Prognostic value of multiple repeated biomarkers in pulmonary arterial hypertension associated with congenital heart disease

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Secondary analyses of the randomized phase III Stop&Go study: efficacy of second-line intermittent versus continuous chemotherapy in HER2-negative advanced breast cancer

Background: Previously, we showed that reintroduction of the same (first-line) chemotherapy at progression could only partially make up for the loss in efficacy as compared to continuously delivered first-line chemotherapy. Here, we report the probability of starting second-line study chemotherapy in the Stop&Go trial, and the progression-free survival (PFS) and overall survival (OS) of patients who received both the first- and second-line treatment in an intermittent versus continuous schedule. Methods: First-line chemotherapy comprised paclitaxel plus bevacizumab, second-line capecitabine or non-pegylated liposomal doxorubicin, given per treatment line as two times four cycles (intermittent) or as eight consecutive cycles (continuous). Results: Of the 420 patients who started first-line treatment within the Stop&Go trial (210:210), a total of 270 patients continued on second-line study treatment (64% of all), which consisted of capecitabine in 201 patients and of non-pegylated liposomal doxorubicin in 69 patients, evenly distributed between the treatment arms. Median PFS was 3.7 versus 5.0 months (HR 1.07; 95% CI: 0.82–1.38) and median OS 10.9 versus 12.4 months (HR 1.27; 95% CI: 0.98–1.66) for intermittent versus continuous second

Froude supercritical flow processes and sedimentary structures: new insights from experiments with a wide range of grain sizes

Recognition of Froude supercritical flow deposits in environments that range from rivers to the ocean floor has triggered a surge of interest in their flow processes, bedforms and sedimentary structures. Interpreting these supercritical flow deposits is especially important because they often represent the most powerful flows in the geological record. Insights from experiments are key to reconstruct palaeo‐flow processes from the sedimentary record. So far, all experimentally produced supercritical flow deposits are of a narrow grain‐size range (fine to medium sand), while deposits in the rock record often consist of a much wider grain‐size distribution. This paper presents results of supercritical‐flow experiments with a grain‐size distribution from clay to gravel. These experiments show that cyclic step instabilities can produce more complex and a larger variety of sedimentary structures than the previously suggested backsets and ‘scour and fill’ structures. The sedimentary structures are composed of irregular lenses, mounds and wedges with backsets and foresets, as well as undulating planar to low‐angle upstream and downstream dipping laminae. The experiments also demonstrate that the Froude number is not the only control on the sedimentary structures formed by supercritical‐flow processes. Additional controls include the size and migration rate of the hydraulic jump and the substrate cohesion. This study further demonstrates that Froude supercritical flow promotes suspension transport of all grain sizes, including gravels. Surprisingly, it was observed that all grain sizes were rapidly deposited just downstream of hydraulic jumps, including silt and clay. These results expand the range of dynamic mud deposition into supercritical‐flow conditions, where local transient shear stress reduction rather than overall flow waning conditions allow for deposition of fines. Comparison of the experimental deposits with outcrop datasets composed of conglomerates to mudstones, shows significant similarities and highlights the role of hydraulic jumps, rather than overall flow condition changes, in producing lithologically and geometrically complex stratigraphy

Subchondral Bone Trabecular Integrity Predicts and Changes Concurrently with Radiographic and MRI Determined Knee Osteoarthritis Progression

OBJECTIVE: To evaluate subchondral bone trabecular integrity (BTI) on radiographs as a predictor of knee osteoarthritis (OA) progression. METHODS: Longitudinal (baseline, 12-month, and 24-month) knee radiographs were available for 60 female subjects with knee OA. OA progression was defined by 12- and 24-month changes in radiographic medial compartment minimal joint space width (JSW) and medial joint space area (JSA), and by medial tibial and femoral cartilage volume on magnetic resonance imaging. BTI of the medial tibial plateau was analyzed by fractal signature analysis using commercially available software. Receiver operating characteristic (ROC) curves for BTI were used to predict a 5% change in OA progression parameters. RESULTS: Individual terms (linear and quadratic) of baseline BTI of vertical trabeculae predicted knee OA progression based on 12- and 24-month changes in JSA (P < 0.01 for 24 months), 24-month change in tibial (P < 0.05), but not femoral, cartilage volume, and 24-month change in JSW (P = 0.05). ROC curves using both terms of baseline BTI predicted a 5% change in the following OA progression parameters over 24 months with high accuracy, as reflected by the area under the curve measures: JSW 81%, JSA 85%, tibial cartilage volume 75%, and femoral cartilage volume 85%. Change in BTI was also significantly associated (P < 0.05) with concurrent change in JSA over 12 and 24 months and with change in tibial cartilage volume over 24 months. CONCLUSION: BTI predicts structural OA progression as determined by radiographic and MRI outcomes. BTI may therefore be worthy of study as an outcome measure for OA studies and clinical trials. Copyright 2013 by the American College of Rheumatology

Intra‐clinothem variability in sedimentary texture and process regime recorded down slope profiles

Shelf‐margin clinothem successions can archive process interactions at the shelf to slope transition, and their architecture provides constraints on the interplay of factors that control basin‐margin evolution. However, detailed textural analysis and facies distributions from shelf to slope transitions remain poorly documented. This study uses quantitative grain‐size and sorting data from coeval shelf and slope deposits of a single clinothem that crops out along a 5 km long, dip‐parallel transect of the Eocene Sobrarbe Deltaic Complex (Ainsa Basin, south‐central Pyrenees, Spain). Systematic sampling of sandstone beds tied to measured sections has captured vertical and basinward changes in sedimentary texture and facies distributions at an intra‐clinothem scale. Two types of hyperpycnal flow‐related slope deposits, both rich in mica and terrestrial organic matter, are differentiated according to grain size, sorting and bed geometry: (i) sustained hyperpycnal flow deposits, which are physically linked to coarse channelized sediments in the shelf setting and which deposit sand down the complete slope profile; (ii) episodic hyperpycnal flow deposits, which are disconnected from, and incise into, shelf sands and which are associated with sediment bypass of the proximal slope and coarse‐grained sand deposition on the medial and distal slope. Both types of hyperpycnites are interbedded with relatively homogenous, organic‐free and mica‐free, well‐sorted, very fine‐grained sandstones, which are interpreted to be remobilized from wave‐dominated shelf environments; these wave‐dominated deposits are found only on the proximal and medial slope. Coarse‐grained sediment bypass into the deeper‐water slope settings is therefore dominated by episodic hyperpycnal flows, whilst sustained hyperpycnal flows and turbidity currents remobilizing wave‐dominated shelf deposits are responsible for the full range of grain sizes in the proximal and medial slope, thus facilitating clinoform progradation. This novel dataset highlights previously undocumented intra‐clinothem variability related to updip changes in the shelf process‐regime, which is therefore a key factor controlling downdip architecture and resulting sedimentary texture

Depositional setting, provenance and tectonic-volcanic setting of Eocene-Recent deep-sea sediments of the oceanic Izu-Bonin forearc, NW Pacific (IODP Expedition 352)

New biostratigraphical, geochemical, and magnetic evidence is synthesized with IODP Expedition 352 shipboard results to understand the sedimentary and tectono-magmatic development of the Izu–Bonin outer forearc region. The oceanic basement of the Izu–Bonin forearc was created by supra-subduction zone seafloor spreading during early Eocene (c. 50–51 Ma). Seafloor spreading created an irregular seafloor topography on which talus locally accumulated. Oxide-rich sediments accumulated above the igneous basement by mixing of hydrothermal and pelagic sediment. Basaltic volcanism was followed by a hiatus of up to 15 million years as a result of topographic isolation or sediment bypassing. Variably tuffaceous deep-sea sediments were deposited during Oligocene to early Miocene and from mid-Miocene to Pleistocene. The sediments ponded into extensional fault-controlled basins, whereas condensed sediments accumulated on a local basement high. Oligocene nannofossil ooze accumulated together with felsic tuff that was mainly derived from the nearby Izu–Bonin arc. Accumulation of radiolarian-bearing mud, silty clay, and hydrogenous metal oxides beneath the carbonate compensation depth (CCD) characterized the early Miocene, followed by middle Miocene–Pleistocene increased carbonate preservation, deepened CCD and tephra input from both the oceanic Izu–Bonin arc and the continental margin Honshu arc. The Izu–Bonin forearc basement formed in a near-equatorial setting, with late Mesozoic arc remnants to the west. Subduction-initiation magmatism is likely to have taken place near a pre-existing continent–oceanic crust boundary. The Izu–Bonin arc migrated northward and clockwise to collide with Honshu by early Miocene, strongly influencing regional sedimentation

Palaeoenvironment of Eocene prodelta in Spitsbergen recorded by the trace fossil Phycosiphon incertum

Ichnological, sedimentological and geochemical analyses were conducted on the Eocene Frysjaodden Formation in order to interpret palaeoenvironment prodelta sediments in the Central Basin of Spitsbergen. Phycosiphon incertum is the exclusive ichnotaxon showing differences in size, distribution, abundance and density, and relation to laminated/bioturbated intervals. Large P. incertum mainly occur dispersed, isolated and randomly distributed throughout the weakly laminated/non-laminated intervals. Small P. incertum occur occasionally in patches of several burrows within laminated intervals or as densely packed burrows in thin horizons in laminated intervals or constituting fully bioturbated intervals that are several centimetres thick. Ichnological changes are mainly controlled by oxygenation, although the availability of benthic food cannot be discarded. Changes in oxygenation and rate of sedimentation can be correlated with the registered variations in the Bouma sequence of the distal turbiditic beds within prodeltal shelf sediments.Funding for this research was provided by Project CGL2012-33281 (Secretaría de Estado de Investigación, Desarrollo e Innovación, Spain), Project RYC-2009-04316 (Ramón y Cajal Programme) and Projects RNM-3715 and RNM-7408 and Research Group RNM-178 (Junta de Andalucía). The authors benefited from a bilateral agreement between the universities of Granada and Oslo, supported by the University of Granada

From marine bands to hybrid flows: sedimentology of a Mississippian black shale

Organic‐rich mudstones have long been of interest as conventional and unconventional source rocks and are an important organic carbon sink. Yet the processes that deposited organic‐rich muds in epicontinental seaways are poorly understood, partly because few modern analogues exist. This study investigates the processes that transported and deposited sediment and organic matter through part of the Bowland Shale Formation, from the Mississippian Rheic–Tethys seaway. Field to micron‐scale sedimentological analysis reveals a heterogeneous succession of carbonate‐rich, siliceous, and siliciclastic, argillaceous muds. Deposition of these facies at basinal and slope locations was moderated by progradation of the nearby Pendle delta system, fourth‐order eustatic sea‐level fluctuation and localized block and basin tectonism. Marine transgressions deposited bioclastic ‘marine band’ (hemi)pelagic packages. These include abundant euhaline macrofaunal tests, and phosphatic concretions of organic matter and radiolarian tests interpreted as faecal pellets sourced from a productive water column. Lens‐rich (lenticular) mudstones, hybrid, debrite and turbidite beds successively overlie marine band packages and suggest reducing basin accommodation promoted sediment deposition via laminar and hybrid flows sourced from the basin margins. Mud lenses in lenticular mudstones lack organic linings and bioclasts and are equant in early‐cemented lenses and in plan‐view, and are largest and most abundant in mudstones overlying marine band packages. Thus, lenses likely represent partially consolidated mud clasts that were scoured and transported in bedload from the shelf or proximal slope, as a ‘shelf to basin’ conveyor, during periods of reduced basin accommodation. Candidate in situ microbial mats in strongly lenticular mudstones, and as rip‐up fragments in the down‐dip hybrid beds, suggest that these were potentially key biostabilizers of mud. Deltaic mud export was fast, despite the intrabasinal complexity, likely an order of magnitude higher than similar successions deposited in North America. Epicontinental basins remotely linked to delta systems were therefore capable of rapidly accumulating both sediment and organic matter