A Unified System for Ensuring Drug Safety

There are currently two systems in the United States to ensure the safety of pharmaceutical products: tort and regulation. The shared goal of tort law and Food and Drug Administrative (“FDAâ€) regulation is to make beneficial drugs available to patients while keeping unsafe drugs off the market. This goal will be better served if the two are combined into a unified system, wherein each functions in the role best suited to its relative strengths and weaknesses. In the proposed unified system FDA would be the decision maker, setting the standard for drug safety, and tort would be the enforcer, safeguarding the process of FDA regulation. FDA is the better institution for making scientific decisions on a society-wide basis. Tort is the better institution for ensuring FDA has all available information about a drug’s safety and for restraining undue political influence over FDA decision-making. Tort should therefore hold pharmaceutical manufacturers liable if they withhold safety information from FDA or if they attempt to force a decision on any basis except safety. Absent interference with FDA regulation, there is no need for tort liability. In these distinct roles, regulation and tort can each complement the decision-making of the other instead of overruling it. This shared governance of drug safety promises greater efficiency, less confusion, and ultimately more protection for patients

Mastery Learning: Improving the Model

In this paper, we report on developments in the Mastery Learning (ML) curriculum and assessment model that has been successfully implemented in a metropolitan university for teaching first-year mathematics. Initial responses to ML were positive; however, we ask whether the nature of the ML tests encourages a focus on shallow learning of procedures, and whether the structure of the assessment regime provides sufficient motivation for learning more complex problem solving. We analysed assessment data, as well as student reports and survey responses in an attempt to answer these questions

A Theoretical Investigation of the Ground and Low‐Lying Excited States of Butadiene Radical Cation

Results are presented from ab initio calculations on the ground and several low‐lying excited states of the butadiene radical cation. In particular, we have calculated geometries for the ground and several excited states at the multiconfiguration self‐consistent field level and characterized the planar stationary points. The vertical ionization potentials from the neutral molecule ground state and vertical excitation energies at the computed equilibrium geometry of the cation were also examined. A variety of methods were tested for the calculation of ionization potentials and excitation energies, including multiconfiguration self‐consistent field, multireference singles and doubles configuration interaction (with and without size‐consistency correction), and multireference averaged coupled pair functional theory. It is found that several of the excited states are strong mixtures of so‐called Koopmans’ and non‐Koopmans’ configurations. In most cases, good agreement is found with experiment, but the excitation energy for the second excited π state, a state which is multiconfigurational at zeroth order, is apparently overestimated at all levels of theory employed here

Treatment of human lens epithelium with high levels of nanoceria leads to reactive oxygen species mediated apoptosis

Nanoceria (cerium oxide nanoparticles) have been shown to protect human lens epithelial cells (HLECs) from oxidative stress when used at low concentrations. However, there is a lack of understanding about the mechanism of the cytotoxic and genotoxic effects of nanoceria when used at higher concentrations. Here, we investigated the impact of 24-hour exposure to nanoceria in HLECs. Nanoceria’s effects on basal reactive oxygen species (ROS), mitochondrial morphology, membrane potential, ATP, genotoxicity, caspase activation and apoptotic hallmarks were investigated. Scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX) studies on isolated mitochondria revealed significant uptake and localization of nanoceria in the mitochondria. At high nanoceria concentrations (400 µg mL−1), intracellular levels of ROS were increased and the HLECs exhibited classical hallmarks of apoptosis. These findings concur with the cells maintaining normal ATP levels necessary to execute the apoptotic process. These results highlight the need for nanoceria dose-effect studies on a range of cells and tissues to identify therapeutic concentrations in vitro or in viv

Utilizing Mucosal Protrusion Angles to Discriminate Between True and False Masses of the Small Bowel on Video Capsule Endoscopy

Background: Video capsule endoscopy (VCE) has significantly improved our ability to detect small bowel tumors. However, diagnosing small bowel tumors has remained a challenge due to their low incidence, nonspecific presentations, and the inability to use VCE to biopsy lesions identified during passage through the small bowel. To address this challenge, Girelli et al. developed a novel scoring system called the “smooth, protruding lesions index at capsule endoscopy” (SPICE) to distinguish true submucosal masses from innocent bulges1. In our study, we compared the utility of an additional morphologic criterion, the mucosal protrusion angle, with SPICE scores in detecting true submucosal masses of the small-bowel. Methods: We retrospectively reviewed the charts of 300 patients over the age of 18 who had undergone VCE for suspected small bowel lesions between the years of 2002 and 2017. In total, we analyzed the VCEs of 36 patients. SPICE scores were calculated for each patient as outlined in Girelli et al. and mucosal protrusion angles were measured using a protractor placed on the computer screen. We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of both SPICE and protrusion angle. The protrusion angle was defined as the angle between the polyp and surrounding mucosa, and we hypothesized that an angle \u3e 900 suggested an external protrusion while an angle \u3c 900 suggested a submucosal mass or true polyp. Results: 25 patients had true submucosal masses (2 GIST, 6 carcinoid, 5 Peutz-Jeghers, 3 inflammatory polyps, 2 hamartomatous polyps, 1 lymphoma, 1 lipomatous polyp, 2 tubular adenomas, 1 leiomyoma, 1 cavernous hemangioma, 1 hyperplastic polyp, 1 lymphatic nodule), and 10 patients had innocent bulges due to extrinsic compression. True submucosal masses when compared to innocent bulges had an average measured angle of protrusion of 45.70 ± 20.80 vs. 108.60 ± 16.30 (p \u3c 0.0001; unpaired t-test). When compared with SPICE scores, a mucosal protrusion angle \u3c 900 had a higher sensitivity (96.0% vs. 35.0%), specificity (90.0% vs. 82.0%), PPV (96.0% vs. 82.0%) and NPV (90.0% vs. 35.0%). Acute angle of protrusion accurately discriminated between true submucosal masses and extrinsic compression bulges on Fisher’s exact test (p = 0.0001). Conclusion: Protrusion angle is a simple and useful tool for differentiating between true submucosal masses and innocent bulges of the small-bowel. Further prospective studies are needed to validate its utility in minimizing invasive interventions

Why are “What” and “Where” Processed by Separate Cortical Visual Systems? A Computational Investigation

In the primate visual system, the identification of objects and the processing of spatial information are accomplished by different cortical pathways. The computational properties of this “two-systems” design were explored by constructing simplifying connectionist models. The models were designed to simultaneously classify and locate shapes that could appear in multiple positions in a matrix, and the ease of forming representations of the two kinds of information was measured. Some networks were designed so that all hidden nodes projected to all output nodes, whereas others had the hidden nodes split into two groups, with some projecting to the output nodes that registered shape identity and the remainder projecting to the output nodes that registered location. The simulations revealed that splitting processing into separate streams for identifying and locating a shape led to better performance only under some circumstances. Provided that enough computational resources were available in both streams, split networks were able to develop more efficient internal representations, as revealed by detailed analyses of the patterns of weights between connections.Psycholog

Raman Microspectroscopy Analysis in the Treatment of Acanthamoeba Keratitis

Acanthamoeba keratitis is a rare but serious corneal disease, often observed in contact lens wearers. Clinical treatment of infected patients frequently involves the use of polyhexamethylene biguanide (PHMB), a polymer used as a disinfectant and antiseptic, which is toxic also for the epithelial cells of the cornea. Prompt and effective diagnostic tools are hence highly desiderable for both starting early therapy and timely suspension of the treatment. In this work we use Raman microspectroscopy to analyse in vitro a single Acanthamoeba cell in cystic phase. In particular, we investigate the effect of PHMB at the single-cell level, providing useful information on both the underlying biochemical mechanism and the time frame for Acanthamoeba eradication in ocular infections. Furthermore, we demonstrate that Raman spectroscopy, in conjunction with standard multivariate analysis methods, allows discriminating between live and dead Acanthamoebas, which is fundamental to optimizing patients' treatment

IonMonger: a free and fast planar perovskite solar cell simulator with coupled ion vacancy and charge carrier dynamics

Details of an open-source planar perovskite solar cell simulator, that includes ion vacancy migration within the perovskite layer coupled to charge carrier transport throughout the perovskite and adjoining transport layers in one dimension, are presented. The model equations are discretised in space using a finite element scheme and temporal integration of the resulting system of differential-algebraic equations is carried out in MATLAB. The user is free to modify device parameters, as well as the incident illumination and applied voltage. Time-varying voltage and/or illumination protocols can be specified, e.g. to simulate current-voltage sweeps, or to track the open-circuit conditions as the illumination is varied. Typical simulations, e.g. current-voltage sweeps, only require computation times of seconds to minutes on a modern personal computer. An example set of hysteretic current-voltage curves is presented

Vitamin B12 (cobalamin) and micronutrient fortification in food crops using nanoparticle technology

It is necessary to develop a resilient food supply that will withstand unexpected future shocks and deliver the required amounts of nutrients to consumers. By increasing the sustainability of food and agriculture, the food system will be able to handle challenges such as climate change, declining agricultural resources, growing population/urbanization, pandemics, and recessions/shortages. Micronutrient deficiency, otherwise called hidden hunger, is one of the major malnutrition consequences worldwide, particularly in middle- or low- income countries. Unlike essential mineral or nutrient compounds, micronutrients could be less of a priority due to their small levels of requirement. However, insufficient micronutrients caused critical adverse health symptoms and are excessively vital for young children’s development. Therefore, there have been numerous attempts to enhance minerals and nutrients in food crops, including biofortification, food fortification, and supplementation. Based on several interventions involving micronutrients, modern technology, such as nanotechnology, can be applied to enhance sustainability and to reduce the food system’s environmental impact. Previous studies have addressed various strategies or interventions to mitigate major micronutrient deficiency including iron, iodine, zinc, and vitamin A. Comparably small amounts of studies have addressed vitamin B12 deficiency and its fortification in food crops. Vitamin B12 deficiency causes serious adverse health effects, including in the nervous or blood systems, and occurs along with other micronutrient deficiencies, such as folate, iron, and zinc, worldwide, particularly in middle- and low-income countries. Mitigation for B12 deficiency has mainly focused on developing pharmacological and medical treatments such as vitamin B12 serum or supplements. Further studies are required to undertake a sustainable approach to fortify vitamin B12 in plant-based food sources for public health worldwide. This review paper highlights nanoparticle application as a promising technology for enhancing vitamin B12 without conventional genetic modification requirements. The nanoparticle can efficiently deliver the mineral/nutrient using coating techniques to targeted sites into the plant. This is mainly because nanoparticles have better solubility and permeability due to their nano size with high surface exposure. Vitamin B12-coated nanoparticles would be absorbed, translocated, and accumulated by the plant and eventually enhance the bioavailability in food crops. Furthermore, by reducing adverse environmental effects, such as leaching issues that mainly occur with conventional fertilizer usage, it would be possible to develop more sustainable food fortification

Giardia duodenalis assemblages and Entamoeba species infecting non-human primates in an Italian zoological garden: zoonotic potential and management traits

<p>Abstract</p> <p>Background</p> <p><it>Giardia duodenalis </it>and <it>Entamoeba </it>spp. are among the most common intestinal human protozoan parasites worldwide and they are frequently reported in captive non-human primates (NHP). From a public health point of view, infected animals in zoos constitute a risk for animal caretakers and visitors. In this study we carried out the molecular identification of <it>G. duodenalis </it>and <it>Entamoeba </it>spp. from nine species of primates housed in the zoological garden of Rome, to better ascertain their occurrence and zoonotic potential.</p> <p>Results</p> <p><it>G. duodenalis </it>was found only in <it>Lemur catta </it>(47.0%). <it>Entamoeba </it>spp. were detected in all species studied, with the exception of <it>Eulemur macaco </it>and <it>Varecia rubra</it>. The number of positive pools ranged from 5.9% in <it>L. catta </it>to 81.2% in <it>Mandrillus sphinx; </it>in <it>Pan troglodytes </it>the observed prevalence was 53.6%. A mixed <it>Entamoeba</it>-<it>Giardia </it>infection was recorded only in one sample of <it>L. catta</it>. All <it>G. duodenalis </it>isolates belonged to the zoonotic assemblage B, sub assemblage BIV. Three <it>Entamoeba </it>species were identified: <it>E. hartmanni</it>, <it>E. coli </it>and <it>E. dispar</it>.</p> <p>Conclusions</p> <p>Our results highlight the importance of regularly testing animals kept in zoos for the diagnosis of zoonotic parasites, in order to evaluate their pathogenic role in the housed animals and the zoonotic risk linked to their presence. A quick detection of the arrival of pathogens into the enclosures could also be a prerequisite to limit their spread into the structure via the introduction of specific control strategies. The need for molecular identification of some parasite species/genotype in order to better define the zoonotic risk is also highlighted.</p