On the formalism of the screening paradox.
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ABSTRACT:
SUBMITTER: Balayla J
PROVIDER: S-EPMC8409690 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundUniversal screening for postnatal depression is currently being promoted in Australia to assist detection and treatment of affected women, yet debate continues internationally about the effectiveness of screening. One rural shire in Victoria has been screening all women for postnatal depression at maternal and child health checks for many years. This paper explores the views of women affected by this intervention.MethodsA postal survey was sent to an entire one year cohort of women resident in the shire and eligible for this program [n = 230]. Women were asked whether they recalled having been screened for postnatal depression and what their experience had been, including any referrals made as a result of screening. Women interested in providing additional information were invited to give a phone number for further contact. Twenty women were interviewed in-depth about their experiences. The interview sample was selected to include both depressed and non-depressed women living in town and on rural properties, who represented the range of circumstances of women living in the shire.ResultsThe return rate for the postal survey was 62% [n = 147/230]. Eighty-seven women indicated that they were interested in further contact, 80 of whom were able to be reached by telephone and 20 were interviewed in-depth. Women had diverse views and experiences of screening. The EPDS proved to be a barrier for some women, and a facilitator for others, in accessing support and referrals. The mediating factor appeared to be a trusting relationship with the nurse able to communicate her concern for the woman and offer support and referrals if required.ConclusionsDetection of maternal depression requires more than administration of a screening tool at a single time point. While this approach did work for some women, for others it actually made appropriate care and support more difficult. Rather, trained and empathic healthcare providers working in a coordinated primary care service should provide multiple and flexible opportunities for women to disclose and discuss their emotional health issues.
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Project description:OBJECTIVE:To improve the efficacy of newborn screening (NBS) for very long chain acyl-CoA dehydrogenase deficiency (VLCADD). PATIENTS AND METHODS:Data on all dried blood spots collected by the Dutch NBS from October 2007 to 2010 (742.728) were included. Based solely on the C14:1 levels (cutoff ?0.8 ?mol/L), six newborns with VLCADD had been identified through NBS during this period. The ratio of C14:1 over C2 was calculated. DNA of all blood spots with a C14:1/C2 ratio of ?0.020 was isolated and sequenced. Children homozygous or compound heterozygous for mutations in the ACADVL gene were traced back and invited for detailed clinical, biochemical, and genetic evaluation. RESULTS:Retrospective analysis based on the C14:1/C2 ratio with a cutoff of ?0.020 identified an additional five children with known ACADVL mutations and low enzymatic activity. All were still asymptomatic at the time of diagnosis (age 2-5 years). Increasing the cutoff to ?0.023 resulted in a sensitivity of 93% and a positive predictive value of 37%. The sensitivity of the previously used screening approach (C14:1 ?0.8) was 50%. CONCLUSION:This study shows that the ratio C14:1/C2 is a more sensitive marker than C14:1 for identifying VLCADD patients in NBS. However, as these patients were all asymptomatic at the time of diagnosis, this suggests that a more sensitive screening approach may also identify individuals who may never develop clinical disease. Long-term follow-up studies are needed to establish the risk of these VLCADD-deficient individuals for developing clinical signs and symptoms.
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Project description:The key to the development of advanced materials is to understand their electronic structure-property relationship. Utilization of this understanding to design new electronic materials with desired properties led to modern epitaxial growth approaches for synthesizing artificial lattices, which for almost half a century have become the mainstay of electronic and photonic technologies. In contrast to previous scalar modulation approaches, we now study synthetic crystal lattices that have a tensor artificial modulation and develop a theory for photons and conduction band states in these lattices in a regime with an unusual departure from the familiar consequences of translational symmetry and Bloch's theorem. This study reveals that a nonmagnetic crystal lattice modulated by a purely geometrical orientational superlattice potential can lead to localized states or to spiral states for electrons and photons, as well as weakly or strongly localized states that could be used to markedly slow down the propagation of light and for optical energy storage applications.
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Project description:Automatic knowledge grounding is still an open problem in cognitive robotics. Recent research in developmental robotics suggests that a robot's interaction with its environment is a valuable source for collecting such knowledge about the effects of robot's actions. A useful concept for this process is that of an affordance, defined as a relationship between an actor, an action performed by this actor, an object on which the action is performed, and the resulting effect. This paper proposes a formalism for defining and identifying affordance equivalence. By comparing the elements of two affordances, we can identify equivalences between affordances, and thus acquire grounded knowledge for the robot. This is useful when changes occur in the set of actions or objects available to the robot, allowing to find alternative paths to reach goals. In the experimental validation phase we verify if the recorded interaction data is coherent with the identified affordance equivalences. This is done by querying a Bayesian Network that serves as container for the collected interaction data, and verifying that both affordances considered equivalent yield the same effect with a high probability.
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Project description:Systems Biology has established numerous approaches for mechanistic modeling of molecular networks in the cell and a legacy of models. The current frontier is the integration of models expressed in different formalisms to address the multi-scale biological system organization challenge. We present MUFINS (MUlti-Formalism Interaction Network Simulator) software, implementing a unique set of approaches for multi-formalism simulation of interaction networks. We extend the constraint-based modeling (CBM) framework by incorporation of linear inhibition constraints, enabling for the first time linear modeling of networks simultaneously describing gene regulation, signaling and whole-cell metabolism at steady state. We present a use case where a logical hypergraph model of a regulatory network is expressed by linear constraints and integrated with a Genome-Scale Metabolic Network (GSMN) of mouse macrophage. We experimentally validate predictions, demonstrating application of our software in an iterative cycle of hypothesis generation, validation and model refinement. MUFINS incorporates an extended version of our Quasi-Steady State Petri Net approach to integrate dynamic models with CBM, which we demonstrate through a dynamic model of cortisol signaling integrated with the human Recon2 GSMN and a model of nutrient dynamics in physiological compartments. Finally, we implement a number of methods for deriving metabolic states from ~omics data, including our new variant of the iMAT congruency approach. We compare our approach with iMAT through the analysis of 262 individual tumor transcriptomes, recovering features of metabolic reprogramming in cancer. The software provides graphics user interface with network visualization, which facilitates use by researchers who are not experienced in coding and mathematical modeling environments.
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Project description:Adjuvant Temozolomide is considered the front-line Glioblastoma chemotherapeutic treatment; yet not all patients respond. Latest trends in clinical trials usually refer to Doxorubicin; yet it can lead to severe side-effects if administered in high doses. While Glioblastoma prognosis remains poor, little is known about the combination of the two chemotherapeutics. Patient-derived spheroids were generated and treated with a range of Temozolomide/Doxorubicin concentrations either as monotherapy or in combination. Optical microscopy was used to monitor the growth pattern and cell death. Based on the monotherapy experiments, we developed a probabilistic mathematical framework in order to describe the drug-induced effect at the single-cell level and simulate drug doses in combination assuming probabilistic independence. Doxorubicin was found to be effective in doses even four orders of magnitude less than Temozolomide in monotherapy. The combination therapy doses tested in vitro were able to lead to irreversible growth inhibition at doses where monotherapy resulted in relapse. In our simulations, we assumed both drugs are anti-mitotic; Temozolomide has a growth-arrest effect, while Doxorubicin is able to cumulatively cause necrosis. Interestingly, under no mechanistic synergy assumption, the in silico predictions underestimate the in vitro results. In silico models allow the exploration of a variety of potential underlying hypotheses. The simulated-biological discrepancy at certain doses indicates a supra-additive response when both drugs are combined. Our results suggest a Temozolomide-Doxorubicin dual chemotherapeutic scheme to both disable proliferation and increase cytotoxicity against Glioblastoma.
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Project description:BackgroundMany cellular processes involve substantial shape changes. Traditional simulations of these cell shape changes require that grids and boundaries be moved as the cell's shape evolves. Here we demonstrate that accurate cell shape changes can be recreated using level set methods (LSM), in which the cellular shape is defined implicitly, thereby eschewing the need for updating boundaries.ResultsWe obtain a viscoelastic model of Dictyostelium cells using micropipette aspiration and show how this viscoelastic model can be incorporated into LSM simulations to recreate the observed protrusion of cells into the micropipette faithfully. We also demonstrate the use of our techniques by simulating the cell shape changes elicited by the chemotactic response to an external chemoattractant gradient.ConclusionOur results provide a simple but effective means of incorporating cellular deformations into mathematical simulations of cell signaling. Such methods will be useful for simulating important cellular events such as chemotaxis and cytokinesis.
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Project description:Data on ligand-target (LT) interactions has played a growing role in drug research for several decades. Even though the amount of data has grown significantly in size and coverage during this period, most datasets remain difficult to analyze because of their extreme sparsity, as there is no activity data whatsoever for many LT pairs. Even within clusters of data there tends to be a lack of data completeness, making the analysis of LT datasets problematic. The current effort extends earlier works on the development of set-theoretic formalisms for treating thresholded LT datasets. Unlike many approaches that do not address pairs of unknown interaction, the current work specifically takes account of their presence in addition to that of active and inactive pairs. Because a given LT pair can be in any one of three states, the binary logic of classical set-theoretic methods does not strictly apply. The current work develops a formalism, based on ternary set-theoretic relations, for treating thresholded LT datasets. It also describes an extension of the concept of data completeness, which is typically applied to sets of ligands and targets, to the local data completeness of individual ligands and targets. The set-theoretic formalism is applied to the analysis of simple and joint polypharmacologies based on LT activity profiles, and it is shown that null pairs provide a means for determining bounds to these values. The methodology is applied to a dataset of protein kinase inhibitors as an illustration of the method. Although not dealt with here, work is currently underway on a more refined treatment of activity values that is based on increasing the number of activity classes.
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Project description:The cognitive state of mind concerning a range of choices to be made can be modelled efficiently by use of an element of a high-dimensional Hilbert space. The dynamics of the state of mind resulting from information acquisition can be characterised by the von Neumann-Lüders projection postulate of quantum theory. This is shown to give rise to an uncertainty-minimising dynamical behaviour equivalent to Bayesian updating, hence providing an alternative approach to representing the dynamics of a cognitive state, consistent with the free energy principle in brain science. The quantum formalism, however, goes beyond the range of applicability of classical reasoning in explaining cognitive behaviour, thus opening up new and intriguing possibilities.
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Project description:The product-operator formalism is the most commonly used tool for describing and designing multidimensional NMR experiments. In spite of its relative simplicity and sound theoretical underpinnings, however, students and practitioners often find it difficult to relate the mathematical manipulations to a physical picture. In an effort to address this pedagogical challenge, the present paper begins with a quantum-mechanical treatment of pure populations of scalar-coupled spin-pairs, rather than the equilibrium population of spin-pairs in different quantum states, which is the usual starting point for treatments based on the density matrix and product operators. In the context of pure populations, the product operators are shown to represent quantum correlations between the nuclei in individual molecules, and a new variation on the classical vector diagram is introduced to represent these correlations. The treatment is extended to mixed populations that begin at thermal equilibrium, and the density matrix is introduced as an efficient means of carrying out quantum calculations for a mixed population. Finally, it is shown that the operators for observable magnetization and correlations can be used as a basis set for the density matrix, providing the formal justification for the widely-used rules of the product-operator treatment. Throughout the discussion, the vector diagrams are used to help maintain a connection between the mathematics and the sometimes subtle physical principles. An electronic supplement created with the Mathematica computer program is used to provide additional mathematical details and the means to carry out further calculations.
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