Reconstructing paleoseismic deformation, 2: 1000 years of great earthquakes at Chucalén, south central Chile

In this paper we adopt a quantitative biostratigraphic approach to establish a 1000-year-long coastal record of megathrust earthquake and tsunami occurrence in south central Chile. Our investigations focus on a site in the centre of the rupture segment of the largest instrumentally recorded earthquake, the AD 1960 magnitude 9.5 Chile earthquake. At Chucalén coseismic subsidence in 1960 is recorded in the lithostratigraphy and biostratigraphy of coastal marshes, with peat overlain by minerogenic sediment and changes in the assemblages of diatoms (unicellular algae) indicating an abrupt increase in relative sea level. In addition to the 1960 earthquake, the stratigraphy at Chucalén records three earlier earthquakes, the historically documented earthquake of 1575 and two prehistoric earthquakes, radiocarbon dated to AD 1270–1450 and 1070–1220. Laterally extensive sand sheets containing marine or brackish diatom assemblages suggest tsunami deposition associated with at least two of the three pre-1960 earthquakes. The record presented here suggests a longer earthquake recurrence interval, averaging 270 years, than the historical recurrence interval, which averages 128 years. The lack of geologic evidence at Chucalén of two historically documented earthquakes, in 1737 and 1837, supports the previously suggested hypothesis of variability in historical earthquake characteristics. Our estimates of coseismic land-level change for the four earthquakes range from meter-scale subsidence to no subsidence or slight uplift, suggesting earthquakes completing each ∼270 year cycle may not share a common, characteristic slip distribution. The presence of buried soils at elevations below their modern equivalents implies net relative sea-level rise over the course of the Chucalén paleoseismic record, in contrast to relative sea-level fall over preceding millennia inferred from sites on the mainland. Sea-level rise may contribute to the preservation of evidence for multiple earthquakes during the last millennium, while net relative sea-level fall over the last 2000–5000 years may explain the lack of evidence for older earthquakes

Myeloma cells down‐regulate adiponectin in bone marrow adipocytes via TNF‐alpha

Multiple myeloma is caused by abnormal plasma cells that accumulate in the bone marrow and interact with resident cells of the bone microenvironment to drive disease progression and development of an osteolytic bone disease. Bone marrow adipocytes (BMAds) are emerging as having important endocrine functions that can support myeloma cell growth and survival. However, how BMAds respond to infiltrating tumor cells remains poorly understood. Using the C57BL/KaLwRij murine model of myeloma, bone marrow adiposity was found to be increased in early stage myeloma with BMAds localizing along the tumor‐bone interface at later stages of disease. Myeloma cells were found to uptake BMAd‐derived lipids in vitro and in vivo, although lipid uptake was not associated with the ability of BMAds to promote myeloma cell growth and survival. However, BMAd‐derived factors were found to increase myeloma cell migration, viability, and the evasion of apoptosis. BMAds are a major source of adiponectin, which is known to be myeloma‐suppressive. Myeloma cells were found to downregulate adiponectin specifically in a model of BMAds but not in white adipocytes. The ability of myeloma cells to downregulate adiponectin was dependent at least in part on TNF‐α. Collectively our data support the link between increased bone marrow adiposity and myeloma progression. By demonstrating how TNF‐α downregulates BMAd‐derived adiponectin, we reveal a new mechanism by which myeloma cells alter the bone microenvironment to support disease progression. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research

‘Test n Treat (TnT)’– Rapid testing and same-day, on-site treatment to reduce rates of chlamydia in sexually active further education college students: study protocol for a cluster randomised feasibility trial

Background Sexually active young people attending London further education (FE) colleges have high rates of chlamydia, but screening rates are low. We will conduct a cluster randomised feasibility trial of frequent, rapid, on-site chlamydia testing and same-day treatment (Test and Treat (TnT)) in six FE colleges (with parallel qualitative and economic assessments) to assess the feasibility of conducting a future trial to investigate if TnT reduces chlamydia rates. Methods We will recruit 80 sexually active students aged 16–24 years from public areas at each of six colleges. All participants (total n = 480) will be asked to provide samples (urine for males, self-taken vaginal swabs for females) and complete questionnaires on sexual lifestyle and healthcare use at baseline and after 7 months. Participants will be informed that baseline samples will not be tested for 7 months and be advised to get screened separately. Colleges will be randomly allocated to the intervention (TnT) or the control group (no TnT). One and 4 months after recruitment, participants at each intervention college (n = 3) will be texted and invited for on-site chlamydia tests using the 90-min Cepheid GeneXpert system. Students with positive results will be asked to see a visiting nurse health adviser for same-day treatment and partner notification, (backed by genitourinary medicine follow-up). Participants in control colleges (n = 3) will receive ‘thank you’ texts 1 and 4 months after recruitment. Seven months after recruitment, participants from both groups will be invited to complete questionnaires and provide samples for TnT. All samples will be tested, and same-day treatment offered to students with positive results. Acceptability of TnT will be assessed by qualitative interviews of purposively sampled students (n = 30) and college staff (n = 12). We will collect data on costs of TnT and usual healthcare. Discussion Findings will provide key values to inform feasibility, sample size and timescales of a future definitive trial of TnT in FE colleges, including: Recruitment rates TnT uptake rates Follow-up rates Prevalence of chlamydia in participants at baseline and 7 months Acceptability of TnT to students and college staff Estimate of the cost per person screened/treated in TnT versus usual care Trial registration International Standard Randomised Controlled Trials Registry, ID: ISRCTN58038795, Registered on 31 August 2016

Reconstruction of ice-sheet changes in the Antarctic Peninsula since the Last Glacial Maximum

This paper compiles and reviews marine and terrestrial data constraining the dimensions and configuration of the Antarctic Peninsula Ice Sheet (APIS) from the Last Glacial Maximum (LGM) through deglaciation to the present day. These data are used to reconstruct grounding-line retreat in 5ka time-steps from 25kaBP to present. Glacial landforms and subglacial tills on the eastern and western Antarctic Peninsula (AP) shelf indicate that the APIS was grounded to the outer shelf/shelf edge at the LGM and contained a series of fast-flowing ice streams that drained along cross-shelf bathymetric troughs. The ice sheet was grounded at the shelf edge until ~20calkaBP. Chronological control on retreat is provided by radiocarbon dates on glacimarine sediments from the shelf troughs and on lacustrine and terrestrial organic remains, as well as cosmogenic nuclide dates on erratics and ice moulded bedrock. Retreat in the east was underway by about 18calkaBP. The earliest dates on recession in the west are from Bransfield Basin where recession was underway by 17.5calkaBP. Ice streams were active during deglaciation at least until the ice sheet had pulled back to the mid-shelf. The timing of initial retreat decreased progressively southwards along the western AP shelf; the large ice stream in Marguerite Trough may have remained grounded at the shelf edge until about 14calkaBP, although terrestrial cosmogenic nuclide ages indicate that thinning had commenced by 18kaBP. Between 15 and 10calkaBP the APIS underwent significant recession along the western AP margin, although retreat between individual troughs was asynchronous. Ice in Marguerite Trough may have still been grounded on the mid-shelf at 10calkaBP. In the Larsen-A region the transition from grounded to floating ice was established by 10.7-10.6calkaBP. The APIS had retreated towards its present configuration in the western AP by the mid-Holocene but on the eastern peninsula may have approached its present configuration several thousand years earlier, by the start of the Holocene. Mid to late-Holocene retreat was diachronous with stillstands, re-advances and changes in ice-shelf configuration being recorded in most places. Subglacial topography exerted a major control on grounding-line retreat with grounding-zone wedges, and thus by inference slow-downs or stillstands in the retreat of the grounding line, occurring in some cases on reverse bed slopes

A community-based geological reconstruction of Antarctic Ice Sheet deglaciation since the Last Glacial Maximum

A robust understanding of Antarctic Ice Sheet deglacial history since the Last Glacial Maximum is important in order to constrain ice sheet and glacial-isostatic adjustment models, and to explore the forcing mechanisms responsible for ice sheet retreat. Such understanding can be derived from a broad range of geological and glaciological datasets and recent decades have seen an upsurge in such data gathering around the continent and Sub-Antarctic islands. Here, we report a new synthesis of those datasets, based on an accompanying series of reviews of the geological data, organised by sector. We present a series of timeslice maps for 20ka, 15ka, 10ka and 5ka, including grounding line position and ice sheet thickness changes, along with a clear assessment of levels of confidence. The reconstruction shows that the Antarctic Ice sheet did not everywhere reach the continental shelf edge at its maximum, that initial retreat was asynchronous, and that the spatial pattern of deglaciation was highly variable, particularly on the inner shelf. The deglacial reconstruction is consistent with a moderate overall excess ice volume and with a relatively small Antarctic contribution to meltwater pulse 1a. We discuss key areas of uncertainty both around the continent and by time interval, and we highlight potential priorit. © 2014 The Authors

Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci.

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms