Reply to J.J. Muñoz-Perez et al. Comments on “Confirmation of beach accretion by grain-size trend analysis: Camposoto beach, Cádiz, SWSpain” by E. Poizot et al. (2013) Geo-Marine Letters 33(4)

In a novel finding for a beach environment, Poizot et al. (2013) identified an FB+ trend (sediments becoming finer, better sorted and more positively skewed upshore) on a well-developed swash bar on the upper foreshore of the Camposoto beach of Cádiz in SW Spain. In their Discussion of that paper, Muñoz-Perez et al. (2014) provide some supporting arguments and also report grain-size, beach profile and other data from nearby beaches which differ from those of Poizot and colleagues for Camposoto beach, pointing out that a trend observed on one beach may not apply to a neighbouring beach. However, even though the absolute values differ, the overall trends actually do show the same general behaviour. In our Reply to their comments, we also address some difficulties in comparing granulometric datasets generated by different analytical techniques

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Loss of mammary epithelial prolactin receptor delays tumor formation by reducing cell proliferation in low-grade preinvasive lesions

Top quartile serum prolactin levels confer a twofold increase in the relative risk of developing breast cancer. Prolactin exerts this effect at an ill defined point in the carcinogenic process, via mechanisms involving direct action via prolactin receptors within mammary epithelium and/or indirect action through regulation of other hormones such as estrogen and progesterone. We have addressed these questions by examining mammary carcinogenesis in transplants of mouse mammary epithelium expressing the SV40T oncogene, with or without the prolactin receptor, using host animals with a normal endocrine system. In prolactin receptor knockout transplants the area of neoplasia was significantly smaller (7 versus 17%; P<0.001 at 22 weeks and 7 versus 14%; P=0.009 at 32 weeks). Low-grade neoplastic lesions displayed reduced BrdU incorporation rate (11.3 versus 17% P=0.003) but no change in apoptosis rate. Tumor latency increased (289 days versus 236 days, P<0.001). Tumor frequency, growth rate, morphology, cell proliferation and apoptosis were not altered. Thus, prolactin acts directly on the mammary epithelial cells to increase cell proliferation in preinvasive lesions, resulting in more neoplasia and acceleration of the transition to invasive carcinoma. Targeting of mammary prolactin signaling thus provides a strategy to prevent the early progression of neoplasia to invasive carcinoma. © 2007 Nature Publishing Group All rights reserved

The ideal technique for processing SpyBite tissue specimens: a prospective, single-blinded, pilot-study of histology and cytology techniques.

Background and study aims  Diagnostic sensitivity for indeterminate biliary lesions remains suboptimal. Cytology techniques may mitigate the impediment of small cholangioscopic specimens. Our primary aim was to compare cell block cytology (CB) with standard histology for foregut SpyBite (SB) specimens. Our secondary aim was to assess CB in biliary SB biopsies. Patients and methods  This was a two-phase prospective pilot study. In phase one, a prospective pilot study, foregut SB specimens from three sites (4 per site per patient per processing technique) were allocated to CB or histology, and assessed by a single, blinded pathologist. The gold standard comprised two standard forceps (CFB) histological specimens per site per patient. Specimen ease of processing, size and number, adequacy for diagnosis and artefact were evaluated. In phase two, CB was used for consecutive patients with indeterminate biliary lesions, and compared with phase one CB results. Results  In phase one, 240 SB foregut biopsies were performed in 10 patients, 227 specimens recorded by pathologist. Specimen origin was identified in 100 % and 97 % of histology and CB batches respectively. Specimens were significantly larger in the histology group (2.02 mm vs 1.49 mm, P  < 0.05). There was a trend to less crush artifact with CB, and no difference in processing difficulty. In phase two, 11 patients (63.0 ±12.7 years, 91 % female) underwent SpyGlass (SG) assessment of suspected indeterminate stricture (n = 8) or mass (n = 3), and six underwent SB. All CB specimens were adequate for diagnosis. Specimen parameters were not significantly different from luminal CB outcomes. Conclusions  In this pilot study, cell block cytology showed similar results as histological analysis of SpyBite specimens in the analysis of biliary stricture

Expression of LMO4 and outcome in pancreatic ductal adenocarcinoma

Identification of a biomarker of prognosis and response to therapy that can be assessed preoperatively would significantly improve overall outcomes for patients with pancreatic cancer. In this study, patients whose tumours exhibited high LMO4 expression had a significant survival advantage following operative resection, whereas the survival of those patients whose tumours had low or no LMO4 expression was not significantly different when resection was compared with operative biopsy alone

Ecological consequences of sediment on high-energy coral reefs

Sediments are widely accepted as a threat to coral reefs but our understanding of their ecological impacts is limited. Evidence has suggested that benthic sediments bound within the epilithic algal matrix (EAM) suppress reef fish herbivory, a key ecological process maintaining reef resilience. An experimental combination of caging and sediment addition treatments were used to investigate the effects of sediment pulses on herbivory and EAMs and to determine whether sediment addition could trigger a positive-feedback loop, leading to deep, sediment-rich turfs. A 1-week pulsed sediment addition resulted in rapid increases in algal turf length with effects comparable to those seen in herbivore exclusion cages. Contrary to the hypothesised positive-feedback mechanism, benthic sediment loads returned to natural levels within 3 weeks, however, the EAM turfs remained almost 60% longer for at least 3 months. While reduced herbivore density is widely understood to be a major threat to reefs, we show that acute disturbances to reef sediments elicit similar ecological responses in the EAM. With reefs increasingly threatened by both reductions in herbivore biomass and altered sediment fluxes, the development of longer turfs may become more common on coral reefs

Impacts of climate change on marine resources in the Pacific Island region

In the Pacific Island region, marine resources make vital contributions to food security, livelihoods and economic development. Climate change is expected to have profound effects on the status and distribution of coastal and oceanic habitats, the fish and invertebrates they support and, as a result, the communities and industries that depend on these resources. To prepare for and respond to these impacts—and ensure the ongoing sustainability of marine ecosystems, and the communities and industries that rely on them economically and culturally—it is necessary to understand the main impacts and identify effective adaptation actions. In particular, declines in coral reef habitats and associated coastal fisheries productivity, more eastward distribution of tuna and impacts of more intense storms and rainfall on infrastructure are expected to present the greatest challenges for Pacific communities and economies. Some species of sharks and rays, and aquaculture commodities with calcareous shells, will also be impacted by habitat degradation, ecosystem changes, increasing temperature and ocean acidification. The projected declines in coastal fish and invertebrate populations will widen the gap between fish needed by growing human populations and sustainable harvests from coastal fisheries, with shortages expected in some nations (e.g. Papua New Guinea, Solomon Islands) by 2035. There will also be a need to diversify livelihoods based on fisheries, aquaculture and tourism because some of these operations are expected to be negatively affected by climate change. In some cases, building the resilience of Pacific communities to climate change will involve reducing dependence on, or finding alternatives, vulnerable marine resources