed by magnetic resonance angiography (MRA) because of the local signal void of currently used stainless steel stents. The aim of this study was to investigate the potential of a new, dedicated, coronary MR imaging (MRI) stent for artifact-free, coronary MRA and in-stent lumen and vessel wall visualization. METHODS AND RESULTS: Fifteen prototype stents were deployed in coronary arteries of 15 healthy swine and investigated with a double-oblique, navigator-gated, free-breathing, T2-prepared, 3D cartesian gradient-echo sequence; a T2-prepared, 3D spiral gradient-echo sequence; and a T2-prepared, 3D steady-state, free-precession coronary MRA sequence. Furthermore, black-blood vessel wall imaging by a dual-inversion-recovery, turbo spin-echo sequence was performed. Artifacts of the stented vessel segment and signal intensities of the coronary vessel lumen inside and outside the stent were assessed. With all investigated sequences, the vessel lumen and wall could be visualized without artifacts, including the stented vessel segment. No signal intensity alterations inside the stent when compared with the vessel lumen outside the stent were found. CONCLUSIONS: The new, coronary MRI stent allows for completely artifact-free coronary MRA and vessel wall imaging.

The ciliary smooth muscle electrotransfer: basic principles and potential for sustained intraocular production of therapeutic proteins.

BACKGROUND: We have developed a nonviral gene therapy method based on the electrotransfer of plasmid in the ciliary muscle. These easily accessible smooth muscle cells could be turned into a biofactory for any therapeutic proteins to be secreted in a sustained manner in the ocular media. METHODS: Electrical conditions, design of electrodes, plasmid formulation, method and number of injections were optimized in vivo in the rat by localizing β-galactosidase expression and quantifying reporter (luciferase) and therapeutic (anti-tumor necrosis factor) proteins secretion in the ocular media. Anatomical measurements were performed via human magnetic resonance imaging to design a human eye-sized prototype that was tested in the rabbit. RESULTS: In the rat, transscleral injection of 30 µg of plasmid diluted in half saline (77 mM NaCl) followed by application of eight square-wave electrical pulses (15 V, 10 ms, 5.3 Hz) using two platinum/iridium electrodes, an internal wire and an external sheet, delivered plasmid efficiently to the ciliary muscle fibers. Gene transfer resulted in a long-lasting (at least 5 months) and plasmid dose-/injection number- dependent secretion of different molecular weight proteins mainly in the vitreous, without any systemic exposure. Because ciliary muscle anatomical measurements remained constant among ages in adult humans, an integrated device comprising needle-electrodes was designed and manufactured. Its usefulness was validated in the rabbit. CONCLUSIONS: Plasmid electrotransfer to the ciliary muscle with a suitable medical device represents a promising local and sustained protein delivery system for treating posterior segment diseases, avoiding repeated intraocular injections.

Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial.

BACKGROUND: Platinum-based doublet chemotherapy is recommended to treat advanced non-small-cell lung cancer (NSCLC) in fit, non-elderly adults, but monotherapy is recommended for patients older than 70 years. We compared a carboplatin and paclitaxel doublet chemotherapy regimen with monotherapy in elderly patients with advanced NSCLC. METHODS: In this multicentre, open-label, phase 3, randomised trial we recruited patients aged 70-89 years with locally advanced or metastatic NSCLC and WHO performance status scores of 0-2. Patients received either four cycles (3 weeks on treatment, 1 week off treatment) of carboplatin (on day 1) plus paclitaxel (on days 1, 8, and 15) or five cycles (2 weeks on treatment, 1 week off treatment) of vinorelbine or gemcitabine monotherapy. Randomisation was done centrally with the minimisation method. The primary endpoint was overall survival, and analysis was done by intention to treat. This trial is registered, number NCT00298415. FINDINGS: 451 patients were enrolled. 226 were randomly assigned monotherapy and 225 doublet chemotherapy. Median age was 77 years and median follow-up was 30.3 months (range 8.6-45.2). Median overall survival was 10.3 months for doublet chemotherapy and 6.2 months for monotherapy (hazard ratio 0.64, 95% CI 0.52-0.78; p<0.0001); 1-year survival was 44.5% (95% CI 37.9-50.9) and 25.4% (19.9-31.3), respectively. Toxic effects were more frequent in the doublet chemotherapy group than in the monotherapy group (most frequent, decreased neutrophil count (108 [48.4%] vs 28 [12.4%]; asthenia 23 [10.3%] vs 13 [5.8%]). INTERPRETATION: Despite increased toxic effects, platinum-based doublet chemotherapy was associated with survival benefits compared with vinorelbine or gemcitabine monotherapy in elderly patients with NSCLC. We feel that the current treatment paradigm for these patients should be reconsidered. FUNDING: Intergroupe Francophone de Cancérologie Thoracique, Institut National du Cancer.

Moeglichkeiten der systemischen Therapie im metastasierten Stadium [Treatment options for chemotherapy in metastatic gastric cancer]

Die Ergebnisse mehrerer, in letzter Zeit publizierter Phase-III-Studien haben die therapeutischen Möglichkeiten in der Behandlung des metastasierten Magenkarzinoms deutlich erweitert. Die Dauerinfusion von 5-Fluorouracil (5-FU) kann ohne Verlust an Wirkung durch Capecitabin ersetzt werden, ebenso wie Cisplatin durch Oxaliplatin. Nach den Ergebnissen der REAL-2-Studie zeigt die Kombination aus Epirubicin, Oxaliplatin und Capecitabin (EOX) eine Verbesserung des Gesamtüberlebens (9,9 vs. 11,2 Monate; HR 0,8) im Vergleich zu Epirubicin, Cisplatin und 5-FU (ECF). Die Frage, ob in der First-Line-Therapie eine Dreifachkombination oder eine Zweifachkombination eingesetzt werden sollte, ist allerdings weiterhin umstritten. Die Kombination aus Irinotecan und 5-FU stellt für solche Patienten, bei denen aufgrund von Komorbiditäten eine platinfreie Therapie bevorzugt wird, eine Alternative zur Kombination Cisplatin/5-FU dar. Docetaxel, 5-FU und Cisplatin (DCF) hat sich bezüglich des Überlebens in einer randomisierten Phase-III-Studie als statistisch signifikant überlegen erwiesen, allerdings besteht eine ausgeprägte hämatologische Toxizität, welche die Anwendbarkeit insbesondere bei den häufig älteren Patienten mit einem Magenkarzinom limitiert. Randomisierte Phase-III-Studien zum Vergleich von DCF mit anderen Dreierkombinationen, wie z. B. EOX, stehen aus. Recently published results from several phase III trials have significantly increased the therapeutic options in the treatment of metastatic stomach cancer: The continuous infusion of 5-FU can be replaced by capecitabine, and cisplatin can be replaced by oxaliplatin in both cases without impairing efficacy. According to the results of the REAL-2 trial, the combination of epirubicin, oxaliplatin and capecitabine (EOX) achieved superior results for overall survival compared to epirubicin, cisplatin und 5-FU (ECF) (9.9 versus 11.2 months, HR 0.8). However, the question of whether an optimal first line therapy should include a triplet regimen or the sequential use of doublets is a matter of debate. The combination of irinotecan and 5-FU may serve as an alternative to platinum-containing regimens in patients where, due to co-morbidity, a platinum-free regimen is preferred. The 3-drug combination of docetaxel, 5-FU and cisplatin (DCF) demonstrated a statistically significant survival benefit compared to the 2-drug combination of 5-FU and cisplatin in a randomized phase III trial, although results were limited by a particularly significant hematological toxicity, which prevents its application in the large group of elderly patients with gastric cancer. Direct randomized phase III comparisons of DCF with other 3-drug combinations, such as EOX are still missing.

The role of cisplatin and NAMI-A plasma-protein interactions in relation to combination therapy

The aim of the study is to evaluate the differences of protein binding of NAMI-A, a new ruthenium drug endowed with selective antimetastatic properties, and of cisplatin and to ascertain the possibility to use two drugs based on heavy metals in combination to treat solid tumour metastases. For this purpose, we have developed a technique that allows the proteins, to which metal drugs bind, to be identified from real protein mixtures. Following incubation with the drugs, the bands containing platinum and/or ruthenium are separated by native PAGE, SDS-PAGE and 2D gel electrophoresis, and identified using laser ablation inductively coupled plasma mass spectrometry. Both drugs interact with essentially the same proteins which, characterised by proteomics, are human serum albumin precursor, macroglobulin alpha 2 and human serotransferrin precursor. The interactions of NAMI-A are largely reversible whereas cisplatin forms stronger interactions that are less reversible. These data correlate well with the MCa mammary carcinoma model on which full doses of NAMI-A combined with cisplatin show additive effects as compared to each treatment taken alone, independently of whether NAMI-A precedes or follows cisplatin. Furthermore, the implication from this study is that the significantly lower toxicity of NAMI-A, compared to cisplatin, could be a consequence of differences in the mode of binding to plasma proteins, involving weaker interactions compared to cisplatin.

Operative Treatment of Ovarian Cancer and Borderline Tumors in Different Hospital Categories in Finland

Surgery is the cornerstone of ovarian cancer treatment and maximal cytoreduction is important. In the early 1980’s primary surgical treatment of ovarian cancer was performed in over 80 hospitals in Finland. The significance of the operative volume of the hospital, of the training of the surgeons and of centralization of surgical treatment has been widely discussed. The aim of the present study was to evaluate the outcome of surgical treatment of ovarian cancer in different hospital categories retrospectively and prospectively, and to analyze if any differences are reflected in survival. The retrospective study included 3851 ovarian cancer patients operated between 1983 and 1994 in Finland. The data was analyzed according to hospital category (university, central, and other) and by quartiles of the hospital operative volume. The results showed that patients operated in the highest operative volume hospitals had the best relative survival. When stratifying the analysis by the period of diagnosis (1983-1988 and 1989-1994), the university hospitals improved their performance the most. The prospective part of the thesis was initiated in 1999 and included 307 patients with invasive ovarian cancer and 65 patients with an ovarian borderline tumor. The baseline and 5-year surveys used a questionnaire that was filled in by the operating surgeons. For analysis of the 5-year followup data, the hospitals were divided into three categories (<10, 10-20, or >20 patients operated in 1999). The effect of the surgical volume was analyzed also as a continuous variable (1-47 operations per year). In university hospitals, pelvic lymphadenectomy was performed in 88 %, and para-aortic lymphadenectomy in 73 %, of the patients with stage I disease. The corresponding figures ranged from 11 % to 21 % in the other hospitals. For stage III ovarian cancer patients operated by gynecological oncologists, the estimated odds ratio for no macroscopic residual tumor was 3.0 times higher (95 % CI 1.2-7.5) than for those operated by general gynecologists. In the university and other hospitals 82% of the patients received platinum-based chemotherapy. Platinum + taxane combination was given to 63 % of the patients in the university and in 49 % in the other hospitals (p = 0.0763). Only a minority of the patients with tumors of borderline malignancy were staged according to recommendations, most often multiple peritoneal biopsies and omentectomy were neglected. FIGO stage, patient age, and residual tumor were independent prognostic factors of cancer-specific 5-year survival. A higher hospital operative volume was also a significant prognostic factor for better cancer-specific survival (p = 0.036) and disease-free survival (p = 0.048). In conclusion, ovarian cancer patients operated in high-volume university hospitals were more often optimally debulked and had a significantly better cancer-specific survival than patients operated in other hospitals. These results favor centralization of primary surgical treatment of ovarian cancer.

Electrochemical synthesis of mesoporous CoPt nanowires for methanol oxidation

A new electrochemical method to synthesize mesoporous nanowires of alloys has been developed. Electrochemical deposition in ionic liquid-in-water (IL/W) microemulsion has been successful to grow mesoporous CoPt nanowires in the interior of polycarbonate membranes. The viscosity of the medium was high, but it did not avoid the entrance of the microemulsion in the interior of the membrane"s channels. The structure of the IL/W microemulsions, with droplets of ionic liquid (4 nm average diameter) dispersed in CoPt aqueous solution, defined the structure of the nanowires, with pores of a few nanometers, because CoPt alloy deposited only from the aqueous component of the microemulsion. The electrodeposition in IL/W microemulsion allows obtaining mesoporous structures in which the small pores must correspond to the size of the droplets of the electrolytic aqueous component of the microemulsion. The IL main phase is like a template for the confined electrodeposition. The comparison of the electrocatalytic behaviours towards methanol oxidation of mesoporous and compact CoPt nanowires of the same composition, demonstrated the porosity of the material. For the same material mass, the CoPt mesoporous nanowires present a surface area 16 times greater than compact ones, and comparable to that observed for commercial carbon-supported platinum nanoparticles.

Consolidation whole abdomen irradiation following adjuvant carboplatin-paclitaxel based chemotherapy for advanced uterine epithelial cancer: feasibility, toxicity and outcomes.

BACKGROUND: To evaluate feasibility and preliminary outcomes associated with sequential whole abdomen irradiation (WAI) as consolidative treatment following comprehensive surgery and systemic chemotherapy for advanced endometrial cancer. METHODS: We conducted a retrospective analysis of patients treated at our institution from 2000 to 2011. Inclusion criteria were stage III-IV endometrial cancer patients with histological proof of one or more sites of extra-uterine abdomen-confined disease, treated with WAI as part of multimodal therapy. Endpoints were feasibility, acute toxicity, late effects, recurrence-free survival (RFS) and overall survival (OS). Twenty patients were identified. Chemotherapy consisted of 3 to 6 cycles of a platinum-paclitaxel regimen in 18 patients. WAI was delivered using conventional technique to a median total dose of 27.5 Gy. RESULTS: No grade 4 toxicities occurred during chemotherapy or radiotherapy. No radiation dose reduction was necessary. Three patients developed small bowel obstruction, all in the context of recurrent intraperitoneal disease. Kaplan-Meier estimates and 95% confidence intervals for RFS and OS at one year were 63% (38-80%) and 83% (56-94%) and at 3 years 57% (33-76%) and 62% (34-81%), respectively. On univariate Cox analysis, stage IVB and serous papillary (SP) histology were found to be statistically significantly (at the p = 0.05 level) associated with worse RFS and OS. The peritoneal cavity was the most frequent site of initial failure. CONCLUSIONS: Consolidative WAI following chemotherapy is feasible and can be performed without interruption with manageable acute and late toxicity. Patients with endometrioid adenocarcinoma, especially stage FIGO III, had favorable outcomes possibly meriting prospective evaluation of the addition of WAI following chemotherapy in selected patients. Patients with SP do poorly and do not routinely benefit from this approach.

Allianssit metsä- ja ICT -sektoreilla vuosina 1990-2005 - globaalin kehityksen analyysi

Pro gradu -tutkielman tavoitteena on tarkastella metsä- ja ICT-sektorin allianssien kehitystä vuosina 1990-2005. Lisäksi tarkoituksena on tutkia, voidaanko osoittaa yhteys allianssien ja yrityksen taloudellisen menestymisen välillä. Yhteyden testaamissa käytetään lineaarista regressiota. Aineisto perustuu SDC Platinum -tietokannasta haettuihin allianssitietoihin sekä Thomson One Banker -tietokannan tilinpäätöstietoihin, jotka koskevat 70 liikevaihdoltaan maailman suurinta metsäyritystä ja 43 liikevaihdoltaanmaailman suurinta ICT-yritystä. Hypoteesit vahvistuivat osittain. Toimialan kehitysvaihetta ja alliansseja koskevat hypoteesit vahvistuivat kahta lukuun ottamatta, eli toimialan luonne ja kehitysvaihe vaikuttavat allianssimääriin ja -laatuun. Allianssien ja taloudellisen menestymisen yhteyttä koskevat hypoteesit vahvistuivat osittain. Testauksessa löydettiin positiivinen, tilastollisesti merkitsevä yhteys allianssien ja liikevaihdon välillä sekä sijoitetunpääoman tuoton väliltä. Allianssien yhteismäärä vaikutti positiivisesti liikevaihdon kasvuprosenttiin ICT- ja yhdistelmäaineistossa. Uusien allianssien osuus vaikutti positiivisesti vain sijoitetun pääoman tuottoon. Strategisten allianssien osalta saatiin vain ristiriitaisia tuloksia. Metsäaineistossa ne vaikuttivat negatiivisesti liikevaihdon kasvuun, mutta yhdistelmäaineistossa löydettiin positiivinen yhteys. Liiketuottoprosentin ja allianssien välillä ei voitu osoittaa lainkaan yhteyttä.

Complexes of Pd(II) and Pt(II) with 9-aminoacridine: reactions with DNA and study of their antiproliferative activity

Four new metal complexes {M = Pd(II) or Pt(II)} containing the ligand 9-aminoacridine (9AA) were prepared. The compounds were characterized by FT-IR and 1H, 13C, and 195Pt NMR spectroscopies. Crystal structure of the palladium complex of formulae [Pd(9AA)(μ-Cl)]2 · 2DMF was determined by X-ray diffraction. Two 9-acridine molecules in the imine form bind symmetrically to the metal ions in a bidentate fashion through the imine nitrogen atom and the C(1) atom of the aminoacridine closing a new five-membered ring. By reaction with phosphine or pyridine, the Cl bridges broke and compounds with general formulae [Pd(9AA)Cl(L)] (where L = PPh3 or py) were formed. A mononuclear complex of platinum of formulae [Pt(9AA)Cl(DMSO)] was also obtained by direct reaction of 9-aminoacridine and the complex [PtCl2(DMSO)2]. The capacity of the compounds to modify the secondary and tertiary structures of DNA was evaluated by means of circular dichroism and electrophoretic mobility. Both palladium and platinum compounds proved active in the modification of both the secondary and tertiary DNA structures. AFM images showed noticeable modifications of the morphology of the plasmid pBR322 DNA by the compounds probably due to the intercalation of the complexes between base pairs of the DNA molecule. Finally, the palladium complex was tested for antiproliferative activity against three different human tumor cell lines. The results suggest that the palladium complex of formula [Pd(9AA)(μ-Cl)]2 has significant antiproliferative activity, although it is less active than cisplatin.

Complexes of Pd(II) and Pt(II) with 9-aminoacridine: reactions with DNA and study of their antiproliferative activity

Four new metal complexes {M = Pd(II) or Pt(II)} containing the ligand 9-aminoacridine (9AA) were prepared. The compounds were characterized by FT-IR and 1H, 13C, and 195Pt NMR spectroscopies. Crystal structure of the palladium complex of formulae [Pd(9AA)(μ-Cl)]2 · 2DMF was determined by X-ray diffraction. Two 9-acridine molecules in the imine form bind symmetrically to the metal ions in a bidentate fashion through the imine nitrogen atom and the C(1) atom of the aminoacridine closing a new five-membered ring. By reaction with phosphine or pyridine, the Cl bridges broke and compounds with general formulae [Pd(9AA)Cl(L)] (where L = PPh3 or py) were formed. A mononuclear complex of platinum of formulae [Pt(9AA)Cl(DMSO)] was also obtained by direct reaction of 9-aminoacridine and the complex [PtCl2(DMSO)2]. The capacity of the compounds to modify the secondary and tertiary structures of DNA was evaluated by means of circular dichroism and electrophoretic mobility. Both palladium and platinum compounds proved active in the modification of both the secondary and tertiary DNA structures. AFM images showed noticeable modifications of the morphology of the plasmid pBR322 DNA by the compounds probably due to the intercalation of the complexes between base pairs of the DNA molecule. Finally, the palladium complex was tested for antiproliferative activity against three different human tumor cell lines. The results suggest that the palladium complex of formula [Pd(9AA)(μ-Cl)]2 has significant antiproliferative activity, although it is less active than cisplatin.

Complexes of Pd(II) and Pt(II) with 9-aminoacridine: reactions with DNA and study of their antiproliferative activity

Four new metal complexes {M = Pd(II) or Pt(II)} containing the ligand 9-aminoacridine (9AA) were prepared. The compounds were characterized by FT-IR and 1H, 13C, and 195Pt NMR spectroscopies. Crystal structure of the palladium complex of formulae [Pd(9AA)(μ-Cl)]2 · 2DMF was determined by X-ray diffraction. Two 9-acridine molecules in the imine form bind symmetrically to the metal ions in a bidentate fashion through the imine nitrogen atom and the C(1) atom of the aminoacridine closing a new five-membered ring. By reaction with phosphine or pyridine, the Cl bridges broke and compounds with general formulae [Pd(9AA)Cl(L)] (where L = PPh3 or py) were formed. A mononuclear complex of platinum of formulae [Pt(9AA)Cl(DMSO)] was also obtained by direct reaction of 9-aminoacridine and the complex [PtCl2(DMSO)2]. The capacity of the compounds to modify the secondary and tertiary structures of DNA was evaluated by means of circular dichroism and electrophoretic mobility. Both palladium and platinum compounds proved active in the modification of both the secondary and tertiary DNA structures. AFM images showed noticeable modifications of the morphology of the plasmid pBR322 DNA by the compounds probably due to the intercalation of the complexes between base pairs of the DNA molecule. Finally, the palladium complex was tested for antiproliferative activity against three different human tumor cell lines. The results suggest that the palladium complex of formula [Pd(9AA)(μ-Cl)]2 has significant antiproliferative activity, although it is less active than cisplatin.