Preparation and Characterization of Multimodal Hybrid Organic and Inorganic Nanocrystals of Camptothecin and Gold

We demonstrate a novel inorganic-organic crystalline nanoconstruct, where gold atoms were imbedded in the crystal lattices as defects of camptothecin nanocrystals, suggesting its potential use as simultaneous agents for cancer therapy and bioimaging. The incorporation of gold, a potential computed tomography (CT) contrast agent, in the nanocrystals of camptothecin was detected by transmission electron microscope (TEM) and further quantified by energy dispersive X-ray spectrometry (EDS) and inductively coupled plasma-optical emission spectrometers (ICP-OES). Due to gold\u27s high attenuation coefficient, only a relatively small amount needs to be present in order to create a good noise-to-contrast ratio in CT imaging. The imbedded gold atoms and clusters are expected to share the same biological fate as the camptothecin nanocrystals, reaching and accumulating in tumor site due to the enhanced permeation and retention (EPR) effect

Uncertainty Assessment of Hypersonic Aerothermodynamics Prediction Capability

The present paper provides the background of a focused effort to assess uncertainties in predictions of heat flux and pressure in hypersonic flight (airbreathing or atmospheric entry) using state-of-the-art aerothermodynamics codes. The assessment is performed for four mission relevant problems: (1) shock turbulent boundary layer interaction on a compression corner, (2) shock turbulent boundary layer interaction due a impinging shock, (3) high-mass Mars entry and aerocapture, and (4) high speed return to Earth. A validation based uncertainty assessment approach with reliance on subject matter expertise is used. A code verification exercise with code-to-code comparisons and comparisons against well established correlations is also included in this effort. A thorough review of the literature in search of validation experiments is performed, which identified a scarcity of ground based validation experiments at hypersonic conditions. In particular, a shortage of useable experimental data at flight like enthalpies and Reynolds numbers is found. The uncertainty was quantified using metrics that measured discrepancy between model predictions and experimental data. The discrepancy data is statistically analyzed and investigated for physics based trends in order to define a meaningful quantified uncertainty. The detailed uncertainty assessment of each mission relevant problem is found in the four companion papers

Mesoarchean partial melting of mafic crust and tonalite production during high-T–low-P stagnant tectonism, Akia Terrane, West Greenland

The Ministry of Mineral Resources and Labour, Greenland Government supported field and analytical work. NJG acknowledges support from Australian Research Council grant FL160100168.Different geodynamic models exist for the growth and differentiation of Archean continental crust, ranging from horizontal tectonics with subduction zones to vertical tectonics with foundering of greenstone sequences. U–Pb zircon geochronology, field relationships, and pressure–temperature constraints from granulite-facies metabasite of the Akia Terrane of the North Atlantic Craton in West Greenland show that this terrane grew through two major magmatic growth episodes: an earlier one at c. 3.2 Ga, and a later one at c. 3.05–2.97 Ga. Phase equilibrium modelling for assemblages related to the latter indicates temperatures of >800 °C at 0.8 GPa in the stability field of garnet. U–Pb zircon geochronology and existing Hf isotope data are also consistent with a model involving protracted Mesoarchean magmatic growth with limited mantle addition during a prolonged period of high temperatures in a relatively stagnant tectonic regime prior to Neoarchean compressional tectonism in the Akia Terrane.Publisher PDFPeer reviewe

Solar-driven variation in the atmosphere of Uranus

Long-term measurements (1972-2015) of the reflectivity of Uranus at 472 and 551 nm display variability that is incompletely explained by seasonal effects. Spectral analysis shows this non-seasonal variability tracks the 11-year solar cycle. Two mechanisms could cause solar modulation, (a) nucleation onto ions or electrons created by galactic cosmic rays (GCR), or (b) UV-induced aerosol colour changes. Ion-aerosol theory is used to identify expected relationships between reflectivity fluctuations and GCR flux, tested with multiple regression and compared to the linear response predicted between reflectivity and solar UV flux. The statistics show that 24% of the variance in reflectivity fluctuations at 472 nm is explained by GCR ion-induced nucleation, compared to 22% for a UV-only mechanism. Similar GCR-related variability exists in Neptune’s atmosphere, hence the effects found at Uranus provide the first example of common variability in two planetary atmospheres driven through energetic particle modulation by their host star

In situ identification of Palaeoarchaean biosignatures using co-located Perseverance rover analyses: perspectives for in situ Mars science and sample return

The NASA Mars 2020 Perseverance rover is currently exploring Jezero crater, a Noachian locality that once hosted a delta–lake system with high habitability and biosignature preservation potential. Perseverance conducts detailed appraisals of rock targets using a synergistic payload capable of geological characterisation from kilometre to micron scales. The highest-resolution textural and chemical information will be provided by correlated WATSON (imaging), SHERLOC (deep-UV Raman and fluorescence spectroscopy) and PIXL (X-ray lithochemistry) analyses, enabling the distributions of organic and mineral phases within rock targets to be comprehensively established. Herein, we analyse Palaeoarchaean microbial mats from the ~3.42 Ga Buck Reef Chert (Barberton greenstone belt) – considered astrobiological analogues for a putative Martian biosphere – following a WATSON–SHERLOC–PIXL protocol identical to that conducted by Perseverance on Mars during each sampling activities. Correlating deep-UV Raman and fluorescence spectroscopic mapping with X-ray elemental mapping, we show that the Perseverance payload has the capability to detect thermally and texturally mature organic materials of biogenic origin and can highlight organic–mineral interrelationships and elemental co-location at fine spatial scales. We also show that the Perseverance protocol obtains very similar results to high-performance laboratory imaging, Raman spectroscopy and µXRF instruments. This is encouraging for the prospect of detecting micro-scale organic-bearing textural biosignatures on Mars using the correlative micro-analytical approach enabled by WATSON, SHERLOC and PIXL; indeed, laminated, organic-bearing samples such as those studied herein are considered plausible biosignatures for a potential Noachian–Hesperian biosphere and would make compelling targets for sampling during the mission

The Mesoarchaean Akia terrane, West Greenland, revisited : new insights based on spatial integration of geophysics, field observation, geochemistry and geochronology

NJG thanks Australian Research Council grant FL160100168 for financial support.The northern part of the North Atlantic Craton (NAC) in southern West Greenland comprises a large tract of exposed Meso-Neoarchaean continental crust, divided into the ca 3300–2900 Ma Akia and ca 2900–2500 Ma Tuno terranes. We combine aeromagnetic, stream sediment geochemical, new litho-chemical and zircon geochronological data with previously published data to re-evaluate the crustal architecture and evolution of the Akia terrane and its boundary towards the Tuno terrane. The previously recognised, but overlooked, Alanngua complex, situated between the Akia and Tuno terranes is bounded by aeromagnetic lineaments interpreted as Neoarchaean shear zones and has a distinct spectrum of Neoarchaean magmatic and metamorphic zircon ages that are rare in the Akia terrane. The Alanngua complex comprises components derived from both the Akia and Tuno terranes and is interpreted as a tectonic melange created during the Neoarchaean assembly of the NAC. Within the Akia terrane, the chemistry of orthogneiss samples indicate that a large percentage is too mafic to classify as TTG s.s., implying that not only partial melting of mafic crust, but also some yet unaddressed mantle involvement is necessary in their formation. Previous models for the generation of the ca. 3015–2990 Ma quartz-dioritic Finnefjeld and Taserssuaq complexes conflict with their geochemical variation. The complexes are spatially associated with strong aeromagnetic responses that are interpreted to reflect a large gabbro-diorite intrusion, and we propose that the protoliths of the Finnefjeld and Taserssuaq complexes are genetically linked to such intrusion. Formed at same time are carbonatite, high-Mg gabbro and tonalite-trondhjemite, and we propose that this wide spectrum of rocks could have formed by lithospheric and crustal melting in response to asthenospheric upwelling possibly in an extensional setting. Periods of extensive magmatism in the Akia terrane were previously recognised at ca. 3220-3180 Ma and 3070-2970 Ma. We now subdivide the latter period into three episodes: juvenile basaltic-andesitic volcanism at 3070–3050 Ma; tonalitic and dioritic plutonism at 3050–3020 Ma, and gabbroic-dioritic plus tonalitic-trondhjemitic plutonism at 3020–2985 Ma. This last episode was immediately followed by crustal reworking during collision at 2980–2950 Ma.Publisher PDFPeer reviewe

Integration of computational modeling for the Los Alamos National Laboratory low level radioactive waste disposal performance assessment

The preliminary Performance Assessment for the Los Alamos National Laboratory Low Level Radioactive Waste Disposal Facility at Area G is drawing to completion. The disposal site is located on the top of a finger mesa in the complex terrain of a semi-arid region which leads to considerable complications in the atmospheric and subsurface transport and in the requisite modeling. Infiltration and run-off are evaluated for the proposed disposal unit closure configuration. A new analytic source release model characterizes the disposal unit performance utilizing detailed source term characterization from the inventory data base. This analysis provides input to the subsurface modeling done by the sophisticated finite element transport code, FEHM, using realistic 2-D cross-sections of the geologic units stratigraphies and the disposal units. Subsurface transport via lateral flow to intermittent alluvial waters in adjacent canyons is evaluated in addition to the usual deep aquifer. Vapor phase flow has been treated separately and calibrated to field data for tritium migration. Atmospheric transport is based on Gaussian dispersion with a correction for complex canyon terrain evaluated from on-going 3-D atmospheric transport studies. Indications to date are that the Performance Assessment objectives are met for all migration pathways

Trends and variations in the rates of hospital complications, failure-to-rescue and 30-day mortality in surgical patients in New South Wales, Australia, 2002-2009

BACKGROUND: Despite the increased acceptance of failure-to-rescue (FTR) as an important patient safety indicator (defined as the percentage of deaths among surgical patients with treatable complications), there has not been any large epidemiological study reporting FTR in an Australian setting nor any evaluation on its suitability as a performance indicator. METHODS: We conducted a population-based study on elective surgical patients from 82 public acute hospitals in New South Wales, Australia between 2002 and 2009, exploring the trends and variations in rates of hospital complications, FTR and 30-day mortality. We used Poisson regression models to derive relative risk ratios (RRs) after adjusting for a range of patient and hospital characteristics. RESULTS: The average rates of complications, FTR and 30-day mortality were 13.8 per 1000 admissions, 14.1% and 6.1 per 1000 admission, respectively. The rates of complications and 30-day mortality were stable throughout the study period however there was a significant decrease in FTR rate after 2006, coinciding with the establishment of national and state-level peak patient safety agencies. There were marked variations in the three rates within the top 20% of hospitals (best) and bottom 20% of hospitals (worst) for each of the four peer-hospital groups. The group comprising the largest volume hospitals (principal referral/teaching hospitals) had a significantly higher rate of FTR in comparison to the other three groups of smaller-sized peer hospital groups (RR = 0.78, 0.57, and 0.61, respectively). Adjusted rates of complications, FTR and 30-day mortality varied widely for individual surgical procedures between the best and worst quintile hospitals within the principal referral hospital group. CONCLUSIONS: The decrease in FTR rate over the study period appears to be associated with a wide range of patient safety programs. The marked variations in the three rates between- and within- peer hospital groups highlight the potential for further quality improvement intervention opportunities.Lixin Ou, Jack Chen, Hassan Assareh, Stephanie J. Hollis, Ken Hillman, Arthas Flabouri

Geographic variation of Failure-to-Rescue in public acute hospitals in New South Wales, Australia

Despite the wide acceptance of Failure-to-Rescue (FTR) as a patient safety indicator (defined as the deaths among surgical patients with treatable complications), no study has explored the geographic variation of FTR in a large health jurisdiction. Our study aimed to explore the spatiotemporal variations of FTR rates across New South Wales (NSW), Australia. We conducted a population-based study using all admitted surgical patients in public acute hospitals during 2002-2009 in NSW, Australia. We developed a spatiotemporal Poisson model using Integrated Nested Laplace Approximation (INLA) methods in a Bayesian framework to obtain area-specific adjusted relative risk. Local Government Area (LGA) was chosen as the areal unit. LGA-aggregated covariates included age, gender, socio-economic and remoteness index scores, distance between patient residential postcode and the treating hospital, and a quadratic time trend. We studied 4,285,494 elective surgical admissions in 82 acute public hospitals over eight years in NSW. Around 14% of patients who developed at least one of the six FTR-related complications (58,590) died during hospitalization. Of 153 LGAs, patients who lived in 31 LGAs, accommodating 48% of NSW patients at risk, were exposed to an excessive adjusted FTR risk (10% to 50%) compared to the state-average. They were mostly located in state's centre and western Sydney. Thirty LGAs with a lower adjusted FTR risk (10% to 30%), accommodating 8% of patients at risk, were mostly found in the southern parts of NSW and Sydney east and south. There were significant spatiotemporal variations of FTR rates across NSW over an eight-year span. Areas identified with significantly high and low FTR risks provide potential opportunities for policy-makers, clinicians and researchers to learn from the success or failure of adopting the best care for surgical patients and build a self-learning organisation and health system.Hassan Assareh, Lixin Ou, Jack Chen, Kenneth Hillman, Arthas Flabouris, Stephanie J. Holli

Rate of venous thromboembolism among surgical patients in Australian hospitals: a multicentre retrospective cohort study

OBJECTIVES: Despite the burden of venous thromboembolism (VTE) among surgical patients on health systems in Australia, data on VTE incidence and its variation within Australia are lacking. We aim to explore VTE and subsequent mortality rates, trends and variations across Australian acute public hospitals. SETTING: A large retrospective cohort study using all elective surgical patients in 82 acute public hospitals during 2002-2009 in New South Wales, Australia. PARTICIPANTS: Patients underwent elective surgery within 2 days of admission, aged between 18 and 90 years, and who were not transferred to another acute care facility; 4 362 624 patients were included. OUTCOME MEASURES: VTE incidents were identified by secondary diagnostic codes. Poisson mixed models were used to derive adjusted incidence rates and rate ratios (IRR). RESULTS: 2/1000 patients developed postoperative VTE. VTE increased by 30% (IRR=1.30, CI 1.19 to 1.42) over the study period. Differences in the VTE rates, trends between hospital peer groups and between hospitals with the highest and those with the lowest rates were significant (between-hospital variation). Smaller hospitals, accommodated in two peer groups, had the lowest overall VTE rates (IRR=0.56:0.33 to 0.95; IRR=0.37:0.23 to 0.61) and exhibited a greater increase (64% and 237% vs 19%) overtime and greater between-hospital variations compared to larger hospitals (IRR=8.64:6.23 to 11.98; IRR=8.92:5.49 to 14.49 vs IRR=3.70:3.32 to 4.12). Mortality among patients with postoperative VTE was 8% and remained stable overtime. No differences in post-VTE death rates and trends were seen between hospital groups; however, larger hospitals exhibited less between-hospital variations (IRR=1.78:1.30 to 2.44) compared to small hospitals (IRR>23). Hospitals performed differently in prevention versus treatment of postoperative VTE. CONCLUSIONS: VTE incidence is increasing and there is large variation between-hospital and within-hospital peer groups suggesting a varied compliance with VTE preventative strategies and the potential for targeted interventions and quality improvement opportunities.Hassan Assareh, Jack Chen, Lixin Ou, Stephanie J Hollis, Kenneth Hillman, Arthas Flabouri