Iodine Brachytherapy for Large Uveal Melanomas

Uveal melanoma is the most common primary intraocular malignancy in adults. Vision in the affected eye is threatened by both the tumor and side-effects from the treatments currently available. Poor prognosis for saving vision increases with tumor size and, consequently, enucleation has been the treatment of choice for large uveal melanomas in most centers. However, increasing evidence suggests that no survival benefit is gained (nor lost) by enucleation as compared to eye-conserving methods. The Helsinki University Eye Hospital has since 1990 offered episcleral iodine-125 plaque brachytherapy (IBT) for all patients unwilling to undergo enucleation for a large uveal melanoma. The primary aim of this study was to assess survival, local tumor recurrence and preservation of the eye and vision after IBT in a population-based series of 97 patients with uveal melanomas classified as large by the Collaborative Ocular Melanoma Study (COMS) criteria. Further aims included reporting the incidence of side-effects and assessing the role of intraocular dose distribution and clinical risk factors in their development. Finally, means to improve the current treatment were investigated by using computer models to compare existing plaques with collimating ones and by comparing the outcome of a subgroup of 54 IBT patients with very thick tumors with 33 patients with similarly-sized tumors managed with transscleral local resection (TSR) in Liverpool, United Kingdom. Kaplan-Meier estimates of all-cause and melanoma-specific survival at 5 years after IBT were 62% and 65%, respectively, and visually comparable with the survival experience of patients reported after enucleation by the COMS. Local recurrence developed in 6% of eyes and 84% of eyes were conserved at 5 years. Visual prognosis was guarded with 11% avoiding loss of 20/70 vision and 26% avoiding loss of 20/400 vision in the tumor eye at 2 years. Large tumor height and short distance from the posterior pole were independently associated with loss of vision. Using cumulative incidence analysis to account for competing risks, such as enucleation and metastatic death, the 5-year incidence of cataract after IBT was 79%, glaucoma 60%, optic neuropathy 46%, maculopathy 52%, persistent or recurring retinal detachment (RD) 25%, and vitreous hemorrhage 36%. In multivariate competing risks regression models, increasing tumor height was associated with cataract, iris neovascularization and RD. Maculopathy and optic neuropathy were associated with distance from the tumor to the respective structure. Median doses to the tumor apex, macula and optic disc were 81 Gy (range, 40-158), 79 Gy (range, 12-632), and 83 Gy (range, 10-377), respectively. Dose to the optic disc was independently associated with optic neuropathy, and both dose to the optic disc and dose to the macula predicted vision loss after IBT. Simulated treatment using collimating plaques resulted in clinically meaningful reduction in both optic disc (median reduction, 30 Gy) and macular (median reduction, 36 Gy) doses as compared to the actual treatment with standard plaques. In the subgroup of patients with uveal melanomas classified as large because of tumor height, cumulative incidence analysis revealed that while long-term preservation of 20/70 vision was rare after both IBT and TSR, preservation of 20/400 vision was better after TSR (32% vs. 5% at 5 years). In multivariate logistic regression models, TSR was independently associated with better preservation of 20/400 vision (OR 0.03 at 2 years, P=0.005) No cases of secondary glaucoma were observed after TSR and optic neuropathy was rare. However, local tumor recurrence was more common after TSR than it was after IBT (Cumulative incidence 41% vs. 7% at 5 years, respectively). In terms of survival, IBT seems to be a safe alternative to enucleation in managing large uveal melanomas. Local tumor control is no worse than with medium-sized tumors and the chances of avoiding secondary enucleation are good. Unfortunately, side-effects from radiotherapy are frequent, especially in thick tumors, and long-term prognosis of saving vision is consequently guarded. Some complications can be limited by using collimating plaques and by managing uveal melanomas that are large because of tumor height with TSR instead of IBT. However, the patient must be willing to accept a substantial risk of local tumor recurrence after TSR and it is best suited for cases in which the preservation of vision in the tumor eye is critical.

Conflits de norms de justice distributive dans les fusions entre égaux Le cas de BioM.rieux-Pierre Fabre

Les strictes fusions entre égaux constituent un phénomène très rare. Pourtant, de nombreux dirigeants communiquent sur l’aspect égalitaire des fusions et acquisitions qu’ils conçoivent. Dans cet article, les auteurs expliquent pourquoi les dirigeants <> leurs F&A en <> ; montrent en quoi le postulat égalitaire initial accroît la probabilité de conflits entre deux normes de justice distributive pourtant compl.mentaires : l’égalité et l’équité ; et illustrent leurs propos avec un cas spectaculaire : la fusion égalitaire, puis la separation des entreprises BioMérieux et Pierre Fabre. Paradoxalement, la simple formulation en termes égalitaire des F&A favorise la diffusion de sentiments d’injustice distributive, qui nuit in fine à la performance de l’opération.

Spam – Spim – Spit. En marknadsrättslig undersökning av marknadsföring via nya kommunikationstekniker

I boken behandlas nya kommunikationstekniker och olika marknadsföringsmetoder som har uppkommit till följd av den tekniska utvecklingen. Marknadsföring via de nya kommunikationskanalerna har givit upphov till vissa olägenheter för mottagarna. Olägenheterna som mottagarna förorsakas vid marknadsföring via de nya teknikerna kan delas in i tre kategorier; 1) meddelandet förorsakar kostnader för mottagaren, 2) meddelandet hindrar mottagaren samt 3) meddelandet upplevs vara påträngande och utgöra ett intrång i mottagarens privatliv. Under de senaste åren har det förekommit hektiska lagstiftningsåtgärder på många håll i världen. Såväl enskilda stater, nationella myndigheter samt internationella organisationer har utarbetat regler om marknadsföring via de nya teknikerna. En av kärnfrågorna i regleringen är huruvida man skall ha ett system med ”opt-in” eller ”opt-out”. En opt-in-lösning innebär att marknadsföraren måste inhämta mottagarens samtycke på förhand, medan en opt-out-lösning innebär att det är tillåtet att sända marknadsföring om inte mottagaren motsatt sig detta. Enligt gällande lagstiftning faller marknadsföring via följande tre tekniker under opt-in: automatiserade uppringningssystem, telefax samt e-post. Det huvudsakliga syftet med avhandlingen är att utreda om nuvarande opt-in-lista är tillräckligt omfattande med beaktande av de olägenheter som marknadsföring via de nya teknikerna förorsakar, eller om den bör utvidgas. I genomgången av marknadsföring via nya tekniker har marknadsföring via bl.a. följande tekniker undersökts: Internet (www-sidor), reklamfönster, reklambanner, e-post, mobiltelefon, telefax, bloggar, RSS, Instant Messaging samt Internettelefoni. Vid sidan av nya tekniker har även vissa ”traditionella” marknadsföringsmetoder undersökts, i syfte att utreda huruvida även de bör falla in under en opt-in-lösning. De traditionella marknadsföringsmetoder som ingår i avhandlingen är hemförsäljning, telemarketing, TV- och radioreklam samt adresserad och oadresserad direktreklam. En annan central del i avhandlingen är frågan hur påföljdssystemet vid överträdelser av opt-in-bestämmelserna bör utformas. Hur skall de enskilda mottagarna få ersättning för de kostnader de åsamkats av marknadsföringen? Är det dags att införa straffskadestånd i Finland? Hög tid att även Finland får grupptalan? Kan tvisterna avgöras virtuellt via domstolar on-line eller ODR?

Screening Cycles

We demonstrate how endogenous information acquisition in credit markets creates lending cycles when competing banks undertake their screening decisions in an uncoordinated way, thereby highlighting the role of intertemporal screening externalities induced by lending market competition as a structural source of instability. We show that uncoordinated screening behavior of competing banks may be not only the source of an important financial multiplier, but also an independent source of fluctuations inducing business cycles. The screening cycle mechanism is robust to generalizations along many dimensions such as the lending market structure, the lending rate determination and the imperfections in the screening technology.

Guessers for Finite-State Transducer Lexicons

Language software applications encounter new words, e.g., acronyms, technical terminology, names or compounds of such words. In order to add new words to a lexicon, we need to indicate their inflectional paradigm. We present a new generally applicable method for creating an entry generator, i.e. a paradigm guesser, for finite-state transducer lexicons. As a guesser tends to produce numerous suggestions, it is important that the correct suggestions be among the first few candidates. We prove some formal properties of the method and evaluate it on Finnish, English and Swedish full-scale transducer lexicons. We use the open-source Helsinki Finite-State Technology to create finitestate transducer lexicons from existing lexical resources and automatically derive guessers for unknown words. The method has a recall of 82-87 % and a precision of 71-76 % for the three test languages. The model needs no external corpus and can therefore serve as a baseline.

Designing a Dependency Representation and Grammar Definition Corpus for Finnish

We outline the design and creation of a syntactically and morphologically annotated corpora of Finnish for use by the research community. We motivate a definitional, systematic “grammar definition corpus” as a first step in an three-year annotation effort to help create higher-quality, better-documented extensive parsebanks at a later stage. The syntactic representation, consisting of a dependency structure and a basic set of dependency functions, is outlined with examples. Reference is made to double-blind annotation experiments to measure the applicability of the newgrammar definition corpus methodology.