Distant Genocides

I am deeply honored to be invited to deliver the Leslie H. Arps Memorial Lecture. I never met Les Arps, but I understand we had a kinship of trial by fire. We both worked as young lawyers for the great, and not easily pleased, Henry Friendly. By all that I have heard, Les Arps was an extraordinary lawyer, a distinguished public servant, a mensch. And what a spectacular achievement to have been one of the progenitors of the great Skadden Arps firm. I will speak on two subjects. The first does not exist. The second may be about to disappear. This may therefore be the most useless talk of all time. Both of my subjects concern a private, civil suit by which a plaintiff seeks redress for atrocities in violation of the law of nations committed in another nation-a nation where the plaintiff cannot get justice because the abusing regime remains in power. By a private, civil suit, I mean a suit that seeks only a private, civil remedy, such as money damages in compensation for personal injury, and does not seek imprisonment, fine, or any sort of criminal punishment

\u3ci\u3eCampbell\u3c/i\u3e as Fair Use Blueprint?

Friends, copyright geeks, I come not to bury Campbell, but to praise it. I might reasonably be considered a biased critic as Campbell took a number of suggestions from an article I wrote. Biased or not, I submit Campbell is a beautifully reasoned opinion, which has demonstrated in its twenty-one years that it provides a healthy framework for fair use analysis. That framework promotes the overall objectives of copyright; it protects the interests of rights holders; and it guards against putting “manacles upon science.

The use of an adapted model allows contributing to the “Reduction” of mice used in experimental protocols: the case of the apoE–deficient (apo E-/-) mice in a model of atherosclerosis control

Atherosclerosis is a chronic vascular disease whose development is influenced by several mediators 1. Among them, the prostanoids large family lipids generated from the metabolism of arachidonic acid by the action of COX includes various types of PGs and thromboxane. Thromboxane A2 and PGI2 are present in abnormally elevated concentration in atherosclerosis 2-3. To exert its effects TXA2 and its precursor PGH2 act at a specific receptor termed TP receptor 4. As a result, TXA2 synthase inhibitors and TP antagonists have been developed to reduce and to prevent TXA2 production and actions, respectively. The present study was undertaken in order to investigate whether BM-573, an original sulfonylurea derivate synthesized in our lab 5, and aspirin would be effective in preventing the progression of atherosclerosis in an apo E deficient mouse model.Evaluation de l’effet de modulateurs originaux du thromboxane A2 (TXA2) dans un modèle murin d’athéroscléros

Low 5-year cumulative incidence of post-transplant lymphoproliferative disorders after solid organ transplantation in Switzerland.

Post-transplant lymphoproliferative disorder (PTLD) is a potentially life-threatening complication of transplantation occurring in the setting of immunosuppression and oncogenic viral infections. However, little is known about the cumulative incidence, histological subtypes, risk determinants and outcome of PTLD in solid organ transplant (SOT) recipients in Switzerland. This retrospective observational study investigated adult SOT recipients from two sequential cohorts, the pre-SCTS (Swiss Transplant Cohort Study) series, with data collected from January 1986 to April 2008, and the STCS series, with data collected from May 2008 to December 2014 in Switzerland. SOT recipients were cross-referenced with the data of all the patients with a lymphoma diagnosis in each transplant centre and with the data of the Swiss Transplant Cohort Study (STCS) to determine the cumulative incidence of PTLD, pre-therapeutic clinical features, clinical course and outcome. Kaplan-Meier analysis was performed for overall survival after PTLD. We identified 79 cases of PTLD during the study period in the two cohorts: pre-STCS from 1986 to 2008 (n = 62) and STCS from 2008 to 2014 (n = 17). Histological subgroups included: early lesions (pre-STCS n = 2, STCS n = 0); polymorphic PTLD (pre-STCS n = 8, STCS n = 7); monomorphic PTLD (pre-STCS n = 47, STCS n = 10), and Hodgkin's lymphoma (pre-STCS n = 5, STCS n = 0). Median time to PTLD diagnosis was 90 months (range 3-281 months) and 14 months (range 2-59 months) in the pre-STCS and STCS cohorts, respectively. Median follow-up after transplantation was 141 months for the pre-STCS patients and 33 months for the STCS patients. Cumulative incidences of PTLD during the STCS period at 0.5, 1 and 5 years were 0.17% (95% confidence interval 0.07-0.46%), 0.22% (0.09-0.53%) and 0.96% (0.52-1.80%), respectively. For the pre-STCS case series, it was not possible to estimate the incidence rate of PTLD. Survival after PTLD diagnosis was 80% (68-87%) at 1 year and 56% (42-68%) at 5 years for the pre-STCS and STCS cohorts combined. At 5 years, the cumulative incidence of PTLD, regardless of the organ transplanted, was only 0.96% in the STCS cohort, which is lower than that reported in the literature

The EHA Research Roadmap : Malignant Lymphoid Diseases

Peer reviewe

The Genetic Basis of Hepatosplenic T-cell Lymphoma

Hepatosplenic T cell lymphoma (HSTL) is a rare and lethal lymphoma; the genetic drivers of this disease are unknown. Through whole exome sequencing of 68 HSTLs, we define recurrently mutated driver genes and copy number alterations in the disease. Chromatin modifying genes including SETD2, INO80 and ARID1B were commonly mutated in HSTL, affecting 62% of cases. HSTLs manifest frequent mutations in STAT5B (31%), STAT3 (9%), and PIK3CD (9%) for which there currently exist potential targeted therapies. In addition, we noted less frequent events in EZH2, KRAS and TP53. SETD2 was the most frequently silenced gene in HSTL. We experimentally demonstrated that SETD2 acts as a tumor suppressor gene. In addition, we found that mutations in STAT5B and PIK3CD activate critical signaling pathways important to cell survival in HSTL. Our work thus defines the genetic landscape of HSTL and implicates novel gene mutations linked to HSTL pathogenesis and potential treatment targets