Neoadjuvant and adjuvant strategies in renal cell carcinoma: more questions than answers.

The current standard treatment for early stage (I-III) renal cell cancer (RCC) is surgery. While the prognosis of stage I tumors is excellent, stage II and particularly stage III have a high risk of relapse. The adjuvant treatment of patients with RCC remains an area of investigation, with patient selection being a key aspect. There are currently two prognostic nomograms to establish the risk of relapse in patients with resected RCC. The results of earlier studies of adjuvant therapy, including the use chemotherapy and/or immunotherapy after nephrectomy have failed to show any benefit in the outcome of patients at risk of developing local recurrence or distant metastases. Two recent phase III trials with vaccines (autologous tumor cell vaccine and autologous tumor-derived heat shock protein peptide complex-96) have shown promising, albeit still preliminary, results. In the metastatic RCC setting, recent advances in the molecular understanding of oncogenic pathways have led to the development of new therapeutic strategies with the use of targeted therapies in the adjuvant setting. Neoadjuvant treatment is another treatment modality currently being evaluated for patients with early disease and in patients with metastatic RCC with inoperable primary tumors. The questions that remain unanswered include activity of these agents in early stages of the disease, patient selection, optimal start time of the adjuvant treatment, and finally, the optimal length of treatment.

Choice of partners in multiple two-person prisoner's dilemma games: An experimental study

We examine the effect of unilateral and mutual partner selection in the context of prisoner's dilemmas experimentally. Subjects play simultaneously several finitely repeated two-person prisoner's dilemma games. We find that unilateral choice is the best system. It leads to low defection and fewer singles than with mutual choice. Furthermore, with the unilateral choice setup we are able to show that intendingdefectors are more likely to try to avoid a match than intending cooperators. We compare our results of multiple games with single game PD-experiments and find no difference in aggregate behavior. Hence the multiple game technique is robust and might therefore be an important tool in the future for testing the use of mixed strategies.

Base Política e Jurídica da “Operação Liberdade Iraquiana” e a necessidade de auto-preservação do Estado Liberal

Este artigo visa analisar a recente intervenção anglo- -americana no Iraque a partir da sua conexão com o Direito Internacional e com a política internacional. Defenderei que do ponto de vista jurídico, a ‘operação liberdade iraquiana’ assenta em bases muito frágeis. A razão disso é que nem o amparo dos Estados Unidos na legítima defesa preventiva, nem o britânico na ideia de autorização implícita do Conselho de Segurança têm respaldo nas normas que regulamentam o uso da força nas relações internacionais. A melhor justificação jurídica, no entanto, o direito à intervenção humanitária unilateral, que, sem dúvida se adequaria à situação reinante no Iraque, somente foi utilizada secundariamente, ainda que tenha servido para aplacar as condenações internacionais. De qualquer modo, submeto a tese de que, mesmo a subsistirem dúvidas, quanto à legalidade da intervenção, ela justifica-se do ponto de vista da necessidade política, já que Estados liberais não devem esperar serem atingidos para tomar medidas contra agressores contumazes e tão pouco tolerar regimes tirânicos que oprimem o seu próprio povo.

Intervenções Externas Humanitárias: Legitimidade e Limites. O caso dos estados “frágeis”, “falhados” ou “colapsados”

Este artigo se centra em uma análise crítica das intervenções externas humanitárias, principalmente no panorama pós-Guerra Fria, nos denominados Estados “frágeis”, “falhados” ou “colapsados”. Incide, concretamente, sobre as causas e as consequências da emergência das intervenções externas militares unilaterais nos finais da década de 90 do século passado, abordando os casos mais emblemáticos e controversos, como os ocorridos em Kosovo, Afeganistão, Iraque e, mais recentemente, na Líbia e no Mali. Ele procura traçar, também, de forma embrionária, os caminhos que podem levar à ultrapassagem dos limites apresentados pela solução multilateral e unilateral no tque ange às intervenções externas militares de cariz humanitário.

Optimal negligence rule under limited liability

We study the standard economic model of unilateral accidents, in its simplest form, assumingthat the injurers have limited assets.We identify a second-best optimal rule that selects as duecare the minimum of first-best care, and a level of care that takes into account the wealth ofthe injurer. We show that such a rule in fact maximizes the precautionary effort by a potentialinjurer. The idea is counterintuitive: Being softer on an injurer, in terms of the required level ofcare, actually improves the incentives to take care when he is potentially insolvent. We extendthe basic result to an entire population of potentially insolvent injurers, and find that the optimalgeneral standards of care do depend on wealth, and distribution of income. We also show theconditions for the result that higher income levels in a given society call for higher levels of carefor accidents.

The effect of divorce laws on divorce rates in Europe

This paper analyzes a panel of 18 European countries spanning from 1950 to 2003 toexamine the extent to which the legal reforms leading to easier divorce that took placeduring the second half of the 20th century have contributed to the increase in divorce rates across Europe. We use a quasi-experimental set-up and exploit the different timing of the reforms in divorce laws across countries. We account for unobserved country-specificfactors by introducing country fixed effects, and we include country-specific trends tocontrol for time-varying factors at the country level that may be correlated with divorcerates and divorce laws, such as changing social norms or slow moving demographictrends. We find that the reforms were followed by significant increases in divorce rates.Overall, we estimate that the introduction of no-fault, unilateral divorce increased thedivorce rate by about 1, a sizeable effect given the average rate of 4.2 divorces per 1,000married people in 2002.

Responsabilidade do armador por abalroação

Esta dissertação tem por objectivo delimitar os rasgos que configuram a responsabilidade do armador pelos danos derivados da abalroação marítima. Neste trabalho centraremos a atenção no regime previsto no Código Marítimo de Cabo Verde, mas também atenderemos a Convenção de Bruxelas de 1910 sobre abalroação, a normativa estrangeira inspirada nela, entre os quais particularmente a da Espanha e a do Direito comparado. Qualquer expedição marítima está sujeita a certos perigos donde pode resultar perdas, danos e despesas para o navio, carga e pessoas. Com efeito o facto destes danos ou gastos terem um carácter extraordinário, não se lhes atribui nenhuma característica comum que permita unificá-los juridicamente. Em alguns casos, os danos ou gastos interessam somente as partes comprometidas contratualmente no transporte de pessoas ou coisas, e coloca-se simplesmente um problema de assumir os riscos no âmbito destes contratos. Em outros casos, tratase de eventos que geram uma responsabilidade civil extracontratual frente a terceiros alheios a viagem. Nos textos legais mais modernos (el Codice della Navigacione italiano de 1942, la Ley de Navegación argentina de 1973, la Ley de Navegación mexicana de 1994) aparece a expressão “acidentes de navegação” de conteúdo material mais abrangente do que a prévia “avarias”, mas com uma força unificadora bem marcante. Resulta então que é a especialidade derivada do dado técnico (a navegação marítima) o que justifica que certos acidentes marítimos mereçam um tratamento jurídico particularizado em relação aos danos extracontratuais contidos no Código civil. E esta especialidade é a que apresentam a abalroação, a avaria grossa, a assistência marítima, os bens resultantes de um naufrágio e certa classe de danos causados a terceiros por contaminação por hidrocarbonetos ou por outras substâncias nocivas ou perigosas transportadas, ou mesmo pelo combustível do navio. A abalroação é, sem dúvida, o risco mais grave que corre uma expedição marítima, sobretudo se tivermos em conta a importância das avarias que dela A responsabilidade do armador por abalroação resultam. A produção de uma abalroação ou de qualquer outro acidente coloca diversas questões, como por exemplo, a determinação dos supostos concretos em que devem ser indemnizados os danos causados, as pessoas obrigadas a indemnizá-los, a quantia da reparação, etc.; em definitiva, coloca-se a necessidade de se precisar do regime jurídico aplicável a abalroação. As disposições relativamente a abalroação contidas no Código Marítimo de Cabo Verde, na Convenção de 1910 e na normativa estrangeira, configuram um regime de responsabilidade civil extracontratual que constitui uma aplicação concreta dos princípios comuns da responsabilidade aquiliana. O Código civil traça as linhas básicas do regime de responsabilidade civil, a que será necessário recorrer, quando a normativa marítima não apresenta soluções para as questões resultantes do regime de responsabilidade civil por abalroação. A metodologia utilizada nesta dissertação, tem por base a pesquisa, entrevista e investigação científica quer no Direito Comparado com recurso a outros ordenamentos jurídicos, como no Direito Positivo com recurso aos instrumentos legais e convencionais. O plano de exposição deste trabalho divide-se em quatro Capítulos. O primeiro Capítulo centraliza-se na normativa reguladora da abalroação que deve delimitar-se, por princípio, das restantes normativas devido a introdução do termo técnico “acidente de navegação”. O segundo Capítulo foca-se no estudo do conceito de abalroação marítima e determinação das suas diversas modalidades em matéria de abalroação, tanto por culpa unilateral como por culpa comum. No terceiro Capítulo analisam-se os elementos que delimitam a responsabilidade extracontratual do armador pelos danos derivados da abalroação marítima. Desta maneira é possível, por uma parte, identificar os sujeitos que devem responder pelos danos referidos e, por outra, diferenciar este tipo da responsabilidade contratual, concretizando a normativa aplicável às abalroações constitutivos de ilícito penal. Capítulo quarto contempla por um lado, o Direito consagrado, em qualquer ordenamento jurídico, que é o de compensar ao prejudicado por qualquer dano causado, por outro lado identificar os sujeitos que devem indemnizar ou solicitar indemnização. Por último, as conclusões, permitem fazer uma resenha geral de todo o trabalho.

A new way of quantifying dominant upper-limb mobility in healthy and painful shoulders

Introduction: Quantification of daily upper-limb activity is determinant in the evaluation of shoulder surgery. For a number of shoulder diseases, roblems in performing daily activities have been expressed in terms of upper-limb usage. Althought many instruments measure upper-limb movements, there is no accepted standard or widely used objective measure and no device to differenciate left or right shoulder usage. We present an objective method to measure the mobility and quantify the usage of dominant and healthy or painfull shoulder movement during daily life. Methods: 12 patients with unilateral pathological shoulder (rotator cuff disease) are compared to 18 control subjects (10 right and 8 left handed). Both SST and DASH questionnaires were completed by each one. Three inertial miniature modules including triaxial gyroscopes and accelerometers were fixed on the dorsal side of both humerus, and on the thorax. An ambulatory datalogger have recorded the signals during one day. Results: We observed that right handed healthy subjects used 18% and 26% more their dominant shoulder during respectively stand and sit postures while left handed subjects used 8% and 18% more their left side. In walking periods, shoulder mobility was quite alike for both sides. Patients affected on their dominant arm (PD group) mostly used their non-dominant side (respectively 5% and 9% during stand and sit). For the patients affected on their non-dominant shoulder (PND group), this difference is respectively 28% and 26%. Moreover, we can note that, during walking periods, a difference can be observed (on the contrary to controls). Patients used 13% and 15% more their nonpathologic side respectively for PD and PND groups. Conclusion: Inertial sensors, during long-term ambulatory monitoring of upper limbs, can quantify the difference between dominant and nondominant sides. Patients used more their non affected shoulder during daily life. For the PD group, the difference with control can be shown during walking. These results are very encouraging for future evaluation of patients with shoulder injuries since it can provide an objective evaluation of the shoulder mobility and of the treatment outcome during daily life.

Management of severe pediatric subglottic stenosis with glottic involvement.

OBJECTIVE: We sought to describe our experience in the management of complex glotto-subglottic stenosis in the pediatric age group. METHODS: Between 1978 and 2008, 33 children with glotto-subglottic stenosis underwent partial cricotracheal resection, and they form the focus of this study. They were compared with 67 children with isolated subglottic stenosis (no glottic involvement). The outcomes measured were need for revision open surgical intervention, delayed decannulation (>6 months), and operation-specific and overall decannulation rates. Fisher's exact test was used for comparison of outcomes. RESULTS: Results of preoperative evaluation showed Myer-Cotton grade III or IV stenosis in 32 (97%) patients and grade II stenosis in 1 patient. All patients with glotto-subglottic stenosis were treated with partial cricotracheal resection and simultaneous repair of the glottic pathology. Bilateral fixed vocal cords were seen in 19 (58%) of 33 patients, bilateral restricted abduction was seen in 7 (21%) of 33 patients, and unilateral fixed vocal cord was seen in 7 (21%) of 33 patients. Ten patients underwent single-stage partial cricotracheal resection with excision of interarytenoid scar tissue. The endotracheal tube was kept for a mean period of 7 days as a stent. Twenty-three patients underwent extended partial cricotracheal resection with LT-Mold (Bredam S.A., St. Sulpice, Switzerland) or T-tube stenting. The overall decannulation rate included 26 (79%) patients, and the operation-specific decannulation rate included 20 (61%) patients. CONCLUSIONS: Glotto-subglottic stenosis is a complex laryngeal injury associated with delayed decannulation and decreased overall and operation-specific decannulation rates when compared with those after subglottic stenosis without glottic involvement after partial cricotracheal resection.

Shorter time to diagnosis and improved stage at presentation in Swiss patients with retinoblastoma treated from 1963 to 2004

Rapport de synthèse : Le rétinoblastome est la tumeur de l'oeil la plus fréquente chez l'enfant. Un diagnostic précoce est important pour sauver le globe oculaire et la survie du patient. Le but de notre étude est de déterminer l'évolution de l'intervalle diagnostique, c'est-à-dire le délai entre les premiers symptômes et la date du diagnostic officiel du rétinoblastome, sur une période de 40 ans en Suisse. Matériel et méthode : Il s'agit d'une étude rétrospective faite sur 139 patients suisses traités pour rétinoblastome durant trois différentes périodes : (1) 1963-1983 ; (2) 1984-1993 ; et (3) 1994-2004. On compare certaines caractéristiques : le sexe du patient, la latéralité de la maladie, les premiers symptômes, leurs observateurs, l'intervalle diagnostique, l'âge au diagnostic, le stade de la maladie, l'histoire familiale. Résultats : 37 patients (26.6%) ont été traités dans la première période ; 44 (31.7%) dans la période 2 et 58 (41.7%) dans la période 3. L'intervalle diagnostique diminue de façon significative de 6.97 mois dans la période 1 à 3.58 dans la période 2 à 2.25 dans la période 3 pour le total des malades. Ceci reste significatif pour les rétinoblastomes unilatéraux. De plus, dans ce même groupe, on observe une diminution significative des stades avancés de la maladie, groupe E selon Murphree (61.5% dans la période 1 ; 46.7% dans la période 2 et 22.2 % dans la période 3). Lorsque la maladie est bilatérale, les mêmes observations se font de façon un peu moins marquée. Il n'y a aucun patient diagnostiqué au stade E de la maladie en présence d'une anamnèse familiale positive. Leucocorie (48.2%) et strabisme (20.1 %) sont les symptômes les plus fréquents durant les 3 périodes. Les seuls facteurs qui influencent significativement le risque d'avoir un stade E de la maladie sont la durée de l'intervalle diagnostic et la période de diagnostic. Conclusion : On constate un progrès dans le diagnostic du rétinoblastome en Suisse, surtout lors de maladie unilatérale. De même, des améliorations sont notées dans la maladie bilatérale mais de façon non significative. Il est donc important de mieux enseigner aux médecins à reconnaître les symptômes oculaires de la maladie et à référer les patients plus tôt aux spécialistes. Abstract : OBECTIVES : Retinoblastoma is the most frequent intraocular malignancy in children. Early diagnosis is essential for globe salvage and patient survival. The aim of our study was to determine how time to diagnosis of retinoblastoma has evolved over a 40-year period in Switzerland. METHOD AND PATIENTS : A retrospective study of 139 Swiss patients with retinoblastoma was performed comparing 3 periods: (1) 1963-1983; (2) 1984-1993; and (3) 1994-2004. Factors taken into account were gender, laterality of retínoblastoma, age at first symptoms, type and first observer of symptoms, time to diagnosis, age at diagnosis, disease stage, and family history. RESULTS : Thirty-seven patients (26.6%) were treated in period 1, 44 (31.7%) in period 2, and S8 (41.7%) in period 3.Overall, the diagnostic interval decreased in a significant way from 6.97 months in period 1 to 3.58 in period 2 and to 2.25 in period 3. When looking separately at unilateral and bilateral disease, the decrease oí the diagnostic interval remained statistically significant in unilateral retinoblastoma; there was also a significant reduction in the number of patients with advanced group E disease (Murphree classification) (61.5% in period 1, 46.7% in period 2, 22.2% in period 3). In bilateral disease, the same observations were made to a lesser extent. However, there were no cases with group E disease in 10 patients with positive family history. Leukornria (48.2%) and strabismus (20.1 %) were the 2 most frequent symptoms throughout the 3 periods. The only factors that statistically influenced the chances of having a diagnosis of group E disease were the diagnostic interval and period of diagnosis. Conclusion : Progress has been made in the diagnosis of retinoblastoma in Switzerland, notably in unilateral disease. Improvement to a lesser extent has also been observed in bilateral cases but without statistical significance. Greater effort is needed to teach physians-in-training to recognize the importance of ocular symptoms and refer patients earlier.

Granulomatous uveitis and congenital cataract: a rare association.

INTRODUCTION: The association of a granulomatous uveitis and congenital cataract and is rarely observed in newborn children. We describe the history of two patients presenting simultaneously with these two features in the absence of a TORCH infection. PATIENTS AND METHODS: The first patient, a boy born in 1997, presented to our hospital two days after birth with multiples Koeppe's and Busacca's nodules and bilateral cataract. The second patient, a boy born in 2006, was referred two weeks after birth. He presented with a severe unilateral granulomatous uveitis, multiples iris nodules, a high intraocular pressure of 45 mmHg and a congenital cataract. THERAPY AND OUTCOME: Lens extraction produced a rapid resolution of uveitis in these two patients. TORCH infection was ruled out in both children by history, extensive serologies performed simultaneously in mother and child or PCR of ocular fluids. CONCLUSIONS: A congenital cataract associated with a granulomatous uveitis is an extremely rare association. The removal of the lens resulted in complete resolution of the inflammation: a phacogenic mechanism could be at the origin of ocular inflammation in both cases.

Laparoscopic inguinal hernia repair with extraperitoneal double-mesh technique.

Totally extraperitoneal laparoscopic hernia repair is an efficient but technically demanding procedure. As mechanisms of hernia recurrence may be related to these technical difficulties, we have modified a previously described double-mesh technique in an effort to simplify the procedure. Extraperitoneal laparoscopic hernia repairs were performed in 82 male and 17 female patients having inguinal, femoral, and recurrent bilateral hernias. A standard propylene mesh measuring 15 x 15 cm was cut into two pieces of 4 x 15 cm and 11 x 15 cm. The smaller mesh was placed over both inguinal rings without splitting. The larger mesh was then inserted over the first mesh and stapled to low-risk zones, reinforcing the large-vessel area and the nerve transition zone. The mean procedure duration was 60 minutes for unilateral and 100 minutes for bilateral hernia repair. Patients were discharged from the hospital within 48 hours. The mean postoperative follow-up was 22 months, with no recurrences, neuralgia, or bleeding complications. Over a 2-year period, this technique was found to be satisfactory without recurrences or significant complications. In our hands, this technique was easier to perform: it allows for a less than perfect positioning of the meshes and avoids most of the stapling to crucial zones.

Maxillary advancement and transpalatal expansion using internal distraction in a patient with cleft lip and palate.

Correction of sagittal and transverse maxillary discrepancies in patients with cleft lip or palate remains a challenge for craniofacial surgeons. Distraction osteogenesis has revolutionized the conceptualization and approach to the craniofacial malformations and has become a reliable and irreplaceable part of the surgical armamentarium. We are reporting a case of sequential maxillary advancement and transpalatal expansion using internal distraction in a patient with unilateral cleft lip and palate presenting with severe maxillary sagittal and transverse deficiencies.

Dyadic pulsations as a signature of sustainability in correspondence networks

In this paper, we introduce the concept of dyadic pulsations as a measure of sustainability in online discussion groups. Dyadic pulsations correspond to new communication exchanges occurring between two participants in a discussion group. A group that continuously integrates new participants in the on-going conversation is characterized by a steady dyadic pulsation rhythm. On the contrary, groups that either pursue close conversation or unilateral communication have no or very little dyadic pulsations. We show on two examples taken from Usenet discussion groups, that dyadic pulsations permit to anticipate future bursts in response delay time which are signs of group discussion collapses. We discuss ways of making this measure resilient to spam and other common algorithmic production that pollutes real discussions

Pupillographic investigation of the relative afferent pupillary defect associated with a midbrain lesion.

OBJECTIVE: To identify clinical and pupillographic features of patients with a relative afferent pupillary defect (RAPD) without visual acuity or visual field loss caused by a lesion in the dorsal midbrain. DESIGN: Experimental study. PARTICIPANTS AND CONTROLS: Four patients with a dorsal midbrain lesion who had normal visual fields and a clinically detectable RAPD. METHODS: The pupil response from full-field and hemifield light stimulation over a range of light intensities was measured by computerized binocular pupillography. MAIN OUTCOME MEASURES: The mean of the direct and consensual pupil response to full-field and hemifield light stimulation was plotted as a function of stimulus light intensity. RESULTS: All 4 subjects showed decreased pupillographic responses at all intensities to full-field light stimulation in the eye with the clinical RAPD. The pupillographic responses to hemifield stimulation showed a homonymous pattern of deficit on the side ipsilateral to the RAPD, similar to that observed in a previously reported patient with an optic tract lesion. CONCLUSIONS: The basis of a midbrain RAPD is the nasal-temporal asymmetry of pupillomotor input that becomes manifest when a unilateral postchiasmal lesion interrupts homonymously paired fibers traveling in the contralateral optic tract or midbrain pathway to the pupillomotor center, respectively. The pupillographic characteristics of an RAPD resulting from a dorsal midbrain lesion thus resemble those of an RAPD resulting from a unilateral optic tract lesion, but without the homonymous visual field defect. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.