Seismic modelling and paleoceanography at DSDP Site 574

The analysis of high-resolution watergun seismic profiles collected in support of DSDP Leg 85 drilling reveals sev eral major, regionally traceable reflectors that can be correlated over more than 360,000 km2 in the central equatorial Pacific. Synthetic seismograms generated from shipboard physical property measurements (carefully corrected to in situ values) for DSDP Site 574 show excellent agreement with the field records; the agreement suggests that the traveltime to-depth conversion is accurate and permits the precise (± 5 m) location of reflectors in the cored section. The reflectors can be dated (±0.5 Ma) as follows: Orange, 21.5 to 22.5 Ma; Yellow, 20.5 to 21.5 Ma; Lavender, 16 to 17 Ma; Red, 13.5 to 14.5 Ma; Purple, 11 to 12 Ma; Brown, 7 to 8 Ma; and Green, 3 to 4 Ma. Similar analyses at the other Leg 85 sites result in identical ages. The reflectors are thus time surfaces; this chapter relates them to major paleoceanographic events and changes in the relative sea-level curve. The Orange and Yellow reflectors are associated with a marked increase in δ 1 3C, a major change in planktonic foraminiferal assemblages, the development of the deep Circum-Antarctic Current, and the establishment of steep thermal gradients between tropical and polar regions. This reorganization of the oceanic circulation system was probably a response to the opening of the Drake Passage, and it resulted in changes in the chemistry of tropical Pacific waters that caused the induration (and thus impedance contrasts) associated with these reflectors. The Lavender reflector is associated with a large carbonate minimum, the Chron 16 carbon shift, a widespread hiatus (NH2), major eustatic sea-level fluctuations, and a significant increase in silica deposition in the Pacific. It is not associated with 18O enrichment or climatic cooling. We conclude that this event represents an intensification in Antarc tic Bottom Water (AABW) circulation and the partitioning of silica between the Atlantic and the Pacific, caused by the introduction of North Atlantic Deep Water (NADW) in response to paleobathymetric and tectonic events. The Red re flector is associated with a subdued carbonate minimum, a widespread hiatus (NH3), a sea-level drop, significant changes in microfossil assemblages, and a major increase in δ 1 8 that has been linked with the buildup of Antarctic ice. Detailed isotopic analyses reveal that this isotopic shift occurred within an interval of 30,000 yr. and precisely at the depth of the Red reflector. The Purple reflector is associated with an extremely large carbonate minimum, a change in the style of carbonate deposition in the Pacific, a major lithologic boundary, a widespread hiatus (NH4), an increase in the provincialism be tween low and high latitudes in all planktonic microfossil assemblages, an apparent fall in eustatic sea level, an enrich ment in δ 1 8 , and a major North Atlantic reflector interpreted as representing an intensification of North Atlantic bot tom-water circulation. The Brown reflector is roughly associated with a small carbonate minimum, an enrichment in δ 1 8 , the late Miocene 1 3C depletion, a drop in the relative sea-level curve, and major faunal changes. The Green reflector is associated with a large carbonate minimum, an enrichment in δ 1 8 , a major western North Atlantic erosional event, and a widespread eastern Atlantic seismic reflector. The bulk of evidence supports correlation with the onset of Northern Hemisphere glaciation, but detailed isotopic analyses indicate that this isotopic event may be linked to the establishment of colder bottom waters without major ice-sheet development. Several types of reflectors have been identified. The reflectors in the older section result from diagenetic effects; the regionally correctable reflectors are associated with global events. In the younger (post-18 Ma) section, local reflectors are characterized by velocity contrasts, whereas regional reflectors are associated with density contrasts caused by car bonate minima. Two modes of generation of carbonate minima (and thus of reflectors) spanning the equatorial Pacific are (1) the intensification of AABW without the concurrent intensification of NADW and so without fractionation of silica between the Atlantic and the Pacific; this mode results in the less extreme carbonate minima; and (2) the intensifi cation of AABW in response to the intensification of NADW; this mode results in extreme carbonate minima and a cor relation of equatorial Pacific reflectors with North Atlantic events

Basement structure of the northern Ontong Java Plateau

Site surveys conducted in conjunction with Leg 130 on the Ontong Java Plateau reveal a strong seismic reflector at 0.8 to 1.0 s below the seafloor that drilling at Sites 803 and 807 confirmed is Cretaceous basalt. This reflector is generally smooth, except for the northeastern margin of the plateau, where it forms a series of small, irregularly shaped depressions. Correlatable reflectors present at the bottom of the depressions are also present on the adjacent highs, suggesting that these depressions are original volcanic topography. A strong sub-basalt reflector occurs on many seismic profiles on the northeastern portion of the plateau. This reflection may be caused by a density and velocity contrast between pillow lavas and flood basalt flows or it may result from interbedded sediment and thus may represent significant lulls in volcanic activity. The presence of sub-basalt reflectors near Site 803 may indicate that later volcanic episodes occurred there, in contrast to Site 807, where this reflector was not observed and where older basalt ages were obtained

Seismic stratigraphy of the Ontong Java Plateau

The Ontong Java Plateau, a large, deep-water carbonate plateau in the western equatorial Pacific, is an ideal location for studying responses of carbonate sedimentation to the effects of changing paleoceanographic conditions. These carbonate responses are often reflected in the physical properties of the sediment, which in turn control the appearance of seismic reflection profiles. Seismic stratigraphy analyses, correlating eight reflector horizons to each drill site, have been conducted in an attempt to map stratigraphic data. Accurate correlation of seismic stratigraphic data to drilling results requires conversion of traveltime to depth in meters. Synthetic seismogram models, using shipboard physical properties data, have been generated in an attempt to provide this correlation. Physical properties, including laboratory-measured and well-log data, were collected from sites drilled during Deep Sea Drilling Project Legs 30 and 89, and Ocean Drilling Program Leg 130, on the top and flank of the Ontong Java Plateau. Laboratory-measured density is corrected to in-situ conditions by accounting for porosity rebound resulting from removal of the sediment from its overburden. The correction of laboratory-measured compressional velocity to in situ appears to be largely a function of increases in elastic moduli (especially shear rigidity) with depth of burial, more than a function of changes in temperature, pressure, or density (porosity rebound). Well-log velocity and density data for the ooze intervals were found to be greatly affected by drilling disturbance; hence, they were disregarded and replaced by lab data for these intervals. Velocity and density data were used to produce synthetic seismograms. Correlation of seismic reflection data with synthetic data, and hence with depth below seafloor, at each drill site shows that a single velocity-depth function exists for sediments on the top and flank of the Ontong Java Plateau. A polynomial fit of this function provides an equation for domain conversion: Depth (mbsf) = 44.49 + 0.800(traveltime[ms]) + 3.308 × 10 4 (traveltime[ms]2 ) Traveltime (ms) = -35.18 + 1.118(depth[mbsf]) - 1.969 × KT* (depth[mbsf]2 ) Seismic reflection profiles down the flank of the plateau undergo three significant changes: (1) a drastic thinning of the sediment column with depth, (2) changes in the echo-character of the profile (development of seismic facies), and (3) loss of continuous, coherent reflections. Sediments on the plateau top were largely deposited by pelagic processes, with little significant postdepositional or syndepositional modification. Sediments on the flank of the plateau are also pelagic, but they have been modified by faulting, erosion, and mass movement. These processes result in disrupted and incoherent reflectors, development of seismic facies, and redistribution of sediment on the flank of the plateau. Seismic stratigraphic analyses have shown that the sediment section decreases in thickness by as much as 65% between water depths of 2000 m water depth (at the top of the plateau) and 4000 m (near the base of the plateau). Thinning is attributed to increasing carbonate dissolution with depth. If this assumption is correct, then changes in the relative thicknesses of seismostratigraphic units at each drill site are indicative of changes in the position of the lysocline and the dissolution gradient between the lysocline and the carbonate compensation depth. We think that a shallow lysocline in the early Miocene caused sediment thinning. A deepening of the lysocline in the late-early Miocene caused relative thickening at each site. Within the middle Miocene, a sharp rise in lysoclinal depth occurs, concurrent with a steepening of the dissolution gradient. These events result in sediment thinning at all four sites. The thicker sections in the late Miocene likely correspond to a deepening of the lysocline, and a subsequent rise in the lysocline again hinders accumulation of sediment in the very late Miocene and Pliocene

Cardiovascular Risk Factors Associated With Venous Thromboembolism.

IMPORTANCE: It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). OBJECTIVE: To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. DESIGN, SETTING, AND PARTICIPANTS: This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731 728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421 537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018. EXPOSURES: A panel of several established cardiovascular risk factors. MAIN OUTCOMES AND MEASURES: Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CHD], 25 131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI). RESULTS: Of the 731 728 participants from the ERFC, 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421 537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers. CONCLUSIONS AND RELEVANCE: Older age, smoking, and adiposity were consistently associated with higher VTE risk.This research has been conducted using the UK Biobank resource under Application Number 26865. This work was supported by underpinning grants from the UK Medical Research Council (grant G0800270), the British Heart Foundation (grant SP/09/002), the British Heart Foundation Cambridge Cardiovascular Centre of Excellence, UK National Institute for Health Research Cambridge Biomedical Research Centre, European Research Council (grant 268834), the European Commission Framework Programme 7 (grant HEALTH-F2-2012-279233), and Health Data Research UK. Dr Danesh holds a British Heart Foundation Personal Chair and a National Institute for Health Research Senior Investigator Award

World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions

BACKGROUND: To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. METHODS: In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40-80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. FINDINGS: Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0·685 (95% CI 0·629-0·741) to 0·833 (0·783-0·882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40-64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. INTERPRETATION: We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. FUNDING: World Health Organization, British Heart Foundation (BHF), BHF Cambridge Centre for Research Excellence, UK Medical Research Council, and National Institute for Health Research

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.

Telomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality. The proliferation of whole genome sequencing represents an unprecedented opportunity to glean new insights into telomere biology on a previously unimaginable scale. To this end, a number of approaches for estimating telomere length from whole-genome sequencing data have been proposed. Here we present Telomerecat, a novel approach to the estimation of telomere length. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors. We show that Telomerecat performs well at telomere length estimation when compared to leading experimental and computational methods. Furthermore, we show that it detects expected patterns in longitudinal data, repeated measurements, and cross-species comparisons. We also apply the method to a cancer cell data, uncovering an interesting relationship with the underlying telomerase genotype

Publisher Correction: Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.

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Equatorial Pacific Seismic Reflectors as Indicators of Global Oceanographic Events

The origin of a series of regionally correlatable seismic horizons in the Neogene sediments of the centralequatorial Pacific is examined through seismic modeling and the detailed analyses of stratigraphic and physical property relationships in Deep Sea Drilling Project cores. These regionally traceable reflectors are synchronous; the younger reflectors are the direct result of carbonate dissolution events, the older ones ofstratigraphically selective diagenetic processes. The changes in ocean chemistry associated with theseevents appear to be linked to global reorganizations of surface and bottom-water circulation patterns, the most dramatic of which are associated with reorganizations of North Atlantic bottom waters. These deepwaterseismic horizons appear to correlate with the major events on the relative sea-level curve of Vail et al. for the Neogene