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Physical Review. E Dec 2022Perceptual learning (PL) involves long-lasting improvement in perceptual tasks following extensive training and is accompanied by modified neuronal responses in sensory...
Perceptual learning (PL) involves long-lasting improvement in perceptual tasks following extensive training and is accompanied by modified neuronal responses in sensory cortical areas in the brain. Understanding the dynamics of PL and the resultant synaptic changes is important for causally connecting PL to the observed neural plasticity. This is theoretically challenging because learning-related changes are distributed across many stages of the sensory hierarchy. In this paper, we modeled the sensory hierarchy as a deep nonlinear neural network and studied PL of fine discrimination, a common and well-studied paradigm of PL. Using tools from statistical physics, we developed a mean-field theory of the network in the limit of a large number of neurons and large number of examples. Our theory suggests that, in this thermodynamic limit, the input-output function of the network can be exactly mapped to that of a deep linear network, allowing us to characterize the space of solutions for the task. Surprisingly, we found that modifying synaptic weights in the first layer of the hierarchy is both sufficient and necessary for PL. To address the degeneracy of the space of solutions, we postulate that PL dynamics are constrained by a normative minimum perturbation (MP) principle, which favors weight matrices with minimal changes relative to their prelearning values. Interestingly, MP plasticity induces changes to weights and neural representations in all layers of the network, except for the readout weight vector. While weight changes in higher layers are not necessary for learning, they help reduce overall perturbation to the network. In addition, such plasticity can be learned simply through slow learning. We further elucidate the properties of MP changes and compare them against experimental findings. Overall, our statistical mechanics theory of PL provides mechanistic and normative understanding of several important empirical findings of PL.
Topics: Learning; Brain; Neural Networks, Computer; Neuronal Plasticity; Neurons
PubMed: 36671118
DOI: 10.1103/PhysRevE.106.064406 -
Journal of Biopharmaceutical Statistics 2015In quality control of drug products, tolerance intervals are commonly used methods to assure a certain proportion of the products covered within a pre-specified... (Review)
Review
In quality control of drug products, tolerance intervals are commonly used methods to assure a certain proportion of the products covered within a pre-specified acceptance interval. Depending on the nature of the quality attributes, the corresponding acceptance interval could be one-sided or two-sided. Thus, the tolerance intervals can also be one-sided or two-sided. To better utilize tolerance intervals for quality assurance, we reviewed the computation method and studied their statistical properties in terms of batch acceptance probability in this article. We also illustrate the application of one-sided and two-sided tolerance, as well as two one-sided tests through the examples of dose content uniformity test, delivered dose uniformity test, and dissolution test.
Topics: Biopharmaceutics; Chemistry, Pharmaceutical; Computer Simulation; Confidence Intervals; Data Interpretation, Statistical; Guidelines as Topic; Models, Statistical; Pharmaceutical Preparations; Quality Control; Solubility; Technology, Pharmaceutical
PubMed: 25356617
DOI: 10.1080/10543406.2014.972512 -
Expert Opinion on Drug Delivery Sep 2014Fueled by a growing global expectation of the health and medical fields, billions of dollars/euros/pounds are invested every year in the research of new biological and... (Review)
Review
INTRODUCTION
Fueled by a growing global expectation of the health and medical fields, billions of dollars/euros/pounds are invested every year in the research of new biological and chemical entities. However, little interest is seen in the development of novel drug delivery systems. One such system, pre-filled syringe (PFS), was invented decades ago but is still a rare mode of delivery in many therapeutic segments.
AREAS COVERED
This review comprises properties and effects of extractables, leachables and discuss the characteristics of PFS technology; its composition, glass and polymer types, configuration of PFS, advantages over glass, technical and commercial applicability; its significance against patient, industry, quality, environment and cost; and its business potential. We discuss in brief about PFS used in various major and life-threatening disorders and future prospects. It provides showers of knowledge in the field of PFS drug delivery technology to the reader's, industrialist's and researcher's point of view.
EXPERT OPINION
The PFS drug delivery system offers a wonderful panorama to lifesaving drugs that are currently only available in conventional vials and ampoules in the market. A novel approach of Form Fill Seal technology can be adopted for this particular ready-to-use dosage form also, which opens the new global doors for budding researchers in the field of pre-filled drug delivery system.
Topics: Drug Delivery Systems; Drug Packaging; Glass; Humans; Pharmaceutical Preparations; Polymers; Syringes; Technology, Pharmaceutical
PubMed: 25082570
DOI: 10.1517/17425247.2014.923400 -
Journal of Oncology Pharmacy Practice :... Jan 2022Radioiodine therapy can be used in differentiated thyroid carcinoma and requires extensive evaluation to ensure effectiveness and safety. Therefore, it is necessary to...
Radioiodine therapy can be used in differentiated thyroid carcinoma and requires extensive evaluation to ensure effectiveness and safety. Therefore, it is necessary to evaluate all health problems and medications used in the pre-radioiodine therapy period and comprehensive medication managementservices can serve as a screening tool in this context. The present study aims to describe critical clinical situations identified during the initial assessments of a comprehensive medication management service offered to differentiated thyroid carcinoma patients pre-radioiodine therapy, and the pharmaceutical interventions performed to solve them. A descriptive study with regard to the initial ten months of a comprehensive medication management service was carried out in a large oncology hospital (Rio de Janeiro, Brazil). Descriptive analysis was used to describe the critical clinical situations identified, as well as the correspondent drug therapy problems and the type, acceptability, and outcomes of the pharmaceutical interventions performed to solve them. Thirty patients with an average of 45.8 years and 5.1 medications were evaluated. Five critical clinical situations were identified; corresponding to drug therapy problems two(needs additional drug therapy - = 4) and drug therapy problems four (dosage too low - = 1). All pharmaceutical interventions were accepted. The comprehensive medication management service provision pre-radioiodine therapy is feasible and represents an important screening strategy.
Topics: Brazil; Humans; Iodine Radioisotopes; Pharmaceutical Preparations; Pharmacy; Pharmacy Service, Hospital
PubMed: 34661492
DOI: 10.1177/10781552211045361 -
Physical Review. E Sep 2021Determination of the spin echo signal evolution and of transverse relaxation rates is of high importance for microstructural modeling of muscle tissue in magnetic...
Determination of the spin echo signal evolution and of transverse relaxation rates is of high importance for microstructural modeling of muscle tissue in magnetic resonance imaging. So far, numerically exact solutions for the NMR signal dynamics in muscle tissue models have been reported only for the gradient echo free induction decay, with spin echo problems usually solved by approximate methods. In this work, we modeled the spin echo signal numerically exact by discretizing the radial dimension of the Bloch-Torrey equation and expanding the angular dependency in terms of even Chebyshev polynomials. This allows us to express the time dependence of the local magnetization as a closed-form matrix expression. Using this method, we were able to accurately capture the spin echo local and total magnetization dynamics. The obtained transverse relaxation rates showed a high concordance with random walker and finite-element simulations. We could demonstrate that in cases of smaller diffusion coefficients, the commonly used strong collision approximation significantly underestimates the true value considerably. Instead, the limiting behavior in this regime is correctly described either by the full solution or by the slow diffusion approximation. Experimentally measured transverse relaxation rates of a mouse limb muscle showed an angular dependence in accordance with the theoretical prediction.
PubMed: 34654209
DOI: 10.1103/PhysRevE.104.034419 -
Frontiers in Public Health 2023Correct medicine dosing is an important component in the safe and effective delivery of medicines, particularly for the pediatric population. However, there is a...
BACKGROUND
Correct medicine dosing is an important component in the safe and effective delivery of medicines, particularly for the pediatric population. However, there is a scarcity of public campaigns on the correct administration and choice of dosing aids for oral liquid dosage form in many countries, leading to medicine safety issues and therapeutic failures.
METHODS
The study targeted the assessment of the knowledge and practice of university students. It utilizes pre- and post-intervention surveys administered through google forms as a survey tool during online zoom and in-person sessions. The intervention included a short video presentation detailing the selection and use of medicine spoons and other aids for the administration of oral liquid dosage. The Fischer Exact test was used to assess the pre- and post-test shift of responses.
RESULTS
Nine-degree programs were engaged in the activity, and 108 students attended this health awareness activity after obtaining formal consent. A significant decline (CI = 95%, -value < 0.05) in the choice of selecting tablespoon and a shift to a low-volume spoon, as well as rejection of an entire variety of household spoons, were observed. A significant improvement in the correct naming of spoons, the meaning of the abbreviation "tsp," and the correct volume of a standard teaspoon were also observed with a -value of <0.001.
CONCLUSION
A deficit in the knowledge of the proper use of measuring devices for oral liquid medicines in the educated population was observed, which can be enhanced through simple tools like short video presentations and awareness seminars.
Topics: Humans; Child; Medication Errors; Administration, Oral; Pharmaceutical Preparations; Surveys and Questionnaires; Students
PubMed: 36891337
DOI: 10.3389/fpubh.2023.1084667 -
Physical Review. E May 2021We show an amazing complexity of the chimeras in small networks of coupled phase oscillators with inertia. The network behavior is characterized by heteroclinic...
We show an amazing complexity of the chimeras in small networks of coupled phase oscillators with inertia. The network behavior is characterized by heteroclinic switching between multiple saddle chimera states and riddling basins of attractions, causing an extreme sensitivity to initial conditions and parameters. Additional uncertainty is induced by the presumable coexistence of stable phase-locked states or other stable chimeras as the switching trajectories can eventually tend to them. The system dynamics becomes hardly predictable, while its complexity represents a challenge in the network sciences.
PubMed: 34134258
DOI: 10.1103/PhysRevE.103.L050204 -
Advanced Drug Delivery Reviews Mar 2019Since the development of self-emulsifying drug delivery systems (SEDDS) in 1980's, they attract the attention of researchers in order to confront the challenge of poor... (Review)
Review
Since the development of self-emulsifying drug delivery systems (SEDDS) in 1980's, they attract the attention of researchers in order to confront the challenge of poor water-solubility of orally given drugs. Within recent years, SEDDS were also discovered for oral administration of hydrophilic macromolecular drugs such as peptides, proteins, polysaccharides and pDNA. Due to hydrophobic ion pairing (HIP) with oppositely charged lipophilic auxiliary agents the resulting complexes can be incorporated in the lipophilic phase of SEDDS. Depending on the solubility of the complex in the SEDDS pre-concentrate and in the release medium drug release can be adjusted on purpose by choosing more or less lipophilic auxiliary agents in appropriate quantities for HIP. Within the oily droplets formed in the GI-tract drugs are protected towards degradation by proteases and nucleases and thiol-disulfide exchange reactions with dietary proteins. The oily droplets can be made mucoadhesive or highly mucus permeating depending on their target site. Furthermore, even their cellular uptake properties can be tuned by adjusting their zeta potential or decorating them with cell penetrating peptides. The potential of SEDDS for oral administration of hydrophilic macromolecular drugs could meanwhile be demonstrated via various in vivo studies showing a bioavailability at least in the single digit percentage range. Owing to these properties advanced SEDDS turned out to be a game changing approach for the oral administration of hydrophilic macromolecular drugs.
Topics: Administration, Oral; Animals; Drug Delivery Systems; Emulsions; Humans; Hydrophobic and Hydrophilic Interactions; Pharmaceutical Preparations
PubMed: 29981355
DOI: 10.1016/j.addr.2018.07.001 -
Expert Opinion on Drug Metabolism &... Jun 2024Advances in the accessibility of manufacturing technologies and iPSC-based modeling have accelerated the overall progress of organs-on-a-chip. Notably, the progress in... (Review)
Review
INTRODUCTION
Advances in the accessibility of manufacturing technologies and iPSC-based modeling have accelerated the overall progress of organs-on-a-chip. Notably, the progress in multi-organ systems is not progressing with equal speed, indicating that there are still major technological barriers to overcome that may include biological relevance, technological usability as well as overall accessibility.
AREAS COVERED
We here review the progress in the field of multi-tissue- and body-on-a-chip pre and post- SARS-CoV-2 pandemic and review five selected studies with increasingly complex multi-organ chips aiming at pharmacological studies.
EXPERT OPINION
We discuss future and necessary advances in the field of multi-organ chips including how to overcome challenges regarding cell diversity, improved culture conditions, model translatability as well as sensor integrations to enable microsystems to cover organ-organ interactions in not only toxicokinetic but more importantly pharmacodynamic and -kinetic studies.
Topics: Humans; Lab-On-A-Chip Devices; Animals; COVID-19; Pharmacokinetics; Pharmaceutical Preparations; Models, Biological; Microphysiological Systems
PubMed: 38832686
DOI: 10.1080/17425255.2024.2362183 -
Physical Review. E Jun 2020T-cell receptors (TCR) are key proteins of the adaptive immune system, generated randomly in each individual, whose diversity underlies our ability to recognize...
T-cell receptors (TCR) are key proteins of the adaptive immune system, generated randomly in each individual, whose diversity underlies our ability to recognize infections and malignancies. Modeling the distribution of TCR sequences is of key importance for immunology and medical applications. Here, we compare two inference methods trained on high-throughput sequencing data: a knowledge-guided approach, which accounts for the details of sequence generation, supplemented by a physics-inspired model of selection; and a knowledge-free variational autoencoder based on deep artificial neural networks. We show that the knowledge-guided model outperforms the deep network approach at predicting TCR probabilities, while being more interpretable, at a lower computational cost.
Topics: Amino Acid Sequence; Deep Learning; Ligands; Models, Biological; Receptors, Antigen, T-Cell
PubMed: 32688532
DOI: 10.1103/PhysRevE.101.062414