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Hydrogels have gained recent attention for biomedical applications because of their large water content, which imparts biocompatibility. However, their mechanical properties can be limiting. There has been significant recent interest in the strength and fracture toughness of hydrogel materials in addition to their stiffness and time-dependent behavior. Hydrogels can fail in a brittle manner, although they are extremely compliant. In this work, the failure and fracture of hydrogels are examined using a compression test of spherical hydrogel particles. Spheres of commercially available polyacrylamide–potassium polyacrylate were hydrated and tested to failure in compression as a function of loading rate. The spheres exhibited little relaxation when compressed to small fixed displacements. The distributions of strength values obtained were examined in a particle fracture framework previously used for brittle ceramics. There was loading rate dependence apparent in the measured peak force and calculated peak strength values, but the data fell on a single empirical distribution function of strength for the hydrogels regardless of loading rate. Strength values for these hydrogels were mostly in the range of 0.05–0.3 MPa, illustrating the challenges using hydrogels for mechanically demanding applications such as tissue engineering.
Registry-based trials have emerged as a potentially cost-saving study methodology. Early estimates of cost savings, however, conflated the benefits associated with registry utilisation and those associated with other aspects of pragmatic trial designs, which might not all be as broadly applicable. In this study, we sought to build a practical tool that investigators could use across disciplines to estimate the ranges of potential cost differences associated with implementing registry-based trials versus standard clinical trials.
We built simulation Markov models to compare unique costs associated with data acquisition, cleaning, and linkage under a registry-based trial design versus a standard clinical trial. We conducted one-way, two-way, and probabilistic sensitivity analyses, varying study characteristics over broad ranges, to determine thresholds at which investigators might optimally select each trial design.
Registry-based trials were more cost effective than standard clinical trials 98.6% of the time. Data-related cost savings ranged from $4300 to $600,000 with variation in study characteristics. Cost differences were most reactive to the number of patients in a study, the number of data elements per patient available in a registry, and the speed with which research coordinators could manually abstract data. Registry incorporation resulted in cost savings when as few as 3768 independent data elements were available and when manual data abstraction took as little as 3.4 seconds per data field.
Registries offer important resources for investigators. When available, their broad incorporation may help the scientific community reduce the costs of clinical investigation. We offer here a practical tool for investigators to assess potential costs savings.
Introduction: Emergency care serves as an important health resource for First Nations (FN) persons. Previous reporting shows that FN persons visit emergency departments at almost double the rate of non-FN persons. Working collaboratively with FN partners, academic researchers and health authority staff, the objective of this study is to investigate FN emergency care patient visit statistics in Alberta over a five year period. Methods: Through a population-based retrospective cohort study for the period from April 1, 2012 to March 31, 2017, patient demographics and emergency care visit characteristics for status FN patients in Alberta were analyzed and compared to non-FN statistics. Frequencies and percentages (%) describe patients and visits by categorical variables (e.g., Canadian Triage Acuity Scale (CTAS)). Means and standard deviations (medians and interquartile ranges (IQR)) describe continuous variables (e.g., distances) as appropriate for the data distribution. These descriptions are repeated for the FN and non-FN populations, separately. Results: The data set contains 11,686,288 emergency facility visits by 3,024,491 unique persons. FN people make up 4.8% of unique patients and 9.4% of emergency care visits. FN persons live further from emergency facilities than their non-FN counterparts (FN median 6 km, IQR 1-24; vs. non-FN median 4 km, IQR 2-8). FN visits arrive more often by ground ambulance (15.3% vs. 10%). FN visits are more commonly triaged as less acute (59% CTAS levels 4 and 5, compared to non-FN 50.4%). More FN visits end in leaving without completing treatment (6.7% vs. 3.6%). FN visits are more often in the evening – 4:01pm to 12:00am (43.6% vs. 38.1%). Conclusion: In a collaborative validation session, FN Elders and health directors contextualized emergency care presentation in evenings and receiving less acute triage scores as related to difficulties accessing primary care. They explained presentation in evenings, arrival by ambulance, and leaving without completing treatment in terms of issues accessing transport to and from emergency facilities. Many factors interact to determine FN patients’ emergency care visit characteristics and outcomes. Further research needs to separate the impact of FN identity from factors such as reasons for visiting emergency facilities, distance traveled to care, and the size of facility where care is provided.
Articular cartilage plays an important role in synovial joint function, but this function is diminished when cartilage tissue breaks down in osteoarthritis. Tissue engineering is a promising approach for replacing failed cartilage, as cartilage is a relatively simple tissue with no blood supply and very few biological cells. To imitate the structure of natural cartilage extracellular matrix material, three components must be included: the hydrated ground substance, the charges that contribute to compressive stiffness via electrostatic repulsion, and the nanofibrous collagen network that resists tensile deformation and failure. Here, the nanofiber network is considered, with examination of its fracture behavior in an as-electrospun state and following a mild chemical crosslinking process. Mode III fracture testing was used to quantify the tear toughness of the fibrous mats, and failure behavior was qualitatively examined with scanning electron microscopy. In ongoing work, this nanofibrous structure will be combined with a charged polyelectrolyte hydrogel gel to create a biomimetic cartilage-like material. By using biomimicry to replicate what is present in native cartilage tissue, a superior material can be designed and fabricated for use in tissue repair and replacement.
Neurocognitive impairments robustly predict functional outcome. However, heterogeneity in neurocognition is common within diagnostic groups, and data-driven analyses reveal homogeneous neurocognitive subgroups cutting across diagnostic boundaries.
To determine whether data-driven neurocognitive subgroups of young people with emerging mental disorders are associated with 3-year functional course.
Model-based cluster analysis was applied to neurocognitive test scores across nine domains from 629 young people accessing mental health clinics. Cluster groups were compared on demographic, clinical and substance-use measures. Mixed-effects models explored associations between cluster-group membership and socio-occupational functioning (using the Social and Occupational Functioning Assessment Scale) over 3 years, adjusted for gender, premorbid IQ, level of education, depressive, positive, negative and manic symptoms, and diagnosis of a primary psychotic disorder.
Cluster analysis of neurocognitive test scores derived three subgroups described as ‘normal range’ (n = 243, 38.6%), ‘intermediate impairment’ (n = 252, 40.1%), and ‘global impairment’ (n = 134, 21.3%). The major mental disorder categories (depressive, anxiety, bipolar, psychotic and other) were represented in each neurocognitive subgroup. The global impairment subgroup had lower functioning for 3 years of follow-up; however, neither the global impairment (B = 0.26, 95% CI −0.67 to 1.20; P = 0.581) or intermediate impairment (B = 0.46, 95% CI −0.26 to 1.19; P = 0.211) subgroups differed from the normal range subgroup in their rate of change in functioning over time.
Neurocognitive impairment may follow a continuum of severity across the major syndrome-based mental disorders, with data-driven neurocognitive subgroups predictive of functional course. Of note, the global impairment subgroup had longstanding functional impairment despite continuing engagement with clinical services.
Amidst rising concern about publication bias, pre-registration and results-blind review have grown rapidly in use. Yet discussion of both the problem of publication bias and of potential solutions has been remarkably narrow in scope: publication bias has been understood largely as a problem afflicting quantitative studies, while pre-registration and results-blind review have been almost exclusively applied to experimental or otherwise prospective research. This chapter examines the potential contributions of pre-registration and results-blind review to qualitative and quantitative retrospective research. First, the chapter provides an empirical assessment of the degree of publication bias in qualitative political science research. Second, it elaborates a general analytic framework for evaluating the feasbility and utility of pre-registration and results-blind review for confirmatory studies. Third, through a review of published studies, the paper demonstrates that much observational—and, especially, qualitative—political science research displays features that would make for credible pre-registration. The paper concludes that pre-registration and results-blind review have the potential to enhance the validity of confirmatory research across a range of empirical methods, while elevating exploratory work by making it harder to disguise discovery as testing.
Mechanistic models (MMs) have served as causal pathway analysis and ‘decision-support’ tools within animal production systems for decades. Such models quantitatively define how a biological system works based on causal relationships and use that cumulative biological knowledge to generate predictions and recommendations (in practice) and generate/evaluate hypotheses (in research). Their limitations revolve around obtaining sufficiently accurate inputs, user training and accuracy/precision of predictions on-farm. The new wave in digitalization technologies may negate some of these challenges. New data-driven (DD) modelling methods such as machine learning (ML) and deep learning (DL) examine patterns in data to produce accurate predictions (forecasting, classification of animals, etc.). The deluge of sensor data and new self-learning modelling techniques may address some of the limitations of traditional MM approaches – access to input data (e.g. sensors) and on-farm calibration. However, most of these new methods lack transparency in the reasoning behind predictions, in contrast to MM that have historically been used to translate knowledge into wisdom. The objective of this paper is to propose means to hybridize these two seemingly divergent methodologies to advance the models we use in animal production systems and support movement towards truly knowledge-based precision agriculture. In order to identify potential niches for models in animal production of the future, a cross-species (dairy, swine and poultry) examination of the current state of the art in MM and new DD methodologies (ML, DL analytics) is undertaken. We hypothesize that there are several ways via which synergy may be achieved to advance both our predictive capabilities and system understanding, being: (1) building and utilizing data streams (e.g. intake, rumination behaviour, rumen sensors, activity sensors, environmental sensors, cameras and near IR) to apply MM in real-time and/or with new resolution and capabilities; (2) hybridization of MM and DD approaches where, for example, a ML framework is augmented by MM-generated parameters or predicted outcomes and (3) hybridization of the MM and DD approaches, where biological bounds are placed on parameters within a MM framework, and the DD system parameterizes the MM for individual animals, farms or other such clusters of data. As animal systems modellers, we should expand our toolbox to explore new DD approaches and big data to find opportunities to increase understanding of biological systems, find new patterns in data and move the field towards intelligent, knowledge-based precision agriculture systems.
There is lack of Cameroonian adult neuropsychological (NP) norms, limited knowledge concerning HIV-associated neurocognitive disorders in Sub-Saharan Africa, and evidence of differential inflammation and disease progression based on viral subtypes. In this study, we developed demographically corrected norms and assessed HIV and viral genotypes effects on attention/working memory (WM), learning, and memory.
We administered two tests of attention/WM [Paced Auditory Serial Addition Test (PASAT)-50, Wechsler Memory Scale (WMS)-III Spatial Span] and two tests of learning and memory [Brief Visuospatial Memory Test-Revised (BVMT-R), Hopkins Verbal Learning Test-Revised (HVLT-R)] to 347 HIV+ and 395 seronegative adult Cameroonians. We assessed the effects of viral factors on neurocognitive performance.
Compared to controls, people living with HIV (PLWH) had significantly lower T-scores on PASAT-50 and attention/WM summary scores, on HVLT-R total learning and learning summary scores, on HVLT-R delayed recall, BVMT-R delayed recall and memory summary scores. More PLWH had impairment in attention/WM, learning, and memory. Antiretroviral therapy (ART) and current immune status had no effect on T-scores. Compared to untreated cases with detectable viremia, untreated cases with undetectable viremia had significantly lower (worse) T-scores on BVMT-R total learning, BVMT-R delayed recall, and memory composite scores. Compared to PLWH infected with other subtypes (41.83%), those infected with HIV-1 CRF02_AG (58.17%) had higher (better) attention/WM T-scores.
PLWH in Cameroon have impaired attention/WM, learning, and memory and those infected with CRF02_AG viruses showed reduced deficits in attention/WM. The first adult normative standards for assessing attention/WM, learning, and memory described, with equations for computing demographically adjusted T-scores, will facilitate future studies of diseases affecting cognitive function in Cameroonians.
Mono-2-ethylhexyl phthalate (MEHP) is the primary metabolite of the ubiquitous plasticizer and toxicant, di-2-ethylhexyl phthalate. MEHP exposure has been linked to abnormal development, increased oxidative stress, and metabolic syndrome in vertebrates. Nuclear factor, Erythroid 2 Like 2 (Nrf2), is a transcription factor that regulates gene expression in response to oxidative stress. We investigated the role of Nrf2a in larval steatosis following embryonic exposure to MEHP. Wild-type and nrf2a mutant (m) zebrafish embryos were exposed to 0 or 200 μg/l MEHP from 6 to either 96 (histology) or 120 hours post fertilization (hpf). At 120 hpf, exposures were ceased and fish were maintained in clean conditions until 15 days post fertilization (dpf). At 15 dpf, fish lengths and lipid content were examined, and the expression of genes involved in the antioxidant response and lipid processing was quantified. At 96 hpf, a subset of animals treated with MEHP had vacuolization in the liver. At 15 dpf, deficient Nrf2a signaling attenuated fish length by 7.7%. MEHP exposure increased hepatic steatosis and increased expression of peroxisome proliferator-activated receptor alpha target fabp1a1. Cumulatively, these data indicate that developmental exposure alone to MEHP may increase risk for hepatic steatosis and that Nrf2a does not play a major role in this phenotype.
Land ownership and the rights in property are central to the American character, having originated as part of the colonial dialogue that led to the American revolution. Yet there has also been substantial social conflict over who has claims to property, and in whose interest. This article presents an interpretive history of citizenship claims to land and property from the colonial period to the present. It argues that a theme in this history is an ever expanding realm of citizenship claims against the individual owner, most markedly since the beginning of the twentieth century. The emergence of the modern environmental movement and a counter so-called private property rights movement in the 1970s forward has accentuated this social conflict. The future likely holds increased conflict in an era of social and political polarisation. The outcome is uncertain, and will depend on democratic dialogue among those with strongly opposing perspectives.
This chapter introduces the research background and application of cognitive behavioral therapy (CBT) with older adults. First, an overview of the research literature is presented. Second, the theoretical framework underlying CBT is summarized with a focus on proposed agents of change. Third, research on patient selection, treatment modalities, and special topics is reviewed. Fourth, a session-by-session tutorial on the components of CBT from intake to treatment termination is provided. A case example is included along with several other cases to illustrate therapeutic techniques. Further readings, resources, and trainings are included at the end of the chapter.
Decisions on the use of nature reflect the values and rights of individuals, communities and society at large. The values of nature are expressed through cultural norms, rules and legislation, and they can be elicited using a wide range of tools, including those of economics. None of the approaches to elicit peoples’ values are neutral. Unequal power relations influence valuation and decision-making and are at the core of most environmental conflicts. As actors in sustainability thinking, environmental scientists and practitioners are becoming more aware of their own posture, normative stance, responsibility and relative power in society. Based on a transdisciplinary workshop, our perspective paper provides a normative basis for this new community of scientists and practitioners engaged in the plural valuation of nature.
The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together
programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.
Neonates are at high risk of bleeding after open-heart surgery. We sought to determine pre-operative and intra-operative risk factors for increased bleeding after neonatal open-heart surgery with cardiopulmonary bypass.
We conducted a retrospective cohort study of neonates (0–30 days old) who underwent open-heart surgery with cardiopulmonary bypass from January, 2009, to March, 2013. Cardiac diagnosis; demographic and surgical data; and blood products, haemostatic agents, and anti-thrombotic agents administered before, during, and within 24 hours after surgery were abstracted from the electronic health record and anaesthesia records. The outcome of interest was chest tube output (in ml/kg body weight) within 24 hours. Relationships between chest tube output and putative associated factors were evaluated by unadjusted and adjusted linear regression.
The cohort consisted of 107 neonates, of whom 79% had a Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) Mortality Category of 4 or 5. Median chest tube output was 37 ml/kg (range 9–655 ml/kg). Age, African-American race, and longer durations of surgery and cardiopulmonary bypass each had statistically significant associations with increased chest tube output in unadjusted analyses. In multivariable analysis, African-American race retained an independent, statistically significant association with increased chest tube output; the geometric mean of chest tube output among African-American neonates was 71% higher than that of Caucasians (95% confidence interval, 29–125%; p = 0.001).
Among neonates with CHD undergoing open-heart surgery with cardiopulmonary bypass, African-American race is independently associated with greater chest tube output over the first 24 hours post-operatively.
The Empire of Aksum was one of Africa's most influential ancient civilisations. Traditionally, most archaeological fieldwork has focused on the capital city of Aksum, but recent research at the site of Beta Samati has investigated a contemporaneous trade and religious centre located between Aksum and the Red Sea. The authors outline the discovery of the site and present important finds from the initial excavations, including an early basilica, inscriptions and a gold intaglio ring. From daily life and ritual praxis to international trade, this work illuminates the role of Beta Samati as an administrative centre and its significance within the wider Aksumite world.
In legal orders around the world, commitments to democracy, liberalism and constitutionalism are increasingly eroding. Although political and constitutional theorists often lament this trend, they invariably adopt frameworks that are indifferent to these commitments. My aims in this article are both critical and constructive. As a critical matter, I will expose the indifference of the leading political and constitutional theories to the emergence, maintenance and refinement of liberal democratic constitutional orders. As a constructive matter, I will draw on Immanuel Kant’s constitutional theory to explain why realizing such a form of governance is a public duty and why receding from it is a public wrong.