374 research outputs found
An age-dependent branching process model for the analysis of CFSE-labeling experiments
<p>Abstract</p> <p>Background</p> <p>Over the past decade, flow cytometric CFSE-labeling experiments have gained considerable popularity among experimentalists, especially immunologists and hematologists, for studying the processes of cell proliferation and cell death. Several mathematical models have been presented in the literature to describe cell kinetics during these experiments.</p> <p>Results</p> <p>We propose a multi-type age-dependent branching process to model the temporal development of populations of cells subject to division and death during CFSE-labeling experiments. We discuss practical implementation of the proposed model; we investigate a competing risk version of the process; and we identify the classes of cellular dependencies that may influence the expectation of the process and those that do not. An application is presented where we study the proliferation of human CD8+ T lymphocytes using our model and a competing risk branching process.</p> <p>Conclusions</p> <p>The proposed model offers a widely applicable approach to the analysis of CFSE-labeling experiments. The model fitted very well our experimental data. It provided reasonable estimates of cell kinetics parameters as well as meaningful insights into the processes of cell division and cell death. In contrast, the competing risk branching process could not describe the kinetics of CD8+ T cells. This suggested that the decision of cell division or cell death may be made early in the cell cycle if not in preceding generations. Also, we show that analyses based on the proposed model are robust with respect to cross-sectional dependencies and to dependencies between fates of linearly filiated cells.</p> <p>Reviewers</p> <p>This article was reviewed by Marek Kimmel, Wai-Yuan Tan and Peter Olofsson.</p
Misalignment of the microquasar V4641 Sgr (SAX J1819.3--2525)
In the microquasar V4641 Sgr the spin of the black hole is thought to be
misaligned with the binary orbital axis. The accretion disc aligns with the
black hole spin by the Lense-Thirring effect near to the black hole and further
out becomes aligned with the binary orbital axis. The inclination of the radio
jets and the Fe line profile have both been used to determine the
inclination of the inner accretion disc but the measurements are inconsistent.
Using a steady state analytical warped disc model for V4641 Sgr we find that
the inner disc region is flat and aligned with the black hole up to about . Thus if both the radio jet and fluorescent emission originates in
the same inner region then the measurements of the inner disc inclination
should be the same.Comment: Accepted for publication in MNRA
Predicting Acute Kidney Injury at Hospital Re-entry Using High-dimensional Electronic Health Record Data
Acute Kidney Injury (AKI), a sudden decline in kidney function, is associated
with increased mortality, morbidity, length of stay, and hospital cost. Since
AKI is sometimes preventable, there is great interest in prediction. Most
existing studies consider all patients and therefore restrict to features
available in the first hours of hospitalization. Here, the focus is instead on
rehospitalized patients, a cohort in which rich longitudinal features from
prior hospitalizations can be analyzed. Our objective is to provide a risk
score directly at hospital re-entry. Gradient boosting, penalized logistic
regression (with and without stability selection), and a recurrent neural
network are trained on two years of adult inpatient EHR data (3,387 attributes
for 34,505 patients who generated 90,013 training samples with 5,618 cases and
84,395 controls). Predictions are internally evaluated with 50 iterations of
5-fold grouped cross-validation with special emphasis on calibration, an
analysis of which is performed at the patient as well as hospitalization level.
Error is assessed with respect to diagnosis, race, age, gender, AKI
identification method, and hospital utilization. In an additional experiment,
the regularization penalty is severely increased to induce parsimony and
interpretability. Predictors identified for rehospitalized patients are also
reported with a special analysis of medications that might be modifiable risk
factors. Insights from this study might be used to construct a predictive tool
for AKI in rehospitalized patients. An accurate estimate of AKI risk at
hospital entry might serve as a prior for an admitting provider or another
predictive algorithm.Comment: In revisio
Re-engineering The Clinical Research Enterprise in Response to COVID-19: The Clinical Translational Science Award (CTSA) experience and proposed playbook for future pandemics
The 2020 COVID-19 pandemic has had a profound impact on the clinical research enterprises at the 60 Clinical and Translational Science Award (CTSA) Hubs throughout the nation. There was simultaneously a need to expand research to obtain crucial data about disease prognosis and therapy and enormous limitations on conducting research as localities and institutions limited travel and person-to-person contact. These imperatives resulted in major changes in the way research was conducted, including expediting Institutional Review Board review, shifting to remote interactions with participants, centralizing decision-making in prioritizing research protocols, establishing biobanks, adopting novel informatics platforms, and distributing study drugs in unconventional ways. National CTSA Steering Committee meetings provided an opportunity to share best practices and develop the idea of capturing the CTSA program experiences in a series of papers. Here we bring together the recommendations from those papers in a list of specific actions that research sites can take to strengthen operations and prepare for similar future public health emergencies. Most importantly, creative innovations developed in response to the COVID-19 pandemic deserve serious consideration for adoption as new standards, thus converting the painful trauma of the pandemic into “post-traumatic growth” that makes the clinical research enterprise stronger, more resilient, and more effective
Properties of Healthcare Teaming Networks as a Function of Network Construction Algorithms
Network models of healthcare systems can be used to examine how providers
collaborate, communicate, refer patients to each other. Most healthcare service
network models have been constructed from patient claims data, using billing
claims to link patients with providers. The data sets can be quite large,
making standard methods for network construction computationally challenging
and thus requiring the use of alternate construction algorithms. While these
alternate methods have seen increasing use in generating healthcare networks,
there is little to no literature comparing the differences in the structural
properties of the generated networks. To address this issue, we compared the
properties of healthcare networks constructed using different algorithms and
the 2013 Medicare Part B outpatient claims data. Three different algorithms
were compared: binning, sliding frame, and trace-route. Unipartite networks
linking either providers or healthcare organizations by shared patients were
built using each method. We found that each algorithm produced networks with
substantially different topological properties. Provider networks adhered to a
power law, and organization networks to a power law with exponential cutoff.
Censoring networks to exclude edges with less than 11 shared patients, a common
de-identification practice for healthcare network data, markedly reduced edge
numbers and greatly altered measures of vertex prominence such as the
betweenness centrality. We identified patterns in the distance patients travel
between network providers, and most strikingly between providers in the
Northeast United States and Florida. We conclude that the choice of network
construction algorithm is critical for healthcare network analysis, and discuss
the implications for selecting the algorithm best suited to the type of
analysis to be performed.Comment: With links to comprehensive, high resolution figures and networks via
figshare.co
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Controlled release of microencapsulated docosahexaenoic acid (DHA) by spray–drying processing
The omega-3-fatty acid, docosahexaenoic acid (DHA) 22:6 n-3, is an important food component for the visual and brain development of infants. In this study two approaches have been explored for the encapsulation of DHA in the pH dependant polymer hydroxyl-propyl-methyl-cellulose-acetate-succinate (HPMCAS). In the first approach Direct Spray Drying (DSD) was implemented for the microencapsulation of DHA/HPMCAS organic solutions, whilst in the second approach solid lipid nanoparticle (SLN) dispersions of DHA, were first produced by high-pressure homogenization, prior to being spray dried in HPMCAS aqueous solutions. The DSD approach resulted in significantly higher quantities of DHA being encapsulated, at 2.09 g/100 g compared to 0.60 g/100 g in the spray-dried SLNs. The DHA stability increased with the direct spray-drying approach. Release studies of DHA in the direct sprayed dried samples revealed a lag time for 2 h in acidic media followed by rapid release in phosphate buffer (pH 6.8)
Novel multiplex assay for profiling influenza antibodies in breast milk and serum of mother-infant pairs [version 2; referees: 2 approved]
Background: During early life, systemic protection to influenza is passively provided by transplacental transfer of IgG antibodies and oral and gastrointestinal mucosal protection via breast milk (BM) containing predominantly IgA. Immune imprinting, influenced by initial exposure of the infant immune system to influenza, has recently been recognized as an important determinant of future influenza immune responses. Methods: We utilized stored frozen BM from a prospective birth cohort to assess immune factors in human milk. The earliest available BM and a paired, timed serum sample was assessed from each of 7 mothers. Paired infant serum samples were assayed at up to three time points during the first 12 months of life, one prior to assumed disappearance of transplacentally transferred IgG, and one after. We utilized a novel multiplex assay to assess mothers’ and infants’ IgG and IgA antibodies in serum to a panel of 30 individual recombinant hemagglutinin (rHA) proteins of influenza virus strains and chimeric rHAs. We also characterized IgA and IgG antibody levels in breast milk which provide mucosal protection. Results: Our pilot results, analyzing a small number of samples demonstrate the feasibility of this method for studying paired maternal-infant IgG and IgA anti-influenza immunity patterns. Unlike IgG antibodies, breast milk influenza virus HA-specific IgA antibody levels and patterns were mostly discordant compared to serum. As expected, there was a steady decay of infant influenza specific IgG levels by 6 to 8 months of age, which was not, however, comparable in all infants. In contrast, most of the infants showed an increase in IgA responses throughout the first year of life Conclusions: This new analytical method can be applied in a larger study to understand the impact of maternal imprinting on influenza immunity
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The effect of amino acids on wound healing: a systematic review and meta-analysis on arginine and glutamine
Under stress conditions, the metabolic demand for nutrients increases, which, if not met, may slow down or indeed stop the wound from healing, thus, becoming chronic wounds. This study aims to perform a systematic review and meta-analysis of the effect of arginine and glutamine supplementation on wound healing. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed for the systematic review and ten electronic databases were used. Five and 39 human studies met the inclusion criteria for arginine and glutamine, respectively. The overall meta-analysis demonstrated a significant effect of arginine supplementation on hydroxyproline content (MD: 4.49, 95% CI: 3.54, 4.45, p < 0.00001). Regarding glutamine supplementation, there was significant effect on nitrogen balance levels (MD: 0.39, 95% CI: 0.21, 0.58, p < 0.0001), IL-6 levels (MD: −5.78, 95% CI: −8.71, −2.86, p = 0.0001), TNFα levels (MD: −8.15, 95% CI: −9.34, −6.96, p < 0.00001), lactulose/mannitol (L/M) ratio (MD: −0.01, 95% CI: −0.02, −0.01, p < 0.00001), patient mortality (OR: 0.48, 95% CI: 0.32, 0.72, p = 0.0004), C-reactive protein (CRP) levels (MD: −1.10, 95% CI: −1.26, −0.93, p < 0.00001) and length of hospital stay (LOS) (MD: −2.65, 95% CI: −3.10, −2.21, p < 0.00001). Regarding T-cell lymphocytes, a slight decrease was observed, although it failed to reach significance (MD: −0.16, 95% CI: −0.33, 0.01, p = 0.07). Conclusion: The wound healing might be enhanced in one or at various stages by nutritional supplementation in the right dose
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