An analysis of protocols and publications suggested that most discontinuations of clinical trials were not based on preplanned interim analyses or stopping rules.

OBJECTIVES: To investigate the frequency of interim analyses, stopping rules, and data safety and monitoring boards (DSMBs) in protocols of randomized controlled trials (RCTs); to examine these features across different reasons for trial discontinuation; and to identify discrepancies in reporting between protocols and publications. STUDY DESIGN AND SETTING: We used data from a cohort of RCT protocols approved between 2000 and 2003 by six research ethics committees in Switzerland, Germany, and Canada. RESULTS: Of 894 RCT protocols, 289 prespecified interim analyses (32.3%), 153 stopping rules (17.1%), and 257 DSMBs (28.7%). Overall, 249 of 894 RCTs (27.9%) were prematurely discontinued; mostly due to reasons such as poor recruitment, administrative reasons, or unexpected harm. Forty-six of 249 RCTs (18.4%) were discontinued due to early benefit or futility; of those, 37 (80.4%) were stopped outside a formal interim analysis or stopping rule. Of 515 published RCTs, there were discrepancies between protocols and publications for interim analyses (21.1%), stopping rules (14.4%), and DSMBs (19.6%). CONCLUSION: Two-thirds of RCT protocols did not consider interim analyses, stopping rules, or DSMBs. Most RCTs discontinued for early benefit or futility were stopped without a prespecified mechanism. When assessing trial manuscripts, journals should require access to the protocol.

From breaking the rule to making the rules : the adoption, entrenchment and diffusion of gender quotas in France

Once a country allergic to any type of preferential treatment or quota measure for women, France has become a country that applies gender quotas to regulate women's presence and representation in politics, the business sector, public bodies, public administration, and even some civil society organizations. While research has concentrated on the adoption of electoral gender quotas in many countries and their international diffusion, few studies focus on explaining the successful diffusion of gender quotas from politics to other domains in the same country. This paper proposes to fill this gap by studying the particularly puzzling case of a country that at one point strongly opposed the adoption of gender quotas in politics, but, in less than a decade, transformed into one of the few countries applying gender quotas across several policy domains. This paper argues that the legal entrenchment of the parity principle, the institutionalization of parity in several successive women's policy agencies, and key players in these newly created agencies are mainly responsible for this unexpected development. The diffusion of gender quotas in France thus offers an illuminating example of under which conditions women's policy agencies can act autonomously to diffuse and impose a new tool for gender equality

Complete Analysis of Configuration Rules to Guarantee Reliable Network Security Policies

Peer-reviewed

Performance characteristic of moving average trading rules in the Finnish stock market

The thesis examines the profitability of DMAC trading rules in the Finnish stock market over the 1996-2012 period. It contributes to the existing technical analysis literature by comparing for the first time the performance of DMAC strategies based on individual stock trading portfolios to the performance of index trading strategies based on the trading on the index (OMX Helsinki 25) that consists of the same stocks. Besides, the market frictions including transaction costs and taxes are taken into account, and the results are reported from both institutional and individual investor’s perspective. Performance characteristic of DMAC rules are evaluated by simulating 19,900 different trading strategies in total for two non- overlapping 8-year sub-periods, and decomposing the full-sample-period performance of DMAC trading strategies into distinct bullish- and bearish-period performances. The results show that the best DMAC rules have predictive power on future price trends, and these rules are able to outperform buy-and-hold strategy. Although the performance of the DMAC strategies is highly dependent on the combination of moving average lengths, the best DMAC rules of the first sub-period have also performed well during the latter sub-period in the case of individual stock trading strategies. According to the results, the outperformance of DMAC trading rules over buy-and-hold strategy is mostly attributed to their superiority during the bearish periods, and particularly, during stock market crashes.

Rules of The National Library of Finland

Confirmed by the director of the National Library of Finland on 25 Nov 2013

Novel word learning ability in chronic post-stroke aphasia : variability and modality effects

Novel word learning has been rarely studied in people with aphasia (PWA), although it can provide a relatively pure measure of their learning potential, and thereby contribute to the development of effective aphasia treatment methods. The main aim of the present thesis was to explore the capacity of PWA for associative learning of word–referent pairings and cognitive-linguistic factors related to it. More specifically, the thesis examined learning and long-term maintenance of the learned pairings, the role of lexical-semantic abilities in learning as well as acquisition of phonological versus semantic information in associative novel word learning. Furthermore, the effect of modality on associative novel word learning and the neural underpinnings of successful learning were explored. The learning experiments utilized the Ancient Farming Equipment (AFE) paradigm that employs drawings of unfamiliar referents and their unfamiliar names. Case studies of Finnishand English-speaking people with chronic aphasia (n = 6) were conducted in the investigation. The learning results of PWA were compared to those of healthy control participants, and active production of the novel words and their semantic definitions was used as learning outcome measures. PWA learned novel word–novel referent pairings, but the variation between individuals was very wide, from more modest outcomes (Studies I–II) up to levels on a par with healthy individuals (Studies III–IV). In incidental learning of semantic definitions, none of the PWA reached the performance level of the healthy control participants. Some PWA maintained part of the learning outcomes up to months post-training, and one individual showed full maintenance of the novel words at six months post-training (Study IV). Intact lexical-semantic processing skills promoted learning in PWA (Studies I–II) but poor phonological short-term memory capacities did not rule out novel word learning. In two PWA with successful learning and long-term maintenance of novel word–novel referent pairings, learning relied on orthographic input while auditory input led to significantly inferior learning outcomes (Studies III–IV). In one of these individuals, this previously undetected modalityspecific learning ability was successfully translated into training with familiar but inaccessible everyday words (Study IV). Functional magnetic resonance imaging revealed that this individual had a disconnected dorsal speech processing pathway in the left hemisphere, but a right-hemispheric neural network mediated successful novel word learning via reading. Finally, the results of Study III suggested that the cognitive-linguistic profile may not always predict the optimal learning channel for an individual with aphasia. Small-scale learning probes seem therefore useful in revealing functional learning channels in post-stroke aphasia.

Influence of exercise modality on agreement between gas exchange and heart rate variability thresholds

The main purpose of this study was to investigate the level of agreement between the gas exchange threshold (GET) and heart rate variability threshold (HRVT) during maximal cardiopulmonary exercise testing (CPET) using three different exercise modalities. A further aim was to establish whether there was a 1:1 relationship between the percentage heart rate reserve (%HRR) and percentage oxygen uptake reserve (%V˙O2R) at intensities corresponding to GET and HRVT. Sixteen apparently healthy men 17 to 28 years of age performed three maximal CPETs (cycling, walking, and running). Mean heart rate and V˙O2 at GET and HRVT were 16 bpm (P<0.001) and 5.2 mL·kg-1·min-1 (P=0.001) higher in running than cycling, but no significant differences were observed between running and walking, or cycling and walking (P>0.05). There was a strong relationship between GET and HRVT, with R2 ranging from 0.69 to 0.90. A 1:1 relationship between %HRR and %V˙O2R was not observed at GET and HRVT. The %HRR was higher during cycling (GET mean difference=7%; HRVT mean difference=11%; both P<0.001), walking (GET mean difference=13%; HRVT mean difference=13%; both P<0.001), or running (GET mean difference=11%; HRVT mean difference=10%; both P<0.001). Therefore, using HRVT to prescribe aerobic exercise intensity appears to be valid. However, to assume a 1:1 relationship between %HRR and %V˙O2R at HRVT would probably result in overestimation of the energy expenditure during the bout of exercise.

Making home rules for mother tongues : the legal implications of linguistic diversity in the design of autonomy regimes

Principen om nationalismen där det politiska och det nationella är samspelt kan vara av markant betydelse för uppbyggande av autonomiska regimer. Likaså tillåter decentralicering och delegering av befogenheter för språk och utbildning (officiellt erkännande av språk, standardisering av språk, undervisningsspråk och relaterade läroplaner) formning av identiteter inom dessa autonomiska regimer. Resultatet är en ofullkomlig cirkulär relation där språk, samfund och politiska institutioner ömsesidigt och kontinuerligt formar varandra: lingvistiskt mångfald prägar och formger autonomiska ordningar och vice-versa. De juridiska implikationerna av territoriella och icke-territoriella former av autonomi är dock av en annan art. Emedan territoriell autonomi bygger på idéen om ett eventuellt inkluderande hemland för lingvistiska grupper, vars vistelseort är avgörande, förstärker den icke-territoriella autonomin idéen om ett exclusivt samfund bestående av själv-identifierade medlemmar som är kapabla till självstyre oavsett territoriella gränser. Denna avhandling utgör an analys av sådana juridiska implikationer genom komparativa och institutionella analyser. Avhandlingen föreslår som resultat en serie av normativa och pragmatiska rekommendationer inriktade på att främja demokratiseringsprocesser i linje med principer om multikulturalism.

Incentivising Innovation? The competition law approach to the new challenge clauses in the competition rules for technology licensing agreements of the EU

Tutkielman aiheena on EU:n kilpailuoikeudellinen lähestymistapa challenge-lausekkeisiin teknologinsiirtosopimuksia koskevassa ryhmäpoikkeusasetuksessa. Teknologian lisensoinnin katsotaan olevan tärkeä väline teknologian kehityksen levittämisessä ja innovaation edistämisessä. Joissakin tapauksissa lisenssisopimus voi sisältää kilpailua rajoittavia lausekkeita, joiden voidaan kuitenkin nähdä hyödyttävän kilpailua kokonaisuutta arvostellen. Tällaisia lausekkeita ovat niin sanotut ”no-challenge” – lauseke, eli sopimusehto, jonka nojalla lisenssinsaaja sitoutuu olemaan haastamatta lisensoidun immateriaalioikeuden pätevyyttä ja ”termination-on-challenge” – lauseke, joka antaa lisensoijalle haastettaessa oikeuden päättää lisenssisopimus. Tutkielmassa perehdytään challenge -lausekkeiden hyväksyttävyyden arviointiin Euroopan unionin kilpailuoikeuden näkökulmasta uuden 1.5.2014 voimaan tulleen ryhmäpoikkeusasetuksen valossa. Muissa kuin yksinoikeuksia luovissa teknologiansiirtosopimuksissa olevat termination-on-challenge – lausekkeita tulee uusimmassa ryhmäpoikkeusetuksessa aina perustua yritysten itse suorittamaan tapauskohtaiseen arviointiin. No-challenge – lausekkeet ovat jatkossakin aiemman käytännön mukaisesti ryhmäpoikkeuksen soveltamisalan ulkopuolella. Komission on perustellut challenge - lausekkeiden jättämistä asetuksen ulkopuolelle julkisella intressillä, joka on päästä eroon mitättömistä immateriaalioikeuksista. Komission on katsonut, että challenge – lausekkeiden kilpailua rajoittava ominaisuus on mitättömien immateriaalioikeuksien esiintyminen markkinoilla, mikä osaltaan vääristää kilpailua ja hidastaa toimijoiden markkinoille pääsyä. Toisaalta lausekkeiden voidaan sanoa edistävän kilpailua, sillä ne usein tarjoavat immateriaalioikeuden haltijalle riittävän oikeussuojan ja kannustimen lisensoida teknologia, mikä lisää kilpailua, keksijöiden kannustimia panostaa innovaatioihin sekä vähentää transaktiokustannuksia. Tutkielman keskeinen tulos on ennen kaikkea challenge-lausekkeiden kilpailuvaikutusten tunnistamisessa ja komission perusteluiden kriittisessä arvioinnissa. Komission linjauksen perustelut eivät saa riittävää tukea ottaen huomioon vaikutustenarvioinnin, EU:n tuomioistuinkäytännön sekä taloustieteellisen lähestymistavan. Tutkielman tulosten pohjalta ja tukeutuen eri oikeuslähteisiin, taloustieteellisiin argumentteihin ja oikeusvertailevaan tutkimukseen, on mahdollista tehdä johtopäätöksiä niistä seikoista ja argumenteista, joilla on merkitystä uuden politiikkalinjauksen kilpailuvaikutuksiin.

Credibility, rules and power in the European Union institutions: a transactional analysis of the "Stability and Growth pact"

The credibility of the rules and the elements of power constitute fundamental keys in the analysis of the political institutions. This paper opens the "black box" of the European Union institutions and analyses the problem of credibility in the commitment of the Stability and Growth pact (SGP). This Pact (SGP) constituted a formal rule that tried to enforce budgetary discipline on the European States. Compliance with this contract could be ensured by the existence of "third party enforcement" or by the coincidence of the ex-ante and ex-post interests of the States (reputational capital). The fact is that states such as France or Germany failed to comply with the ruling and managed to avoid the application of sanctions. This article studies the transactions and the hierarchy of power that exists in the European institutions, and analyses the institutional framework included in the new European Constitution.

Trade rules and exchange rate misalignments: in search for a WTO solution

The debate on the link between trade rules and rules on exchange rates is raising the attention of experts on international trade law and economics. The main purpose of this paper is to analyze the impacts of exchange rate misalignments on tariffs as applied by the WTO - World Trade Organization. It is divided into five sections: the first one explains the methodology used to determine exchange rate misalignments and also presents its results for Brazil, U.S. and China; the second summarizes the methodology applied to calculate the impacts of exchange rate misalignments on the level of tariff protection through an exercise of "misalignment tariffication"; the third examines the effects of exchange rate variations on tariffs and their consequences for the multilateral trading system; the fourth one creates a methodology to estimate exchange rates against a currency of the World and a proposal to deal with persistent and significant misalignments related to trade rules. The conclusions are present in the last section.

Charting developmental EEG gamma changes in the auditory modality /

The oscillation of neuronal circuits reflected in the EEG gamma frequency may be fundamental to the perceptual process referred to as binding (the integration of various thoughts and perceptions into a coherent picture). The aim of our study was to expand our knowledge of the developmental course ofEEG gamma in the auditory modality. 2 We investigated EEG 40 Hz gamma band responses (35.2 to 43.0 Hz) using an auditory novelty oddball paradigm alone and with a visual-number-series distracter task in 208 participants as a function of age (7 years to adult) at 9 sites across the sagital and lateral axes (F3, Fz, F4, C3, Cz, C4, P3, Pz, P4). Gamma responses were operationally defined as change in power or a change in phase synchrony level from baseline within two time windows. The evoked gamma response was defined as a significant change from baseline occurring between 0 to 150 ms after stimulus onset; the induced gamma response was measured from 250 to 750 ms after stimulus onset. A significant evoked gamma band response was found when measuring changes in both power and phase synchrony. The increase in both measures was maximal at frontal regions. Decreases in both measures were found when participants were distracted by a secondary task. For neither measure were developmental effects noted. However, evoked gamma power was significantly enhanced with the presentation of a novel stimulus, especially at the right frontal site (F4); frontal evoked gamma phase synchrony also showed enhancement for novel stimuli but only for our two oldest age groups (16-18 year olds and adults). Induced gamma band responses also varied with task-dependent cognitive stimulus properties. In the induced gamma power response in all age groups, target stimuli generated the highest power values at the parietal region, while the novel stimuli were always below baseline. Target stimuli increased induced synchrony in all regions for all participants, but the novel stimulus selectively affected participants dependent on their age and gender. Adult participants, for example, exhibited a reduction in gamma power, but an increase in synchrony to the novel stimulus within the same region. Induced gamma synchrony was more sensitive to the gender of the participant than was induced gamma power. While induced gamma power produced little effects of age, gamma synchrony did have age effects. These results confirm that the perceptual process which regulates gamma power is distinct from that which governs the synchronization for neuronal firing, and both gamma power and synchrony are important factors to be considered for the "binding" hypothesis. However, there is surprisingly little effect of age on the absolute levels of or distribution of EEG gamma in the age range investigated.