Miocene to recent extension in NW Sulawesi, Indonesia

The Malino Metamorphic Complex (MMC) in the western part of the North Arm of Sulawesi (Indonesia) has previously been suggested to be a metamorphic complex exhumed in the Early-Middle Miocene. This idea was based on limited K-Ar and 40Ar/39Ar age data, but no structural data were presented to provide evidence for the mechanism of exhumation. Here we present new field observations, micro-structural analyses and a revised stratigraphy of NW Sulawesi based on new age data, to provide better constraints on the timing and mechanism of exhumation. The data presented here suggest that the MMC is a metamorphic core complex which underwent lithospheric extension during the Early - Middle Miocene. Although the MMC experienced significant extension, there is no evidence that it was exhumed during this time. There is no contact between the MMC and the Pliocene Ongka Volcanics, contradicting a previously inferred unconformable contact. Pliocene undeformed granitoids intruding the MMC indicate the complex was still at depth during their emplacement. Furthermore, Pliocene and Pleistocene cover sequences do not contain metamorphic detritus. A second phase of extensional uplift was accommodated by brittle faulting from the Late Miocene-Pliocene onwards, during which the MMC was exhumed. This extension is widespread, as indicated by synchronous exhumation of the adjacent Palu Metamorphic Complex in West Sulawesi, and rapid subsidence offshore in Gorontalo Bay. It is linked to northward slab rollback of the southward-subducting Celebes Sea since the Pliocene. GPS data show rapid northward motion of the North Arm of Sulawesi with respect to the Celebes Sea, indicating that this process is ongoing at present day

On the nature of the galactic early-B hypergiants

Despite their importance to a number of astrophysical fields, the lifecycles of very massive stars are still poorly defined. In order to address this shortcoming, we present a detailed quantitative study of the physical properties of four early-B hypergiants (BHGs); Cyg OB2 #12, zeta Sco, HD190603 and BP Cru. These are combined with an analysis of their long-term spectroscopic and photometric behaviour in order to determine their evolutionary status. The long-term datasets revealed that they are remarkably stable over long periods (>40yr), with the possible exception of zeta Sco prior to the 20th century, in contrast to the typical excursions that characterise luminous blue variables (LBVs). Zeta Sco, HD190603 and BP Cru possess physical properties intermediate between B supergiants and LBVs; we therefore suggest that BHGs are the immediate descendants and progenitors (respectively) of such stars (for initial masses in the range ~30-60Msun). In contrast, while the wind properties of Cyg OB2 #12 are consistent with this hypothesis, the combination of extreme luminosity and spectroscopic mass (~110Msun) and comparatively low temperature means it cannot be accommodated in such a scheme. Likewise, despite its co-location with several LBVs above the Humphreys-Davidson (HD) limit, the lack of long term variability and its unevolved chemistry apparently excludes such an identification. Since such massive stars are not expected to evolve to such cool temperatures, the properties of Cyg OB2 #12 are difficult to understand under current evolutionary paradigms. [ABRIDGED]Comment: 36 pages, 19 figures (of which 17 pages are online supplemental material). Accepted for publication in Astronomy and Astrophysic

Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy

We review HB stars in a broad astrophysical context, including both variable and non-variable stars. A reassessment of the Oosterhoff dichotomy is presented, which provides unprecedented detail regarding its origin and systematics. We show that the Oosterhoff dichotomy and the distribution of globular clusters (GCs) in the HB morphology-metallicity plane both exclude, with high statistical significance, the possibility that the Galactic halo may have formed from the accretion of dwarf galaxies resembling present-day Milky Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the second-parameter problem is presented. A technique is proposed to estimate the HB types of extragalactic GCs on the basis of integrated far-UV photometry. The relationship between the absolute V magnitude of the HB at the RR Lyrae level and metallicity, as obtained on the basis of trigonometric parallax measurements for the star RR Lyrae, is also revisited, giving a distance modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are studied. Finally, the conductive opacities used in evolutionary calculations of low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and Space Scienc

The UK national breast cancer screening programme for survivors of Hodgkin lymphoma detects breast cancer at an early stage

BACKGROUND: Supradiaphragmatic radiotherapy (SRT) to treat Hodgkin's lymphoma (HL) at a young age increases the risk of breast cancer (BC). A national notification risk assessment and screening programme (NRASP) for women who were treated with SRT before the age of 36 years was instituted in the United Kingdom in 2003. In this study, we report the implementation and screening results from the largest English Cancer Network. METHODS: A total of 417 eligible women were identified through cancer registry/hospital databases and from follow-up (FU) clinics. Screening results were collated retrospectively, and registry searches were used to capture BC cases. RESULTS: Of the 417 women invited for clinical review, 243 (58%) attended. Of these 417 women, 23 (5.5%) have been diagnosed with BC, a standardised incidence ratio of 2.9 compared with the age-matched general population. Of five invasive BCs diagnosed within the NRASP, none involved axillary lymph nodes compared with 7 of 13 (54%) diagnosed outside the programme (P<0.10). The mean latency for BC cases was 19.5±8.35 years and the mean FU duration for those unaffected by BC was 14.6±9.11 years (P<0.01), suggesting that those unaffected by BC remain at high risk. Recall and negative biopsy rates were acceptable (10.5 and 0.8%, respectively). CONCLUSIONS: The NRASP appears to detect BC at an early stage with acceptable biopsy rates, although numbers are small. Determination of NRASP results on a national basis is required for the accurate evaluation of screening efficacy in women previously treated with SRT

Towards an articulation of the material and visual turn in organization studies

International audienceContemporary organizations increasingly rely on images, logos, videos, building materials, graphic andproduct design, and a range of other material and visual artifacts to compete, communicate, form identityand organize their activities. This Special Issue focuses on materiality and visuality in the course of objectifyingand reacting to novel ideas, and, more broadly, contributes to organizational theory by articulating theemergent contours of a material and visual turn in the study of organizations. In this Introduction, weprovide an overview of research on materiality and visuality. Drawing on the articles in the special issue, wefurther explore the affordances and limits of the material and visual dimensions of organizing in relation tonovelty. We conclude by pointing out theoretical avenues for advancing multimodal research, and discusssome of the ethical, pragmatic and identity-related challenges that a material and visual turn could pose fororganizational research

Identification of a BRCA2-Specific modifier locus at 6p24 related to breast cancer risk

Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat