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Abstract Background Young women worldwide face problems like unwanted pregnancy and sexually transmitted infections. Providing sexual and reproductive health education to young women in low- and middle-income countries is a priority. It is unknown if using digital health interventions to deliver health education is effective in resource-constrained settings. Methods We conducted an interventional trial among young women in the low–middle-income country of Lesotho to test the impact of the conversational agent system (“Nthabi”) designed to deliver sexual and reproductive health information on either a smartphone or tablet for up to 6 weeks. We measured participant’s knowledge before and after the discussion of family planning, folic acid use, and healthy eating. The main outcome measure was a change in knowledge among participants in these three topic areas. The number of correct pre- and post-test responses was compared using generalized linear models that directly estimated the proportions and percentages of correct responses. Results We recruited 172 young women (mean age 22.5 years, 91% unmarried, 69% completed high school, 23% unemployed, 66% students) to use Nthabi on a mobile phone (11.6%) or loaned tablet device (88.4%). The mean number of interactions with Nthabi was 8.6. Family planning was chosen to be discussed by 82 of the 172 participants (52.2%), and of those, 49 (31.2%) completed the content on this topic, and 26 (16.6) completed the post-test. For the 11 questions about family planning, the total percent of correct responses increased from 85.5% (796 total responses) on the pre-test to 89.9% (320 responses) on the post-test (p = 0.0233). Folic acid use was chosen to be discussed by 74 (47.1%) of 172 participants, and of those, 27 (17.7%) completed the content on this topic, and all 27 (17.7%) completed the post-test. For the 5 questions about folic acid use, the total percent of correct responses was 45.3% (181 total responses) on the pre-test and 71.6% (111 responses) on the post-test (p

Abstract Acoustic models of railway vehicles in standstill and pass-by conditions can be used as part of a virtual certification process for new trains. For each piece of auxiliary equipment, the sound power measured on a test bench is combined with measured or predicted transfer functions. It is important, however, to allow for installation effects due to shielding by fairings or the train body. In the current work, fast-running analytical models are developed to determine these installation effects. The model for roof-mounted sources takes account of diffraction at the corner of the train body or fairing, using a barrier model. For equipment mounted under the train, the acoustic propagation from the sides of the source is based on free-field Green’s functions. The bottom surfaces are assumed to radiate initially into a cavity under the train, which is modelled with a simple diffuse field approach. The sound emitted from the gaps at the side of the cavity is then assumed to propagate to the receivers according to free-field Green’s functions. Results show good agreement with a 2.5D boundary element model and with measurements. Modelling uncertainty and parametric uncertainty are evaluated. The largest variability occurs due to the height and impedance of the ground, especially for a low receiver. This leads to standard deviations of up to 4 dB at low frequencies. For the roof-mounted sources, uncertainty over the location of the corner used in the equivalent barrier model can also lead to large standard deviations.

Abstract Purpose 5-fluorouracil (5-FU) is inefficiently converted to the active anti-cancer metabolite, fluorodeoxyuridine-monophosphate (FUDR-MP), is associated with dose-limiting toxicities and challenging administration schedules. NUC-3373 is a phosphoramidate nucleotide analog of fluorodeoxyuridine (FUDR) designed to overcome these limitations and replace fluoropyrimidines such as 5-FU. Patients and methods NUC-3373 was administered as monotherapy to patients with advanced solid tumors refractory to standard therapy via intravenous infusion either on Days 1, 8, 15 and 22 (Part 1) or on Days 1 and 15 (Part 2) of 28-day cycles until disease progression or unacceptable toxicity. Primary objectives were maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) and schedule of NUC-3373. Secondary objectives included pharmacokinetics (PK), and anti-tumor activity. Results Fifty-nine patients received weekly NUC-3373 in 9 cohorts in Part 1 (n = 43) and 3 alternate-weekly dosing cohorts in Part 2 (n = 16). They had received a median of 3 prior lines of treatment (range: 0–11) and 74% were exposed to prior fluoropyrimidines. Four experienced dose-limiting toxicities: two Grade (G) 3 transaminitis; one G2 headache; and one G3 transient hypotension. Commonest treatment-related G3 adverse event of raised transaminases occurred in

Abstract Prune belly syndrome (PBS), also known as Eagle-Barret syndrome, is a rare, multi-system congenital myopathy primarily affecting males. Phenotypically, PBS cases manifest three cardinal pathological features: urinary tract dilation with poorly contractile smooth muscle, wrinkled flaccid ventral abdominal wall with skeletal muscle deficiency, and intra-abdominal undescended testes. Genetically, PBS is poorly understood. After performing whole exome sequencing in PBS patients, we identify one compound heterozygous variant in the PIEZO1 gene. PIEZO1 is a cation-selective channel activated by various mechanical forces and widely expressed throughout the lower urinary tract. Here we conduct an extensive functional analysis of the PIEZO1 PBS variants that reveal loss-of-function characteristics in the pressure-induced normalized open probability (NPo) of the channel, while no change is observed in single-channel currents. Furthermore, Yoda1, a PIEZO1 activator, can rescue the NPo defect of the PBS mutant channels. Thus, PIEZO1 mutations may be causal for PBS and the in vitro cellular pathophysiological phenotype could be rescued by the small molecule, Yoda1. Activation of PIEZO1 might provide a promising means of treating PBS and other related bladder dysfunctional states.

Abstract The objective of the current study was to identify potential drug–drug interactions (DDIs) with the drug candidate fb‐PMT, a novel anticancer thyrointegrin αvß3 antagonist. This was accomplished by using several in vitro assays to study interactions of fb‐PMT with both cytochrome P450 (CYP) enzymes and drug transporters, two common mechanisms leading to adverse drug effects. In vitro experiments showed that fb‐PMT exhibited weak reversible inhibition of CYP2C19 and CYP3A4. In addition, fb‐PMT did not show time‐dependent inhibition with any of the seven CYP isoforms tested, including 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4. Human liver microsomal incubations demonstrated that fb‐PMT is stable. Potential transporter‐mediated DDIs with fb‐PMT were assessed with two ATP binding cassette (ABC) family transporters (P‐glycoprotein and breast cancer resistance protein) using Caco2 cells and seven solute carrier family (SLC) transporters (organic cation transporter OCT2, organic anion transporters OAT1 and OAT3, organic anion transporter peptides OATP1B1 and OATP1B3, and the multidrug and toxic extrusion proteins MATE1 and MATE2‐K using transfected HEK293 cells). Fb‐PMT was not a substrate for any of the nine transporters tested in this study, nor did it inhibit the activity of seven of the transporters tested. However, fb‐PMT inhibited the uptake of rosuvastatin by both OATP1B1 and OATP1B3 with half‐maximal inhibitory concentrations greater than 3 and less than 10 μM. In summary, data suggest that the systemic administration of fb‐PMT is unlikely to lead to DDIs through CYP enzymes or ABC and SLC transporters in humans.

The Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (ENPP1) ectoenzyme regulates vascular intimal proliferation and mineralization of bone and soft tissues. ENPP1 variants cause Generalized Arterial Calcification of Infancy (GACI), a rare genetic disorder characterized by ectopic calcification, intimal proliferation, and stenosis of large- and medium-sized arteries. ENPP1 hydrolyzes extracellular ATP to pyrophosphate (PPi) and AMP. AMP is the precursor of adenosine, which has been implicated in the control of neointimal formation. Herein, we demonstrate that an ENPP1-Fc recombinant therapeutic inhibits proliferation of vascular smooth muscle cells (VSMCs) in vitro and in vivo. Addition of ENPP1 and ATP to cultured VSMCs generated AMP, which was metabolized to adenosine. It also significantly decreased cell proliferation. AMP or adenosine alone inhibited VSMC growth. Inhibition of ecto-5′-nucleotidase CD73 decreased adenosine accumulation and suppressed the anti-proliferative effects of ENPP1/ATP. Addition of AMP increased cAMP synthesis and phosphorylation of VASP at Ser157. This AMP-mediated cAMP increase was abrogated by CD73 inhibitors or by A2aR and A2bR antagonists. Ligation of the carotid artery promoted neointimal hyperplasia in wild-type mice, which was exacerbated in ENPP1-deficient ttw/ttw mice. Prophylactic or therapeutic treatments with ENPP1 significantly reduced intimal hyperplasia not only in ttw/ttw but also in wild-type mice. These findings provide the first insight into the mechanism of the anti-proliferative effect of ENPP1 and broaden its potential therapeutic applications beyond enzyme replacement therapy.

Caldera-forming eruptions are amongst the most hazardous events in the Earth’s history, and understanding their formation is essential to forecasting activity at active calderas worldwide. In this study we present new field and geochronological evidence for a Paleocene-Eocene caldera from Skye, NW Scotland. Magma exploited a regional thrust fault as a conduit, and then ponded against intrusive igneous rocks emplaced against a regional extensional fault. Replenishment of silicic magma reservoirs with basaltic magma triggered eruptions. The eruptions typically deposited extremely coarse ignimbrites, demonstrating catastrophic collapse of the caldera, which occurred via an inner ring fault and a complexly faulted marginal zone. Collapse was followed by remobilisation of silicic magma and caldera resurgence. The magma consumed dolostone country rocks, causing significant release of CO2 and contributed to the Paleocene-Eocene Thermal Maximum. Our results demonstrate how tectonics localise magma and caldera development, and how this can cause cataclysmic volcanic and climatic hazards.

The Earth’s most stable quasi-satellite, Kamoʻoalewa, displays an extremely red reflectance spectrum typical of space weathering of lunar-like silicate material which raises the possibility that it is formed of material originating from the Moon

Introduction There is an increasing need for evaluating postintensive care syndrome in adults concerning their long-term physical, psychological, cognitive and/or social outcomes, yet there is no consensus regarding the choice of instruments to measure these. This scoping review aims to identify and examine instruments used to measure postintensive care syndrome in adults.Methods and analysis This scoping review will be conducted following the Arksey and O’Malley and its extended framework, and the Joanna Briggs Institute guideline. It will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Review checklists. Medline via EBSCO, CINAHL complete, EMBASE, Web of Science, AME and APA PsycINFO databases and grey literature will be searched from 2010 to the present. Reference lists of included studies will be manually checked to identify additional sources. The quality of included studies will be appraised using the Crowe Critical Appraisal Tool. All review steps will involve at least two reviewers. Data charting will be performed narratively, comprising study characteristics and findings, and instrument properties. This review will also aim to identify research gaps.Ethics and dissemination There is no ethics disclosure for this review protocol. This scoping review will identify instruments used to measure postintensive care syndrome in adults. The findings will be disseminated through professional bodies, conferences and research papers.

Distant metastasis of Papillary Thyroid Cancer (PTC) to the kidney(s), while rare, has been observed, with approximately 30 cases described in the literature. We present the case of a 28-year-old male who was diagnosed with metastatic PTC following resection of a solitary renal mass. Pathological analysis of the thyroid gland following subsequent thyroidectomy revealed positive regional lymph nodes consistent with metastatic PTC, however, no evidence of malignancy was identified in the thyroid gland. To our knowledge, this is the only known case of metastatic PTC involving the kidney in which no primary lesion was found in the thyroid gland.

Abstract Background People with serious mental illnesses (SMI) such as schizophrenia and bipolar disorder experience excess mortality driven in large part by high rates of poorly controlled and under-treated cardiovascular risk factors. In the USA, integrated “behavioral health home” models in which specialty mental health organizations coordinate and manage physical health care for people with SMI are designed to improve guideline-concordant cardiovascular care for this group. Such models have been shown to improve cardiovascular care for clients with SMI in randomized clinical trials, but real-world implementation has fallen short. Key implementation barriers include lack of alignment of specialty mental health program culture and physical health care coordination and management for clients with SMI and lack of structured protocols for conducting effective physical health care coordination and management in the specialty mental health program context. This protocol describes a pilot study of an implementation intervention designed to overcome these barriers. Methods This pilot study uses a single-group, pre/post-study design to examine the effects of an adapted Comprehensive Unit Safety Program (CUSP) implementation strategy designed to support behavioral health home programs in conducting effective cardiovascular care coordination and management for clients with SMI. The CUSP strategy, which was originally designed to improve inpatient safety, includes provider training, expert facilitation, and implementation of a five-step quality improvement process. We will examine the acceptability, appropriateness, and feasibility of the implementation strategy and how this strategy influences mental health organization culture; specialty mental health providers’ self-efficacy to conduct evidence-based cardiovascular care coordination and management; and receipt of guideline-concordant care for hypertension, dyslipidemia, and diabetes mellitus among people with SMI. Discussion While we apply CUSP to the implementation of evidence-based hypertension, dyslipidemia, and diabetes care, this implementation strategy could be used in the future to support the delivery of other types of evidence-based care, such as smoking cessation treatment, in behavioral health home programs. CUSP is designed to be fully integrated into organizations, sustained indefinitely, and used to continually improve evidence-based practice delivery. Trial registration ClinicalTrials.gov, NCT04696653 . Registered on January 6, 2021

SUMMARY Falsely elevated estradiol is rare, may result from heterophile antibody interference, and can result in unnecessary investigation and intervention. We present the case of a 56-year-old female with falsely elevated estradiol levels inconsistent with her overall clinical picture, which ultimately led to an unnecessary surgical procedure. With the use of alternative analytical platforms and a heterophile antibody blocking agent, we determined the false elevation was due to heterophile antibody interference. Clinicians must suspect and investigate for laboratory error when the clinical picture contradicts laboratory results.

Abstract Background Non-surgical multidisciplinary management is often the first pathway of care for patients with chronic low back pain (LBP). This study explores if patient characteristics recorded at the initial service examination have an association with a poor response to this pathway of care in an advanced practice physiotherapist-led tertiary service. Methods Two hundred and forty nine patients undergoing non-surgical multidisciplinary management for their LBP across 8 tertiary public hospitals in Queensland, Australia participated in this prospective longitudinal study. Generalised linear models (logistic family) examined the relationship between patient characteristics and a poor response at 6 months follow-up using a Global Rating of Change measure. Results Overall 79 of the 178 (44%) patients completing the Global Rating of Change measure (28.5% loss to follow-up) reported a poor outcome. Patient characteristics retained in the final model associated with a poor response included lower Formal Education Level (ie did not complete school) (Odds Ratio (OR (95% confidence interval)) (2.67 (1.17–6.09), p = 0.02) and higher self-reported back disability (measured with the Oswestry Disability Index) (OR 1.33 (1.01–1.77) per 10/100 point score increase, p = 0.046). Conclusions A low level of formal education and high level of self-reported back disability may be associated with a poor response to non-surgical multidisciplinary management of LBP in tertiary care. Patients with these characteristics may need greater assistance with regard to their comprehension of health information, and judicious monitoring of their response to facilitate timely alternative care if no benefits are attained.

Abstract The pantograph and its recess on the train roof are major aerodynamic noise sources on high-speed trains. Reducing this noise is particularly important because conventional noise barriers usually do not shield the pantograph. However, less attention has been paid to the pantograph recess compared with the pantograph. In this paper, the flow features and noise contribution of two types of noise reduction treatments rounded and chamfered edges are studied for a simplified high-speed train pantograph recess, which is represented as a rectangular cavity and numerically investigated at 1/10 scale. Improved delayed detached-eddy simulations are performed for the near-field turbulent flow simulation, and the Ffowcs Williams and Hawkings aeroacoustic analogy is used for far-field noise prediction. The highly unsteady flow over the cavity is significantly reduced by the cavity edge modifications, and consequently, the noise radiated from the cavity is reduced. Furthermore, effects of the rounded cavity edges on the flow and noise of the pantographs (one raised and one folded) are investigated by comparing the flow features and noise contributions from the cases with and without rounding of the cavity edges. Different train running directions are also considered. Flow analysis shows that the highly unsteady flow within the cavity is reduced by rounding the cavity edges and a slightly lower flow speed occurs around the upper parts of the raised pantograph, whereas the flow velocity in the cavity is slightly increased by the rounding. Higher pressure fluctuations occur on the folded pantograph and the lower parts of the raised pantograph, whereas weaker fluctuations are found on the panhead of the raised pantograph. This study shows that by rounding the cavity edges, a reduction in radiated noise at the side and the top receiver positions can be achieved. Noise reductions in the other directions can also be found.

Mechanisms promoting coexistence between closely related species are fundamental for maintaining species diversity. Mechanisms of niche differentiation include allochrony which offsets the peak timing of resource utilisation between species. Many studies focus on spatial and temporal niche partitioning during the breeding season, few have investigated the role allochrony plays in influencing interspecific segregation of foraging distribution and ecology between congeneric species during the non-breeding season. We investigated the non-breeding migrations of Snares (Eudyptes robustus) and Fiordland penguins (Eudyptes pachyrhynchus), closely related species breeding between 100–350 km apart whose migration phenology differs by two months. Using light geolocation tracking, we examined the degree of overlap given the observed allochrony and a hypothetical scenario where the species commence migration simultaneously. We found that Fiordland penguins migrated to the Sub-Antarctic Frontal Zone and Polar Frontal Zone in the austral autumn whereas Snares penguins disperse westwards staying north of the Sub-Tropical Front in the austral winter. Our results suggest that allochrony is likely to be at the root of segregation because the relative profitability of the different water masses that the penguins forage in changes seasonally which results in the two species utilising different areas over their core non-breeding periods. Furthermore, allochrony reduces relatively higher levels of spatiotemporal overlap during the departure and arrival periods, when the close proximity of the two species’ colonies would cause the birds to congregate in similar areas, resulting in high interspecific competition just before the breeding season. Available evidence from other studies suggests that the shift in phenology between these species has arisen from adaptive radiation and phenological matching to the seasonality of local resource availability during the breeding season and reduced competitive overlap over the non-breeding season is likely to be an incidental outcome.

Summary: Amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) is a fatal neurodegenerative disorder, and continued innovation is needed for improved understanding and for developing therapeutics. We have created next-generation genomically humanized knockin mouse models, by replacing the mouse genomic region of Sod1, Tardbp (TDP-43), and Fus, with their human orthologs, preserving human protein biochemistry and splicing with exons and introns intact. We establish a new standard of large knockin allele quality control, demonstrating the utility of indirect capture for enrichment of a genomic region of interest followed by Oxford Nanopore sequencing. Extensive analysis shows that homozygous humanized animals only express human protein at endogenous levels. Characterization of humanized FUS animals showed that they are phenotypically normal throughout their lifespan. These humanized strains are vital for preclinical assessment of interventions and serve as templates for the addition of coding or non-coding human ALS/FTD mutations to dissect disease pathomechanisms, in a physiological context.

Metagenomic sequencing of clinical diagnostic specimens has a potential for unbiased detection of infectious agents, diagnosis of polymicrobial infections and discovery of emerging pathogens. Herein, next generation sequencing (NGS)-based metagenomic approach was used to investigate the cause of illness in a subset of horses recruited for a tick-borne disease surveillance study during 2017–2019. Blood samples collected from 10 horses with suspected tick-borne infection and five apparently healthy horses were subjected to metagenomic analysis. Total genomic DNA extracted from the blood samples were enriched for microbial DNA and subjected to shotgun next generation sequencing using Nextera DNA Flex library preparation kit and V2 chemistry sequencing kit on the Illumina MiSeq sequencing platform. Overall, 0.4–0.6 million reads per sample were analyzed using Kraken metagenomic sequence classification program. The taxonomic classification of the reads indicated that bacterial genomes were overrepresented (0.5 to 1%) among the total microbial reads. Most of the bacterial reads (~91%) belonged to phyla Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria, Cyanobacteria and Tenericutes in both groups. Importantly, 10–42.5% of Alphaproteobacterial reads in 5 of 10 animals with suspected tick-borne infection were identified as Anaplasma phagocytophilum. Of the 5 animals positive for A. phagocytophilum sequence reads, four animals tested A. phagocytophilum positive by PCR. Two animals with suspected tick-borne infection and A. phagocytophilum positive by PCR were found negative for any tick-borne microbial reads by metagenomic analysis. The present study demonstrates the usefulness of the NGS-based metagenomic analysis approach for the detection of blood-borne microbes.

Abstract Introduction The ORBITA trial of percutaneous coronary intervention (PCI) versus a placebo procedure for patients with stable angina was conducted across six sites in the United Kingdom via home monitoring and telephone consultations. Patients underwent detailed assessment of medication adherence which allowed us to measure the efficacy of the implementation of the optimization protocol and interpretation of the main trial endpoints. Methods Prescribing data were collected throughout the trial. Self‐reported adherence was assessed, and urine samples collected at pre‐randomization and at follow‐up for direct assessment of adherence using high‐performance liquid chromatography with tandem mass spectrometry (HPLC MS/MS). Results Self‐reported adherence was >96% for all drugs in both treatment groups at both stages. The percentage of samples in which drug was detected at pre‐randomization and at follow‐up in the PCI versus placebo groups respectively was: clopidogrel, 96% versus 90% and 98% versus 94%; atorvastatin, 95% versus 92% and 92% versus 91%; perindopril, 95% versus 97% and 85% versus 100%; bisoprolol, 98% versus 99% and 96% versus 97%; amlodipine, 99% versus 99% and 94% versus 96%; nicorandil, 98% versus 96% and 94% versus 92%; ivabradine, 100% versus 100% and 100% versus 100%; and ranolazine, 100% versus 100% and 100% versus 100%. Conclusions Adherence levels were high throughout the study when quantified by self‐reporting methods and similarly high proportions of drug were detected by urinary assay. The results indicate successful implementation of the optimization protocol delivered by telephone, an approach that could serve as a model for treatment of chronic conditions, particularly as consultations are increasingly conducted online.

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Introduction Distress is experienced by the majority of cardiac patients, yet no cardiac-specific measure of distress exists. The aim of this project is to develop and validate the Cardiac Distress Inventory (CDI). Using the CDI, health professionals will be able to identify key clusters of psychological, emotional and social concern to address with patients, postcardiac event.Methods and analysis An item pool will be generated through: identification of items by a multidisciplinary group of clinician researchers; review of generic and condition-specific distress measures; focus group testing with cardiac rehabilitation professionals; feedback from patients. The COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) criteria will be used to inform the development of the methodology for determining the CDI’s psychometric properties. The item pool will be tested with 400 cardiac patients and responses subjected to exploratory factor analysis, Rasch analysis, construct validity testing and latent class analysis. Receiver operating characteristic analysis will be used to identify the optimal CDI cut-off score for distinguishing whether a person experiences clinically significant distress.Ethics and dissemination Approved by the Monash Health Human Research Ethics Committee (approval number—RES-19-0000631L-559790). The CDI will be made available to clinicians and researchers without charge. The CDI will be translated for use internationally. Study findings will be shared with cardiac patient support groups; academic and medical communities via publications and presentations; in the training of cardiac secondary prevention professionals; and in reports to funders. Authorship for publications will follow the uniform requirements for manuscripts submitted to biomedical journals.

This work presents spatially compounded plane wave imaging using a laser-induced ultrasound source. The plane wave source consisted of a 30 μm thick film of carbon black-doped PDMS cured on a 100 μm thick polyester substrate and presented a rectangular aperture of 40 × 3 mm. It was placed in front of a linear ultrasound array, passing through the imaging plane allowing overlap of the detection plane and the insonification plane. Illumination was provided by an array of optical fibre bundles placed above the imaging plane, at an angle. We will first present the general imaging set up and instrumentation used, after which details are given on the fabrication of the transmitter itself and on the objects that were imaged. Comparing laser-induced and conventional ultrasound images of wire phantoms shows the point-spread-function to be, in general, slightly better laterally in the conventional case but more homogeneous throughout the imaging plane with the laser-induced source. Imaging of a tissue-mimicking phantom shows a 55% improvement in contrast between a tumour and the background when using laser-induced ultrasound, as compared to the conventional case.

Large-eddy simulation (LES)-based jet noise predictions do not resolve the entire broadband noise spectra, often under-predicting high frequencies that correspond to un-resolved small-scale turbulence. The coupled LES-synthetic turbulence (CLST) model is presented which aims to model the missing high frequencies. The CLST method resolves large-scale turbulent fluctuations from coarse-grid large-eddy simulations (CLES) and models small-scale fluctuations generated by a synthetic eddy method (SEM). Noise is predicted using a formulation of the linearized Euler equations (LEE), where the acoustic waves are generated by source terms from the combined fluctuations of the CLES and the stochastic fields. Sweeping and straining of the synthetic eddies are accounted for by convecting eddies with the large turbulent scales from the CLES flow field. The near-field noise of a Mach 0.9 jet at a Reynolds number of 100,000 is predicted with LES. A high-order numerical algorithm, involving a dispersion relation preserving scheme for spatial discretization and an Adams–Bashforth scheme for time marching, is used for both LES and LEE solvers. Near-field noise spectra from the LES solver are compared to published results. Filtering is applied to the LES flow field to produce an under-resolved CLES flow field, and a comparison to the un-filtered LES spectra reveals the missing noise for this case. The CLST method recovers the filtered high-frequency content, agreeing well with the spectra from LES and showing promise at modeling the high-frequency range in the acoustic noise spectrum at a reasonable expense.

We studied geomorphological controls on methane (CH _4 ) hotspots in the Mackenzie Delta region in northern Canada using airborne imaging spectroscopy collected as part of the Arctic Boreal Vulnerability Experiment. Methane emissions hotspots were retrieved at ∼25 m ^2 spatial resolution from a ∼10 000 km ^2 NASA’s Next Generation Airborne Visible/Infrared Imaging Spectrometer survey of the Mackenzie Delta acquired 31 July–3 August 2017. Separating the region into the permafrost plateau and the lowland delta, we refined the domain wide power law of CH _4 enhancements detected as a function of distance to standing water in different ecoregions. We further studied the spatial decay of the distance to water relationship as a function of land cover across the Delta. We show that geomorphology exerts a strong control on the spatial patterns of emissions at regional to sub-regional scales: compared to methane hotspots detected in the upland, we find that methane hotspots detected in the lowland have a more gradual power law curve indicating a weaker spatial decay with respect to distance from water. Spatial decay of CH _4 hotspots in uplands is more than 2.5 times stronger than in lowlands, which is due to differences in topography and geomorphological influence on hydrology. We demonstrate that while the observed spatial distributions of CH _4 follow expected trends in lowlands and uplands, these quantitatively complement knowledge from conventional wetland and freshwater CH _4 mapping and modeling.

Much of the research into higher education and its role in work-based learning (WBL), and especially in supporting undergraduate students on placements, has focussed on longer term internships and sandwich courses. Research has also focussed on subject areas that have traditionally been associated with the above; for example, Business, Health, and Engineering. By contrast, the aim of this study was to gather data from students on a much shorter period of placement, categorised as a ‘short project’ (Brennan & Little, 1996). Furthermore, the data recovered was from students studying within the social sciences paradigm, undertaking an undergraduate degree in Education Studies (not teacher education). The social sciences and humanities more generally have not been discussed to any great extent within the context of research on placement or work-based learning (see Smith, Clegg, Lawrence, & Todd, 2007); the subject of Education Studies is not covered at all by previous research. This paper considers the different ways practitioners might blend learning and support university students’ experiential and academic learning in this short project format. The results suggest that even a relatively short period of structured placement can be of significant benefit to students although for many respondents, face-to-face contact in the form of lectures and tutorials is still an important component of a blended approach to WBL.

Surgery has traditionally been an important aspect of services offered by mission hospitals, but only in the last 20 years has surgical residency training been incorporated into the mission hospital setting. A working group of surgical educators met in conjunction with the Global Missions Health Conference in November 2015 and discussed the current status of surgical training in the mission setting. This paper outlines the current status and makes recommendations for mission groups who are contemplating starting a residency training program. Potential difficulties and the importance of regional recognition of the program are discussed. The work group felt that it was important to include a strong spiritual emphasis as part of the training. Future directions and the concern about employment opportunities are explored.

Solid waste management represents one of the largest anthropogenic methane emission sources. However, precise quantification of landfill and composting emissions remains difficult due to variety of site-specific factors that contribute to landfill gas generation and effective capture. Remote sensing is an avenue to quantify process-level emissions from waste management facilities. The California Methane Survey flew the Next Generation Airborne Visible/Infrared Imaging Spectrometer (AVIRIS-NG) over 270 landfills and 166 organic waste facilities repeatedly during 2016–2018 to quantify their contribution to the statewide methane budget. We use representative methane retrievals from this campaign to present three specific findings where remote sensing enabled better landfill and composting methane monitoring: (1) Quantification of strong point source emissions from the active face landfills that are difficult to capture by in situ monitoring or landfill models, (2) emissions that result from changes in landfill infrastructure (design, construction, and operations), and (3) unexpected large emissions from two organic waste management methods (composting and digesting) that were originally intended to help mitigate solid waste emissions. Our results show that remotely-sensed emission estimates reveal processes that are difficult to capture in biogas generation models. Furthermore, we find that airborne remote sensing provides an effective avenue to study the temporally changing dynamics of landfills. This capability will be further improved with future spaceborne imaging spectrometers set to launch in the 2020s.

Background: Provider ability to estimate caregiver health literacy (HL) in English-speaking caregivers has been shown to be poor, but estimation of HL in Spanish-speaking caregivers by physicians and staff has yet to be studied. Linguistic differences can further hinder communication in medical care. Objective: This study evaluated how well pediatric providers and staff predict caregiver HL as measured by two HL tools in a bilingual (English/Spanish) population. Method: For this study, we obtained a convenience sample of caregivers, evaluating one group with the Newest Vital Sign (NVS) and the second group with the Short Assessment of Health Literacy (SAHL). Physicians/nurse practitioners (NPs), and medical assistants (MAs) estimated caregiver scores for each tool. We dichotomized estimated and actual scores for each tool using published standards. We used McNemar's test and Cohen's Kappa to evaluate agreement between dichotomized predicted and actual scores. We used log binomial regression to examine how caregiver's language affected agreement between dichotomized caregiver scores and provider estimates. All physicians/NPs were native English speakers only and all MAs were native bilingual English/Spanish speakers. Physicians/NPs used interpretation services when appropriate. Key Results: Fifty caregivers were evaluated using the NVS and 50 using the SAHL. There was no overall association between dichotomized physician/NP or MA estimation and caregiver score for either tool. However, providers' estimates were less likely to match caregiver scores when the caregiver's language was Spanish (NVS: relative risk [RR] = 0.57 [95% CI 0.37, 0.87], SAHL: RR = 0.37 [95% CI 0.23,0.6]). Conclusion: Physician/NP and MA ability to estimate caregiver HL in English proficient and limited English proficiency caregivers is poor. The physician/NP group was less likely to estimate HL correctly if the caregivers spoke Spanish. Providers must use additional caution when providing cross-language care.

This paper documents the predictive capability of rotating blade-resolved unsteady Reynolds averaged Navier-Stokes (URANS) and Improved Delayed Detached Eddy Simulation (IDDES) computations for tidal stream turbine performance and intermediate wake characteristics. Ansys/Fluent and OpenFOAM simulations are performed using mixed-cell, unstructured grids consisting of up to 11 million cells. The thrust, power and intermediate wake predictions compare reasonably well within 10% of the experimental data. For the wake predictions, OpenFOAM performs better than Ansys/Fluent, and IDDES better than URANS when the resolved turbulence is triggered. The primary limitation of the simulations is under prediction of the wake diffusion towards the turbine axis, which in return is related to the prediction of turbulence in the tip-vortex shear layer. The shear-layer involves anisotropic turbulent structures; thus, hybrid RANS/LES models, such as IDDES, are preferred over URANS. Unfortunately, IDDES fails to accurately predict the resolved turbulence in the near-wake region due to the modeled stress depletion issue.

This work presents a transdisciplinary, integrated approach that uses computational mechanics experiments with a flow network strategy to gain fundamental insights into the stress flow of high-performance, lightweight, structured composites by investigating the rostrum of paddlefish. Although computational mechanics experiments give an overall distribution of stress in the structural systems, stress flow patterns formed at nascent stages of loading a biostructure are hard to determine. Computational mechanics experiments on a complex model will involve a high degree of freedom thereby making the extraction of finer details computationally expensive. To address this challenge, the evolution of the stress in the rostrum is formulated as a network flow problem generated by extracting the node and connectivity information from the numerical model of the rostrum. The flow network is weighted based on the parameter of interest, which is stress in the current research. The changing kinematics of the system is provided as input to the mathematical algorithm that computes the minimum cut of the flow network. The flow network approach is verified using two simple classical problems. When applied to the model of the rostrum, the flow network approach identifies strain localization in tensile regions, and buckling/crushing in compressive regions.

**Background:** Asthma and allergic rhinitis (AR) are inflammatory conditions that are similar in pathophysiology. Mild-to-moderate persistent asthma has been widely treated with inhaled corticosteroids, while allergic rhinitis is commonly treated with antihistamines, nasal corticosteroids, anticholinergics, and other allergy specific medications. The introduction of montelukast, a leukotriene receptor antagonist, has opened a treatment pathway that is common to both conditions. Previous real world studies of montelukast (Singulair®) relative to other medications have not investigated the role of race in the management of asthma and AR, specifically as relates to differences among Asian versus non-Asian patients. **Objective:** To contrast montelukast use and patterns of ambulatory care for adult Asian versus non-Asian patients in the United States with asthma and/or AR. **Methods:** Data for adult asthma and AR patients were extracted from a national electronic medical records database for the years 2006-2014. Patients were classified into condition cohort (Asthma-Only, AR-Only, Asthma & AR), and treatment condition (monotherapy or combination therapy, with or without montelukast for Asthma and Asthma & AR cohorts, usual care with or without montelukast for AR-Only) and stratified by race (Asian vs. non-Asian). **Results:** Overall patterns of use of montelukast were similar for Asian and non-Asian patients, but Asians were more likely to receive it as part of a combination therapy regimen. Changes in treatment regimen followed similar patterns for both groups. Asian patients with both asthma and AR were found to have lower service utilization rates if their therapy included montelukast, whereas for non-Asians there was no significant difference between regimens with or without montelukast. **Conclusion:** Differences in montelukast use and outcomes of care exist between Asian and non-Asian patients in the United States. Future research should explore the reasons for these differences and whether they can be replicated in non-US settings.

This paper presents a continuous single-step route that permits preparation of a thermostable polymer/metal nanocomposite film and to combine different functional properties in a unique material. More precisely, palladium nanoparticles are in situ generated in a polyimide matrix thanks to a designed curing cycle which is applied to a polyamic acid/metal precursor solution cast on a glass plate. A metal-rich surface layer which is strongly bonded to the bulk film is formed in addition to homogeneously dispersed metal nanoparticles. This specific morphology leads to obtaining an optically reflective film. The metal nanoparticles act as gas diffusion barriers for helium, oxygen, and carbon dioxide; they induce a tortuosity effect which allows dividing the gas permeation coefficients by a factor near to 2 with respect to the neat polyimide matrix. Moreover, the ability of the in situ synthesized palladium nanoparticles to entrap hydrogen is evidenced. The nanocomposite film properties can be modulated as a function of the location of the film metal-rich surface with respect to the hydrogen feed. The synthesized nanocomposite could represent a major interest for a wide variety of applications, from specific coatings for aerospace or automotive industry, to catalysis applications or sensors.

BACKGROUND: Determining the foraging movements of pelagic seabirds is fundamental for their conservation. However, the vulnerability and elusive lifestyles of these animals have made them notoriously difficult to study. Recent developments in satellite telemetry have enabled tracking of smaller seabirds during foraging excursions. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report the first successful precision tracking of a c. 700 g seabird, the vulnerable Black Petrel, Procellaria parkinsoni, foraging at sea during the breeding season, using miniature GPS-logging technology. Employing a combination of high-resolution fixes and low-power duty-cycles, we present data from nine individual foraging excursions tracked during the chick-rearing period in February 2006. CONCLUSIONS/SIGNIFICANCE: We provide a snapshot of the species' foraging range and behaviour in relation to detailed underlying bathymetry off the coast of New Zealand, finding a significant relationship between foraging movements and regions of the shelf-break. We also highlight the potential of more sophisticated analyses to identify behavioural phenomena from position data alone.

Abstract Physician behaviors that constitute patient-centered examinations are usually modeled informally by preceptors at the bedside. This guide supplements and codifies some of those informal yet critical lessons for medical students learning breast and pelvic exams. Written by second-year medical students—in collaboration with a faculty member in OB/GYN—the guide addresses common points of confusion. Intended as a supplement to textbook chapters and online video tutorials, it can be easily folded into the pockets of students on OB/GYN clerkships or used during physical diagnosis courses as a reference. Included are step-by-step instructions for performing the exam, a list of suggestions for appropriate language, and a sidebar with tips that may not be obvious to students. At our institution, the guide is included in the MS2 physical diagnosis course and is available during the MS3 OB/GYN rotation. It could also be useful to residents from various disciplines while rotating through OB/GYN services. The guide is not intended to replace a textbook chapter but rather to act as a portable reference. One limitation of the guide is that it lacks illustrations, and in future revisions, we plan to include diagrams to illustrate key points. We have received positive anecdotal feedback from students and faculty; an evaluation of the effect of this guide on student attitudes about the pelvic exam as well as its effect on their performance during Observed Structured Clinical Exams (OSCEs) is planned for the near future. We expect the guide to remain useful to students in its current format. Other users and instructors are welcome build upon the guide, and we would be glad to provide the document in Word format to facilitate such endeavors, provided that any improvements include appropriate attribution to the original authors.

The Spallation Neutron Source (SNS) radio-frequency quadrupole (RFQ) had resonance control instabilities at duty factors higher than approximately 4%. Systematic investigations have been carried out to understand the cause of the instability and to ensure the operational stability of the RFQ. The most critical source of the instability is revealed to be an interaction between hydrogen released by beam bombardments and the RFQ rf field resulting in a discharge, which consumes additional rf power and could cause the RFQ to operate in an unstable region. This paper reports improvement of the SNS RFQ operational stability based on the findings during the SNS operation.