Sensory auditory processing and intuitive sound detection : an investigation of musical experts and nonexperts

The auditory system can detect occasional changes (deviants) in acoustic regularities without the need for subjects to focus their attention on the sound material. Deviant detection is reflected in the elicitation of the mismatch negativity component (MMN) of the event-related potentials. In the studies presented in this thesis, the MMN is used to investigate the auditory abilities for detecting similarities and regularities in sound streams. To investigate the limits of these processes, professional musicians have been tested in some of the studies. The results show that auditory grouping is already more advanced in musicians than in nonmusicians and that the auditory system of musicians can, unlike that of nonmusicians, detect a numerical regularity of always four tones in a series. These results suggest that sensory auditory processing in musicians is not only a fine tuning of universal abilities, but is also qualitatively more advanced than in nonmusicians. In addition, the relationship between the auditory change-detection function and perception is examined. It is shown that, contrary to the generally accepted view, MMN elicitation does not necessarily correlate with perception. The outcome of the auditory change-detection function can be implicit and the implicit knowledge of the sound structure can, after training, be utilized for behaviorally correct intuitive sound detection. These results illustrate the automatic character of the sensory change detection function.

Mielikuvat transformatiivisen oppimisen välineenä : Tutkimus mielikuvaoppimisesta luontevan esiintymistavan löytämiseksi

The research focus of this study is imagery-based learning aimed at discovering an authentic way of public speaking in the context of transformative learning. The experiences of the participants in this learning process were also a subject of study. This learning process consisted of both guided and independent imagery-based training techniques. Critical reflection plays an important role in transformative learning. Actions, and interpretations and assumptions guiding them, are recognised and subjected to critical reflection. The goal of the learning process is an authentic and wide meaning perspective. Imagery-based training benefits from the gap between the new and the old experience of public speaking, and this is utilised as an activating factor for learning. The study is qualitative, looking at the imagery learning process and its outcomes from the subjective viewpoint of the participants personal experience. The imagery training acted as an intervention in the process of learning authentic public performance. The number of participants in this study was ten, five men and five women from four different working backgrounds. There were 80 individual training sessions, each attended by one person. The author conducted the imagery-based training. For each participant the learning process took roughly nine months. The research data consisted in the answers to questions in writing, diary entries, interviews and researcher notes. The data gathered by these methods was compiled into a personal report for each participant. The learners perceived authentic public speaking performance at the end of the learning process as wider, more flexible and more genuine than at the start of the training. Authenticity was defined through an internal process of becoming aware instead of some external characteristics. The learners understood the process of imagery learning as training for public performance and as an opportunity to become familiar with one s own personal way of acting and with one s own attitudes. They also perceived it as a tool that enabled the observation of personal experiences from different points of view. The learners reflected on ways of acting related to public speaking as well as on contributing factors to performance anxiety during the imagery learning process. Towards the end of the learning process, even critical reflection took place. The learners were categorized into three groups according to differences in their learning processes: the participants, the actors and the critical reflectors. This grouping reflected the relative amount of transformation in their learning processes. The participants became aware of their actions and assumptions. They took part in guided training sessions only. Worries in private life also had some consequences to their training in imagery learning. Apart from than becoming more conscious, the learning process did not yield much difference to the public speaking experiences of the participants. The actors attended both guided imagery training sessions and did individual training on their own. They became aware of their assumptions and their ways of acting. The encounter of the new and the old way of acting stimulated their learning. The actors advanced towards their own goals or even achieved them. The critical reflectors recognised their own assumptions and ways of acting and started to reflect critically on their own attitudes, as well as external attitudes and interpretations. Their assumptions, interpretations and experiences of public performance started to change in a positive direction. The learning process of the critical reflectors was functioning as a transformative process. This learning process revealed old assumptions hindering learning and old ways of acting resulting from these assumptions, thus opening up an opportunity for critical reflection and transformation. Avainsanat Nyckelord imagery learning, imagery-based training, transformative learning, reflection, critical reflection, public speaking anxiety, authentic public performance

Adenoviral Gene Therapy for Advanced Head and Neck Cancer

Advanced stage head and neck cancers (HNC) with distant metastasis, as well as prostate cancers (PC), are devastating diseases currently lacking efficient treatment options. One promising developmental approach in cancer treatment is the use of oncolytic adenoviruses, especially in combination therapy with conventional cancer therapies. The safety of the approach has been tested in many clinical trials. However, antitumor efficacy needs to be improved in order to establish oncolytic viruses as a viable treatment alternative. To be able to test in vivo the effects on anti-tumor efficiency of a multimodal combination therapy of oncolytic adenoviruses with the standard therapeutic combination of radiotherapy, chemotherapy and Cetuximab monoclonal antibody (mAb), a xenograft HNC tumor model was developed. This model mimics the typical clinical situation as it is initially sensitive to cetuximab, but resistance develops eventually. Surprisingly, but in agreement with recent findings for chemotherapy and radiotherapy, a higher proportion of cells positive for HNC cancer stem cell markers were found in the tumors refractory to cetuximab. In vitro as well as in vivo results found in this study support the multimodal combination therapy of oncolytic adenoviruses with chemotherapy, radiotherapy and monoclonal antibody therapy to achieve increased anti-tumor efficiency and even complete tumor eradication with lower treatment doses required. In this study, it was found that capsid modified oncolytic viruses have increased gene transfer to cancer cells as well as an increased antitumor effect. In order to elucidate the mechanism of how oncolytic viruses promote radiosensitization of tumor cells in vivo, replicative deficient viruses expressing several promising radiosensitizing viral proteins were tested. The results of this study indicated that oncolytic adenoviruses promote radiosensitization by delaying the repair of DNA double strand breaks in tumor cells. Based on the promising data of the first study, two tumor double-targeted oncolytic adenoviruses armed with the fusion suicide gene FCU1 or with a fully human mAb specific for human Cytotoxic T Lymphocyte-Associated Antigen 4 (CTLA-4) were produced. FCU1 encodes a bifunctional fusion protein that efficiently catalyzes the direct conversion of 5-FC, a relatively nontoxic antifungal agent, into the toxic metabolites 5-fluorouracil and 5-fluorouridine monophosphate, bypassing the natural resistance of certain human tumor cells to 5-fluorouracil. Anti-CTLA4 mAb promotes direct killing of tumor cells via apoptosis and most importantly immune system activation against the tumors. These armed oncolytic viruses present increased anti-tumor efficacy both in vitro and in vivo. Furthermore, by taking advantage of the unique tumor targeted gene transfer of oncolytic adenoviruses, functional high tumor titers but low systemic concentrations of the armed proteins were generated. In addition, supernatants of tumor cells infected with Ad5/3-24aCTLA4, which contain anti-CTLA4 mAb, were able to effectively immunomodulate peripheral blood mononuclear cells (PBMC) of cancer patients with advanced tumors. -- In conclusion, the results presented in this thesis suggest that genetically engineered oncolytic adenoviruses have great potential in the treatment of advanced and metastatic HNC and PC.

Primary polyestradiol phosphate versus orchiectomy for advanced prostate cancer : Studies on the efficacy, cardiovascular complications and prognostic factors

Paikallisesti levinnyttä (T3-4 M0) ja luustoon levinnyttä (T1-4 M1) eturauhassyöpää sairastaneet potilaat satunnaistettiin kirurgiseen kastraatioon (orkiektomia) tai lääkkeelliseen kastraatioon lihaksensisäisellä polyestradiolifosfaatilla (PEP) annoksella 240 mg/kk. Verrattiin hoitojen kliinistä tehoa sekä sydän- ja verisuonikomplikaatioita (SV-komplikaatioita). Verrattiin myös hoitoa edeltäviä plasman testosteroni (T) ja estradioli (E2) pitoisuuksia T3-4 M0 ja T1-4 M1 potilaiden välillä sekä selvitettiin potilaiden yleistilan vaikutusta näihin hormonitasoihin. Lopuksi luotiin T1-4 M1 potilaille eturauhassyövän aiheuttaman kuoleman ennusteellinen riskiluokittelu kolmeen riskiryhmään käyttämällä hoitoa edeltäviä ennustetekijöitä. Kliinisessä tehossa ei orkiektomian ja PEP-hoidon välillä todettu tilastollisesti merkitsevää eroa. Odotetusti T1-4 M1 potilaiden ennuste oli huonompi kuin T3-4 M0 potilaiden. T1-4 M1 potilailla ei ollut SV-kuolemissa hoitoryhmien välillä tilastollista eroa, mutta ei-tappavia SV-komplikaatioita oli PEP ryhmässä (5.9%) enemmän kuin orkiektomia ryhmässä (2.0%). T3-4 M0 potilailla PEP-hoitoon liittyi tilastollisesti merkitsevä SV-kuolleisuus riski orkiektomiaan verrattuna (p = 0.001). PEP ryhmässä 67% kuolemista oli akuutteja sydäninfarkteja. Tämä PEP hoitoon liittyvä sydäninfarktiriski (mukaan lukien myös ei-tappavat sydäninfarktit) oli merkitsevästi pienempi potilailla, joiden hoitoa edeltävä E2 taso oli vähintään 93 pmol/l (p = 0.022). E2 taso oli merkitsevästi matalampi T1-4 M1 potilailla (74.7 pmol/l) kuin T3-4 M0 potilailla (87.9 pmol/l), mutta vastaavaa eroa ei ollut T tasoissa. Sekä T3-4 M0 että T1-4 M1 potilailla yleistilan lasku osittain selitti yksilöllisen T ja E2 tasojen laskun. Eturauhassyövän aiheuttaman kuoleman riskiryhmäluokittelu (Rg) kolmeen ryhmään luotiin käyttämällä alkalista fosfataasia (AFOS), prostata spesifistä antigeenia (PSA), laskoa (La) ja potilaan ikää. Yksi riskipiste annettiin, jos AFOS > 180 U/l (tällä hetkellä käytössä olevalla menetelmällä AFOS > 83 U/l), PSA > 35 µg/l, La > 80 mm/h ja ikä < 60 vuotta. Lopuksi pisteet laskettiin yhteen. Muodostettiin seuraavat ryhmät: Rg-a (0 -1 riskipistettä), Rg-b (2 riskipistettä) ja Rg-c (3 – 4 riskipistettä). Eturauhassyövän aiheuttama kuoleman riski lisääntyi merkitsevästi siirryttäessä riskiryhmästä seuraavaan (p < 0.001). Rg-luokittelu oli kliinisesti käytännöllinen ja hyvä havaitsemaan huonon ennusteen potilaat.

Current Care Guidelines for Cardiopulmonary Resuscitation : Implementation, skills and attitudes

Background: The national resuscitation guidelines were published in Finland in 2002 and are based on international guidelines published in 2000. The main goal of the national guidelines, available on the Internet free of charge, is early defibrillation by nurses in an institutional setting. Aim: To study possible changes in cardiopulmonary resuscitation (CPR) practices, especially concerning early defibrillation, nurses and students attitudes of guideline implementation and nurses and students ability to implement the guideline recommendations in clinical practices after publication of the Current Care (CC) guidelines for CPR 2002. Material and methods: CPR practices in Finnish health centres; especially concerning rapid defibrillation programmes, as well as the implementation of CC guidelines for CPR was studied in a mail survey to chief physicians of every health centre in Finland (Study I). The CPR skills using an automated external defibrillator (AED) were compared in a study including Objective stuctured clinical examination (OSCE) of resuscitation skills of nurses and nursing students in Finnish and Swedish hospital and institution (Studies II, III). Attitudes towards CPR-D and CPR guidelines among medical and nursing students and secondary hospital nurses were studied in surveys (Studies IV, V). The nurses receiving different CPR training were compared in a randomized trial including OSCE of CPR skills of nurses in Finnish Hospital (Study VI). Results: Two years after the publication, 40.7% of Finnish health centres used national resuscitation guidelines. The proportion of health centres having at least one AED (66%) and principle of nurse-performed defibrillation without the presence of a physician (42%) had increased. The CPR-D training was estimated to be insufficient regarding basic life support and advanced life support in the majority of health centres (Study I). CPR-D skills of nurses and nursing students in two specific Swedish and Finnish hospitals and institutions (Study II and III) were generally inadequate. The nurses performed better than the students and the Swedish nurses surpassed the Finnish ones. Geriatric nurses receiving traditional CPR-D training performed better than those receiving an Internet-based course but both groups failed to defibrillate within 60 s. Thus, the performance was not satisfactory even two weeks after traditional training (Study VI). Unlike the medical students, the nursing students did not feel competent to perform procedures recommended in the cardiopulmonary resuscitation guidelines including the defibrillation. However, the majority of nursing students felt confident about their ability to perform basic life support. The perceived ability to defibrillate correlated significantly with a positive attitude towards nurse-performed defibrillation and negatively with fear of damaging the patient s heart by defibrillation (Study IV). After the educational intervention, the nurses found their level of CPR-D capability more sufficient than before and felt more confident about their ability to perform defibrillation themselves. A negative attitude toward defibrillation correlated with perceived negative organisational attitudes toward cardiopulmonary resuscitation guidelines. After CPR-D education in the hospital, the majority (64%) of nurses hesitated to perform defibrillation because of anxiety and 27 % hesitated because of fear of injuring the patient. Also a negative personal attitude towards guidelines increased markedly after education (Study V). Conclusions: Although a significant change had occurred in resuscitation practices in primary health care after publication of national cardiopulmonary resuscitation guidelines the participants CPR-D skills were not adequate according to the CPR guidelines. The current way of teaching is unlikely to result in participants being able to perform adequate and rapid CPR-D. More information and more frequent training are needed to diminish anxiety concerning defibrillation. Negative beliefs and attitudes toward defibrillation affect the nursing students and nurses attitudes toward cardiopulmonary resuscitation guidelines. CPR-D education increased the participants self-confidence concerning CPR-D skills but it did not reduce their anxiety. AEDs have replaced the manual defibrillators in most institutions, but in spite of the modern devices the anxiety still exists. Basic education does not provide nursing students with adequate CPR-D skills. Thus, frequent training in the workplace has vital importance. This multi-professional program supported by the administration might provide better CPR-D skills. Distance learning alone cannot substitute for traditional small-group learning, tutored hands-on training is needed to learn practical CPR-D skills. Standardized testing would probably help controlling the quality of learning. Training of group-working skills might improve CPR performance.

Supistamista, rationalisointia vai kehittämistä? : Valtiovarainministeriön järjestelyosaston järjestämän henkilöstökoulutus- ja tutkimustoiminnan rakentuminen osaksi valtionhallintoa vuosina 1943-1971

The study examines the personnel training and research activities carried out by the Organization and Methods Division of the Ministry of Finance and their becoming a part and parcel of the state administration in 1943-1971. The study is a combination of institutional and ideological historical research in recent history on adult education, using a constructionist approach. Material salient to the study comes from the files of the Organization and Methods Division in the National Archives, parliamentary documents, committee reports, and the magazines. The concentrated training and research activities arranged by the Organization and Methods Division, became a part and parcel of the state administration in the midst of controversial challenges and opportunities. They served to solve social problems which beset the state administration as well as contextual challenges besetting rationalization measures, and organizational challenges. The activities were also affected by a dependence on decision-makers, administrative units, and civil servants organizations, by different views on rationalization and the holistic nature of reforms, as well as by the formal theories that served as resources. It chose long-term projects which extended to the political decision-makers and administrative units turf, and which were intended to reform the structures of the state administration and to rationalize the practices of the administrative units. The crucial questions emerged in opposite pairs (a constitutional state vs. the ideology of an administratively governed state, a system of national boards vs. a system of government through ministries, efficiency of work vs. pleasantness of work, centralized vs. decentralized rationalization activities) which were not solvable problems but impossible questions with no ultimate answers. The aim and intent of the rationalization of the state administration (the reform of the central, provincial, and local governments) was to facilitate integrated management and to render a greater amount of work by approaching management procedures scientifically and by clarifying administrative instances and their respon-sibilities in regards to each other. The means resorted to were organizational studies and committee work. In the rationalization of office work and finance control, the idea was to effect savings in administrative costs and to pare down those costs as well as to rationalize and heighten those functions by developing the institution of work study practitioners in order to coordinate employer and employee relationships and benefits (the training of work study practitioners, work study, and a two-tier work study practitioner organization). A major part of the training meant teaching and implementing leadership skills in practice, which, in turn, meant that the learning environment was the genuine work community and efforts to change it. In office rationalization, the solution to regulate the relations between the employer and the employees was the co-existence of the technical and biological rationalization and the human resource administration and the accounting and planning systems at the turn of the 1960s and 1970s. The former were based on the school of scientific management and human relations, the latter on system thinking, which was a combination of the former two. In the rationalization of the state administration, efforts were made to find solutions to stabilize management ideologies and to arrange the relationships of administrative systems in administrative science - among other things, in the Hoover Committee and the Simon decision making theory, and, in the 1960s, in system thinking. Despite the development-related vocabulary, the practical work was advanced rationalization. It was said that the practical activities of both the state administration and the administrative units depended on professional managers who saw to production results and human relations. The pedagogic experts hired to develop training came up with a training system, based on the training-technological model where the training was made a function of its own. The State Training Center was established and the training office of the Organization and Methods Division became the leader and coordinator of personnel training.