Patient-Specific Injury Metrics Predict Early Biomarker Response in Multiply Injured Patients

poster abstractIntroduction: It is important to identify multiply injured patients (MIPs) that can tolerate high-magnitude procedures and those at risk for complications. Determining how injury leads to immunologic dysfunction could identify MIPs at risk for complications. We explored a new precision medicine approach in which we determined how patientspecific injury metrics corresponded to changes in cytokines in a prospective cohort of MIPs. Methods: This was a prospective observational cohort of 40 MIPs, 18-55 yo, admitted to surgical ICU having had full axial CTs done at admission. Mechanical tissue damage was quantified by calculating volumetric measures of injuries from CT scans into the Tissue Damage Volume score (TDV). Ischemic tissue damage was calculated by calculation of all abnormal Shock Volumes (SV) (heart rate/systolic blood pressure > 0.9) in the first 24hr after injury. TIMS was calculated by combining mechanical and ischemic tissue damage: TIMS = TDV+5*SV. Linear regression was performed between TIMS and 21 cytokines including interleukin (IL)-6; IL-8; IL-10; IL-1RA; IL-2RA; MCP-1 drawn at 0hr, 8hr, and 24hr after injury. Linear regression was also performed between the cytokines, Injury Severity Score (ISS) and minimum pH (day 1). Results: Mean and median ISS was 29 (range 9 – 66). Minimum pH demonstrated best correspondence to cytokine levels measured 0hr and 8hr after injury. TIMS demonstrated the best correspondence to cytokine levels 24hr after injury. ISS demonstrated minimal predictive value of cytokines at any timepoint. Discussion: A precision medicine approach using a patient-specific quantity of injury predicted trauma-associated changes in circulating cytokines at 0hr, 8 hr, and 24 hr after surgery. This corresponds favorably with timing of orthopaedic surgical decisions regarding staged fracture interventions. While clinical significance of these findings is unknown, computational data analyses of temporal cytokine changes have been shown to be predictive of adverse outcomes after injury

Predicting beach rotation using multiple atmospheric indices

12 month embargo required

Wave and Tidal Controls on Embayment Circulation and Headland Bypassing for an Exposed, Macrotidal Site

Headland bypassing is the transport of sediment around rocky headlands by wave and tidal action, associated with high-energy conditions and embayment circulation (e.g., mega-rips). Bypassing may be a key component in the sediment budget of many coastal cells, the quantification of which is required to predict the coastal response to extreme events and future coastal change. Waves, currents, and water levels were measured off the headland of a sandy, exposed, and macrotidal beach in 18-m and 26-m depths for 2 months. The observations were used to validate a Delft3D morphodynamic model, which was subsequently run for a wide range of scenarios. Three modes of bypassing were determined: (i) tidally-dominated control during low–moderate wave conditions [flux O (0–102 m3 day−1)]; (ii) combined tidal- and embayment circulation controls during moderate–high waves [O (103 m3 day−1)]; and (iii) multi-embayment circulation control during extreme waves [O (104 m3 day−1)]. A site-specific bypass parameter is introduced, which accurately (R2 = 0.95) matches the modelled bypass rates. A 5-year hindcast predicts bypassing is an order of magnitude less than observed cross-shore fluxes during extreme events, suggesting that bypassing at this site is insignificant at annual timescales. This work serves a starting point to generalise the prediction of headland bypassing

Rip current types, circulation and hazard

AbstractRip currents are narrow and concentrated seaward-directed flows that extend from close to the shoreline, through the surf zone, and varying distances beyond. Rip currents are ubiquitous on wave-exposed coasts. Each year they cause hundreds of drowning deaths and tens of thousands of rescues on beaches worldwide and are therefore the leading deadly hazard to recreational beach users. The broad definition above masks considerable natural variability in terms of rip current occurrence in time and space, flow characteristics and behaviour. In particular, surf-zone rip currents have long been perceived as narrow flows extending well beyond the breakers, flushing out the surf zone at a high rate (‘exit flow’ circulation regime), while more recent studies have shown that rip flow patterns can consist of quasi-steady semi-enclosed vortices retaining most of the floating material within the surf zone (‘circulatory flow’ circulation regime). Building upon a growing body of rip current literature involving numerical modelling and theory together with emergence of dense Lagrangian field measurements, we develop a robust rip current type classification that provides a relevant framework to understand the primary morphological and hydrodynamic parameters controlling surf-zone rip current occurrence and dynamics. Three broad categories of rip current types are described based on the dominant controlling forcing mechanism. Each category is further divided into two types owing to different physical driving mechanisms for a total of six fundamentally different rip current types: hydrodynamically-controlled (1) shear instability rips and (2) flash rips, which are transient in both time and space and occur on alongshore-uniform beaches; bathymetrically-controlled (3) channel rips and (4) focused rips, which occur at relatively fixed locations and are driven by hydrodynamic processes forced by natural alongshore variability of the morphology in both the surf zone and inner shelf zone; and boundary-controlled (5) deflection rips and (6) shadow rips, which flow against rigid lateral boundaries such as natural headlands or anthropogenic structures. For each rip current type, flow response to changes in hydrodynamic and morphologic forcing magnitude is examined in regard to velocity modulation and changes in circulation regime, providing key force-response relationships of rip currents. We also demonstrate that in the real world, rip currents form through a mixture of driving mechanisms and the discrete rip types defined in fact form key elements in a wide and complex spectrum of rip currents on natural beaches. It is anticipated that this rip current type classification will serve as a resource for coastal scientists and non-specialists with an interest in the rip current hazard, and as a platform for future rip current studies. Finally, we suggest some important future research directions highlighting the need for coastal and beach safety communities to collaborate in order to improve rip current education and awareness

Zebrafish behavioural profiling identifies GABA and serotonin receptor ligands related to sedation and paradoxical excitation.

Anesthetics are generally associated with sedation, but some anesthetics can also increase brain and motor activity-a phenomenon known as paradoxical excitation. Previous studies have identified GABAA receptors as the primary targets of most anesthetic drugs, but how these compounds produce paradoxical excitation is poorly understood. To identify and understand such compounds, we applied a behavior-based drug profiling approach. Here, we show that a subset of central nervous system depressants cause paradoxical excitation in zebrafish. Using this behavior as a readout, we screened thousands of compounds and identified dozens of hits that caused paradoxical excitation. Many hit compounds modulated human GABAA receptors, while others appeared to modulate different neuronal targets, including the human serotonin-6 receptor. Ligands at these receptors generally decreased neuronal activity, but paradoxically increased activity in the caudal hindbrain. Together, these studies identify ligands, targets, and neurons affecting sedation and paradoxical excitation in vivo in zebrafish

THE PATIENT-SPECIFIC INJURY SCORE: PRECISION MEDICINE IN TRAUMA PATIENTS PREDICTS ORGAN DYSFUNCTION AND OUTCOMES

poster abstractIntroduction: Current injury scoring systems in polytraumatized patients are limited at predicting patient outcomes. We present a novel method that quantifies mechanical tissue damage and cumulative hypoperfusion using a precision medicine approach. We hypothesized that a Patient-Specific Injury score formulated from individualized injury indices would stratify patient risk for developing organ dysfunction after injury. We compared correspondence between PSI and the Injury Severity Score with outcomes of organ dysfunction and MOF. Methods: Fifty Multiply-injured-patients (MIPs) were studied. Tissue Damage Volume scores were measured from admission pan-axial CT scans using purpose-designed post-processing software to quantify volumetric magnitude and distribution of injuries. Ischemic injury was quantified using Shock Volumes. SV is a time-magnitude integration of shock index. Values above 0.9 were measured in the 24-hours after injury. Metabolic response was quantified by subtracting the lowest first 24 hr pH from 7.40. PSI combines these indices into the formula: PSI=[0.2TDV+SV]*MR. Correspondence coefficients from regression modeling between PSI and organ dysfunction, measured by the Marshall Multiple Organ Dysfunction score averaged from days 2-5 post-injury, were compared to similar regression models of ISS vs. day 2-5 MOD-scores. We compared PSI and ISS in patients that did or did not develop MOF. Results: PSI demonstrated better correlation to organ dysfunction (r2=0.576) in comparison to ISS (r2=0.393) using the MOD-score on days 2-5. Mean PSI increased 3.4x(58.5vs.17.0;p<0.02) and ISS scores increased 1.4x(39.0vs.28.0;p=0.10) in patients that developed MOF versus those that did not. Conclusions: This study shows that a precision medicine approach that integrates patient-specific indices of mechanical tissue damage, ischemic tissue injury, and metabolic response better corresponds to phenotypic changes including organ dysfunction and MOF compared to ISS in MIPs. The PSI-score can be calculated within 24 hours of injury, making it useful for stratifying risk and predicting the magnitude of organ dysfunction to anticipate

Electronic structure of sodium tungsten bronzes Na<SUB>x</SUB>WO<SUB>3</SUB> by high-resolution angle-resolved photoemission spectroscopy

The electronic structure of sodium tungsten bronzes, NaxWO3, for full range of x is investigated by high-resolution angle-resolved photoemission spectroscopy (HR-ARPES). The experimentally determined valence-band structure has been compared with the results of ab initio band-structure calculation. The HR-ARPES spectra taken in both the insulating and metallic phase of NaxWO3 reveal the origin of metal-insulator transition (MIT) in the sodium tungsten bronze system. In the insulating NaxWO3, the near-EF states are localized due to the strong disorder caused by the random distribution of Na+ ions in WO3 lattice. While the presence of an impurity band (level) induced by Na doping is often invoked to explain the insulating state found at low concentrations, there is no signature of impurity band (level) found from our results. Due to disorder and Anderson localization effect, there is a long-range Coulomb interaction of conduction electrons; as a result, the system is insulating. In the metallic regime, the states near EF are populated and the Fermi level shifts upward rigidly with increasing electron doping (x). The volume of electronlike Fermi surface (FS) at the &#915;(X) point gradually increases with increasing Na concentration due to W 5dt2g band filling. A rigid shift of EF is found to give a qualitatively good description of the FS evolution

Role of waves and tides on depth of closure and potential for headland bypassing

No embargo required.© 2018 Depth of closure is a fundamental concept used to define the seaward extent of a morphodynamically active shoreface at a particular temporal scale. The estimation of this limit in relation to the depth in front of the bounding headlands along embayed coastlines allows questioning whether embayments, often deemed closed sediment cells, experience more headland bypassing than expected. Wave-based parameterisations developed for microtidal beaches are most widely used to estimate closure depth; however, a re-evaluation of the concept for shorefaces influenced by geological control (presence of headlands and/or bedrock) and strong tidal currents is appropriate. Here, we use the macrotidal, embayed and high-energy coastline of SW England to identify the ‘active’ nearshore limits with a multi-method approach that includes observations of shoreface morphology and sedimentology, offshore/inshore wave formulations and bed shear stress computations. We identify the basal limit of ‘significant’ (i.e., 0.14 m) morphological change (Depth of Closure; DoC) and a maximum depth of extreme bed activity and sediment transport (Depth of Transport; DoT). Observations of DoC correspond closely to the values predicted by existing formulations based on inshore wave conditions (10–15 m for the study area; relative to mean low water spring water level in this case). The computed DoT, represented by the upper-plane bed transition attained under extreme conditions, exceeds 30 m depth in the study area. The significant implication is that, even though many headlands appear sufficiently prominent to suggest a closed boundary between adjacent embayments, significant wave- and tide-driven sediment transport is likely to occur beyond the headland base during extreme events, especially at low water levels. The maximum depth for significant sediment transport (DoT) was computed across a broad wave-current parameter space, further highlighting that tidal currents can increase this closure depth estimate by ~10 m along macrotidal coastlines, representing a 30% increase compared to tideless settings. This work illustrates the importance of tidal currents in depth of closure calculations and challenges the notion that embayed beaches are generally closed cells, as headland bypassing may be more wide spread than commonly assumed along exposed coastlines globally

Informing innovative peatland conservation in light of palaeoecological evidence for the demise of Sphagnum imbricatum: the case of Oxenhope Moor, Yorkshire, UK

Actively growing mires have high conservation value and the potential to sequester carbon. However, drainage, burning, overgrazing and atmospheric pollution have led to depauperation of native flora and loss of peat at many peatland sites. In order to counteract such degradation, palaeoecological techniques can be applied and the data then used to inform nature conservation practice. The present study exemplifies this approach and was conducted on degraded blanket mire in Yorkshire, UK, in collaboration with a field-based moorland restoration agency. High-resolution, multiproxy palaeoecological analyses on a peat core from Oxenhope Moor were used to reconstruct Holocene vegetation changes spanning approximately the last 7000 years. Humification, pollen, plant macrofossil and charcoal analyses show distinct changes in species composition and indicate their potential causes. Human-induced changes identified at 2100 cal. BP are most likely to reflect deliberate clearance by fire. Sphagnum imbricatum disappears and is subsequently replaced by S. papillosum at ca. 1000 cal. BP, possibly due to drier conditions and competition between the two species. Increased human activity is identified since the Industrial Revolution where monocots and Eriophorum vaginatum increase, interpreted as a result of managed burning. It is intended that the long-term ecological history of the site, derived using palaeoecological techniques, will be used to inform conservation practice and can help set feasible targets for restoration and conservation. Specifically, encouraging a species mix that has pre-19th century longevity is suggested, including the specific recommendation that translocation of S. imbricatum be explored experimentally at this site, with a view to ascertaining likely success elsewhere