Heterogeneities from the first 100 million years recorded in deep mantle noble gases from the Northern Lau Back-arc Basin

Heavy noble gases (Ne, Ar, Xe) can record long-lasting heterogeneities in the mantle because of the production of isotopes from extant (238U, 40K) and extinct (129I and 244Pu)13 radionuclides. However, the presence of ubiquitous atmospheric contamination, particularly for ocean island basalts (OIBs) that sample the Earth’s deep mantle, have largely hampered precise characterization of the mantle source compositions. Here we present new high-precision noble gas data from gas-rich basalts erupted along the Rochambeau Rift in the northwestern corner of the Lau Basin. The strong influence of a deep mantle plume in the Rochambeau source is apparent from low 4He/3He ratios down to 25,600 (3He/4He of 28.1 RA). We find that the Rochambeau source is characterized by low ratios of radiogenic to non-radiogenic nuclides of Ne, Ar, and Xe (i.e., low 21Ne/22Ne, 40Ar/36Ar, and 129Xe/130Xe) compared to the mantle source of mid-ocean ridge basalts (MORBs). Additionally, we observe differences in elemental abundance patterns between the Rochambeau source and the mantle source of MORBs as characterized by the gas-rich popping rock from the Mid-Atlantic Ridge. However, the 3He/22Ne ratio of the Rochambeau plume source is significantly higher than the Iceland and Galapagos plume sources, while the 3He/36Ar and 3He/130Xe ratios appear to be similar. The difference in 3He/22Ne between Rochambeau and the Galapagos and Iceland plume sources could reflect long lasting accretional heterogeneities in the deep mantle or some characteristic of the back-arc mantle source. High-precision xenon isotopic measurements indicate that the lower 129Xe/130Xe ratios in the Rochambeau source cannot be explained solely by mixing atmospheric xenon with MORB31 type xenon; nor can fission-produced Xe be added to MORB Xe to produce the compositions seen in the Rochambeau basalts. Deconvolution of fissiogenic xenon isotopes demonstrate a higher proportion of Pu-derived fission Xe in the Rochambeau 33 source compared to the MORB source. Therefore, both I/Xe and Pu/Xe ratios are different between OIB and MORB mantle sources. Our observations require heterogeneous volatile accretion and a lower degree of processing for the mantle plume source compared to the MORB source. Since differences in 129Xe/130Xe ratios have to be produced while 129I is still alive, OIB and MORB sources were degassed at different rates for the first 100 Ma of Solar System history, and subsequent to this period, the two reservoirs have not been homogenized. In combination with recent results from the Iceland plume, our observations require the preservation of less-degassed, early-formed heterogeneities in the Earth’s deep mantle throughout Earth’s history

Cancer mortality in the first degree relatives of young breast cancer patients.

In a retrospective cohort study, the mothers and sisters of 740 breast cancer patients aged under 36 at diagnosis have been studied for mortality and cancer incidence. Significantly increased breast cancer mortality was observed below age 60 (30 deaths; SMR = 3.4), but not at older ages (four deaths; SMR = 0.9). The cumulative breast cancer incidence in the relatives was 3.6% by age 50, 7.6% by age 60 and 11.6% by age 70. They also suffered excess mortality below age 60 for cancers of reproductive sites (cervix, ovary and endometrium; 15 deaths; SMR = 2.6) and lung (11 deaths; SMR = 3.2), but not for other sites (12 deaths; SMR = 0.9). This large population-based cohort study provides further confirmation of genetic susceptibility to breast cancer at young ages

Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and design.

The Medical Research Council has for some years encouraged collaborative clinical trials in leukaemia and other cancers, reporting the results in the medical literature. One unreported result which deserves such publication is the development of the expertise to design and analyse such trials. This report was prepared by a group of British and American statisticians, but it is intended for people without any statistical expertise. Part I, which appears in this issue, discusses the design of such trials; Part II, which will appear separately in the January 1977 issue of the Journal, gives full instructions for the statistical analysis of such trials by means of life tables and the logrank test, including a worked example, and discusses the interpretation of trial results, including brief reports of 2 particular trials. Both parts of this report are relevant to all clinical trials which study time to death, and wound be equally relevant to clinical trials which study time to other particular classes of untoward event: first stroke, perhaps, or first relapse, metastasis, disease recurrence, thrombosis, transplant rejection, or death from a particular cause. Part I, in this issue, collects together ideas that have mostly already appeared in the medical literature, but Part II, next month, is the first simple account yet published for non-statistical physicians of how to analyse efficiently data from clinical trials of survival duration. Such trials include the majority of all clinical trials of cancer therapy; in cancer trials,however, it may be preferable to use these statistical methods to study time to local recurrence of tumour, or to study time to detectable metastatic spread, in addition to studying total survival. Solid tumours can be staged at diagnosis; if this, or any other available information in some other disease is an important determinant of outcome, it can be used to make the overall logrank test for the whole heterogeneous trial population more sensitive, and more intuitively satisfactory, for it will then only be necessary to compare like with like, and not, by chance, Stage I with Stage III

Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples.

Part I of this report appeared in the previous issue (Br. J. Cancer (1976) 34,585), and discussed the design of randomized clinical trials. Part II now describes efficient methods of analysis of randomized clinical trials in which we wish to compare the duration of survival (or the time until some other untoward event first occurs) among different groups of patients. It is intended to enable physicians without statistical training either to analyse such data themselves using life tables, the logrank test and retrospective stratification, or, when such analyses are presented, to appreciate them more critically, but the discussion may also be of interest to statisticians who have not yet specialized in clinical trial analyses

Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies.

BACKGROUND: Half the epidemiological studies with information about menopausal hormone therapy and ovarian cancer risk remain unpublished, and some retrospective studies could have been biased by selective participation or recall. We aimed to assess with minimal bias the effects of hormone therapy on ovarian cancer risk. METHODS: Individual participant datasets from 52 epidemiological studies were analysed centrally. The principal analyses involved the prospective studies (with last hormone therapy use extrapolated forwards for up to 4 years). Sensitivity analyses included the retrospective studies. Adjusted Poisson regressions yielded relative risks (RRs) versus never-use. FINDINGS: During prospective follow-up, 12 110 postmenopausal women, 55% (6601) of whom had used hormone therapy, developed ovarian cancer. Among women last recorded as current users, risk was increased even with <5 years of use (RR 1·43, 95% CI 1·31-1·56; p<0·0001). Combining current-or-recent use (any duration, but stopped <5 years before diagnosis) resulted in an RR of 1·37 (95% CI 1·29-1·46; p<0·0001); this risk was similar in European and American prospective studies and for oestrogen-only and oestrogen-progestagen preparations, but differed across the four main tumour types (heterogeneity p<0·0001), being definitely increased only for the two most common types, serous (RR 1·53, 95% CI 1·40-1·66; p<0·0001) and endometrioid (1·42, 1·20-1·67; p<0·0001). Risk declined the longer ago use had ceased, although about 10 years after stopping long-duration hormone therapy use there was still an excess of serous or endometrioid tumours (RR 1·25, 95% CI 1·07-1·46, p=0·005). INTERPRETATION: The increased risk may well be largely or wholly causal; if it is, women who use hormone therapy for 5 years from around age 50 years have about one extra ovarian cancer per 1000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1700 users. FUNDING: Medical Research Council, Cancer Research UK

Optical Coherence Tomography in the UK Biobank Study - Rapid Automated Analysis of Retinal Thickness for Large Population-Based Studies

PURPOSE: To describe an approach to the use of optical coherence tomography (OCT) imaging in large, population-based studies, including methods for OCT image acquisition, storage, and the remote, rapid, automated analysis of retinal thickness. METHODS: In UK Biobank, OCT images were acquired between 2009 and 2010 using a commercially available “spectral domain” OCT device (3D OCT-1000, Topcon). Images were obtained using a raster scan protocol, 6 mm x 6 mm in area, and consisting of 128 B-scans. OCT image sets were stored on UK Biobank servers in a central repository, adjacent to high performance computers. Rapid, automated analysis of retinal thickness was performed using custom image segmentation software developed by the Topcon Advanced Biomedical Imaging Laboratory (TABIL). This software employs dual-scale gradient information to allow for automated segmentation of nine intraretinal boundaries in a rapid fashion. RESULTS: 67,321 participants (134,642 eyes) in UK Biobank underwent OCT imaging of both eyes as part of the ocular module. 134,611 images were successfully processed with 31 images failing segmentation analysis due to corrupted OCT files or withdrawal of subject consent for UKBB study participation. Average time taken to call up an image from the database and complete segmentation analysis was approximately 120 seconds per data set per login, and analysis of the entire dataset was completed in approximately 28 days. CONCLUSIONS: We report an approach to the rapid, automated measurement of retinal thickness from nearly 140,000 OCT image sets from the UK Biobank. In the near future, these measurements will be publically available for utilization by researchers around the world, and thus for correlation with the wealth of other data collected in UK Biobank. The automated analysis approaches we describe may be of utility for future large population-based epidemiological studies, clinical trials, and screening programs that employ OCT imaging

The Mesothelioma epidemic in Western Europe: an update

The number of male deaths from pleural cancer in France, Germany and Italy increased from about 8750 in 1990-1994 to 9550 in 1995-1999, suggesting that mesothelioma deaths in males may be levelling off in most of Western Europe