Mixed protocols: Multiple ratios of FSH and LH bioactivity using highly purified, human-derived FSH (BRAVELLE) and highly purified hMG (MENOPUR) are unaltered by mixing together in the same syringe

BACKGROUND: The use of mixed or blended protocols, that utilize both FSH and hMG, for controlled ovarian hyperstimulation is increasing in use. To reduce the number of injections a patient must administer, many physicians instruct their patients to mix their FSH and hMG together to be given as a single injection. Therefore, the goal of this study was to definitively determine if the FSH and LH bioactivities of highly purified, human-derived FSH (Bravelle(R)) and highly purified hMG (Menopur(R)) were altered by reconstituting in 0.9% saline and mixing in the same syringe. METHODS: Bravelle(R) and Menopur(R) were reconstituted in 0.9% saline and mixed in a Becton Dickinson plastic syringe. The FSH and LH bioactivities of the products were determined after injecting female and male rats, respectively, with Bravelle(R), Menopur(R), or a mixture of Bravelle(R) and Menopur(R). Ratios of FSH:LH activity tested were 150:75 IU (1 vial Bravelle(R): 1 vial Menopur(R)), 300:75 IU (3 vials Bravelle(R): 1 vial Menopur(R)) or 300:225 IU (1 vial Bravelle(R): 3 vials of Menopur(R)). RESULTS: There were no statistically significant changes in either FSH or LH bioactivity that occurred after mixing Bravelle(R) with Menopur(R) in the same syringe. The theoretical vs. actual FSH bioactivity for Bravelle(R) and Menopur(R) were 75 vs. 76.58 IU/mL and 75 vs. 76.0 IU/mL, respectively. For the 3 ratios of FSH:LH activity tested, 150:75 IU (1 vial Bravelle(R): 1 vial Menopur(R)), 300:75 IU (3 vials Bravelle(R): 1 vial Menopur(R)) or 300:225 IU (1 vial Bravelle(R): 3 vials of Menopur(R)) tested, the theoretical vs. actual FSH bioactivities were 150 vs. 156.86 IU/mL, 300 vs. 308.69 IU/mL and 300 vs. 306.58 IU/mL, respectively. The theoretical vs. actual LH bioactivity for Menopur(R) in the above mentioned ratios tested were 75 vs. 77.50 IU/mL. For the 3 ratios of FSH:LH activity tested, 150:75 IU (1 vial Bravelle(R): 1 vial Menopur(R)), 300:75 IU (3 vials Bravelle(R): 1 vial Menopur(R)) or 300:225 IU (1 vial Bravelle(R): 3 vials of Menopur(R)), the theoretical vs. actual LH bioactivities were 75 vs. 78.38 IU/mL, 75 vs. 78.63 IU/mL and 225 vs. 233.48 IU/mL, respectively. CONCLUSION: Mixing human-derived FSH (Bravelle(R)) with highly purified hMG (Menopur(R)) in the same diluent, 0.9% NaCL, does not alter the FSH or LH bioactivity of either gonadotropin preparation

Anomalous chlorofluorocarbon uptake by mesoscale eddies in the Drake Passage region

Author Posting. © American Geophysical Union, 2015. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Oceans 120 (2015): 1065–1078, doi:10.1002/2014JC010292.The role of mesoscale eddies in the uptake of anthropogenic chlorofluorocarbon-11 (CFC-11) gas is investigated with a 1/20° eddy-resolving numerical ocean model of a region of the Southern Ocean. With a relatively fast air-sea equilibrium time scale (about a month), the air-sea CFC-11 flux quickly responds to the changes in the mixed layer CFC-11 partial pressure (pCFC-11). At the mesoscale, significant correlations are observed between pCFC-11 anomaly, anomalies in sea surface temperature (SST), net heat flux, and mixed layer depth. An eddy-centric analysis of the simulated CFC-11 field suggests that anticyclonic warm-core eddies generate negative pCFC-11 anomalies and cyclonic cold-core eddies generate positive anomalies of pCFC-11. Surface pCFC-11 is modulated by mixed layer dynamics in addition to CFC-11 air-sea fluxes. A negative cross correlation between mixed layer depth and surface pCFC-11 anomalies is linked to higher CFC-11 uptake in anticyclones and lower CFC-11 uptake in cyclones, especially in winter. An almost exact asymmetry in the air-sea CFC-11 flux between cyclones and anticyclones is found.We gratefully acknowledge NSF support of the MOBY project (grant OCE-1048926 to MIT and OCE-1048897 to WHOI). In addition, P.G. and D.J.M. thank NASA for partial support of this work through grant NNX13AE47G.2015-08-2

Impact of current-wind interaction on vertical processes in the Southern Ocean

Author Posting. © American Geophysical Union, 2020. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research-Oceans 125(4), (2020): e2020JC016046, doi:10.1029/2020JC016046.Momentum input from westerly winds blowing over the Southern Ocean can be modulated by mesoscale surface currents and result in changes in large‐scale ocean circulation. Here, using an eddy‐resolving 1/20 degree ocean model configured near Drake Passage, we evaluate the impact of current‐wind interaction on vertical processes. We find a reduction in momentum input from the wind, reduced eddy kinetic energy, and a modification of Ekman pumping rates. Wind stress curl resulting from current‐wind interaction leads to net upward motion, while the nonlinear Ekman pumping term associated with horizontal gradients of relative vorticity induces net downward motion. The spatially averaged mixed layer depth estimated using a density criteria is shoaled slightly by current‐wind interaction. Current‐wind interaction, on the other hand, enhances the stratification in the thermocline below the mixed layer. Such changes have the potential to alter biogeochemical processes including nutrient supply, biological productivity, and air‐sea carbon dioxide exchange.The MITgcm can be obtained online (http://mitgcm.org). The geostrophic current product derived from the sea level anomaly can be downloaded in the Copernicus Marine and Environment Monitoring Service of Ssalto/Duacs gridded “allsat” series and along‐track Sea Level Anomalies, Absolute Dynamic Topographies and Geostrophic velocities over the Global Ocean, Mediterranean Sea, Black Sea, European Seas and Acrtic Ocean areas, in Delayed‐Time and in Near‐Real‐Time. Resources supporting this work were provided by the NASA High‐End Computing (HEC) Program through the NASA Advanced Supercomputing (NAS) Division at Ames Research Center with the award number SMD‐15‐5752. H. S., J. M., and D. J. M. were supported by the NSF MOBY project (OCE‐1048926 and OCE‐1048897). H. S. acknowledges the support by National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF‐2019R1C1C1003663) and Yonsei University Research Fund of 2018‐22‐0053. D. J. M. also gratefully acknowledges NSF and NASA support, along with the Holger W. Jannasch and Columbus O'Donnell Iselin shared chairs for Excellence in Oceanography. H. Seo acknowledges the support from the ONR (N00014‐17‐1‐2398), NOAA (NA10OAR4310376), and the Andrew W. Mellon Foundation Endowed Fund for Innovative Research at WHOI. We also thank two anonymous referees whose comments significantly improved the presentation of results.2020-09-1

Highly purified human-derived follicle-stimulating hormone (Bravelle®) has equivalent efficacy to follitropin-beta (Follistim ®) in infertile women undergoing in vitro fertilization

BACKGROUND: These data compare the efficacy and safety of highly purified human-derived follicle-stimulating hormone (Bravelle(R)) and recombinant follitropin-β (Follistim(R)) in women undergoing in vitro fertilization. METHODS: This report describes the pooled data from two, nearly identical, randomized, controlled, parallel-group, multicenter studies conducted in a total of 19 academic and private IVF-ET centers in the United States. Infertile premenopausal women underwent pituitary down-regulation using leuprolide acetate followed by a maximum of 12 days of subcutaneous Bravelle(R) (n = 120) or Follistim(R) (n = 118), followed by administration of human chorionic gonadotropin, oocyte retrieval and embryo transfer. The primary efficacy measure was the mean number of oocytes retrieved; secondary efficacy measures included the total dose and duration of gonadotropin treatment; peak serum estradion levels; embryo transfer and implantation rates; chemical, clinical and continuing pregnancies; and live birth rates. All adverse events were recorded and injection site pain was recorded daily using a patient, self-assessment diary. RESULTS: Similar efficacy responses were observed for all outcome parameters in the two treatment groups. Although patients receiving Bravelle(R) consistently reported a greater number of chemical, clinical and continuing pregnancies, as well as an increased rate of live birth, the data did not attain statistical significance (P > 0.05). The overall incidence of adverse events was similar in both groups, but compared to Follistim(R), injections of Bravelle(R) were reported by patients to be significantly less painful (P < 0.001). CONCLUSIONS: Bravelle(R) and Follistim(R) had comparable efficacy in controlled ovarian hyperstimulation in women undergoing IVF-ET. There were no differences in the nature or number of adverse events between the treatment groups although Bravelle(R) injections were reported to be significantly less painful

Distribution and conservation status of the orang-utan (Pongo spp.) on Borneo and Sumatra: how many remain?

In recognition of the fact that orang-utans (Pongo spp.) are severely threatened, a meeting of orang-utan experts and conservationists, representatives of national and regional governmental and non-governmental organizations, and other stakeholders, was convened in Jakarta, Indonesia, in January 2004. Prior to this meeting we surveyed all large areas for which orang-utan population status was unknown. Compilation of all survey data produced a comprehensive picture of orang-utan distribution on both Borneo and Sumatra. These results indicate that in 2004 there were c. 6,500 P. abelii remaining on Sumatra and at least 54,000 P. pygmaeus on Borneo. Extrapolating to 2008 on the basis of forest loss on both islands suggests the estimate for Borneo could be 10% too high but that for Sumatra is probably still relatively accurate because forest loss in orang-utan habitat has been low during the conflict in Aceh, where most P. abelii occur. When those population sizes are compared to known historical sizes it is clear that the Sumatran orang-utan is in rapid decline, and unless extraordinary efforts are made soon, it could become the first great ape species to go extinct. In contrast, our results indicate there are more and larger populations of Bornean orang-utans than previously known. Although these revised estimates for Borneo are encouraging, forest loss and associated loss of orang-utans are occurring at an alarming rate, and suggest that recent reductions of Bornean orang-utan populations have been far more severe than previously supposed. Nevertheless, although orang-utans on both islands are under threat, we highlight some reasons for cautious optimism for their long-term conservatio

Ice core evidence for significant 100-year regional warming on the Antarctic Peninsula

We present a new 150-year, high-resolution, stable isotope record (delta O-18) from the Gomez ice core, drilled on the data sparse south western Antarctic Peninsula, revealing a similar to 2.7 degrees C rise in surface temperatures since the 1950s. The record is highly correlated with satellite-derived temperature reconstructions and instrumental records from Faraday station on the north west coast, thus making it a robust proxy for local and regional temperatures since the 1850s. We conclude that the exceptional 50-year warming, previously only observed in the northern Peninsula, is not just a local phenomena but part of a statistically significant 100-year regional warming trend that began around 1900. A suite of coupled climate models are employed to demonstrate that the 50 and 100 year temperature trends are outside of the expected range of variability from pre-industrial control runs, indicating that the warming is likely the result of external climate forcing. Citation: Thomas, E. R., P. F. Dennis, T. J. Bracegirdle, and C. Franzke (2009), Ice core evidence for significant 100-year regional warming on the Antarctic Peninsula, Geophys. Res. Lett., 36, L20704, doi: 10.1029/2009GL040104

Diagnostic and clinical experience of patients with pantothenate kinase-associated neurodegeneration

BACKGROUND: Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive neurodegenerative disorder with brain iron accumulation (NBIA). OBJECTIVES: To assess PKAN diagnostic pathway, history, and burden across the spectrum of PKAN severity from patient and/or caregiver perspectives. METHODS: Caregivers of patients (n = 37) and patients themselves (n = 2) were interviewed in a validation study of the PKAN-Activities of Daily Living (ADL) scale. The current study used quartiles of the PKAN-ADL total score to divide patients by severity of impairment (Lowest, Second Lowest, Third Lowest, Highest). Diagnostic and treatment history, healthcare utilization, disease burden, and caregiver experience were compared between groups. RESULTS: The analyses included data from 39 patients. Mean age at PKAN symptom onset (P = 0.0007), initial MRI (P = 0.0150), and genetic testing (P = 0.0016) generally decreased across the PKAN severity spectrum. The mean duration of illness did not differ among PKAN severity groups (range, 9.7-15.2 years; P = 0.3029). First MRI led to diagnosis in 56.4% of patients (range, 30.0-90.0%). A mean (SD) of 13.0 (13.1) medical and 55.2 (78.5) therapy visits (eg, physical, speech) occurred in the past year. More patients in the higher PKAN severity groups experienced multiple current functional losses and/or earlier onset of problems (P-values \u3c 0.0500). Over half (56.8%) of caregivers experienced a change in employment because of caregiving. The percentage of patients requiring full-time caregiving increased across the PKAN severity spectrum (range, 11.1-100%; P = 0.0021). CONCLUSIONS: PKAN diagnosis was often delayed, most probably due to low awareness. Considerable burden of functional impairment and high healthcare utilization were found across the PKAN severity spectrum

Living for the weekend: youth identities in northeast England

Consumption and consumerism are now accepted as key contexts for the construction of youth identities in de-industrialized Britain. This article uses empirical evidence from interviews with young people to suggest that claims of `new community' are overstated, traditional forms of friendship are receding, and increasingly atomized and instrumental youth identities are now being culturally constituted and reproduced by the pressures and anxieties created by enforced adaptation to consumer capitalism. Analysis of the data opens up the possibility of a critical rather than a celebratory exploration of the wider theoretical implications of this process