Pharmacogenetic and clinical study on adverse effects induced by psychotropic drugs

Second-generation antipsychotics (SGAs) have become the first-line antipsychotic treatment for psychotic disorders due to their better overall tolerance compared to classical antipsychotics. However, metabolic side effects such as weight gain are frequently described during treatment with SGAs and/or other psychotropic drugs including some antidepressants and mood stabilizers, which may also result in poor adherence to treatment. The aim of this work was to investigate different methods to predict common side effects, in particular weight gain during treatment with weight gain inducing psychotropic drugs. Firstly, clinical data were used to determine the potential predictive power of a one month weight gain on weight increase after three and 12 months of treatment (n=351 patients). A fast and strong weight gain of >5% after a period of one month (>5%WG) was found to be the best predictor for an important weight gain at three (>15%) and 12 months (>20%). Similar analyses in an independent cohort of psychiatric adolescents (n=42), showed that a comparable >4% weight gain at one month is the best predictor for an important weight gain at three months (>15%). Secondly, we aimed to determine whether an extensive analysis of genes could be used, in addition to clinical factors, to predict patients at risk for >5%WG or for type 2 diabetes (T2D). Adding genetic markers to clinical variables to predict >5%WG increased significantly the area under the curve (AUC) of the analysis (AUCfinai:0.92, AUCdmicai:0.75, pcO.OOOl, n=248). Conversely, genetic risk scores were found to be associated with T2D (OR: 2.5, p=0.03, n=285) but without a significant increase of AUC'when compared to the prediction based to clinical factors alone. Finally, therapeutic drug monitoring was used to predict extrapyramidal symptoms during risperidone treatment (n=150). Active moiety (sum of risperidone and of its active metabolite 9- hydroxyrisperidone plasma concentrations) of >40 ng/ml should be targeted only in case of insufficient response. These results highlight different approaches for personalizing psychotropic treatments in order to reduce related side effects. Further research is needed, in particular on the identification of genetic markers, to improve the implementation of these results into clinical practice. Résumé Les antipsychotiques atypiques (APA) sont devenus le traitement antipsychotique de première intention pour le traitement des psychoses, grâce à un profil d'effets secondaires plus favorables comparé aux antipsychotiques typiques. Néanmoins, d'autres effets indésirables d'ordre métabolique (ex. prise pondérale) sont observés sous APA, stabilisateurs de l'humeur et/ou certains antidépresseurs, pouvant aussi limiter l'adhérence au traitement. L'objectif de ce travail est d'explorer différentes méthodes permettant de prédire des effets secondaires courants, en particulier la prise de poids durant un traitement avec des psychotropes pouvant induire un tel effet. Dans une première partie, des données cliniques ont été évaluées pour leurs potentiels prédictifs d'une prise de poids à un mois sur une prise de poids à trois et 12 mois de traitement (n=351 patients). Une prise de poids rapide et forte >5% à un mois (PP>5%) s'est avérée être le meilleur prédicteur pour une prise pondérale importante à trois (>15%) et 12 (>20%) mois de traitement. Des analyses similaires dans une cohorte pédiatrique (n=42) ont indiqué une prise de poids >4% à un mois comme le meilleur prédicteur pour une prise pondérale importante (>15%) à trois mois de traitement. Dans une deuxième partie, des marqueurs génétiques, en complément aux données cliniques, ont été analysés pour leur contribution potentielle à la prédiction d'une PP>5% et au dépistage du diabète de type 2 (DT2). L'ajout de variants génétiques aux données cliniques afin de prédire une PP>5% a augmenté significativement l'aire sous la courbe (ASC) de l'analyse (ASCflnai:0.92, ASCC|inique:0.75, p<0.0001, n=248). Concernant le DT2, un score génétique est associé au DT2 (OR: 2.5, p=0.03, n=285), néanmoins aucune augmentation significative de l'ASC n'a été observée par rapport à l'analyse avec les données cliniques seules. Finalement, des mesures de concentrations plasmatiques de médicaments ont été utilisées pour prédire la survenue de symptômes extrapyramidaux sous rispéridone (n=150). Cette analyse nous a permis d'établir qu'une concentration plasmatique de rispéridone associée à son métabolite actif >40 ng/ml ne devrait être recherchée qu'en cas de réponse clinique insuffisante. Ces différents résultats soulignent différentes approches pour personnaliser la prescription de psychotropes afin de réduire la survenue d'effets secondaires. Des études supplémentaires sont néanmoins nécessaires, en particulier sur l'identification de marqueurs génétiques, afin d'améliorer l'implémentation de ces résultats en pratique clinique. Résumé large publique Les antipsychotiques atypiques et autres traitements psychotropes sont couramment utilisés pour traiter les symptômes liés à la schizophrénie et aux troubles de l'humeur. Comme pour tout médicament, des effets secondaires sont observés. L'objectif de ce travail est d'explorer différentes méthodes qui permettraient de prédire la survenue de certains effets indésirables, en particulier une prise de poids et la survenue d'un diabète. Dans une première partie, nous avons évalué l'effet d'une prise de poids précoce sur une prise de poids au long terme sous traitement psychotrope. Les analyses ont mis en évidence dans une population psychiatrique qu'une prise de poids à un mois >5% par rapport au poids initial permettait de prédire une prise pondérale importante après trois (>15%) et 12 (>20%) mois de traitement. Un résultat semblable a. été observé dans un autre groupe de patients exclusivement pédiatriques. Dans une deuxième partie, nous avons évalué la contribution potentielle de marqueurs génétiques à la prédiction d'une prise pondérale de >5% après un mois de traitement ainsi que dans la survenue d'un diabète de type 2. Pour la prise de poids, la combinaison des données génétiques aux données cliniques a permis d'augmenter de 17% la précision de la prédiction, en passant de 70% à 87%. Concernant la survenue d'un diabète, les données génétiques n'ont pas amélioré la prédiction. Finalement, nous avons analysé la relation possible entre les concentrations sanguines d'un antipsychotique atypique couramment utilisé, la rispéridone, et la survenue d'effets secondaires (ici les tremblements). Il est ressorti de cette étude qu'une concentration plasmatique du médicament supérieure à 40 ng/ml ne devrait être dépassée qu'en cas de réponse thérapeutique insuffisante, au risque de voir augmenter la survenue d'effets secondaires du type tremblements. Ces résultats démontrent la possibilité de prédire avec une bonne précision la survenue de certains effets secondaires. Cependant, en particulier dans le domaine de la génétique, d'autres études sont nécessaires afin de confirmer les résultats obtenus dans nos analyses. Une fois cette étape franchie, il serait possible d'utiliser ces outils dans la pratique clinique. A terme, cela pourrait permettre au prescripteur de sélectionner les traitements les mieux adaptés aux profils spécifiques de chaque patient.

Acute Infection in Total Knee Arthroplasty: Diagnosis and Treatment

Infection is one of the most serious complications after total knee arthroplasty (TKA). The current incidence of prosthetic knee infection is 1-3%, depending on the series(.) For treatment and control to be more cost effective, multidisciplinary groups made up of professionals from different specialities who can work together to eradicate these kinds of infections need to be assembled. About the microbiology, Staphylococcus aureus and coagulase-negative staphylococcus were among the most frequent microorganisms involved (74%). Anamnesis and clinical examination are of primary importance in order to determine whether the problem may point to a possible acute septic complication. The first diagnosis may then be supported by increased CRP and ESR levels. The surgical treatment for a chronic prosthetic knee infection has been perfectly defined and standardized, and consists in a two-stage implant revision process. In contrast, the treatment for acute prosthetic knee infection is currently under debate. Considering the different surgical techniques that already exist, surgical debridement with conservation of the prosthesis and polythene revision appears to be an attractive option for both surgeon and patient, as it is less aggressive than the two-stage revision process and has lower initial costs. The different results obtained from this technique, along with prognosis factors and conclusions to keep in mind when it is indicated for an acute prosthetic infection, whether post-operative or haematogenous, will be analysed by the authors.

Toimintamalli asuinkiinteistö öljyvahingon hoitamiseksi

Pienkiinteistöjen öljyvahingot ovat viime vuosina lisääntyneet. Tämän työn tarkoituksena on luoda öljyvahingon torjuntaan ja jälkihoitoon osallistuvalle urakoitsijalle toimintamalli asuinkiinteistön öljyvahingon hoitamiseksi. Mallin halutaan erityisesti kuvaavan öljyvahingon hoitoon osallistuvien viranomaisten ja muiden tahojen vastuita ja velvollisuuksia. Työn tavoitteena on myös tunnistaa pienkiinteistöissä tapahtuvat öljyvahinkotyypit sekä niille altistavat riskitekijät. Öljyn päästäminen ympäristöön sekä öljyn käsittely ja varastointi niin, että siitä aiheutuu öljyvahingon vaara, kielletään laissa. Vahinkojen torjumiseksi on annettu määräyksiä muun muassa öljylämmityslaitteistojen turvallisuutta koskien. Asuinkiinteistöjen öljyvahingot liittyvät yleensä öljysäiliön täyttötilanteisiin. Vahinkojen syynä on usein säiliön ja sen varusteiden puutteellisuus tai huono kunto. Asuinrakennusten lämmitykseen käytetään kevyttä polttoöljyä. Maahan joutuessaan polttoöljy imeytyy sora- ja hiekkamaahan nopeasti, jolloin vaarana on öljyn kulkeutuminen pohjaveteen ja vesistöihin. Asuinkiinteistön öljyvahingossa öljyä joutuu usein myös rakenteisiin. Öljyvahingosta tulee ilmoittaa aina hätäkeskukseen. Vastuu öljyvahinkojen torjunnasta kuuluu alueelliselle pelastustoimelle. Torjuntatoimiin osallistuu usein myös urakoitsija. Jos vahinkokohdetta ei torjuntatoimin saada kunnostettua, alueellinen ympäristökeskus voi määrätä puhdistamisesta vastuussa olevan selvittämään pilaantuneen alueen laajuuden ja puhdistamistarpeen sekä toteuttamaan mahdollisen kunnostuksen. Pilaantuneen maaperän kunnostus voidaan toteuttaa massan vaihtona tai paikan päällä maata kaivamatta. Likaantuneiden rakenteiden saneerausta tarvitaan sisäilman hajuhaittojen poistamiseksi. Öljyvahingon kustannukset voivat nousta hyvinkin suuriksi. Ensisijainen vastuu niistä kuuluu vahingonaiheuttajalle.

Osingonjakopäätökset pienissä osakeyhtiöissä. Empiirinen tutkimus osakeyhtiölain varojenjakosäännösten toteutumisesta

Tässä väitöstutkimuksessa tarkastellaan Suomen osakeyhtiölain pakottavien varojenjakosäännösten vaikutusta osingonjakopaatoksiin. Lain vaikutuksen seuraamisen lisäksi pyritään muodostamaan kokonaiskuva tekijöistä, jotka vaikuttavat pienissä yhtiöissä tehtäviin osingonjakopäätöksiin. Väitöskirja koostuu kahdesta eri osasta. Ensimmäisessä osassa osoitetaan, kuinka toisen osan artikkelit muodostavat kokonaisuuden ja esitellään tutkimustulokset. Väitöskirjan toinen osa koostuu neljästä toisiaan täydentävästä artikkelista. Tutkimus etenee julkaisujen myötä ensin maksukykytestin määrittelystä maksukykytestiin liittyviin oikeudellisiin ongelmiin sekä tilinpaatoksen merkitykseen osingonjakopäätöksissä, siirtyen sitten omistaja johtajan tarpeisiin ja tavoitteisiin, päättyen lopuksi velkojan näkökulmaan. Tutkimuksen tavoitteeksi asetettiin kokonaiskuvan muodostaminen niistä tekijöistä, jotka vaikuttavat osingonjakopäätöksen tekemiseen pienissä osakeyhtiöissä. Tavoitteena oli myös selvittää kuinka osakeyhtiölain 13 luvun varojenjakosäännökset otetaan huomioon osingonjakopäätöstä tehtäessä. Tutkimusaineistona käytettiin sekä kyselytutkimusaineistoa että tilinpäätöstietoja. Aineistoa analysoitiin kvantitatiivisin menetelmin. Tutkimusaineistosta löydettiin kolme erilaista varallisuuden siirtämisen strategiaa. Ne nimettiin seuraavasti: tulojen maksimointi, verosuunnittelu, palkan jousto. Tutkimuksesta nousee esiin kolme keskeistä tulosta. Ensinnäkin, liiketaloustieteellinen maksukyvyn merkitys poikkeaa oikeustieteessä käsitetystä maksukyvystä. Toiseksi, osakeyhtiölain 13 luvun varojenjakosäännökset tulee ottaa huomioon sekä osingonjakopäätöstä tehtäessä että varojen tosiasiallisesti siirtyessä pois yhtiön vaikutuspiiristä. Kolmanneksi, pääomatuloverotuksen kiristyessä omistaja johtaja saattaa siirtää varallisuutta yhtiöstä yksityistalouteen osingon sijasta palkkana. Tämän seurauksena maksukykytestin merkitys vähenee erityisesti pienissä yhtiöissä. Tulosten perusteella tasetesti näyttää olevan pienissä yhtiöissä maksukykytestiä merkityksellisempi.

"Dov'è la sinistra?" Hemispatial neglect in stroke

As long as the incidence of stroke continues to grow, patients with large right hemisphere lesions suffering from hemispatial neglect will require neuropsychological evaluation and rehabilitation. The inability to process information especially that coming from the left side accompanied by the magnetic orientation to the ipsilesional side represents a real challenge for rehabilitation. This dissertation is concerned with crucial aspects in the clinical neuropsychological practice of hemispatial neglect. In studying the convergence of the visual and behavioural test batteries in the assessment of neglect, nine of the seventeen patients, who completed both the conventional subtests of the Behavioural Inattention Test and the Catherine Bergego Scale assessments, showed a similar severity of neglect and thus good convergence in both tests. However, patients with neglect and hemianopia had poorer scores in the line bisection test and they displayed stronger neglect in behaviour than patients with pure neglect. The second study examined, whether arm activation, modified from the Constraint Induced Movement Therapy, could be applied as neglect rehabilitation alone without any visual training. Twelve acute- or subacute patients were randomized into two rehabilitation groups: arm activation training or traditional voluntary visual scanning training. Neglect was ameliorated significantly or almost significantly in both training groups due to rehabilitation with the effect being maintained for at least six months. In studying the reflections of hemispatial neglect on visual memory, the associations of severity of neglect and visual memory performances were explored. The performances of acute and subacute patients with hemispatial neglect were compared with the performances of matched healthy control subjects. As hypothesized, encoding from the left side and immediate recall of visual material were significantly compromised in patients with neglect. Another mechanism of neglect affecting visual memory processes is observed in delayed visual reproduction. Delayed recall demands that the individual must make a match helped by a cue or it requires a search for relevant material from long-term memory storage. In the case of representational neglect, the search may succeed but the left side of the recollected memory still fails to open. Visual and auditory evoked potentials were measured in 21 patients with hemispatial neglect. Stimuli coming from the left or right were processed differently in both sensory modalities in acute and subacute patients as compared with the chronic patients. The differences equalized during the course of recovery. Recovery from hemispatial neglect was strongly associated with early rehabilitation and with the severity of neglect. Extinction was common in patients with neglect and it did not ameliorate with the recovery of neglect. The presence of pusher symptom hampered amelioration of visual neglect in acute and subacute stroke patients, whereas depression did not have any significant effect in the early phases after the stroke. However, depression had an unfavourable effect on recovery in the chronic phase. In conclusion, the combination of neglect and hemianopia may explain part of the residual behavioural neglect that is no longer evident in visual testing. Further research is needed in order to determine which specific rehabilitation procedures would be most beneficial in patients suffering the combination of neglect and hemianopia. Arm activation should be included in the rehabilitation programs of neglect; this is a useful technique for patients who need bedside treatment in the acute phase. With respect to the deficit in visual memory in association with neglect, the possible mechanisms of lateralized deficit in delayed recall need to be further examined and clarified. Intensive treatment induced recovery in both severe and moderate visual neglect long after the first two to first three months after the stroke.

Searching for keys to successful post-merger integration : a longitudinal case-study following a public sector merger

Unsuccessful mergers are unfortunately the rule rather than the exception. Therefore it is necessary to gain an enhanced understanding of mergers and post-merger integrations (PMI) as well as learning more about how mergers and PMIs of information systems (IS) and people can be facilitated. Studies on PMI of IS are scarce and public sector mergers are even less studied. There is nothing however to indicate that public sector mergers are any more successful than those in the private sector. This thesis covers five studies carried out between 2008 and 2011 in two organizations in higher education that merged in January 2010. The most recent study was carried out two years after the new university was established. The longitudinal case-study focused on the administrators and their opinions of the IS, the work situation and the merger in general. These issues were investigated before, during and after the merger. Both surveys and interviews were used to collect data, to which were added documents that both describe and guide the merger process; in this way we aimed at a triangulation of findings. Administrators were chosen as the focus of the study since public organizations are highly dependent on this staff category, forming the backbone of the organization and whose performance is a key success factor for the organization. Reliable and effective IS are also critical for maintaining a functional and effective organization, and this makes administrators highly dependent on their organizations’ IS for the ability to carry out their duties as intended. The case-study has confirmed the administrators’ dependency on IS that work well. A merger is likely to lead to changes in the IS and the routines associated with the administrators’ work. Hence it was especially interesting to study how the administrators viewed the merger and its consequences for IS and the work situation. The overall research objective is to find key issues for successful mergers and PMIs. The first explorative study in 2008 showed that the administrators were confident of their skills and knowledge of IS and had no fear of having to learn new IS due to the merger. Most administrators had an academic background and were not anxious about whether IS training would be given or not. Before the merger the administrators were positive and enthusiastic towards the merger and also to the changes that they expected. The studies carried out before the merger showed that these administrators were very satisfied with the information provided about the merger. This information was disseminated through various channels and even negative information and postponed decisions were quickly distributed. The study conflicts with the theories that have found that resistance to change is inevitable in a merger. Shortly after the merger the (third) study showed disappointment with the fact that fewer changes than expected had been implemented even if the changes that actually were carried out sometimes led to a more problematic work situation. This was seen to be more prominent for routine changes than IS changes. Still the administrators showed a clear willingness to change and to share their knowledge with new colleagues. This knowledge sharing (also tacit) worked well in the merger and the PMI. The majority reported that the most common way to learn to use new ISs and to apply new routines was by asking help from colleagues. They also needed to take responsibility for their own training and development. Five months after the merger (the fourth study) the administrators had become worried about the changes in communication strategy that had been implemented in the new university. This was perceived as being more anonymous. Furthermore, it was harder to get to know what was happening and to contact the new decision makers. The administrators found that decisions, and the authority to make decisions, had been moved to a higher administrative level than they were accustomed to. A directive management style is recommended in mergers in order to achieve a quick transition without distracting from the core business. A merger process may be tiresome and require considerable effort from the participants. In addition, not everyone can make their voice heard during a merger and consensus is not possible in every question. It is important to find out what is best for the new organization instead of simply claiming that the tried and tested methods of doing things should be implemented. A major problem turned out to be the lack of management continuity during the merger process. Especially problematic was the situation in the IS-department with many substitute managers during the whole merger process (even after the merger was carried out). This meant that no one was in charge of IS-issues and the PMI of IS. Moreover, the top managers were appointed very late in the process; in some cases after the merger was carried out. This led to missed opportunities for building trust and management credibility was heavily affected. The administrators felt neglected and that their competences and knowledge no longer counted. This, together with a reduced and altered information flow, led to rumours and distrust. Before the merger the administrators were convinced that their achievements contributed value to their organizations and that they worked effectively. After the merger they were less sure of their value contribution and effectiveness even if these factors were not totally discounted. The fifth study in November 2011 found that the administrators were still satisfied with their IS as they had been throughout the whole study. Furthermore, they believed that the IS department had done a good job despite challenging circumstances. Both the former organizations lacked IS strategies, which badly affected the IS strategizing during the merger and the PMI. IS strategies deal with issues like system ownership; namely who should pay and who is responsible for maintenance and system development, for organizing system training for new IS, and for effectively run IS even during changing circumstances (e.g. more users). A proactive approach is recommended for IS strategizing to work. This is particularly true during a merger and PMI for handling issues about what ISs should be adopted and implemented in the new organization, issues of integration and reengineering of IS-related processes. In the new university an ITstrategy had still not been decided 26 months after the new university was established. The study shows the importance of the decisive management of IS in a merger requiring that IS issues are addressed in the merger process and that IS decisions are made early. Moreover, the new management needs to be appointed early in order to work actively with the IS-strategizing. It is also necessary to build trust and to plan and make decisions about integration of IS and people.

Comparing adult-youth and adult-adult online sexual solicitation: Manipulative behaviors, situational factors, and outcomes

Online sexual solicitation (solicitation) of youth has received widespread media and research attention during the last decade. The prevalence rates of youth who have experienced solicitation or solicitation attempts vary between studies depending on the methodology used (e.g., whether youth or adults are the target study group). In studies focusing on youth victims, the prevalence of solicitation attempts made by adults during the past year is typically reported to be between 5 and 9%. Adults who solicit youth online have been found to use deception and other manipulative behaviors to gain access to sexual activities with youth. However, previous studies have lacked a control group of adults who solicit other adults online. Without this comparison, one could argue that deceiving others online about one’s identity, and engaging in manipulative behaviors, is an inherent part of most online sexual interactions with strangers. Additionally, little is known about the associations between manipulative behaviors and the solicitation outcomes. In research concerning offline sexual behaviors, it has been noted that situational factors, such as sexual arousal, may alter both sexual interest and behavior. The effects of situational factors on online sexual behaviors have been less extensively studied (especially so with a quantitative approach); no studies have to date focused on adults’ solicitation of youth. Investigating the role of a lowered sexual age preference and the role of situational factors in the soliciting adults could be an important step in order to receive deeper knowledge of the role of traits and states in the context of solicitation. Additionally, there is a lack of knowledge of the effect of the age of the youth. Although previous studies on solicitation has found that older youth, compared with younger youth and children, are more often solicited, the possible reasons for this have not been investigated. Are adults who solicit youth affected by legal deterrence (through the legal age of consent), is it because older youth are more available online, or are the adults’ age preferences merely a product of a normally distributed age preference in the population? The purpose of the present thesis was fivefold: 1) to obtain an estimate of the frequency of adults’ solicitation of youth as self-reported and observed in actual behavior; 2) to explore whether the legal age of consent (LAC) affects solicitation frequency, or whether a normally distributed sexual age preference more accurately describe the proportion of solicited youth of different ages; 3) to investigate the associations of both traits (e.g., lower sexual age preference) and states (immediate situational factors, such as alcohol intoxication), and the solicitation target; 4) to explore whether adults who solicit youth and adults who solicit adults are equally deceitful and manipulative online, and whether the different solicitation outcomes are as common in both groups; and 5) to investigate whether the deceitful and manipulative behaviors engaged in had different associations with the solicitation outcomes depending on the age of the solicited. In the survey study, a convenience sample of 1393 adult participants (aged 18 years or older) self-reported any online communication with strangers during the past year. Of these, 56% (776 respondents) reported that they had solicited or attempted to solicit at least one stranger. Of the respondents, 453 (58.4%) were men, and 323 (41.6%) were women. Participants with only adult contacts (18 years or older) constituted the majority (640 respondents). In contrast, 136 individuals reported a youth contact (a 13 year old or younger, or a 14 to 17-year old). Approximately half of the participants were men in the adult contact group, while 75% of the participants were men in the youth contact group. Approximately 60% of the participants with youth contacts were recruited from two websites associated with a pedophilic sexual interest. In an online quasi-experimental study, with researchers impersonating youth of different ages (10–18 year olds) in chat rooms, 251 online conversations with chat room visitors made up the entire sample. All chat room visitors alleged to be men. The self-reported frequency of having solicited youth (0–17-year olds) during the past year was approximately 10% in our sample of adults who reported communicating with any strangers online. When we observed this behavior in chat rooms, we found that approximately 30% of the chat room visitors who believed they interacted with a 10 to 14 year old attempted to solicit the youth. We found that solicitation attempts increased equally much when increasing the age of the impersonated youth from 14 to 16, as from 16 to 18. Thus, we concluded that a normally distributed age preference in the population was a more plausible explanation to the effect of the age of the solicited, rather than the LAC (here; 15 and 16). If the chat room visitors would have been deterred only by the LAC, we would have expected that the change in amount of solicitation attempts from an illegal age group to a legal age group would have been significantly stronger than changes between age groups within illegal-illegal and legal-legal groups. Our subsample of survey participants from the pedophilia-related websites expectedly reported that they had solicited youth more often in comparison to the sample gathered through general (i.e., not associated with any particular sexual preference) websites. We also found that participants with a youth contact reported higher levels of sexual arousal and shame before the sexual interaction with their online contact, compared with participants with an adult contact. Additionally, the participants with youth contacts who reported consumption of child- and adolescent pornography also reported being more sexually aroused before the interaction, compared to the participants with youth contacts who did not report consumption of these kinds of pornography. We also found clear indications that the online sexual interaction had an alleviatory effect on reported levels of sadness, boredom and stress, independent of the age of the contact. Generally, the participants with youth and adult contacts reported deceiving their contacts as often and suggesting keeping the communication a secret from someone as often. Participants with a youth contact, however, reported using more persuasion techniques for online sexual purposes or for the purpose of an offline meeting, compared to those with an adult contact. In the chat rooms, we found that more indirect ways of future sexual communication (e.g., continuing chatting) was suggested by the chat room visitors that were under the assumption of interacting with youth aged 10 to 14, compared with more direct means (e.g., meeting offline). Survey participants with youth contacts who had used deception, suggested keeping the interactions a secret, and/or persuaded their contact by appealing to the contacts feelings of love and attachment for the participant had also more often engaged in cybersex with the contact. No other manipulative behaviors were associated with the other investigated solicitation outcomes (receiving a sexual picture, meeting offline, and engaging in sexual contact offline) within this group of participants. However, using deception, suggesting secrecy and using persuasion was also positively associated with certain solicitation outcomes within participants with an adult contact. In summary, adults’ solicitation of youth is much more frequent when observed in chat rooms than self-reported. Additionally, an underlying lowered sexual age preference seems to be a motivating factor on a group level in adults who solicit youth. We concluded that directed prevention efforts should be made on pedophiliarelated websites. Additionally, the role of situational factors, especially sexual arousal in persons with a pedo- or hebephilic sexual interest should be investigated further in the context of online sexual solicitation.

Customer Knowledge Transfer in MNCs

The purpose of this Master’s thesis was to study customer knowledge transfer processes in multinational corporations (MNCs). The main objective was to examine how customer knowledge is transferred in MNCs and what kind of factors enhance or inhibit the knowledge transfer process, and to create a framework on the basis of the existing literature and the empirical findings. In this thesis the factors were organized according to whether they are properties of the unit involved in knowledge management, properties of relationships between the units or properties of the knowledge itself. There are various properties that influence knowledge transfer but in this thesis the focus was on examining the relevant findings from the customer knowledge viewpoint. Empirical results show that internal fragmentation in the MNC seems to be inherent in this type of organization, and may cause many problems in customer knowledge transfer and utilization. These knowledge transfer inhibitors rise from the organization’s properties: it’s absorptive capacity, motivation, organizational culture, and the two dimensions of knowledge. However, in spite of the inherent forces causing internal fragmentation and inhibiting knowledge transfer, moderate customer knowledge and expertise codification, cooperative working practices among the experts, and socialization mechanisms posed by the headquarters seem to help maintain customer knowledge transfer, and value creation in the long-term relationship. This value creation can be seen to be based on accessing and integrating a wide variety of knowledge resources in order to create a coherent product and service offering.

Governance of Healthcare Data: International Standards and Recommendations

In the global phenomenon, the aging population becomes a critical issue. Data and information concerning elderly citizens are increasing and are not well organized. In addition, these unstructured data and information cause the problems for decision makers. Since we live in a digital world, Information Technology is considered to be a tool in order to solve problems. Data, information, and knowledge are crucial components to facilitate success in IT service system. Therefore, it is necessary to study how to organize or to govern data from various sources related elderly citizens. The research is conducted due to the fact that there is no internationally accepted holistic framework for governance of data. The research limits the scope to study on the healthcare domain; however, the results can be applied to the other areas. The research starts with an ongoing research of Dahlberg and Nokkala (2015) as a theory. It explains the classification of existing data sources and their characteristics with the focus on managerial perspectives. Then the studies of existing frameworks at international and national level organizations have been performed to show the current frameworks, which have been used and are useful in compiling data on elderly citizens. The international organizations in this research are selected based on their reputations and the reliability to obtain information. The selected countries at national level provide different point of views between two countries. Australia is a forerunner in IT governance while Thailand is the country which the author has familiar knowledge of the current situation. Considered the discussions of frameworks at international and national organizations level illustrate the main characteristics of each framework. At international organization level gives precedence to the interoperability of exchanging data and information between different parties. Whereas at national level shows the importance of the acknowledgement of using frameworks throughout the country in order to make the frameworks to be effective. After the studies of both international and national organization levels, the thesis shows the summarized tables to answer the fitness to the proposed framework by Dahlberg and Nokkala whether the framework help to consolidate data from various sources with different formats, hierarchies, structures, velocities, and other attributes of data storages. In addition, suggestions and recommendations will be proposed for the future research.

Public-private partnership investments in dry ports – Russian logistics markets and risks

The investments have always been considered as an essential backbone and so-called ‘locomotive’ for the competitive economies. However, in various countries, the state has been put under tight budget constraints for the investments in capital intensive projects. In response to this situation, the cooperation between public and private sector has grown based on public-private mechanism. The promotion of favorable arrangement for collaboration between public and private sectors for the provision of policies, services, and infrastructure in Russia can help to address the problems of dry ports development that neither municipalities nor the private sector can solve alone. Especially, the stimulation of public-private collaboration is significant under the exposure to externalities that affect the magnitude of the risks during all phases of project realization. In these circumstances, the risk in the projects also is becoming increasingly a part of joint research and risk management practice, which is viewed as a key approach, aiming to take active actions on existing global and specific factors of uncertainties. Meanwhile, a relatively little progress has been made on the inclusion of the resilience aspects into the planning process of a dry ports construction that would instruct the capacity planner, on how to mitigate the occurrence of disruptions that may lead to million dollars of losses due to the deviation of the future cash flows from the expected financial flows on the project. The current experience shows that the existing methodological base is developed fragmentary within separate steps of supply chain risk management (SCRM) processes: risk identification, risk evaluation, risk mitigation, risk monitoring and control phases. The lack of the systematic approach hinders the solution of the problem of risk management processes of dry port implementation. Therefore, management of various risks during the investments phases of dry port projects still presents a considerable challenge from the practical and theoretical points of view. In this regard, the given research became a logical continuation of fundamental research, existing in the financial models and theories (e.g., capital asset pricing model and real option theory), as well as provided a complementation for the portfolio theory. The goal of the current study is in the design of methods and models for the facilitation of dry port implementation through the mechanism of public-private partnership on the national market that implies the necessity to mitigate, first and foremost, the shortage of the investments and consequences of risks. The problem of the research was formulated on the ground of the identified contradictions. They rose as a continuation of the trade-off between the opportunities that the investors can gain from the development of terminal business in Russia (i.e. dry port implementation) and risks. As a rule, the higher the investment risk, the greater should be their expected return. However, investors have a different tolerance for the risks. That is why it would be advisable to find an optimum investment. In the given study, the optimum relates to the search for the efficient portfolio, which can provide satisfaction to the investor, depending on its degree of risk aversion. There are many theories and methods in finance, concerning investment choices. Nevertheless, the appropriateness and effectiveness of particular methods should be considered with the allowance of the specifics of the investment projects. For example, the investments in dry ports imply not only the lump sum of financial inflows, but also the long-term payback periods. As a result, capital intensity and longevity of their construction determine the necessity from investors to ensure the return on investment (profitability), along with the rapid return on investment (liquidity), without precluding the fact that the stochastic nature of the project environment is hardly described by the formula-based approach. The current theoretical base for the economic appraisals of the dry port projects more often perceives net present value (NPV) as a technique superior to other decision-making criteria. For example, the portfolio theory, which considers different risk preference of an investor and structures of utility, defines net present value as a better criterion of project appraisal than discounted payback period (DPP). Meanwhile, in business practice, the DPP is more popular. Knowing that the NPV is based on the assumptions of certainty of project life, it cannot be an accurate appraisal approach alone to determine whether or not the project should be accepted for the approval in the environment that is not without of uncertainties. In order to reflect the period or the project’s useful life that is exposed to risks due to changes in political, operational, and financial factors, the second capital budgeting criterion – discounted payback period is profoundly important, particularly for the Russian environment. Those statements represent contradictions that exist in the theory and practice of the applied science. Therefore, it would be desirable to relax the assumptions of portfolio theory and regard DPP as not fewer relevant appraisal approach for the assessment of the investment and risk measure. At the same time, the rationality of the use of both project performance criteria depends on the methods and models, with the help of which these appraisal approaches are calculated in feasibility studies. The deterministic methods cannot ensure the required precision of the results, while the stochastic models guarantee the sufficient level of the accuracy and reliability of the obtained results, providing that the risks are properly identified, evaluated, and mitigated. Otherwise, the project performance indicators may not be confirmed during the phase of project realization. For instance, the economic and political instability can result in the undoing of hard-earned gains, leading to the need for the attraction of the additional finances for the project. The sources of the alternative investments, as well as supportive mitigation strategies, can be studied during the initial phases of project development. During this period, the effectiveness of the investments undertakings can also be improved by the inclusion of the various investors, e.g. Russian Railways’ enterprises and other private companies in the dry port projects. However, the evaluation of the effectiveness of the participation of different investors in the project lack the methods and models that would permit doing the particular feasibility study, foreseeing the quantitative characteristics of risks and their mitigation strategies, which can meet the tolerance of the investors to the risks. For this reason, the research proposes a combination of Monte Carlo method, discounted cash flow technique, the theory of real options, and portfolio theory via a system dynamics simulation approach. The use of this methodology allows for comprehensive risk management process of dry port development to cover all aspects of risk identification, risk evaluation, risk mitigation, risk monitoring, and control phases. A designed system dynamics model can be recommended for the decision-makers on the dry port projects that are financed via a public-private partnership. It permits investors to make a decision appraisal based on random variables of net present value and discounted payback period, depending on different risks factors, e.g. revenue risks, land acquisition risks, traffic volume risks, construction hazards, and political risks. In this case, the statistical mean is used for the explication of the expected value of the DPP and NPV; the standard deviation is proposed as a characteristic of risks, while the elasticity coefficient is applied for rating of risks. Additionally, the risk of failure of project investments and guaranteed recoupment of capital investment can be considered with the help of the model. On the whole, the application of these modern methods of simulation creates preconditions for the controlling of the process of dry port development, i.e. making managerial changes and identifying the most stable parameters that contribute to the optimal alternative scenarios of the project realization in the uncertain environment. System dynamics model allows analyzing the interactions in the most complex mechanism of risk management process of the dry ports development and making proposals for the improvement of the effectiveness of the investments via an estimation of different risk management strategies. For the comparison and ranking of these alternatives in their order of preference to the investor, the proposed indicators of the efficiency of the investments, concerning the NPV, DPP, and coefficient of variation, can be used. Thus, rational investors, who averse to taking increased risks unless they are compensated by the commensurate increase in the expected utility of a risky prospect of dry port development, can be guided by the deduced marginal utility of investments. It is computed on the ground of the results from the system dynamics model. In conclusion, the outlined theoretical and practical implications for the management of risks, which are the key characteristics of public-private partnerships, can help analysts and planning managers in budget decision-making, substantially alleviating the effect from various risks and avoiding unnecessary cost overruns in dry port projects.

The TTIP, ISDS and the shift towards transparency in investor-state arbitration

The negotiations between the EU and the US over the Transatlantic Trade and Investment Partnership (TTIP) have generated a lot of discussion about investor-state dispute settlement (ISDS). This discussion provided the inspiration for this thesis, with the TTIP in the background, setting the scene. In this thesis I study the nature of ISDS and the principle of transparency within investor-state arbitration. I aim to determine whether the use of ISDS is restricted to international arbitration and whether ISDS can be considered to constitute a system or regime. Furthermore, I consider whether the introduction of the UNCITRAL Rules on Transparency in Treaty-based Investor-State Arbitration (2014, the UNCITRAL Transparency Rules) changes investor-state arbitration in relation to transparency. To achieve this, I examine ISDS provisions in several different international investment agreements (IIAs) and evaluate the ways in which transparency is incorporated into investment law. Moreover, I compare the provisions on transparency and confidentiality in institutional arbitration rules with the UNCITRAL Transparency Rules. I have formed several conclusions, including that the ISDS provisions may contain methods other than international arbitration and that ISDS does not constitute a system. Furthermore, the UNCITRAL Transparency Rules do change – theoretically, at least – investor-state arbitration to become more transparent. Whether the UNCITRAL Transparency Rules will make investor-state arbitration fully transparent depends on the actions of the contracting state parties when negotiating new IIAs and whether they choose to incorporate the UNCITRAL Transparency Rules in the IIAs already concluded.

Promoting Healthy Lifestyles with Personalized, APOE Genotype Based Health Information: The Effects on Psychological-, Health Behavioral and Clinical Factors

There is an increasing demand for individualized, genotype-based health advice. The general population-based dietary recommendations do not always motivate people to change their life-style, and partly following this, cardiovascular diseases (CVD) are a major cause of death in worldwide. Using genotype-based nutrition and health information (e.g. nutrigenetics) in health education is a relatively new approach, although genetic variation is known to cause individual differences in response to dietary factors. Response to changes in dietary fat quality varies, for example, among different APOE genotypes. Research in this field is challenging, because several non-modifiable (genetic, age, sex) and modifiable (e.g. lifestyle, dietary, physical activity) factors together and with interaction affect the risk of life-style related diseases (e.g. CVD). The other challenge is the psychological factors (e.g. anxiety, threat, stress, motivation, attitude), which also have an effect on health behavior. The genotype-based information is always a very sensitive topic, because it can also cause some negative consequences and feelings (e.g. depression, increased anxiety). The aim of this series of studies was firstly to study how individual, genotype-based health information affects an individual’s health form three aspects, and secondly whether this could be one method in the future to prevent lifestyle-related diseases, such as CVD. The first study concentrated on the psychological effects; the focus of the second study was on health behavior effects, and the third study concentrated on clinical effects. In the fourth study of this series, the focus was on all these three aspects and their associations with each other. The genetic risk and health information was the APOE gene and its effects on CVD. To study the effect of APOE genotype-based health information in prevention of CVD, a total of 151 volunteers attended the baseline assessments (T0), of which 122 healthy adults (aged 20 – 67 y) passed the inclusion criteria and started the one-year intervention. The participants (n = 122) were randomized into a control group (n = 61) and an intervention group (n = 61). There were 21 participants in the intervention Ɛ4+ group (including APOE genotypes 3/4 and 4/4) and 40 participants in the intervention Ɛ4- group (including APOE genotypes 2/3 and 3/3). The control group included 61 participants (including APOE genotypes 3/4, 4/4, 2/3, 3/3 and 2/2). The baseline (T0) and follow-up assessments (T1, T2, T3) included detailed measurements of psychological (threat and anxiety experience, stage of change), and behavioral (dietary fat quality, consumption of vegetables, - high fat/sugar foods and –alcohol, physical activity and health and taste attitudes) and clinical factors (total-, LDL- HDL cholesterol, triglycerides, blood pressure, blood glucose (0h and 2h), body mass index, waist circumference and body fat percentage). During the intervention six different communication sessions (lectures on healthy lifestyle and nutrigenomics, health messages by mail, and personal discussion with the doctor) were arranged. The intervention groups (Ɛ4+ and Ɛ4-) received their APOE genotype information and health message at the beginning of the intervention. The control group received their APOE genotype information after the intervention. For the analyses in this dissertation, the results for 106/107 participants were analyzed. In the intervention, there were 16 participants in the high-risk (Ɛ4+) group and 35 in the low-risk (Ɛ4-) group. The control group had 55 participants in studies III-IV and 56 participants in studies I-II. The intervention had both short-term (≤ 6 months) and long-term (12 months) effects on health behavior and clinical factors. The short-term effects were found in dietary fat quality and waist circumference. Dietary fat quality improved more in the Ɛ4+ group than the Ɛ4- and the control groups as the personal, genotype-based health information and waist circumference lowered more in the Ɛ4+ group compared with the control group. Both these changes differed significantly between the Ɛ4+ and control groups (p<0.05). A long-term effect was found in triglyceride values (p<0.05), which lowered more in Ɛ4+ compared with the control group during the intervention. Short-term effects were also found in the threat experience, which increased mostly in the Ɛ4+ group after the genetic feedback (p<0.05), but it decreased after 12 months, although remaining at a higher level compared to the baseline (T0). In addition, Study IV found that changes in the psychological factors (anxiety and threat experience, motivation), health and taste attitudes, and health behaviors (dietary, alcohol consumption, and physical activity) did not directly explain the changes in triglyceride values and waist circumference. However, change caused by a threat experience may have affected the change in triglycerides through total- and HDL cholesterol. In conclusion, this dissertation study has given some indications that individual, genotypebased health information could be one potential option in the future to prevent lifestyle-related diseases in public health care. The results of this study imply that personal genetic information, based on APOE, may have positive effects on dietary fat quality and some cardiovascular risk markers (e.g., improvement in triglyceride values and waist circumference). This study also suggests that psychological factors (e.g. anxiety and threat experience) may not be an obstacle for healthy people to use genotype-based health information to promote healthy lifestyles. However, even in the case of very personal health information, in order to achieve a permanent health behavior change, it is important to include attitudes and other psychological factors (e.g. motivation), as well as intensive repetition and a longer intervention duration. This research will serve as a basis for future studies and its information can be used to develop targeted interventions, including health information based on genotyping that would aim at preventing lifestyle diseases. People’s interest in personalized health advices has increased, while also the costs of genetic screening have decreased. Therefore, generally speaking, it can be assumed that genetic screening as a part of the prevention of lifestyle-related diseases may become more common in the future. In consequence, more research is required about how to make genetic screening a practical tool in public health care, and how to efficiently achieve long-term changes.

DNA polymerase activity in trophoblast giant cells in the mouse /

In the developing mouse embryo, the diploid trophectoderm is known to undergo a diploid to giant cell transformation. These cells arise by a process of endoreduplication, characterized by replication of the entire genome without subsequent mitosis or cell division, leading to polyploidy and the formation of giant nuclei. Studies of 13.5 day rat trophoblast derived from the parietal yolk sac have indicated a relatively low rate of DNA polymerase a activity, the noinnal eukaryotic replicase, in comparison to that of DNA polymerase g. These results have suggested that endoreduplication in trophoblast giant cells may not employ the normal replicase enzyme, DNA polymerase a. In order to determine whether a 'switch' from DNA polymerase to DNA polymerase is a necessary concomitant of the diploid to giant cell transformation, two distinct populations of trophoblast giant cells, the primary giant cell derived from the mural trophectoderm and the secondary giant cell derived from the polar trophoectoderm were used. These two populations of trophoblast giant cells can be obtained from the tissue outgrowths of 3.5da blastocysts and the extraembryonic ectoderm (EX) and ectoplacental cone (EPC) of 7.5 day embryos respectively. Tissue outgrowths were treated with aphidicolin, a specific reversible inhibitor of eukaryotic DNA polymerase a, on various days after explantation. The effect of aphidicolin treatment was assessed both qualitatively, using autoradiography and quantitatively by scintillation counting and Feulgen staining. 3 DNA synthesis was measured in control and treated cultures after a Hthymidine pulse. Scintillation counts of the embryo proper revealed that DNA synthesis was consistently inhibited by greater than 907. in the presence of aphidicolin. Inhibition of DNA synthesis in the EX and EPC varied between 81-957. and 82-987. respectively, indicating that most DNA synthesis was mediated by DNA polymerase a, but that a small but significant amount of residual synthesis was indicated. A qualitative approach was then applied to determine whether the apparent residual DNA synthesis was restricted to a subpopulation of giant cells or whether all giant cells displayed a low level of DNA synthesis. Autoradiographs of the ICM of blastocysts and the embryo proper of 7.5da embryos, which acted as diploid control population, was completely inhibited regardless of duration in explant culture. In contrast, primary trophoblast giant cells derived from blastocysts and secondary giant cells derived from the EX and EPC were observed to possess some heavily labelled cells after aphidicolin treatment. These results suggest that although DNA polymerase a is the primary replicating enzyme responsible for endoreduplication in mouse trophoblast giant cells, some nonactivity is also observed. A DNA polymerase assay employing tissue lysates of outgrown 7.5da embryo, EX and EPC tissues was used to attempt to confirm the presence of higher nonactivity in tissues possessing trophoblast giant cells. Employing a series of inhibitors of DNA polymerases, it would appear that DNA polymerase a is the major polymerase active in all tissues of the 7.5da mouse embryo. The nature of the putative residual DNA synthetic activity could not be unequivically determined in this study. Therefore, these results suggest that both primary and secondary trophoblast giant cells possess and use DNA polymerase a in endoreduplicative DNA synthesis. It would appear that the high levels of DNA polymerase g activity reported in trophoblast tissue derived from the 13.5 da rat yolk sac was not a general feature of all endoreduplication.

An investigation of the nature and role of historicality in the thought of Dilthey and Heidegger

Introduction The question of the meaning, methods and philosophical manifestations of history is currently rife with contention. The problem that I will address in an exposition of the thought of Wilhelm Dilthey and Martin Heidegger, centers around the intersubjectivity of an historical world. Specifically, there are two interconnected issues. First, since all knowledge occurs to a person from within his or her historical age how can any person in any age make truth claims? In order to answer this concern we must understand the essence and role of history. Yet how can we come to an individual understanding ofwhat history is when the meanings that we use are themselves historically enveloped? But can we, we who are well aware of the knowledge that archaeology has dredged up from old texts or even from 'living' monuments of past ages, really neglect to notice these artifacts that exist within and enrich our world? Charges of wilful blindness would arise if any attempt were made to suggest that certain things of our world did not come down to us from the past. Thus it appears more important 2 to determine what this 'past' is and therefore how history operates than to simply derail the possibility for historical understanding. Wilhelm Dilthey, the great German historicist from the 19th century, did not question the existence of historical artifacts as from the past, but in treating knowledge as one such artifact placed the onus on knowledge to show itself as true, or meaningful, in light ofthe fact that other historical periods relied on different facts and generated different truths or meanings. The problem for him was not just determining what the role of history is, but moreover to discover how knowledge could make any claim as true knowledge. As he stated, there is a problem of "historical anarchy"!' Martin Heidegger picked up these two strands of Dilthey's thought and wanted to answer the problem of truth and meaning in order to solve the problem of historicism. This problem underscored, perhaps for the first time, that societal presuppositions about the past and present oftheir era are not immutable. Penetrating to the core of the raison d'etre of the age was an historical reflection about the past which was now conceived as separated both temporally and attitudinally from the present. But further than this, Heidegger's focus on asking the question of the meaning of Being meant that history must be ontologically explicated not merely ontically treated. Heidegger hopes to remove barriers to a genuine ontology by II 1 3 including history into an assessment ofprevious philosophical systems. He does this in order that the question of Being be more fully explicated, which necessarily for him includes the question of the Being of history. One approach to the question ofwhat history is, given the information that we get from historical knowledge, is whether such knowledge can be formalized into a science. Additionally, we can approach the question of what the essence and role of history is by revealing its underlying characteristics, that is, by focussing on historicality. Thus we will begin with an expository look at Dilthey's conception of history and historicality. We will then explore these issues first in Heidegger's Being and Time, then in the third chapter his middle and later works. Finally, we shall examine how Heidegger's conception may reflect a development in the conception of historicality over Dilthey's historicism, and what such a conception means for a contemporary historical understanding. The problem of existing in a common world which is perceived only individually has been philosophically addressed in many forms. Escaping a pure subjectivist interpretation of 'reality' has occupied Western thinkers not only in order to discover metaphysical truths, but also to provide a foundation for politics and ethics. Many thinkers accept a solipsistic view as inevitable and reject attempts at justifying truth in an intersubjective world. The problem ofhistoricality raises similar problems. We 4 -. - - - - exist in a common historical age, presumably, yet are only aware ofthe historicity of the age through our own individual thoughts. Thus the question arises, do we actually exist within a common history or do we merely individually interpret this as communal? What is the reality of history, individual or communal? Dilthey answers this question by asserting a 'reality' to the historical age thus overcoming solipsism by encasing individual human experience within the historical horizon of the age. This however does nothing to address the epistemological concern over the discoverablity of truth. Heidegger, on the other hand, rejects a metaphysical construel of history and seeks to ground history first within the ontology ofDasein, and second, within the so called "sending" of Being. Thus there can be no solipsism for Heidegger because Dasein's Being is necessarily "cohistorical", Being-with-Others, and furthermore, this historical-Being-in-the-worldwith- Others is the horizon of Being over which truth can appear. Heidegger's solution to the problem of solipsism appears to satisfy that the world is not just a subjective idealist creation and also that one need not appeal to any universal measures of truth or presumed eternal verities. Thus in elucidating Heidegger's notion of history I will also confront the issues ofDasein's Being-alongside-things as well as the Being of Dasein as Being-in-the-world so that Dasein's historicality is explicated vis-a-vis the "sending of Being" (die Schicken des S eins).

Husserl's approach to transcendental intersubjectivity

It is our intention in the course of the development of this thesis to give an account of how intersubjectivity is "eidetically" constituted by means of the application of the phenomenological reduction to our experience in the context of the thought of Edmund Husserl; contrasted with various representative thinkers in what H. Spiegelberg refers to as "the wider scene" of phenomenology. That is to say, we intend to show those structures of both consciousness and the relation which man has to the world which present themselves as the generic conditions for the possibility of overcoming our "radical sol itude" in order that we may gain access to the mental 1 ife of an Other as other human subject. It is clear that in order for us to give expression to these accounts in a coherent manner, along with their relative merits, it will be necessary to develop the common features of any phenomenological theory of consdousness whatever. Therefore, our preliminary inquiry, subordinate to the larger theme, shall be into some of the epistemological results of the application of the phenomenological method used to develop a transcendental theory of consciousness. Inherent in this will be the deliniation of the exigency for making this an lIintentional ll theory. We will then be able to see how itis possible to overcome transcendentally the Other as an object merely given among other merely given objects, and further, how this other is constituted specifically as other ego. The problem of transcendental intersubjectivity and its constitution in experience can be viewed as one of the most compelling, if not the most polemical of issues in phenomenology. To be sure, right from the beginning we are forced to ask a number of questions regarding Husserl's responses to the problem within the context of the methodological genesis of the Cartesian Meditations, and The Crisis of European Sciences and Transcendental Phenomenology. This we do in order to set the stage for amplification. First, we ask, has Husserl lived up to his goal, in this connexion, of an apodictic result? We recall that in his Logos article of 1911 he adminished that previous philosophy does not have at its disposal a merely incomplete and, in particular instances, imperfect doctrinal system; it simply has none whatever. Each and every question is herein controverted, each position is a matter of individual conviction, of the interpretation given byaschool, of a "point of view". 1. Moreover in the same article he writes that his goal is a philosophical system of doctrine that, after the gigantic preparatory work. of generations, really be- . gins from the ground up with a foundation free from doubt and rises up like any skilful construction, wherein stone is set upon store, each as solid as the other, in accord with directive insights. 2. Reflecting upon the fact that he foresaw "preparatory work of generations", we perhaps should not expect that he would claim that his was the last word on the matter of intersubjectivity. Indeed, with 2. 'Edmund Husserl, lIPhilosophy as a Rigorous Science" in Phenomenology and theCrisis6fPhilosophy, trans". with an introduction by Quentin Lauer (New York.: Harper & Row, 1965) pp. 74 .. 5. 2Ibid . pp. 75 .. 6. 3. the relatively small amount of published material by Husserl on the subject we can assume that he himself was not entirely satisfied with his solution. The second question we have is that if the transcendental reduction is to yield the generic and apodictic structures of the relationship of consciousness to its various possible objects, how far can we extend this particular constitutive synthetic function to intersubjectivity where the objects must of necessity always remain delitescent? To be sure, the type of 'object' here to be considered is unlike any other which might appear in the perceptual field. What kind of indubitable evidence will convince us that the characteristic which we label "alter-ego" and which we attribute to an object which appears to resemble another body which we have never, and can never see the whole of (namely, our own bodies), is nothing more than a cleverly contrived automaton? What;s the nature of this peculiar intentional function which enables us to say "you think just as I do"? If phenomenology is to take such great pains to reduce the takenfor- granted, lived, everyday world to an immanent world of pure presentation, we must ask the mode of presentation for transcendent sub .. jectivities. And in the end, we must ask if Husserl's argument is not reducible to a case (however special) of reasoning by analogy, and if so, tf this type of reasoning is not so removed from that from whtch the analogy is made that it would render all transcendental intersubjective understandtng impos'sible? 2. HistoticalandEidetic Priority: The Necessity of Abstraction 4. The problem is not a simple one. What is being sought are the conditions for the poss ibili:ty of experi encing other subjects. More precisely, the question of the possibility of intersubjectivity is the question of the essence of intersubjectivity. What we are seeking is the absolute route from one solitude to another. Inherent in this programme is the ultimate discovery of the meaning of community. That this route needs be lIabstract" requires some explanation. It requires little explanation that we agree with Husserl in the aim of fixing the goal of philosophy on apodictic, unquestionable results. This means that we seek a philosophical approach which is, though, not necessarily free from assumptions, one which examines and makes explicit all assumptions in a thorough manner. It would be helpful at this point to distinguish between lIeidetic ll priority, and JlhistoricallJpriority in order to shed some light on the value, in this context, of an abstraction.3 It is true that intersubjectivity is mundanely an accomplished fact, there havi.ng been so many mi.llions of years for humans to beIt eve in the exi s tence of one another I s abili ty to think as they do. But what we seek is not to study how this proceeded historically, but 3Cf• Maurice Natanson;·TheJburne in 'Self, a Stud in Philoso h and Social Role (Santa Cruz, U. of California Press, 1970 . rather the logical, nay, "psychological" conditions under which this is possible at all. It is therefore irrelevant to the exigesis of this monograph whether or not anyone should shrug his shoulders and mumble IIwhy worry about it, it is always already engaged". By way of an explanation of the value of logical priority, we can find an analogy in the case of language. Certainly the language 5. in a spoken or written form predates the formulation of the appropriate grammar. However, this grammar has a logical priority insofar as it lays out the conditions from which that language exhibits coherence. The act of formulating the grammar is a case of abstraction. The abstraction towards the discovery of the conditions for the poss; bi 1 ity of any experiencing whatever, for which intersubjective experience is a definite case, manifests itself as a sort of "grammar". This "grammar" is like the basic grammar of a language in the sense that these "rulesil are the ~ priori conditions for the possibility of that experience. There is, we shall say, an "eidetic priority", or a generic condition which is the logical antecedent to the taken-forgranted object of experience. In the case of intersubjectivity we readily grant that one may mundanely be aware of fellow-men as fellowmen, but in order to discover how that awareness is possible it is necessary to abstract from the mundane, believed-in experience. This process of abstraction is the paramount issue; the first step, in the search for an apodictic basis for social relations. How then is this abstraction to be accomplished? What is the nature of an abstraction which would permit us an Archimedean point, absolutely grounded, from which we may proceed? The answer can be discovered in an examination of Descartes in the light of Husserl's criticism. 3. The Impulse for Scientific Philosophy. The Method to which it Gives Rise. 6. Foremost in our inquiry is the discovery of a method appropriate to the discovery of our grounding point. For the purposes of our investigations, i.e., that of attempting to give a phenomenological view of the problem of intersubjectivity, it would appear to be of cardinal importance to trace the attempt of philosophy predating Husserl, particularly in the philosophy of Descartes, at founding a truly IIscientific ll philosophy. Paramount in this connexion would be the impulse in the Modern period, as the result of more or less recent discoveries in the natural sciences, to found philosophy upon scientific and mathematical principles. This impulse was intended to culminate in an all-encompassing knowledge which might extend to every realm of possible thought, viz., the universal science ot IIMathexis Universalis ll •4 This was a central issue for Descartes, whose conception of a universal science would include all the possible sciences of man. This inclination towards a science upon which all other sciences might be based waS not to be belittled by Husserl, who would appropriate 4This term, according to Jacab Klein, was first used by Barocius, the translator of Proclus into Latin, to designate the highest mathematical discipline. . 7. it himself in hopes of establishing, for the very first time, philosophy as a "rigorous science". It bears emphasizing that this in fact was the drive for the hardening of the foundations of philosophy, the link between the philosophical projects of Husserl and those of the philosophers of the modern period. Indeed, Husserl owes Descartes quite a debt for indicating the starting place from which to attempt a radical, presupositionless, and therefore scientific philosophy, in order not to begin philosophy anew, but rather for the first time.5 The aim of philosophy for Husserl is the search for apodictic, radical certitude. However while he attempted to locate in experience the type of necessity which is found in mathematics, he wished this necessity to be a function of our life in the world, as opposed to the definition and postulation of an axiomatic method as might be found in the unexpurgated attempts to found philosophy in Descartes. Beyond the necessity which is involved in experiencing the world, Husserl was searching for the certainty of roots, of the conditi'ons which underl ie experience and render it pOssible. Descartes believed that hi~ MeditatiOns had uncovered an absolute ground for knowledge, one founded upon the ineluctable givenness of thinking which is present even when one doubts thinking. Husserl, in acknowledging this procedure is certainly Cartesian, but moves, despite this debt to Descartes, far beyond Cartesian philosophy i.n his phenomenology (and in many respects, closer to home). 5Cf. Husserl, Philosophy as a Rigorous Science, pp. 74ff. 8 But wherein lies this Cartesian jumping off point by which we may vivify our theme? Descartes, through inner reflection, saw that all of his convictions and beliefs about the world were coloured in one way or another by prejudice: ... at the end I feel constrained to reply that there is nothing in a all that I formerly believed to be true, of which I cannot in some measure doubt, and that not merely through want of thought or through levity, but for reasons which are very powerful and maturely considered; so that henceforth I ought not the less carefully to refrain from giving credence to these opinions than to that which is manifestly false, if I desire to arrive at any certainty (in the sciences). 6 Doubts arise regardless of the nature of belief - one can never completely believe what one believes. Therefore, in order to establish absolutely grounded knowledge, which may serve as the basis fora "universal Science", one must use a method by which one may purge oneself of all doubts and thereby gain some radically indubitable insight into knowledge. Such a method, gescartes found, was that, as indicated above by hi,s own words, of II radical doubt" which "forbids in advance any judgemental use of (previous convictions and) which forbids taking any position with regard to their val idi'ty. ,,7 This is the method of the "sceptical epoche ll , the method of doubting all which had heretofor 6Descartes,Meditations on First Philosophy, first Med., (Libera 1 Arts Press, New York, 1954) trans. by L. LaFl eur. pp. 10. 7Husserl ,CrisiS of Eliroeari SCiences and Trariscendental Phenomenology, (Northwestern U. Press, Evanston, 1 7 ,p. 76. 9. been considered as belonging to the world, including the world itself. What then is left over? Via the process of a thorough and all-inclusive doubting, Descartes discovers that the ego which performs the epoche, or "reduction", is excluded from these things which can be doubted, and, in principle provides something which is beyond doubt. Consequently this ego provides an absolute and apodictic starting point for founding scientific philosophy. By way of this abstention. of bel ief, Desca'rtes managed to reduce the worl d of everyday 1 ife as bel ieved in, to mere 'phenomena', components of the rescogitans:. Thus:, having discovered his Archimedean point, the existence of the ego without question, he proceeds to deduce the 'rest' of the world with the aid of innate ideas and the veracity of God. In both Husserl and Descartes the compelling problem is that of establ ishing a scientific, apodictic phi'losophy based upon presuppos itionless groundwork .. Husserl, in thi.s regard, levels the charge at Descartes that the engagement of his method was not complete, such that hi.S: starting place was not indeed presupositionless, and that the validity of both causality and deductive methods were not called into question i.'n the performance of theepoche. In this way it is easy for an absolute evidence to make sure of the ego as: a first, "absolute, indubitablyexisting tag~end of the worldll , and it is then only a matter of inferring the absolute subs.tance and the other substances which belon.g to the world, along with my own mental substance, using a logically val i d deductive procedure. 8 8Husserl, E.;' Cartesian 'Meditation;, trans. Dorion Cairns (Martinus Nijhoff, The Hague, 1970), p. 24 ff.