Selective serotonin reuptake inhibitor antidepressant use in first trimester pregnancy and risk of specific congenital anomalies: A European register-based study

Evidence of an association between early pregnancy exposure to selective serotonin reuptake inhibitors (SSRI) and congenital heart defects (CHD) has contributed to recommendations to weigh benefits and risks carefully. The objective of this study was to determine the specificity of association between first trimester exposure to SSRIs and specific CHD and other congenital anomalies (CA) associated with SSRI exposure in the literature (signals). A population-based case-malformed control study was conducted in 12 EUROCAT CA registries covering 2.1 million births 1995-2009 including livebirths, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly. Babies/fetuses with specific CHD (n = 12,876) and non-CHD signal CA (n = 13,024), were compared with malformed controls whose diagnosed CA have not been associated with SSRI in the literature (n = 17,083). SSRI exposure in first trimester pregnancy was associated with CHD overall (OR adjusted for registry 1.41, 95% CI 1.07-1.86, fluoxetine adjOR 1.43 95% CI 0.85-2.40, paroxetine adjOR 1.53, 95% CI 0.91-2.58) and with severe CHD (adjOR 1.56, 95% CI 1.02-2.39), particularly Tetralogy of Fallot (adjOR 3.16, 95% CI 1.52-6.58) and Ebstein's anomaly (adjOR 8.23, 95% CI 2.92-23.16). Significant associations with SSRI exposure were also found for ano-rectal atresia/stenosis (adjOR 2.46, 95% CI 1.06-5.68), gastroschisis (adjOR 2.42, 95% CI 1.10-5.29), renal dysplasia (adjOR 3.01, 95% CI 1.61-5.61), and clubfoot (adjOR 2.41, 95% CI 1.59-3.65). These data support a teratogenic effect of SSRIs specific to certain anomalies, but cannot exclude confounding by indication or associated factors

Apoptosis- and necrosis-induced changes in light attenuation measured by optical coherence tomography

Optical coherence tomography (OCT) was used to determine optical properties of pelleted human fibroblasts in which necrosis or apoptosis had been induced. We analysed the OCT data, including both the scattering properties of the medium and the axial point spread function of the OCT system. The optical attenuation coefficient in necrotic cells decreased from 2.2 ± 0.3 mm−1 to 1.3 ± 0.6 mm−1, whereas, in the apoptotic cells, an increase to 6.4 ± 1.7 mm−1 was observed. The results from cultured cells, as presented in this study, indicate the ability of OCT to detect and differentiate between viable, apoptotic, and necrotic cells, based on their attenuation coefficient. This functional supplement to high-resolution OCT imaging can be of great clinical benefit, enabling on-line monitoring of tissues, e.g. for feedback in cancer treatment

Processing of the MCC K-26 Plutonium-bearing Sludges to Recover Weapons-grade Plutonium That is Not Under Any Treaty or Monitoring Agreement

Russian Federation (RF) and United States (US) collaborations from July 1998 through July 2001 conducted investigations of the Pu-bearing sludges in storage at the Mining Chemical Combine (MCC) K-26 site in order to dispose of weapons-grade plutonium and decommission the radiochemical plant. This RF work resulted in the recovery of approximately 20 kg of weapons-grade plutonium (and {approx}19 MT of uranium) from the sludges which was stored as oxide. Another method investigated and partially developed as joint collaborative efforts during this time period was direct immobilization of plutonium with no recovery of plutonium. This method melts the untreated recovered sludges by microwave ultrahigh frequency (UHF) heating with glass formers. After cooling, melter-crucibles of vitrified sludge are stored on site in underground cavities for eventual disposal in a geologic repository. Cost and technical feasibility studies of the two methods show that direct immobilization (i.e., vitrification) of the plutonium-containing sludge is the preferred alternative. It is also preferred from the ecological point of view. However, RF funding alone is insufficient to continue this work, and US funding has been suspended. It appears unlikely that development of full scale vitrification technologies for the plutonium-bearing sludges can be undertaken without continuing support from the US or from others. Thus, the only demonstrated technology for the MCC for removing weapons-grade plutonium in sludges will remain recovery and extraction of plutonium for storage and reuse for the indefinite future. It is estimated the about 1200 to 1800 kg of weapons plutonium are in the sludges that must be removed and treated as part of the MCC facility decommissioning. This specific plutonium is not covered under any current monitoring or treaty agreement between the RF and the US

Processing of the MCC K26 Plutonium-Bearing Sludges to Recover Weapons-Grade Plutonium That is Not Under any Treaty or Monitoring Agreement

Russian Federation (RF) and United States (US) collaborations from July 1998 through July 2001 conducted investigations of the Pu-bearing sludges in storage at the Mining Chemical Combine (MCC) K-26 site in order to dispose of weapons-grade plutonium and decommission the radiochemical plant. This RF work resulted in the recovery of approximately 20 kg of weapons-grade plutonium (and {approx}19 MT of uranium) from the sludges which was stored as oxide. Another method investigated and partially developed as joint collaborative efforts during this time period was direct immobilization of plutonium with no recovery of plutonium. This method melts the untreated recovered sludges by microwave ultrahigh frequency (UHF) heating with glass formers. After cooling, melter-crucibles of vitrified sludge are stored on site in underground cavities for eventual disposal in a geologic repository. Cost and technical feasibility studies of the two methods show that direct immobilization (i.e., vitrification)of the plutonium-containing sludge is the preferred alternative. It is also preferred from the ecological point of view. However, RF funding alone is insufficient to continue this work, and US funding has been suspended. It appears unlikely that development of full scale vitrification technologies for the plutonium-bearing sludges can be undertaken without continuing support from the US or from others. Thus, the only demonstrated technology for the MCC for removing weapons-grade plutonium in sludges will remain recovery and extraction of plutonium for storage and reuse for the indefinite future. It is estimated the about 1200 to 1800 kg of weapons plutonium are in the sludges that must be removed an d treated as part of the MCC facility decommissioning. This specific plutonium is not covered under any current monitoring or treaty agreement between the RF and the US

Pregnancy Outcome Following Maternal Exposure To Statins: A Multicenter Prospective Study

Introduction: Statin use for the treatment of hypercholesterolemia in women of childbearing age is increasingly common. However, published data on pregnancy outcome after exposure to statins are scarce and conflicting. This contribution addresses the safety of exposure to statins during pregnancy.Method: In a multi-center (n = 11) observational, prospective study we compared the outcomes of 249 women exposed during the 1st trimester of pregnancy to simvastatin (n = 124), atorvastatin (n = 67), pravastatin (n = 32), rosuvastatin (n = 18), fluvastatin (n = 7) or cerivastatin (n = 1) with a control group exposed to agents known to be non-teratogenic (n = 249). The data were collected by members of the European Network of Teratology Information Services (ENTIS) during individual risk counseling between 1990 and 2009. Standardized procedures for data collection were used in each center.Results: The difference in the rate of major birth defects between the statin-exposed group and the control group was not statistically significant (4.0% vs. 2.7% OR 1.5; 95% CI 0.5-4.5, P = 0.44). The crude rate of spontaneous abortions (12.8% vs. 7.1%, OR 1.9, 95% CI 1.0-3.6, P = 0.04) was higher in the exposed group. However, after adjustment to maternal age and gestational age at initial contact, the difference became statistically insignificant. The rate of elective pregnancy-termination (8.8% vs. 4.4%, P = 0.05) was higher and the rate of deliveries resulting in live births was significantly lower in the statin exposed group (77.9% vs. 88.4%, P = 0.002). Prematurity was more frequent in exposed pregnancies (16.1% vs. 8.5%; OR 2.1, 95% CI 1.1-3.8, P = 0.02). Nonetheless, gestational age at birth (median 39 weeks, IQR 37-40 vs. 39 weeks, IQR 38-40, P = 0.27) and birth weight (median 3280 g, IQR 2835-3590 vs. 3250 g, IQR 2880-3600, P = 0.95) did not differ between exposed and non-exposed pregnancies.Conclusion: This study did not detect a clear teratogenic effect of statins. Its statistical power however is not sufficient to reverse the recommendation of treatment discontinuation during pregnancy. At most, the results are reassuring in case of inadvertent exposure