The timing of basaltic volcanism at the Apollo landing sites

Precise crystallisation ages have been determined for a range of Apollo basalts from Pb-Pb isochrons generated using Secondary Ion Mass Spectrometry (SIMS) analyses of multiple accessory phases including K-feldspar, K-rich glass and phosphates. The samples analysed in this study include five Apollo 11 high-Ti basalts, one Apollo 14 high-Al basalt, seven Apollo 15 low-Ti basalts, and five Apollo 17 high-Ti basalts. Together with the samples analysed in two previous similar studies, Pb-Pb isochron ages have been determined for all of the major basaltic suites sampled during the Apollo missions. The accuracy of these ages has been assessed as part of a thorough review of existing age determinations for Apollo basalts, which reveals a good agreement with previous studies of the same samples, as well as with average ages that have been calculated for the emplacement of the different basaltic suites at the Apollo landing sites. Furthermore, the precision of the new age determinations helps to resolve distinctions between the ages of different basaltic suites in more detail than was previously possible. The proposed ages for the basaltic surface flows at the Apollo landing sites have been reviewed in light of these new sample ages. Finally, the data presented here have also been used to constrain the initial Pb isotopic compositions of the mare basalts, which indicate a significant degree of heterogeneity in the lunar mantle source regions, even among the basalts collected at individual landing sites

Are publicly available internet resources enabling women to make informed fertility preservation decisions before starting cancer treatment: an environmental scan?

Background To identify publicly available internet resources and assess their likelihood to support women making informed decisions about, and between, fertility preservation procedures before starting their cancer treatment. Methods A survey of publically available internet resources utilising an environmental scan method. Inclusion criteria were applied to hits from searches of three data sources (November 2015; repeated June 2017): Google (Chrome) for patient resources; repositories for clinical guidelines and projects; distribution email lists to contact patient decision aid experts. The Data Extraction Sheet applied to eligible resources elicited: resource characteristics; informed and shared decision making components; engagement health services. Results Four thousand eight hundred fifty one records were identified; 24 patient resources and 0 clinical guidelines met scan inclusion criteria. Most resources aimed to inform women with cancer about fertility preservation procedures and infertility treatment options, but not decision making between options. There was a lack of consistency about how health conditions, decision problems and treatment options were described, and resources were difficult to understand. Conclusions Unless developed as part of a patient decision aid project, resources did not include components to support proactively women’s fertility preservation decisions. Current guidelines help people deliver information relevant to treatment options within a single disease pathway; we identified five additional components for patient decision aid checklists to support more effectively people’s treatment decision making across health pathways, linking current with future health problems

IL-10 Suppression of NK/DC Crosstalk Leads to Poor Priming of MCMV-Specific CD4 T Cells and Prolonged MCMV Persistence

IL-10 is an anti-inflammatory cytokine that regulates the extent of host immunity to infection by exerting suppressive effects on different cell types. Herpes viruses induce IL-10 to modulate the virus-host balance towards their own benefit, resulting in prolonged virus persistence. To define the cellular and molecular players involved in IL-10 modulation of herpes virus-specific immunity, we studied mouse cytomegalovirus (MCMV) infection. Here we demonstrate that IL-10 specifically curtails the MCMV-specific CD4 T cell response by suppressing the bidirectional crosstalk between NK cells and myeloid dendritic cells (DCs). In absence of IL-10, NK cells licensed DCs to effectively prime MCMV-specific CD4 T cells and we defined the pro-inflammatory cytokines IL-12, IFN-γ and TNF-α as well as NK cell activating receptors NKG2D and NCR-1 to regulate this bidirectional NK/DC interplay. Consequently, markedly enhanced priming of MCMV-specific CD4 T cells in Il10-/-mice led to faster control of lytic viral replication, bu

Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial

Background Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS. Methods In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor-positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358. Results Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7·2 years (IQR 5·6–8·9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0·89 [95% CI 0·64–1·23]). The non-inferiority of anastrozole was established (upper 95% CI <1·25), but its superiority to tamoxifen was not (p=0·49). A total of 69 deaths were recorded (33 for anastrozole vs 36 for tamoxifen; HR 0·93 [95% CI 0·58–1·50], p=0·78), and no specific cause was more common in one group than the other. The number of women reporting any adverse event was similar between anastrozole (1323 women, 91%) and tamoxifen (1379 women, 93%); the side-effect profiles of the two drugs differed, with more fractures, musculoskeletal events, hypercholesterolaemia, and strokes with anastrozole and more muscle spasm, gynaecological cancers and symptoms, vasomotor symptoms, and deep vein thromboses with tamoxifen. Conclusions No clear efficacy differences were seen between the two treatments. Anastrozole offers another treatment option for postmenopausal women with hormone-receptor-positive DCIS, which may be be more appropriate for some women with contraindications for tamoxifen. Longer follow-up will be necessary to fully evaluate treatment differences

Seizure prediction : ready for a new era

Acknowledgements: The authors acknowledge colleagues in the international seizure prediction group for valuable discussions. L.K. acknowledges funding support from the National Health and Medical Research Council (APP1130468) and the James S. McDonnell Foundation (220020419) and acknowledges the contribution of Dean R. Freestone at the University of Melbourne, Australia, to the creation of Fig. 3.Peer reviewedPostprin

HIV-1 subtype C transmitted founders modulate dendritic cell inflammatory responses

Background Heterosexual transmission remains the main route of HIV-1 transmission and female genital tract (FGT) inflammation increases the risk of infection. However, the mechanism(s) by which inflammation facilitates infection is not fully understood. In rhesus macaques challenged with simian immunodeficiency virus, dendritic cell (DC) mediated recruitment of CD4+ T cells to the FGT was critical for infection. The aim of this study was to delineate the mechanisms underlying DC-mediated HIV infection by comparing chemokine and pro-inflammatory cytokine production in response to transmitted founder (TF) and chronic infection (CI) Envelope (Env) pseudotyped viruses (PSV). Results Monocyte-derived DCs (MDDCs) were stimulated with PSV and recombinant gp140 representing matched TF and CI pairs of four individuals and cytokine secretion measured by multiplex immuno-assay. We found that 4/9 Env induced robust MDDC inflammatory responses and of those, three were cloned from TFs. Overall, TF Env induced MDDCs from healthy donors to secrete higher concentrations of inflammatory cytokines and chemokines than those from CI, suggesting TF Env were better inducers of inflammation. Assessing the signalling pathway associated with inflammatory cytokines, we found that PSV of matched TF and CI variants and a gp140 clone activated ERK and JNK to similar levels. Recombinant soluble DC-SIGN inhibited cytokine release and activation of ERK by PSV, suggesting that Env-DC-SIGN binding was partly involved in MDDC stimulation. Therefore, Env clones might differentially stimulate MDDC immune responses via alternative, yet unidentified signalling pathways. Conclusion Overall, this could suggest that the genetics of the virus itself influences inflammatory responses during HIV infection. In the absence of pre-existing infections, induction of greater inflammatory response by TFs might favour virus survival within the healthy FGT by driving an influx of target cells to sites of infection while suppressing immune responses via IL-10

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29