Earthquake slip surfaces identified by biomarker thermal maturity within the 2011 Tohoku-Oki earthquake fault zone.

Extreme slip at shallow depths on subduction zone faults is a primary contributor to tsunami generation by earthquakes. Improving earthquake and tsunami risk assessment requires understanding the material and structural conditions that favor earthquake propagation to the trench. We use new biomarker thermal maturity indicators to identify seismic faults in drill core recovered from the Japan Trench subduction zone, which hosted 50 m of shallow slip during the Mw9.1 2011 Tohoku-Oki earthquake. Our results show that multiple faults have hosted earthquakes with displacement ≥ 10 m, and each could have hosted many great earthquakes, illustrating an extensive history of great earthquake seismicity that caused large shallow slip. We find that lithologic contrasts in frictional properties do not necessarily determine the likelihood of large shallow slip or seismic hazard

Repurposing of Meropenem and Nadifloxacin for Treatment of Burn Patients?

The escalating number of multidrug resistant pathogens has demanded the swift development of new and potent antibiotics (ref. 2). Metallo-[beta]-lactamases (MBLs) continue to evolve, rendering the latest generation of carbapenem antibiotics useless (ref. 8). SPM-1, a recently discovered MBL, was isolated from a juvenile leukemia patient residing in a hospital in San Palo, Brazil just prior to the patient succumbing to septicemia brought on by Pseudomonas aeruginosa expressing SPM-1 (ref. 8). Screening of the Johns Hopkins Compound library of 1,514 FDA or FAD approved drugs (ref. 1) identified a novel SPM-1 inhibitor that is synergistically compatible with meropenem. Using clinically achievable concentrations, meropenem coupled with nadifloxacin inhibits Pseudomonas aeruginosa expressing SPM-1. This shotgun approach to new drug discovery provided a prompt solution to the grave problem of antibiotic resistant pathogens that are thriving in hospitals today

Structural characteristics of positionally-disordered lattices: relation to the first sharp diffraction peak in glasses

Positional disorder has been introduced into the atomic structure of certain crystalline lattices, and the orientationally-averaged structure factor S(k) and pair-correlation function g(r) of these disordered lattices have been studied. Analytical expressions for S(k) and g(r) for Gaussian positional disorder in 2D and 3D are confirmed with precise numerical simulations. These analytic results also have a bearing on the unsolved Gauss circle problem in mathematics. As the positional disorder increases, high-k peaks in S(k) are destroyed first, eventually leaving a single peak, that with the lowest-k value. The pair-correlation function for lattices with such high levels of positional disorder exhibits damped oscillations, with a period equal to the separation between the furthest-separated (lowest-k) lattice planes. The last surviving peak in S(k) is, for example for silicon and silica, at a wavevector nearly identical to that of the experimentally-observed first sharp diffraction peak (FSDP) in the amorphous phases of those materials. Thus, for these amorphous materials at least, the FSDP can be regarded as arising from scattering from atomic configurations equivalent to the single family of positionally-disordered local Bragg planes having the furthest separation.Comment: v2: changes in response to referees' comments: Figure 2 made more readable, improved discussion of height of peaks in S(k), other minor changes 4 pages, 3 figures, submitted to Physical Review

A putative serine protease, SpSsp1, from Saprolegnia parasitica is recognised by sera of rainbow trout, Oncorhynchus mykiss

Acknowledgements Our work was supported by the BBSRC (BB/C518457/1, BB/G012075/1, BB/J018333/1) (K.L.M., C.J.S., J.S.C., K.S.D., and P.v.W.), the University of Aberdeen (V.L.A., C.J.S., and P.v.W.), MSD Animal Health (J.S.C., K.S.D., and A.H.v.d.B), and The Royal Society (P.v.W.). This work was also supported by a Marie Curie Initial Training Networks with the SAPRO (sustainable approaches to reduce Oomycete (Saprolegnia) infections in aquacultures) grant PITN-GA-2009-238550 (A.H.v.d.B., L.L., C.J.S., P.v.W.). We would like to acknowledge Aberdeen Proteomics for carrying out LC–MS/MS and Laura Grenville-Briggs for valuable discussion and technical help. We are grateful to the Broad Institute (Carsten Russ, Rays Jiang, Brian Haas, and Chad Nusbaum), Brett Tyler (VBI), and P.v.W. for early release of draft supercontigs of the genome sequence of isolate CBS233.65, which helped us identify SpSsp1.Peer reviewedPublisher PD

Buckwheat, Fava Bean and Hemp Flours Fortified with Anthocyanins and Other Bioactive Phytochemicals as Sustainable Ingredients for Functional Food Development

Funding: This research was funded by the Scottish government’s Rural and Environment Science and Analytical Services Division (RESAS). Acknowledgments: The authors acknowledge Viv Buchan from the Analytical Department, The Rowett Institute, University of Aberdeen, for her help with the sugar content determinations.Peer reviewedPublisher PD

Influenza Hospitalisations in England during the 2022/23 Season: do different data sources drive divergence in modelled waves? A comparison of surveillance and administrative data

Accurate and representative data is vital for precisely reporting the impact of influenza in healthcare systems. Northern hemisphere winter 2022/23 experienced the most substantial influenza wave since the COVID-19 pandemic began in 2020. Simultaneously, new data streams become available within health services because of the pandemic. Comparing these data, surveillance and administrative, supports the accurate monitoring of population level disease trends. We analysed admissions rates per capita from four different collection mechanisms covering National Health Service hospital Trusts in England over the winter 2022/23 wave. We adjust for difference in reporting and extracted key epidemic characteristics including the maximum admission rate, peak timing, cumulative season admissions and growth rates by fitting generalised additive models at national and regional levels. By modelling the admission rates per capita across surveillance and administrative data systems we show that different data measuring the epidemic produce different estimates of key quantities. Nationally and in most regions the data correspond well for the maximum admission rate, date of peak and growth rate, however, in subnational analysis discrepancies in estimates arose, particularly for the cumulative admission rate. This research shows that the choice of data used to measure seasonal influenza epidemics can influence analysis substantially at sub-national levels. For the admission rate per capita there is comparability in the sentinel surveillance approach (which has other important functions), rapid situational reports, operational databases and time lagged administrative data giving assurance in their combined value. Utilising multiple sources of data aids understanding of the impact of seasonal influenza epidemics in the population

Cenozoic Global Sea Level, Sequences, and the New Jersey Transect: Results from Coastal Plain and Continental Slope Drilling

The New Jersey Sea Level Transect was designed to evaluate the relationships among global sea level (eustatic) change, unconformity-bounded sequences, and variations in subsidence, sediment supply, and climate on a passive continental margin. By sampling and dating Cenozoic strata from coastal plain and continental slope locations, we show that sequence boundaries correlate (within ±0.5 myr) regionally (onshore-offshore) and interregionally (New Jersey-Alabama-Bahamas), implicating a global cause. Sequence boundaries correlate with δ18O increases for at least the past 42 myr, consistent with an ice volume (glacioeustatic) control, although a causal relationship is not required because of uncertainties in ages and correlations. Evidence for a causal connection is provided by preliminary Miocene data from slope Site 904 that directly link δ18O increases with sequence boundaries. We conclude that variation in the size of ice sheets has been a primary control on the formation of sequence boundaries since ∼42 Ma. We speculate that prior to this, the growth and decay of small ice sheets caused small-amplitude sea level changes (less than 20 m) in this supposedly ice-free world because Eocene sequence boundaries also appear to correlate with minor δ18O increases. Subsidence estimates (backstripping) indicate amplitudes of short-term (million-year scale) lowerings that are consistent with estimates derived from δ18O studies (25–50 m in the Oligocene-middle Miocene and 10–20 m in the Eocene) and a long-term lowering of 150–200 m over the past 65 myr, consistent with estimates derived from volume changes on mid-ocean ridges. Although our results are consistent with the general number and timing of Paleocene to middle Miocene sequences published by workers at Exxon Production Research Company, our estimates of sea level amplitudes are substantially lower than theirs. Lithofacies patterns within sequences follow repetitive, predictable patterns: (1) coastal plain sequences consist of basal transgressive sands overlain by regressive highstand silts and quartz sands; and (2) although slope lithofacies variations are subdued, reworked sediments constitute lowstand deposits, causing the strongest, most extensive seismic reflections. Despite a primary eustatic control on sequence boundaries, New Jersey sequences were also influenced by changes in tectonics, sediment supply, and climate. During the early to middle Eocene, low siliciclastic and high pelagic input associated with warm climates resulted in widespread carbonate deposition and thin sequences. Late middle Eocene and earliest Oligocene cooling events curtailed carbonate deposition in the coastal plain and slope, respectively, resulting in a switch to siliciclastic sedimentation. In onshore areas, Oligocene sequences are thin owing to low siliciclastic and pelagic input, and their distribution is patchy, reflecting migration or progradation of depocenters; in contrast, Miocene onshore sequences are thicker, reflecting increased sediment supply, and they are more complete downdip owing to simple tectonics. We conclude that the New Jersey margin provides a natural laboratory for unraveling complex interactions of eustasy, tectonics, changes in sediment supply, and climate change

The Phanerozoic Record of Global Sea-Level Change

We review Phanerozoic sea-level changes [543 million years ago (Ma) to the present] on various time scales and present a new sea-level record for the past 100 million years (My). Long-term sea level peaked at 100 ± 50 meters during the Cretaceous, implying that ocean-crust production rates were much lower than previously inferred. Sea level mirrors oxygen isotope variations, reflecting ice-volume change on the 104- to 106-year scale, but a link between oxygen isotope and sea level on the 107-year scale must be due to temperature changes that we attribute to tectonically controlled carbon dioxide variations. Sea-level change has influenced phytoplankton evolution, ocean chemistry, and the loci of carbonate, organic carbon, and siliciclastic sediment burial. Over the past 100 My, sea-level changes reflect global climate evolution from a time of ephemeral Antarctic ice sheets (100 to 33 Ma), through a time of large ice sheets primarily in Antarctica (33 to 2.5 Ma), to a world with large Antarctic and large, variable Northern Hemisphere ice sheets (2.5 Ma to the present)

Treatment with ETC-1002 alone and in combination with ezetimibe lowers LDL cholesterol in hypercholesterolemic patients with or without statin intolerance

BackgroundETC-1002 is an oral, once-daily, first-in-class medication being developed to treat hypercholesterolemia.ObjectivesTo compare 2 doses of ETC-1002, alone or combined with ezetimibe 10 mg (EZE), vs EZE monotherapy for lowering low-density lipoprotein cholesterol (LDL-C).MethodsThis phase 2b, multicenter, double-blind trial-evaluated hypercholesterolemic patients (LDL-C, 130 to 220 mg/dL) with (n = 177) or without (n = 171) muscle-related intolerance to ≥2 statins; 1 at lowest approved dose. Subjects were randomized to 12-week treatment with ETC-1002 120 mg or ETC-1002 180 mg alone, EZE alone, ETC-1002 120 mg plus EZE, or ETC-1002 180 mg plus EZE.ResultsEZE alone lowered LDL-C by 21%, whereas ETC-1002 monotherapy with 120 mg or 180 mg reduced LDL-C by 27% (P = .0008 vs EZE) and 30% (P < .0001 vs EZE), respectively. The combination of ETC-1002, 120 mg or 180 mg plus EZE reduced LDL-C by 43% and 48%, respectively (both P < .0001 vs EZE). ETC-1002 alone or combined with EZE also reduced non–high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, LDL particle number, and high-sensitivity C-reactive protein compared with EZE alone. Across all treatment groups, statin-intolerant patients reported more muscle-related adverse events than did statin-tolerant patients. ETC-1002 was safe and well tolerated, and rates of muscle-related adverse events were similar in all treatment groups.ConclusionsIn patients with and without statin intolerance, daily treatment with ETC-1002 120 mg and 180 mg alone or with EZE reduced LDL-C more than EZE alone and had a similar tolerability profile (NCT01941836)