Transient landscape and stratigraphic responses to drainage integration in the actively extending central Italian Apennines

Drainage networks in continental rifts are generally reported as dynamic features that produce transitions between endorheic and exorheic conditions. While this is of major importance for landscape development, sediment dispersal, and basin stratigraphy, the controls of drainage network evolution across an array of normal fault bounded basins are still not well understood. In this study we use the central Italian Apennines – an area that has been affected by active normal faulting and regional uplift over the last ~3 Myrs – to determine the controls on drainage network evolution and its impact on transient landscape evolution and basin stratigraphy. We compile previously published stratigraphic and fault-related data with new geomorphological constraints for the Aterno River system (~1300 km2), for which a wealth of data has been collected following the destructive L'Aquila earthquake in 2009. We use this compilation to demonstrate how the different basins along the river system were initially isolated during the Early Pleistocene but became fluvially integrated with one another and the Adriatic coast between ca. 1.2 and 0.65 Ma. We conclude that the spatial and temporal pattern of drainage integration is mostly explained by a long-term increase in sediment and water supply relative to basin subsidence due to the Early to Middle Pleistocene climatic transition, the progressive increase in fault-related topography, and the transport of sediment and water down-system as drainage integration occurred. Overall we conclude that rates of sedimentation and basin subsidence in the central Apennines are well-matched, allowing tipping points between over- and under-filled conditions to be easily reached. We also show that consecutive drainage integration events produce discrete waves of river incision and terrace formation, and conclude that drainage integration is of major importance, at least equivalent to tectonics and climate, in controlling transient landscape evolution and rift basin stratigraphy.publishedVersio

Intestinal barrier tightening by a cell-penetrating antibody to Bin1, a candidate target for immunotherapy of ulcerative colitis.

Patients afflicted with ulcerative colitis (UC) are at increased risk of colorectal cancer. While its causes are not fully understood, UC is associated with defects in colonic epithelial barriers that sustain inflammation of the colon mucosa caused by recruitment of lymphocytes and neutrophils into the lamina propria. Based on genetic evidence that attenuation of the bridging integrator 1 (Bin1) gene can limit UC pathogenicity in animals, we have explored Bin1 targeting as a therapeutic option. Early feasibility studies in the dextran sodium sulfate mouse model of experimental colitis showed that administration of a cell-penetrating Bin1 monoclonal antibody (Bin1 mAb 99D) could prevent lesion formation in the colon mucosa in part by preventing rupture of lymphoid follicles. In vivo administration of Bin1 mAb altered tight junction protein expression and cecal barrier function. Strikingly, electrophysiology studies in organ cultures showed that Bin1 mAb could elevate resistance and lowe

Rift kinematics preserved in deep-time erosional landscape below the northern North Sea

Our understanding of continental rifting is, in large parts, derived from the stratigraphic record. This record is, however, incomplete as it does not often capture the geomorphic and erosional signal of rifting. New 3D seismic reflection data reveal a Late Permian-Early Triassic landscape incised into the pre-rift basement of the northern North Sea. This landscape, which covers at least 542 km2, preserves a drainage system bound by two major tectonic faults. A quantitative geomorphic analysis of the drainage system reveals 68 catchments, with channel steepness and knickpoint analysis of catchment-hosted palaeo-rivers showing that the landscape preserved a >2 Myr long period of transient tectonics. We interpret that this landscape records a punctuated uplift of the footwall of a major rift-related normal fault (Vette Fault) at the onset of rifting. The landscape was preserved by a combination of relatively rapid subsidence in the hangingwall of a younger fault (Øygarden Fault) and burial by post-incision sediments. As such, we show how and why erosional landscapes are preserved in the stratigraphic record, and how they can help us understand the tectono-stratigraphic evolution of ancient continental rifts.publishedVersio

Modern microwave methods in solid state inorganic materials chemistry: from fundamentals to manufacturing

No abstract available

Integrating isotopes and documentary evidence : dietary patterns in a late medieval and early modern mining community, Sweden

We would like to thank the Archaeological Research Laboratory, Stockholm University, Sweden and the Tandem Laboratory (Ångström Laboratory), Uppsala University, Sweden, for undertaking the analyses of stable nitrogen and carbon isotopes in both human and animal collagen samples. Also, thanks to Elin Ahlin Sundman for providing the δ13C and δ15N values for animal references from Västerås. This research (Bäckström’s PhD employment at Lund University, Sweden) was supported by the Berit Wallenberg Foundation (BWS 2010.0176) and Jakob and Johan Söderberg’s foundation. The ‘Sala project’ (excavations and analyses) has been funded by Riksens Clenodium, Jernkontoret, Birgit and Gad Rausing’s Foundation, SAU’s Research Foundation, the Royal Physiographic Society of Lund, Berit Wallenbergs Foundation, Åke Wibergs Foundation, Lars Hiertas Memory, Helge Ax:son Johnson’s Foundation and The Royal Swedish Academy of Sciences.Peer reviewedPublisher PD

Triangleland. I. Classical dynamics with exchange of relative angular momentum

In Euclidean relational particle mechanics, only relative times, relative angles and relative separations are meaningful. Barbour--Bertotti (1982) theory is of this form and can be viewed as a recovery of (a portion of) Newtonian mechanics from relational premises. This is of interest in the absolute versus relative motion debate and also shares a number of features with the geometrodynamical formulation of general relativity, making it suitable for some modelling of the problem of time in quantum gravity. I also study similarity relational particle mechanics (`dynamics of pure shape'), in which only relative times, relative angles and {\sl ratios of} relative separations are meaningful. This I consider firstly as it is simpler, particularly in 1 and 2 d, for which the configuration space geometry turns out to be well-known, e.g. S^2 for the `triangleland' (3-particle) case that I consider in detail. Secondly, the similarity model occurs as a sub-model within the Euclidean model: that admits a shape--scale split. For harmonic oscillator like potentials, similarity triangleland model turns out to have the same mathematics as a family of rigid rotor problems, while the Euclidean case turns out to have parallels with the Kepler--Coulomb problem in spherical and parabolic coordinates. Previous work on relational mechanics covered cases where the constituent subsystems do not exchange relative angular momentum, which is a simplifying (but in some ways undesirable) feature paralleling centrality in ordinary mechanics. In this paper I lift this restriction. In each case I reduce the relational problem to a standard one, thus obtain various exact, asymptotic and numerical solutions, and then recast these into the original mechanical variables for physical interpretation.Comment: Journal Reference added, minor updates to References and Figure

A Cenozoic uplift history of Mexico and its surroundings from longitudinal river profiles

Geodynamic models of mantle convection predict that Mexico and western North America share a history of dynamic support. We calculate admittance between gravity and topography, which indicates that the elastic thickness of the plate in Mexico is 11 km and in western North America it is 12 km. Admittance at wavelengths > 500 km in these regions suggests that topography is partly supported by subcrustal processes. These results corroborate estimates of residual topography from isostatic calculations and suggest that the amount of North American topography supported by the mantle may exceed 1 km. The Cenozoic history of magmatism, sedimentary flux, thermochronometric denudation estimates, and uplifted marine terraces imply that North American lithosphere was uplifted and eroded during the last 30 Ma. We jointly invert 533 Mexican and North American longitudinal river profiles to reconstruct a continent-scale rock uplift rate history. Uplift rate is permitted to vary in space and time. Erosional parameters are calibrated using incision rate data in southwest Mexico and the Colorado Plateau. Calculated rock uplift rates were 0.15-0.2 mm/yr between 25 and 10 Ma. Central Mexico experienced the highest uplift rates. Central and southern Mexico continued to uplift at 0.1 mm/yr until recent times. This uplift history is corroborated by independent constraints. We predict clastic flux to the Gulf of Mexico and compare it to independent estimates. We tentatively suggest that the loop between uplift, erosion, and deposition can be closed here. Mexico’s staged uplift history suggests that its dynamic support has changed during the last 30 Ma.G.G.R. was supported by an Imperial College London JRF

Levofloxacin prophylaxis in patients with newly diagnosed myeloma (TEAMM): a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial.

BACKGROUND: Myeloma causes profound immunodeficiency and recurrent, serious infections. Around 5500 new cases of myeloma are diagnosed per year in the UK, and a quarter of patients will have a serious infection within 3 months of diagnosis. We aimed to assess whether patients newly diagnosed with myeloma benefit from antibiotic prophylaxis to prevent infection, and to investigate the effect on antibiotic-resistant organism carriage and health care-associated infections in patients with newly diagnosed myeloma. METHODS: TEAMM was a prospective, multicentre, double-blind, placebo-controlled randomised trial in patients aged 21 years and older with newly diagnosed myeloma in 93 UK hospitals. All enrolled patients were within 14 days of starting active myeloma treatment. We randomly assigned patients (1:1) to levofloxacin or placebo with a computerised minimisation algorithm. Allocation was stratified by centre, estimated glomerular filtration rate, and intention to proceed to high-dose chemotherapy with autologous stem cell transplantation. All investigators, patients, laboratory, and trial co-ordination staff were masked to the treatment allocation. Patients were given 500 mg of levofloxacin (two 250 mg tablets), orally once daily for 12 weeks, or placebo tablets (two tablets, orally once daily for 12 weeks), with dose reduction according to estimated glomerular filtration rate every 4 weeks. Follow-up visits occurred every 4 weeks up to week 16, and at 1 year. The primary outcome was time to first febrile episode or death from all causes within the first 12 weeks of trial treatment. All randomised patients were included in an intention-to-treat analysis of the primary endpoint. This study is registered with the ISRCTN registry, number ISRCTN51731976, and the EU Clinical Trials Register, number 2011-000366-35. FINDINGS: Between Aug 15, 2012, and April 29, 2016, we enrolled and randomly assigned 977 patients to receive levofloxacin prophylaxis (489 patients) or placebo (488 patients). Median follow-up was 12 months (IQR 8-13). 95 (19%) first febrile episodes or deaths occurred in 489 patients in the levofloxacin group versus 134 (27%) in 488 patients in the placebo group (hazard ratio 0·66, 95% CI 0·51-0·86; p=0·0018. 597 serious adverse events were reported up to 16 weeks from the start of trial treatment (308 [52%] of which were in the levofloxacin group and 289 [48%] of which were in the placebo group). Serious adverse events were similar between the two groups except for five episodes (1%) of mostly reversible tendonitis in the levofloxacin group. INTERPRETATION: Addition of prophylactic levofloxacin to active myeloma treatment during the first 12 weeks of therapy significantly reduced febrile episodes and deaths compared with placebo without increasing health care-associated infections. These results suggest that prophylactic levofloxacin could be used for patients with newly diagnosed myeloma undergoing anti-myeloma therapy. FUNDING: UK National Institute for Health Research