Aneurysmal growth in type-B aortic dissection: assessing the impact of patient-specific inlet conditions on key haemodynamic indices.

Type-B aortic dissection is a cardiovascular disease in which a tear develops in the intimal layer of the descending aorta, allowing pressurized blood to delaminate the layers of the vessel wall. In medically managed patients, long-term aneurysmal dilatation of the false lumen (FL) is considered virtually inevitable and is associated with poorer disease outcomes. While the pathophysiological mechanisms driving FL dilatation are not yet understood, haemodynamic factors are believed to play a key role. Computational fluid dynamics (CFD) and 4D-flow MRI (4DMR) analyses have revealed correlations between flow helicity, oscillatory wall shear stress and aneurysmal dilatation of the FL. In this study, we compare CFD simulations using a patient-specific, three-dimensional, three-component inlet velocity profile (4D IVP) extracted from 4DMR data against simulations with flow rate-matched uniform and axial velocity profiles that remain widely used in the absence of 4DMR. We also evaluate the influence of measurement errors in 4DMR data by scaling the 4D IVP to the degree of imaging error detected in prior studies. We observe that oscillatory shear and helicity are highly sensitive to inlet velocity distribution and flow volume throughout the FL and conclude that the choice of IVP may greatly affect the future clinical value of simulations.

Increased warm water intrusions could cause mass loss in East Antarctica during the next 200 years.

The East Antarctic Ice Sheet (EAIS) is currently surrounded by relatively cool water, but climatic shifts have the potential to increase basal melting via intrusions of warm modified Circumpolar Deep Water (mCDW) onto the continental shelf. Here we use an ice sheet model to show that under the current ocean regime, with only limited intrusions of mCDW, the EAIS will likely gain mass over the next 200 years due to the increased precipitation from a warming atmosphere outweighing increased ice discharge due to ice-shelf melting. However, if the ocean regime were to become dominated by greater mCDW intrusions, the EAIS would have a negative mass balance, contributing up to 48 mm of SLE over this time period. Our modelling finds George V Land to be particularly at risk to increased ocean induced melting. With warmer oceans, we also find that a mid range RCP4.5 emissions scenario is likely to result in a more negative mass balance than a high RCP8.5 emissions scenario, as the relative difference between increased precipitation due to a warming atmosphere and increased ice discharge due to a warming ocean is more negative in the mid range RCP4.5 emission scenario.

The Influence of Minor Aortic Branches in Patient-Specific Flow Simulations of Type-B Aortic Dissection.

Type-B aortic dissection (TBAD) is a disease in which a tear develops in the intimal layer of the descending aorta forming a true lumen and false lumen (FL). Because disease outcomes are thought to be influenced by haemodynamic quantities such as pressure and wall shear stress (WSS), their analysis via numerical simulations may provide valuable clinical insights. Major aortic branches are routinely included in simulations but minor branches are virtually always neglected, despite being implicated in TBAD progression and the development of complications. As minor branches are estimated to carry about 7-21% of cardiac output, neglecting them may affect simulation accuracy. We present the first simulation of TBAD with all pairs of intercostal, subcostal and lumbar arteries, using 4D-flow MRI (4DMR) to inform patient-specific boundary conditions. Compared to an equivalent case without minor branches, their inclusion improved agreement with 4DMR velocities, reduced time-averaged WSS (TAWSS) and transmural pressure and elevated oscillatory shear in regions where FL dilatation and calcification were observed in vivo. Minor branch inclusion resulted in differences of 60-75% in these metrics of potential clinical relevance, indicating a need to account for minor branch flow loss if simulation accuracy is sought.

Extended Detection Window for Gamma-Hydroxybutyrate in the Urine of an Elderly Woman.

Gamma-hydroxybutyrate (GHB) is a central nervous system depressant that has gained popularity as an illicit recreational drug. We describe a case of an elderly woman who was found unconscious in her home. The paramedics initially suspected an intracranial incident. A head computed tomography was negative, as was the initial urinary drug screening. The diagnosis of GHB intoxication was made with the detection of GHB in a urine sample obtained 28-29 hours after the assumed time of intake. Our case underscores the importance of considering drug testing in a broad range of patients and shows that elderly patients may have an extended detection window of GHB.

Interprofessional Collaborative Care Skills and Behaviors: Perception Differences Between Allied Health Students and an Independent Observer.

Interprofessional practice and education (IPE) is incorporated into pre-licensure healthcare programs to prepare students for collaboration in clinical practice and to improve patient outcomes. The use of interprofessional simulation as a teaching strategy is increasing, but most literature involves medical and nursing students, and outcomes measure students' knowledge, perceptions, or attitudes. The purpose of this study was to compare allied health students' self-assessment of their team's interprofessional collaborative care (IPCC) skills and behaviors with an independent observer's perception during an interprofessional simulation discharge planning event with standardized patients. Students (n = 177) were recruited from the Departments of Occupational Therapy (OT), Physical Therapy (PT), and Physician Assistant Studies (PA). Students reflected on their team's performance, and an independent observer assessed each team's IPCC skills and behaviors with a valid and reliable tool developed from the IPEC Core Competencies. The results showed that students' assessments of their teams' IPCC were significantly greater than the independent observer's ratings. Additionally, the observer found that the students demonstrated higher levels of interprofessional collaboration during a team huddle without a standardized patient present. This study suggests that IPE program evaluation should include observations of interprofessional skills and behaviors and that students involved in interprofessional simulation may benefit from a team huddle prior to team interactions with a standardized patient.

Assessing Class 1 Integron Presence in Poultry Litter Amended with Wood Biochar and Wood Vinegar.

Class 1 integrons are mobile genetic elements that facilitate the spread of antibiotic resistance genes among bacteria. The use of prophylactic antibiotics has resulted in the rise of antibiotic resistance genes accumulating in a wide range of settings, including poultry houses and the agricultural fields where poultry litter is applied as a fertilizer. Biochar and wood vinegar are forest products wastes that have generated increasing attention as additives to agricultural soils. The objectives of this study were to observe the prevalence of class 1 integrons in poultry litter blended with biochar and wood vinegar over time and to verify a modified class 1 integron screening assay. Poultry litter blends were sampled and screened for class 1 integrons using polymerase chain reaction, and 80 products, 79 of which showed positive, were sent for DNA sequencing. The GenBank® BLAST database was used to verify the presence of the class 1 integron-integrase gene (intI1). There was no change in prevalence over time in poultry litter blends. Out of 79 PCR products that were intI1 positive, 78 showed at least 95% sequence identity to intI1 encoding bacteria and 64 showed at least 97% sequence identity. This indicates that this method was effective for conducting baseline surveillance of class 1 integrons in poultry litter and poultry litter-blended biochar and/or wood vinegar. Most significantly, class 1 integron prevalence did not decrease over time, further supporting the recalcitrance of these elements and the need for improved monitoring systems.

Effects of Loblolly Pine Biochar and Wood Vinegar on Poultry Litter Nutrients and Microbial Abundance.

Biochar, wood vinegar, and poultry litter are waste streams that can be utilized as soil amendments and fertilizers. However, poultry litter releases several pollutants through nutrient leaching and carries heavy microbial loads, including potential human pathogens. Improving nutrient retention and reducing microbial load in poultry litter may help protect environmental and human health and improve its value as a soil amendment. The objectives of this study were to determine how blending varying proportions of loblolly pine (Pinus taeda L.) biochar, wood vinegar, and poultry litter affected nutrient profiles and microbial abundance over time. Biochar inclusion rates were 0%, 5%, 10%, and 20%, and wood vinegar was applied at 2% w/w. Samples were taken at Day 0, 57, and 112 to measure nitrogen, phosphorus, potassium, pH, total fungi, and total bacteria. Nutrient levels generally decreased with increasing biochar level; however, biochar inclusion rates of 10% and 20% retained nitrogen and phosphorus and exhibited improved physical properties. Overall, adding wood vinegar decreased nutrient concentrations and showed a biocidal effect for bacteria and fungi. Bacteria and fungi showed different relationships with biochar inclusion rates, with fungi preferring higher biochar inclusion rates and bacteria flourishing at lower biochar inclusion rates.

Interprofessional education for health science students' attitudes and readiness to work interprofessionally: a prospective cohort study.

BACKGROUND: Interprofessional education of healthcare providers is necessary to foster collaborative practice and improve patient outcomes. OBJECTIVE: To examine the effectiveness of the single-session interprofessional education in improving interprofessional attitudes, increasing knowledge of healthcare professions, and improving perceived-readiness for working interprofessionally and with older adults in students in occupational therapy, physical therapy, and physician assistant graduate programs. METHODS: We used a prospective, pre-post cohort design. Fall risk evaluation for older adults was selected as the topic of the 4-hour interprofessional education session. Graduate students from three professional programs including occupational therapy (n=20), physical therapy (n=26), and physician assistant studies (n=35) participated in the study, and 17 older adults aged 65 years or older volunteered for the session. Our primary outcome measure was the Interprofessional Attitudes Scale measuring interprofessional attitudes, and our secondary outcome measure was the study-specific questionnaire measuring the direct effect of our interprofessional education session. RESULTS: Graduate students showed significant improvements in the subscale of teamwork, roles, and responsibilities in the Interprofessional Attitudes Scale. Students also showed significant improvements in "understanding of other professions," "perceived-readiness to work interprofessionally," and "perceived-readiness to work with older adults" in the study-specific questionnaire. Ceiling effects were observed in most of the subscales in the Interprofessional Attitudes Scale. CONCLUSION: This study demonstrates that a single 4-hour interprofessional education session can improve interprofessional attitudes, knowledge of other professions, and perceived-readiness of health science graduate students to work interprofessionally and to work with older adults.

Fungal Communities and Functional Guilds Shift Along an Elevational Gradient in the Southern Appalachian Mountains.

Nitrogen deposition alters forest ecosystems particularly in high elevation, montane habitats where nitrogen deposition is greatest and continues to increase. We collected soils across an elevational (788-1940 m) gradient, encompassing both abiotic (soil chemistry) and biotic (vegetation community) gradients, at eight locations in the southern Appalachian Mountains of southwestern North Carolina and eastern Tennessee. We measured soil chemistry (total N, C, extractable PO4, soil pH, cation exchange capacity [ECEC], percent base saturation [% BS]) and dissected soil fungal communities using ITS2 metabarcode Illumina MiSeq sequencing. Total soil N, C, PO4, % BS, and pH increased with elevation and plateaued at approximately 1400 m, whereas ECEC linearly increased and C/N decreased with elevation. Fungal communities differed among locations and were correlated with all chemical variables, except PO4, whereas OTU richness increased with total N. Several ecological guilds (i.e., ectomycorrhizae, saprotrophs, plant pathogens) differed in abundance among locations; specifically, saprotroph abundance, primarily attributable to genus Mortierella, was positively correlated with elevation. Ectomycorrhizae declined with total N and soil pH and increased with total C and PO4 where plant pathogens increased with total N and decreased with total C. Our results demonstrate significant turnover in taxonomic and functional fungal groups across elevational gradients which facilitate future predictions on forest ecosystem change in the southern Appalachians as nitrogen deposition rates increase and regional temperature and precipitation regimes shift.

The development and role of microbial-host interactions in gut mucosal immune development.

At birth the piglet's immune system is immature and it is dependent upon passive maternal protection until weaning. The piglet's mucosal immune system develops over the first few weeks but has not reached maturity at weaning ages which are common on commercial farms. At weaning piglets are presented with a vast and diverse range of microbial and dietary/environmental antigens. Their ability to distinguish between antigens and mount a protective response to potential pathogens and to develop tolerance to dietary antigens is critical to their survival and failure to do so is reflected in the high incidence of morbidity and mortality in the post-weaning period. A growing recognition that the widespread use of antibiotics to control infection during this critical period should be controlled has led to detailed studies of those factors which drive the development of the mucosal immune system, the role of gut microbiota in driving this process, the origin of the bacteria that colonise the young piglet's intestine and the impact of rearing environment. This review briefly describes how the mucosal immune system is equipped to respond "appropriately" to antigenic challenge and the programmed sequence by which it develops. The results of studies on the critical interplay between the host immune system and gut microbiota are discussed along with the effects of rearing environment. By comparing these with results from human studies on the development of allergies in children, an approach to promote an earlier maturation of the piglet immune system to resist the challenges of weaning are outlined.

Quantitative Assessment of Population Variability in Hepatic Drug Metabolism Using a Perfused Three-Dimensional Human Liver Microphysiological System.

In this work, we first describe the population variability in hepatic drug metabolism using cryopreserved hepatocytes from five different donors cultured in a perfused three-dimensional human liver microphysiological system, and then show how the resulting data can be integrated with a modeling and simulation framework to accomplish in vitro-in vivo translation. For each donor, metabolic depletion profiles of six compounds (phenacetin, diclofenac, lidocaine, ibuprofen, propranolol, and prednisolone) were measured, along with metabolite formation, mRNA levels of 90 metabolism-related genes, and markers of functional viability [lactate dehydrogenase (LDH) release, albumin, and urea production]. Drug depletion data were analyzed with mixed-effects modeling. Substantial interdonor variability was observed with respect to gene expression levels, drug metabolism, and other measured hepatocyte functions. Specifically, interdonor variability in intrinsic metabolic clearance ranged from 24.1% for phenacetin to 66.8% for propranolol (expressed as coefficient of variation). Albumin, urea, LDH, and cytochrome P450 mRNA levels were identified as significant predictors of in vitro metabolic clearance. Predicted clearance values from the liver microphysiological system were correlated with the observed in vivo values. A population physiologically based pharmacokinetic model was developed for lidocaine to illustrate the translation of the in vitro output to the observed pharmacokinetic variability in vivo. Stochastic simulations with this model successfully predicted the observed clinical concentration-time profiles and the associated population variability. This is the first study of population variability in drug metabolism in the context of a microphysiological system and has important implications for the use of these systems during the drug development process.

Ice stream activity scaled to ice sheet volume during Laurentide Ice Sheet deglaciation.

The contribution of the Greenland and West Antarctic ice sheets to sea level has increased in recent decades, largely owing to the thinning and retreat of outlet glaciers and ice streams. This dynamic loss is a serious concern, with some modelling studies suggesting that the collapse of a major ice sheet could be imminent or potentially underway in West Antarctica, but others predicting a more limited response. A major problem is that observations used to initialize and calibrate models typically span only a few decades, and, at the ice-sheet scale, it is unclear how the entire drainage network of ice streams evolves over longer timescales. This represents one of the largest sources of uncertainty when predicting the contributions of ice sheets to sea-level rise. A key question is whether ice streams might increase and sustain rates of mass loss over centuries or millennia, beyond those expected for a given ocean-climate forcing. Here we reconstruct the activity of 117 ice streams that operated at various times during deglaciation of the Laurentide Ice Sheet (from about 22,000 to 7,000 years ago) and show that as they activated and deactivated in different locations, their overall number decreased, they occupied a progressively smaller percentage of the ice sheet perimeter and their total discharge decreased. The underlying geology and topography clearly influenced ice stream activity, but--at the ice-sheet scale--their drainage network adjusted and was linked to changes in ice sheet volume. It is unclear whether these findings can be directly translated to modern ice sheets. However, contrary to the view that sees ice streams as unstable entities that can accelerate ice-sheet deglaciation, we conclude that ice streams exerted progressively less influence on ice sheet mass balance during the retreat of the Laurentide Ice Sheet.

Human rhinovirus-induced inflammatory responses are inhibited by phosphatidylserine containing liposomes.

Human rhinovirus (HRV) infections are major contributors to the healthcare burden associated with acute exacerbations of chronic airway disease, such as chronic obstructive pulmonary disease and asthma. Cellular responses to HRV are mediated through pattern recognition receptors that may in part signal from membrane microdomains. We previously found Toll-like receptor signaling is reduced, by targeting membrane microdomains with a specific liposomal phosphatidylserine species, 1-stearoyl-2-arachidonoyl-sn-glycero-3-phospho-L-serine (SAPS). Here we explored the ability of this approach to target a clinically important pathogen. We determined the biochemical and biophysical properties and stability of SAPS liposomes and studied their ability to modulate rhinovirus-induced inflammation, measured by cytokine production, and rhinovirus replication in both immortalized and normal primary bronchial epithelial cells. SAPS liposomes rapidly partitioned throughout the plasma membrane and internal cellular membranes of epithelial cells. Uptake of liposomes did not cause cell death, but was associated with markedly reduced inflammatory responses to rhinovirus, at the expense of only modest non-significant increases in viral replication, and without impairment of interferon receptor signaling. Thus using liposomes of phosphatidylserine to target membrane microdomains is a feasible mechanism for modulating rhinovirus-induced signaling, and potentially a prototypic new therapy for viral-mediated inflammation.

Physiome-on-a-Chip: The Challenge of "Scaling" in Design, Operation, and Translation of Microphysiological Systems.

Scaling of a microphysiological system (MPS) or physiome-on-a-chip is arguably two interrelated, modeling-based activities: on-platform scaling and in vitro-in vivo translation. This dual approach reduces the need to perfectly rescale and mimic in vivo physiology, an aspiration that is both extremely challenging and not substantively meaningful because of uncertain relevance of any specific physiological condition. Accordingly, this perspective offers a tractable approach for designing interacting MPSs and relating in vitro results to analogous context in vivo.

Quantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): Data Interpretation and Multi-MPS Integration.

Our goal in developing Microphysiological Systems (MPS) technology is to provide an improved approach for more predictive preclinical drug discovery via a highly integrated experimental/computational paradigm. Success will require quantitative characterization of MPSs and mechanistic analysis of experimental findings sufficient to translate resulting insights from in vitro to in vivo. We describe herein a systems pharmacology approach to MPS development and utilization that incorporates more mechanistic detail than traditional pharmacokinetic/pharmacodynamic (PK/PD) models. A series of studies illustrates diverse facets of our approach. First, we demonstrate two case studies: a PK data analysis and an inflammation response--focused on a single MPS, the liver/immune MPS. Building on the single MPS modeling, a theoretical investigation of a four-MPS interactome then provides a quantitative way to consider several pharmacological concepts such as absorption, distribution, metabolism, and excretion in the design of multi-MPS interactome operation and experiments.

Femoroacetabular impingement osteoplasty: is any resected amount safe? A laboratory based experiment with sawbones.

There is an increased risk of fracture following osteoplasty of the femoral neck for cam-type femoroacetabular impingement (FAI). Resection of up to 30% of the anterolateral head-neck junction has previously been considered to be safe, however, iatrogenic fractures have been reported with resections within these limits. We re-evaluated the amount of safe resection at the anterolateral femoral head-neck junction using a biomechanically consistent model. In total, 28 composite bones were studied in four groups: control, 10% resection, 20% resection and 30% resection. An axial load was applied to the adducted and flexed femur. Peak load, deflection at time of fracture and energy to fracture were assessed using comparison groups. There was a marked difference in the mean peak load to fracture between the control group and the 10% resection group (p < 0.001). The control group also tolerated significantly more deflection before failure (p < 0.04). The mean peak load (p = 0.172), deflection (p = 0.547), and energy to fracture (p = 0.306) did not differ significantly between the 10%, 20%, and 30% resection groups. Any resection of the anterolateral quadrant of the femoral head-neck junction for FAI significantly reduces the load-bearing capacity of the proximal femur. After initial resection of cortical bone, there is no further relevant loss of stability regardless of the amount of trabecular bone resected. Based on our findings we recommend any patients who undergo anterolateral femoral head-neck junction osteoplasty should be advised to modify their post-operative routine until cortical remodelling occurs to minimise the subsequent fracture risk.

Discover Dentistry: encouraging wider participation in dentistry using a massive open online course (MOOC).

This paper describes how a relatively new style of online learning, a massive open online course (MOOC), may be used to raise aspirations and widen participation in dental professions. A MOOC was designed and run with the aim of engaging prospective students of dental professions in learning and discussion. Over 4,200 learners signed up, and 450 students fully completed this first run of the course. The course attracted a significantly younger demographic than is typical for MOOCs, and nearly a third who responded to the pre-course survey reported they were doing the course specifically as preparation for a dental degree. The approach also provided a platform for public engagement on the subject of dentistry with participants, both dental professionals and members of the public, contributing to discussion around the learning materials from around the world, providing a unique, internationalised perspective of oral healthcare for learners. This study shows that there is genuine potential for MOOCs to involve people from disadvantaged backgrounds in higher education by offering free, accessible, enjoyable and engaging educational experiences. The data gives us cautious optimism that these courses can play a significant role within a platform of other WP interventions.