The effect of bariatric surgery on the direct oral anticoagulant rivaroxaban: the extension study.

Thromboembolic disease is a potentially serious complication in bariatric surgery patients. Direct oral anticoagulants (DOAC) have been investigated in orthopedic surgery patients. DOAC data after bariatric surgery are still limited to the early postsurgical period. Whether postsurgical midterm adaptations due to anatomic and physiologic alterations influence drug pharmacology is currently not known. The aim of this study was to investigate the influence of weight loss and type of bariatric surgery on midterm postsurgical pharmacokinetic and pharmacodynamic parameters of rivaroxaban. University hospital. In this monocentric study, bariatric patients received a single oral dose of rivaroxaban (10 mg) 6 to 8 months after sleeve gastrectomy (SG) or Roux-en-Y-gastric bypass (RYGB). Pharmacokinetic and pharmacodynamic parameters were assessed and compared with prebariatric surgery results. We included 6 RYGB and 6 SG patients. Percent excess weight loss was 71.4% (interquartile range 56.4, 87.9) in the SG group and 76.6% (64.5, 85.7) in the RYGB group. Rivaroxaban mean areas under the curve 6 to 8 months after the bariatric procedure (922.4 µg × h/L, coefficient of variation 43.2) were comparable to those measured preoperatively (952.6 µg × h/L, 16.8). There was no relevant difference between the 2 surgical procedure groups. Rivaroxaban led to a decrease of prothrombin fragments F1+2 over 12 hours after oral intake confirming in vivo efficacy. Significant weight loss and altered anatomy after RYGB and SG procedures do not appear to affect the pharmacokinetics and pharmacodynamics of prophylactic rivaroxaban. A single dose of Rivaroxaban was well tolerated and considered safe in this trial

Pharmacokinetics and pharmacodynamics of single doses of rivaroxaban in obese patients prior to and after bariatric surgery.

Venous thromboembolism is an important cause of postoperative morbidity and mortality in bariatric surgery. Studies of direct oral anticoagulants (DOACs) are not available in this surgical field. The objective of this phase 1 clinical trial was to investigate pharmacokinetic and pharmacodynamic (PK/PD) parameters of rivaroxaban in bariatric patients. In this single-centre study, obese patients received single oral doses of rivaroxaban (10 mg) 1 day prior to and 3 days after bariatric surgery. PK and PD parameters were assessed at baseline and during 24 h after drug ingestion. Six Roux-en-Y gastric bypass patients and six sleeve gastrectomy patients completed the study. Mean rivaroxaban area under plasma concentration-time curve, peak plasma concentration, time to peak plasma concentration and terminal half-life were 971.9 μg·h l javax.xml.bind.JAXBElement@700c5f48 (coefficient of variation: 10.6), 135.3 μg l javax.xml.bind.JAXBElement@2d9cd44f (26.7), 1.5 h and 13.1 h (34.1) prior to and 1165.8 (21.9), 170.0 (15.9), 1.5 and 8.9 (44.6) postsurgery for SG patients and 933.7 μg·h l javax.xml.bind.JAXBElement@156b37e4 (22.3), 136.5 μg l javax.xml.bind.JAXBElement@3f807e6c (10.7), 1.5 h und 13.8 h (46.6) prior to and 1029.4 (7.4), 110.8 (31.8), 2.5 and 15 (60.0) postsurgery for Roux-en-Y gastric bypass patients, respectively. Prothrombin fragments (F1 + 2) decreased during the first 12 hours and increased thereafter in the pre- and the postbariatric setting. Thrombin-antithrombin complexes dropped within 1-3 h in the prebariatric setting and remained low after surgery until they increased at 24 h postdose. Rivaroxaban was well tolerated and no relevant safety issues were observed. Bariatric surgery does not appear to alter PK of rivaroxaban in a clinically relevant way. Effective prophylactic postbariatric anticoagulation is supported by changes in PD

Higgs Boson Studies at the Tevatron

We combine searches by the CDF and D0 Collaborations for the standard model Higgs boson with mass in the range 90--200 GeV$/c^2$ produced in the gluon-gluon fusion, $WH$, $ZH$, $t{\bar{t}}H$, and vector boson fusion processes, and decaying in the $H\rightarrow b{\bar{b}}$, $H\rightarrow W^+W^-$, $H\rightarrow ZZ$, $H\rightarrow\tau^+\tau^-$, and $H\rightarrow \gamma\gamma$ modes. The data correspond to integrated luminosities of up to 10 fb$^{-1}$ and were collected at the Fermilab Tevatron in $p{\bar{p}}$ collisions at $\sqrt{s}=1.96$ TeV. The searches are also interpreted in the context of fermiophobic and fourth generation models. We observe a significant excess of events in the mass range between 115 and 140 GeV/$c^2$. The local significance corresponds to 3.0 standard deviations at $m_H=125$ GeV/$c^2$, consistent with the mass of the Higgs boson observed at the LHC, and we expect a local significance of 1.9 standard deviations. We separately combine searches for $H \to b\bar{b}$, $H \to W^+W^-$, $H\rightarrow\tau^+\tau^-$, and $H\rightarrow\gamma\gamma$. The observed signal strengths in all channels are consistent with the presence of a standard model Higgs boson with a mass of 125 GeV/$c^2$

Desenvolvimento folicular no pós-parto de vacas da raça Gir tratadas com acetato de buserelina (GnRH) ou gonadotrofina coriônica humana (hCG) Follicular development in Gir breed cows (Bos indicus) treated with buserelin acetate or human chorionic gonadotrophin during the postpartum period

Foram utilizadas 22 vacas da raça Gir (Bos indicus) em anestro pós-parto, amamentando e mantidas sob regime de pastejo. O padrão de crescimento folicular foi estudado em 15 animais, enquanto os outros sete foram utilizados somente no acompanhamento da resposta aos tratamentos hormonais. Ultra-sonografia em tempo real foi realizada diariamente, do quarto ao qüinquagésimo dia de lactação, por meio de aparelho equipado com probe de 5MHz. Nenhum animal apresentou estro, ovulação ou luteinização folicular durante o período de avaliação. Verificaram-se quatro a oito ondas foliculares surgindo em intervalos de seis a sete dias, cujo diâmetro máximo dos folículos dominantes e subordinados foi de 8,9±0,6 e 6,3±0,7mm, respectivamente. Aos 56 dias pós-parto, as 22 vacas foram divididas em dois grupos: 11 tratadas com 4,2 mig de acetato de buserelina e 11 com 3.000UI de hCG. A ovulação, regressão e luteinização folicular foram verificadas em animais dos dois tratamentos e uma nova onda folicular surgiu dentro de dois a três dias após a terapia hormonal. Corpos lúteos de menor tamanho e concentrações de progesterona abaixo de 1ng/mL indicaram baixa atividade luteal.<br>This experiment was carried out with 22 anestrus Gir cows (Bos indicus), with the postpartum follicular growth studied in 15 of these suckling and kept on pasture, while the seven others were used only for hormonal treatments. Daily real time ultrasonography was done from 4th to the 50th day, using B-mode ultrasound scanner equipped with a linear array 5.0MHz probe. No animal showed estrus, ovulation or follicular luteinization during de experimental period. Four to eight follicular waves emerged each six or seven days and maximum diameter of dominant and subordinate follicles were 8.9±0.6mm and 6.3±0.7mm, respectively. On day 56 of postpartum all cows were separated in two groups: 11 cows were treated either with 4.2 mug of buserelin acetate and 11 with 3,000UI of hCG. Ovulation, follicular regression and luteinization were observed in the two treatments animals, and one new follicular wave emerged within two to three days after the hormonal treatments. Small size corpus luteum and progesterone concentrations under 1ng/mL showed lower luteal activity

Evidence for a Particle Produced in Association with Weak Bosons and Decaying to a Bottom-Antibottom Quark Pair in Higgs Boson Searches at the Tevatron

We combine searches by the CDF and D0 Collaborations for the associated production of a Higgs boson with a W or Z boson and subsequent decay of the Higgs boson to a bottom-antibottom quark pair. The data, originating from Fermilab Tevatron p[bar over p] collisions at √s=1.96  TeV, correspond to integrated luminosities of up to 9.7  fb[superscript -1]. The searches are conducted for a Higgs boson with mass in the range 100–150  GeV/c[superscript 2]. We observe an excess of events in the data compared with the background predictions, which is most significant in the mass range between 120 and 135  GeV/c[superscript 2]. The largest local significance is 3.3 standard deviations, corresponding to a global significance of 3.1 standard deviations. We interpret this as evidence for the presence of a new particle consistent with the standard model Higgs boson, which is produced in association with a weak vector boson and decays to a bottom-antibottom quark pair

GM in Asian Auto Markets

We combine searches by the CDF and D0 collaborations for a Higgs boson decaying to W+W-. The data correspond to an integrated total luminosity of 4.8 (CDF) and 5.4 (D0) fb-1 of p-pbar collisions at sqrt{s}=1.96 TeV at the Fermilab Tevatron collider. No excess is observed above background expectation, and resulting limits on Higgs boson production exclude a standard-model Higgs boson in the mass range 162-166 GeV at the 95% C.L