Bayesian Plackett--Luce Mixture Models for Partially Ranked Data

The elicitation of an ordinal judgment on multiple alternatives is often required in many psychological and behavioral experiments to investigate preference/choice orientation of a specific population. The Plackett–Luce model is one of the most popular and frequently applied parametric distributions to analyze rankings of a finite set of items. The present work introduces a Bayesian finite mixture of Plackett–Luce models to account for unobserved sample heterogeneity of partially ranked data. We describe an efficient way to incorporate the latent group structure in the data augmentation approach and the derivation of existing maximum likelihood procedures as special instances of the proposed Bayesian method. Inference can be conducted with the combination of the Expectation-Maximization algorithm for maximum a posteriori estimation and the Gibbs sampling iterative procedure.We additionally investigate several Bayesian criteria for selecting the optimal mixture configuration and describe diagnostic tools for assessing the fitness of ranking distributions conditionally and unconditionally on the number of ranked items. The utility of the novel Bayesian parametric Plackett–Luce mixture for characterizing sample heterogeneity is illustrated with several applications to simulated and real preference ranked data. We compare our method with the frequentist approach and a Bayesian nonparametric mixture model both assuming the Plackett–Luce model as a mixture component. Our analysis on real datasets reveals the importance of an accurate diagnostic check for an appropriate in-depth understanding of the heterogenous nature of the partial ranking data

Tissue Specific Microenvironments: A Key Tool for Tissue Engineering and Regenerative Medicine

The accumulated evidence points to the microenvironment as the primary mediator of cellular fate determination. Comprised of parenchymal cells, stromal cells, structural extracellular matrix proteins, and signaling molecules, the microenvironment is a complex and synergistic edifice that varies tissue to tissue. Furthermore, it has become increasingly clear that the microenvironment plays crucial roles in the establishment and progression of diseases such as cardiovascular disease, neurodegeneration, cancer, and ageing. Here we review the historical perspectives on the microenvironment, and how it has directed current explorations in tissue engineering. By thoroughly understanding the role of the microenvironment, we can begin to correctly manipulate it to prevent and cure diseases through regenerative medicine techniques

Evaluation of Load Distribution in a Mandibular Model with Four Implants Depending on the Number of Prosthetic Screws Used for OT-Bridge System: A Finite Element Analysis (FEA)

In full-arch implant rehabilitations, when the anterior screw abutment channel compromises the aesthetic of the patient, the OT-Bridge system used with its Seeger rings may provide the necessary retention of the prosthesis. However, no studies have evaluated the forces generated at the Seeger level during loading. This Finite Element Analysis aims to investigate the mechanical behavior of Seeger rings in a mandibular model with four implants and an OT-Bridge system, used without one or two anterior prosthetic screws. A 400 N unilateral load was virtually applied on a 7 mm distal cantilever. Two different variables were considered: the constraint conditions using two or three screws instead of four and the three different framework materials (fiberglass reinforced resin, cobalt-chrome, TiAl6V4). The FEA analysis exhibited tensile and compressive forces on the Seeger closest to the loading point. With the resin framework, a tension force on abutment 3.3 generates a displacement from 5 to 10 times greater than that respectively expressed in metal framework materials. In a full-arch rehabilitation with four implants, the case with three prosthetic screws seems to be a safer and more predictable configuration instead of two. Considering the stress value exhibited and the mechanical properties of the Seeger, the presence of only two prosthetic screws could lead to permanent deformation of the Seeger in the screwless abutment closest to the loading point

Quantification of calsequestrin 2 (CSQ2) in sheep cardiac muscle and Ca 2+ -binding protein changes in CSQ2 knockout mice

Calsequestrin 2 (CSQ2) is generally regarded as the primary Ca2+-buffering molecule present inside the sarcoplasmic reticulum (SR) in cardiac cells, but findings from CSQ2 knockout experiments raise major questions about its role and necessity. This study determined the absolute amount of CSQ2 present in cardiac ventricular muscle to gauge its likely influence on SR free Ca2+ concentration ([Ca2+]) and maximal Ca2+ capacity. Ventricular tissue from hearts of freshly killed sheep was examined by SDS-PAGE without any fractionation, and CSQ2 was detected by Western blotting; this method avoided the >90% loss of CSQ2 occurring with usual fractionation procedures. Band intensities were compared against those for purified CSQ2 run on the same blots. Fidelity of quantification was verified by demonstrating that CSQ2 added to homogenates was detected with equal efficacy as purified CSQ2 alone. Ventricular tissue from sheep (n = 8) contained 24 ± 2 μmol CSQ2/kg wet wt. Total Ca2+ content of the ventricular tissue, measured by atomic absorption spectroscopy, was 430 ± 20 μmol/kg (with SR Ca2+ likely <250 μmol/kg) and displayed a linear correlation with CSQ2 content, with gradient of ∼10 Ca2+ per CSQ2. The large amount of CSQ2 bestows the SR with a high theoretical maximal Ca2+-binding capacity (∼1 mmol Ca2+/kg ventricular tissue, assuming a maximum of ∼40 Ca2+ per CSQ2) and would keep free [Ca2+] within the SR relatively low, energetically favoring Ca2+ uptake and reducing SR leak. In mice with CSQ2 ablated, histidinerich Ca2+-binding protein was upregulated ∼35% in ventricular tissue, possibly in compensation

State Scorecard on Long-Term Services and Supports for Older Adults, People with Physical Disabilities, and Family Caregivers

This State Long-Term Services and Supports (LTSS) Scorecard is a multidimensional approach to measure state-level performance of LTSS systems that assist older people, adults with disabilities, and their family caregivers. This second edition of the State LTSS Scorecard measures LTSS system performance across five key dimensions: (1) affordability and access, (2) choice of setting and provider, (3) quality of life and quality of care, (4) support for family caregivers, and (5) effective transitions. Performance varies tremendously across the states, with LTSS systems in leading states having markedly different characteristics than those in lagging states. LTSS performance is gradually improving, both nationally and in most states. Progress is notable in many areas where public policy has a direct impact, including performance of the Medicaid safety net and legal and system supports for family caregivers. But the pace of improvement must accelerate as the Baby Boom Generation moves toward advanced ages

Stem Cell Differentiation and Effects of Three-Dimensional Cellular Microenvironments

The cellular microenvironment has been shown to play a fundamental role in the regulation of cell function, stem cell fate determination, maintenance of cell potency and tissue homeostasis. Our laboratory focuses on the study of the effects of cellular microenvironment in the context of cancer and neurological models, based on the observation that a healthy environment can induce the suppression of tumorigenesis in mouse models. Insights concerning the molecular mechanisms that drive these processes are very limited, partly due to the inability of the current traditional methods of investigation, such as two-dimensional cell cultures and animal models, to accurately represent the human in vivo cellular microenvironment. Three-dimensional cell cultures allow to overcome the structural limitations posed by monolayer cultures, and maintain the ease of experiment design, monitoring and data analysis associated with in vitro procedures. Our laboratory has established systems to overcome some of these limitations and rely on the strengths of three-dimensional culture methods to elucidate mechanisms that govern stem cell differentiation. A customized 3D extrusion-based bioprinter was developed starting from a commercially available model, allowing for precise and controlled injection of cells within three-dimensional substrates. This tool allows for design of highly controlled experiments, in which the effects of cellular microenvironment on stem cell differentiation can be studied at a single-cell resolution. For increased levels of biomimicry, tissue specific substrates are generated from extracted tissue. Collected tissue is subjected to a chemical decellularization process, followed by lyophilization, enzymatic digestion and neutralization, to generate a self-gelling product upon incubation at 37°C. Mammary and brain extracellularmatrix-derived substrates have been shown to support the growth of cells of the epithelial and neuronal lineages, respectively. Here, we apply these established systems to study the effects of the environment constituted by the three-dimensional substrates on the differentiation of injected stem cells.https://digitalcommons.odu.edu/engineering_batten/1016/thumbnail.jp

Assessment of chest high-field magnetic resonance imaging in children and young adults with noncystic fibrosis chronic lung disease: comparison to high-resolution computed tomography and correlation with pulmonary function.

Magnetic resonance imaging (MRI) has been proposed as a radiation-free alternative to high resolution computed tomography (HRCT) for the assessment and follow-up of chest disorders. Thus far, no study has compared the efficacy of high-field MRI and HRCT in children and adults with noncystic fibrosis (CF) chronic lung disease. The aims of our study were: (1) to assess whether chest high-field MRI is as effective as chest HRCT in identifying pulmonary abnormalities; and (2) to investigate the relationships between the severity and extent of lung disease, and functional data in patients with non-CF chronic lung disease. Forty-one subjects (median age, 13.8 years; range, 5.9-29.3 years; 30 children/11 adults) with primary ciliary dyskinesia (n = 14), primary immunodeficiency (n = 14), or recurrent pneumonia (n = 13) underwent pulmonary function tests, chest HRCT (120 kV, dose-modulated mAs) and high-field 3.0-T MRI (HASTE; transversal orientation; repetition time/echo time/flip angle/acquisition time, infinite/92 milliseconds/150 degrees/approximately 90 seconds). HRCT and MRI images were scored in consensus by 2 raters using a modified version of the Helbich scoring system. The maximal score was 25. HRCT and high-field MRI total scores were 11 (range: 1-20) and 11 (range: 1-17), respectively. There was good agreement between the 2 techniques for all scores (r > 0.8). HRCT and MRI total scores, and extent of bronchiectasis scores were significantly related to pulmonary function tests (r = -0.4, P < 0.05). The MRI mucous plugging score was significantly related to pulmonary function tests (r = -0.4, P < 0.05). Chest high-field 3.0-T MRI appears to be as effective as HRCT in assessing the extent and severity of lung abnormalities in non-CF chronic lung diseases, and might be a reliable radiation-free option to HRCT

Preventive strategies for acute kidney injury in cancer patients

Acute kidney injury (AKI) is a common complication of cancer that occurs in up to 50% of neoplastic patients during the natural history of their disease; furthermore, it has a huge impact on key outcomes such as overall prognosis, length of hospitalization and costs. AKI in cancer patients has different causes, either patient-, tumour-or treatment-related. Patient-related risk factors for AKI are the same as in the general population, whereas tumour-related risk factors are represented by compression, obstruction, direct kidney infiltration from the tumour as well by precipitation, aggregation, crystallization or misfolding of paraprotein (as in the case of multiple myeloma). Finally, treatment-related risk factors are the most common observed in clinical practice and may present also with the feature of tumour lysis syndrome or thrombotic microangiopathies. In the absence of validated biomarkers, a multidisciplinary clinical approach that incorporates adequate assessment, use of appropriate preventive measures and early intervention is essential to reduce the incidence of this life-threatening condition in cancer patients

Anti-inflammatory activity of American yam Dioscorea trifida L.f. in food allergy induced by ovalbumin in mice

AbstractTropical ecosystems are particularly rich in edible plant species with different bioactive substances. Among the plants with promising benefits for health are species from the genus Dioscorea (Dioscoreaceae), especially those named yam. Recent studies have shown the beneficial effects of different species of Dioscorea, and its main constituent, diosgenine, in the treatment of food allergy. In this study we evaluated the potential of D. trifida, the only yam native from South America, in the treatment of ovalbumin (OVA) induced food allergy in Balb/c mice. HPLC/DAD analysis showed the presence of three very distinctive groups of natural products in extracts and fractions: (I) very polar substances, including allantoin, (II) phenolic substances as flavonoids and phenolic acids and (III) diosgenin and derivatives. Sensitive mice received casein feed with supplementation of crude extract (CE) and fractions. The supplementation with all products from D. trifida reduced IGE, intestinal oedema and mucus production, parameters observed in OVA allergic mice. The results showed the potential of this food to prevent or treat this disease and the necessity to be better explored

Accessible Bioprinting: Adaptation of a Low-Cost 3D-Printer for Precise Cell Placement and Stem Cell Differentiation

The precision and repeatability offered by computer-aided design and computer-numerically controlled techniques in biofabrication processes is quickly becoming an industry standard. However, many hurdles still exist before these techniques can be used in research laboratories for cellular and molecular biology applications. Extrusion-based bioprinting systems have been characterized by high development costs, injector clogging, difficulty achieving small cell number deposits, decreased cell viability, and altered cell function post-printing. To circumvent the high-price barrier to entry of conventional bioprinters, we designed and 3D printed components for the adaptation of an inexpensive \u27off-the-shelf\u27 commercially available 3D printer. We also demonstrate via goal based computer simulations that the needle geometries of conventional commercially standardized, \u27luer-lock\u27 syringe-needle systems cause many of the issues plaguing conventional bioprinters. To address these performance limitations we optimized flow within several microneedle geometries, which revealed a short tapered injector design with minimal cylindrical needle length was ideal to minimize cell strain and accretion. We then experimentally quantified these geometries using pulled glass microcapillary pipettes and our modified, low-cost 3D printer. This systems performance validated our models exhibiting: reduced clogging, single cell print resolution, and maintenance of cell viability without the use of a sacrificial vehicle. Using this system we show the successful printing of human induced pluripotent stem cells (hiPSCs) into Geltrex and note their retention of a pluripotent state 7 d post printing. We also show embryoid body differentiation of hiPSC by injection into differentiation conducive environments, wherein we observed continuous growth, emergence of various evaginations, and post-printing gene expression indicative of the presence of all three germ layers. These data demonstrate an accessible open-source 3D bioprinter capable of serving the needs of any laboratory interested in 3D cellular interactions and tissue engineering