Développement d'une nouvelle méthodologie pour la synthèse de N-hétérocycles par réarrangement photochimique de lactames N-hétérosubstituées et son application vers la synthèse de la (+)-géphyrotoxine

Cette thèse présente le développement du réarrangement photochimique des lactames N -hétérosubstituées ainsi que son potentiel d'application en synthèse organique. Le premier chapitre traite de l'étude des possibilités et limitations de la photolyse des N -chlorolactames, les premiers précurseurs rapportés pour cette nouvelle contraction de cycle. Une variété de substrats ont été synthétisés et réarrangés afin d'établir la généralité de cette nouvelle réaction. Une discussion élaborée sur les résultats obtenus ainsi que les preuves mécanistiques apportées par ceux-ci y est faite. Une proposition mécanistique de cette nouvelle réaction est également apportée. Le deuxième chapitre présente la synthèse et contraction de cycle des N -mésyloxylactames. Celles-ci ont été élaborées afin d'inhiber la voie radicalaire secondaire en compétition lors de la photolyse des N -chlorolactames et par ce fait augmenter le rendement provenant de cette nouvelle migration [1,2].Cette nouvelle modification réactionnelle a démontré des rendements beaucoup plus élevés et synthétiquement viables pour les carbamates isolés et une bonne généralité pour le type de précurseurs pouvant subir cette migration stéréospécifique. Le réarrangement photochimique des lactames N -hétérosusbtituées est donc devenu une méthode fiable et prévisible pour la formation de liens C-N de manière stéréospécifique et ainsi une nouvelle réaction complémentaire aux réarrangements ioniques existants. Le troisième chapitre traite de l'application de cette nouvelle méthodologie vers la synthèse de la (+)-géphyrotoxine. Deux approches synthétiques racémiques ont été développées et un précurseur avancé vers cet alcaloïde a été synthétisé de manière expéditive avec un bon rendement et la bonne stéréochimie relative. Une version énantiosélective a été proposée en employant cette nouvelle stratégie

Flight test evaluation of an RAF high altitude partial pressure protective assembly

A partial pressure suit was evaluated during tests in an F-104 and F-15 as a protective garment for emergency descents. The garment is an pressure jerkin and modified anti-g suit combined with an oronasal mask. The garment can be donned and doffed at the aircraft to minimize thermal buildup. The oronasal mask was favored by the pilots due to its immobility on the face during high g-loading. The garment was chosen to provide optimum dexterity for the pilot, which is not available in a full pressure suit, while protecting the pilot at altitudes up to 18,288 meters, during a cabin decompression, and subsequent aircraft descent. During cabin decompressions in the F-104 and F-15, cabin pressure altitude was measured at various aircraft angles of attack, Mach numbers, and altitudes to determine the effect of the aerodynamic slipstream on the cabin altitude

Beneficial Betrayal Aversion

Many studies demonstrate the social benefits of cooperation. Likewise, recent studies convincingly demonstrate that betrayal aversion hinders trust and discourages cooperation. In this respect, betrayal aversion is unlike socially “beneficial” preferences including altruism, fairness and inequity aversion, all of which encourage cooperation and exchange. To our knowledge, other than the suggestion that it acts as a barrier to rash trust decisions, the benefits of betrayal aversion remain largely unexplored. Here we use laboratory experiments with human participants to show that groups including betrayal-averse agents achieve higher levels of reciprocity and more profitable social exchange than groups lacking betrayal aversion. These results are the first rigorous evidence on the benefits of betrayal aversion, and may help future research investigating cultural differences in betrayal aversion as well as future research on the evolutionary roots of betrayal aversion. Further, our results extend the understanding of how intentions affect social interactions and exchange and provide an effective platform for further research on betrayal aversion and its effects on human behavior

Resectable pancreatic small cell carcinoma

Primary pancreatic small cell carcinoma (SCC) is rare, with just over 30 cases reported in the literature. Only 7 of these patients underwent surgical resection with a median survival of 6 months. Prognosis of SCC is therefore considered to be poor, and the role of adjuvant therapy is uncertain. Here we report two institutions' experience with resectable pancreatic SCC. Six patients with pancreatic SCC treated at the Johns Hopkins Hospital (4 patients) and the Mayo Clinic (2 patients) were identified from prospectively collected pancreatic cancer databases and re-reviewed by pathology. All six patients underwent a pancreaticoduodenectomy. Clinicopathologic data were analyzed, and the literature on pancreatic SCC was reviewed. Median age at diagnosis was 50 years (range 27–60). All six tumors arose in the head of the pancreas. Median tumor size was 3 cm, and all cases had positive lymph nodes except for one patient who only had five nodes sampled. There were no perioperative deaths and three patients had at least one postoperative complication. All six patients received adjuvant therapy, five of whom were given combined modality treatment with radiation, cisplatin, and etoposide. Median survival was 20 months with a range of 9–173 months. The patient who lived for 9 months received chemotherapy only, while the patient who lived for 173 months was given chemoradiation with cisplatin and etoposide and represents the longest reported survival time from pancreatic SCC to date. Pancreatic SCC is an extremely rare form of cancer with a poor prognosis. Patients in this surgical series showed favorable survival rates when compared to prior reports of both resected and unresectable SCC. Cisplatin and etoposide appears to be the preferred chemotherapy regimen, although its efficacy remains uncertain, as does the role of combined modality treatment with radiation

Infinite-Duration Poorman-Bidding Games

In two-player games on graphs, the players move a token through a graph to produce an infinite path, which determines the winner or payoff of the game. Such games are central in formal verification since they model the interaction between a non-terminating system and its environment. We study bidding games in which the players bid for the right to move the token. Two bidding rules have been defined. In Richman bidding, in each round, the players simultaneously submit bids, and the higher bidder moves the token and pays the other player. Poorman bidding is similar except that the winner of the bidding pays the “bank” rather than the other player. While poorman reachability games have been studied before, we present, for the first time, results on infinite-duration poorman games. A central quantity in these games is the ratio between the two players’ initial budgets. The questions we study concern a necessary and sufficient ratio with which a player can achieve a goal. For reachability objectives, such threshold ratios are known to exist for both bidding rules. We show that the properties of poorman reachability games extend to complex qualitative objectives such as parity, similarly to the Richman case. Our most interesting results concern quantitative poorman games, namely poorman mean-payoff games, where we construct optimal strategies depending on the initial ratio, by showing a connection with random-turn based games. The connection in itself is interesting, because it does not hold for reachability poorman games. We also solve the complexity problems that arise in poorman bidding games

Serological Markers for Inflammatory Bowel Disease in AIDS Patients with Evidence of Microbial Translocation

Background: Breakdown of the gut mucosal barrier during chronic HIV infection allows translocation of bacterial products such as lipopolysaccharides (LPS) from the gut into the circulation. Microbial translocation also occurs in inflammatory bowel disease (IBD). IBD serological markers are useful in the diagnosis of IBD and to differentiate between Crohn's disease (CD) and ulcerative colitis (UC). Here, we evaluate detection of IBD serological markers in HIV-infected patients with advanced disease and their relationship to HIV disease markers.Methods IBD serological markers (ASCA, pANCA, anti-OmpC, and anti-CBir1) were measured by ELISA in plasma from AIDS patients (n = 26) with low CD4 counts (<300 cells/$\mu$l) and high plasma LPS levels, and results correlated with clinical data. For meta-analysis, relevant data were abstracted from 20 articles. Results: IBD serological markers were detected in approximately 65% of AIDS patients with evidence of microbial translocation. An antibody pattern consistent with IBD was detected in 46%; of these, 75% had a CD-like pattern. Meta-analysis of data from 20 published studies on IBD serological markers in CD, UC, and non-IBD control subjects indicated that IBD serological markers are detected more frequently in AIDS patients than in non-IBD disease controls and healthy controls, but less frequently than in CD patients. There was no association between IBD serological markers and HIV disease markers (plasma viral load and CD4 counts) in the study cohort. Conclusions: IBD serological markers may provide a non-invasive approach to monitor HIV-related inflammatory gut disease. Further studies to investigate their clinical significance in HIV-infected individuals are warranted

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives