10,132 research outputs found
Abstract 219: Use of Machine Learning Models to Identify Atherosclerotic Cardiovascular Disease Patients at Very High Risk for Future Events in a Multi-state Health Care System
Background: In the 2018 AHA/ACC Blood Cholesterol Guideline, it is recommended that ASCVD patients be classified as very high-risk (VHR) vs not-VHR (NVHR) to guide treatment decisions. This has important implications for ezetimibe and PCSK9 inhibitor eligibility. We aimed to develop a tool that could assist in more easily identifying VHR patients based on machine learning (ML) techniques. This approach offers a powerful, assumption-free alternative to conventional methods, such as logistic regression, to identify potential interactions among risk factors while incorporating the hierarchy of interaction among variables.
Method: We used EHR-derived ICD-10 codes to identify patients within our health system with ASCVD. VHR was defined by ≥2 major ASCVD events (ACS ≤12 months, history of MI \u3e12 months, ischemic stroke, or symptomatic PAD) or 1 major ASCVD event and ≥2 high-risk conditions (age ≥65, diabetes, hypertension, smoking, heterozygous familial hypercholesterolemia, CKD, CHF, persistently elevated LDL-C ≥100 mg/dl, or prior CABG/PCI). Patients not meeting these criteria were classified as NVHR. We randomly assigned patients into a training set and a testing set. Classification and regression tree (CART) modeling was performed on the training set and validated on the testing set. The results were compared with a random forest model. Variables in both models included age, sex, race, ethnicity, and each of the VHR criteria above. The primary outcome for both models was VHR classification. Performance of the two models were compared using area under the curve (AUC).
Result: A total of 180,669 ASCVD patients were identified in 2018: 104,123 (58%) were VHR and 76,546 (42%) were NVHR. Mean age and sex were 73.1±11.9 years, 55% male and 70.1±13.4 years, 54% male for the VHR and NVHR groups, respectively. Half the population was randomly selected as the training dataset (n=90,334) and the other half was used as the testing dataset (n=90,335). Both CART and random forest models identified recent ACS, ischemic stroke, hypertension, PAD, and history of MI as the top five predictors of VHR status. Ninety-six percent of patients with recent ACS were classified as VHR. Among patients with no recent ACS, 95% were classified as VHR if they had a stroke and hypertension. Among patients with no ACS or stroke, 89% were classified as VHR if they had PAD. Finally, among patients with no ACS, stroke or PAD, 90% were classified as VHR if they had a history of MI. The misclassification rate of the CART model on the testing set was 4.3%. The AUC for the CART and random forest models was 0.949 and 0.968, respectively.
Conclusion: Both ML methods were highly predictive of VHR status among those with ASCVD. Use of this approach affords a simplified means to drive clinical decision making at the point of care
Shock waves in strongly coupled plasmas
Shock waves are supersonic disturbances propagating in a fluid and giving
rise to dissipation and drag. Weak shocks, i.e., those of small amplitude, can
be well described within the hydrodynamic approximation. On the other hand,
strong shocks are discontinuous within hydrodynamics and therefore probe the
microscopics of the theory. In this paper we consider the case of the strongly
coupled N=4 plasma whose microscopic description, applicable for scales smaller
than the inverse temperature, is given in terms of gravity in an asymptotically
space. In the gravity approximation, weak and strong shocks should be
described by smooth metrics with no discontinuities. For weak shocks we find
the dual metric in a derivative expansion and for strong shocks we use
linearized gravity to find the exponential tail that determines the width of
the shock. In particular we find that, when the velocity of the fluid relative
to the shock approaches the speed of light the penetration depth
scales as . We compare the results with second
order hydrodynamics and the Israel-Stewart approximation. Although they all
agree in the hydrodynamic regime of weak shocks, we show that there is not even
qualitative agreement for strong shocks. For the gravity side, the existence of
shock waves implies that there are disturbances of constant shape propagating
on the horizon of the dual black holes.Comment: 47 pages, 8 figures; v2:typos corrected, references adde
MFV Reductions of MSSM Parameter Space
The 100+ free parameters of the minimal supersymmetric standard model (MSSM)
make it computationally difficult to compare systematically with data,
motivating the study of specific parameter reductions such as the cMSSM and
pMSSM. Here we instead study the reductions of parameter space implied by using
minimal flavour violation (MFV) to organise the R-parity conserving MSSM, with
a view towards systematically building in constraints on flavour-violating
physics. Within this framework the space of parameters is reduced by expanding
soft supersymmetry-breaking terms in powers of the Cabibbo angle, leading to a
24-, 30- or 42-parameter framework (which we call MSSM-24, MSSM-30, and MSSM-42
respectively), depending on the order kept in the expansion. We provide a
Bayesian global fit to data of the MSSM-30 parameter set to show that this is
manageable with current tools. We compare the MFV reductions to the
19-parameter pMSSM choice and show that the pMSSM is not contained as a subset.
The MSSM-30 analysis favours a relatively lighter TeV-scale pseudoscalar Higgs
boson and with multi-TeV sparticles.Comment: 2nd version, minor comments and references added, accepted for
publication in JHE
Serum Neurofilament Light, Glial Fibrillary Acidic Protein and Tau Are Possible Serum Biomarkers for Activity of Brain Metastases and Gliomas
BACKGROUND: Primary central nervous system (CNS) tumors and brain metastases (BMs) are major causes of morbidity and mortality, accompanied by low survival rates. Efforts to early discovery of CNS malignancies are critical. However, to date, there are no biomarkers approved for detection of cancer activity in the brain. Blood levels of neurofilament light (NfL) and tau, as well as glial fibrillary acidic protein (GFAp), show promise as biomarkers for brain injury in previous studies. Therefore, we performed a cross-sectional study to investigate correlations of those biomarkers with CNS activity of gliomas and BMs. METHODS: Serum samples of 36 participants of a single centered institution were tested for NfL, GFAp and tau with Simoa immunoassay, and correlated with clinical and radiological data. RESULTS: fL and GFAp levels were significantly associated with the state of intracranial disease (analysis of variance (ANOVA), P_{sNfL} = 0.03; ANOVA, P_{GFAp} = 0.03). Although statistically significant (P = 0.04), differences in concentrations were not clinically meaningful for tau levels. Serum NfL (sNfL) and GFAp concentrations were higher in the group of patients with CNS tumors with disease in progression versus CNS with stable disease (P = 0.03 and P = 0.01, respectively). In addition, sNfL were higher in patients with metastatic solid tumors with known BMs than in those with metastatic tumors with no BM (P = 0.0004). CONCLUSION: sNfL and GFAp both apparently vary closely with presence and activity of gliomas and BMs. Further studies in larger populations are needed to expand these findings
Protein crystals in adenovirus type 5-infected cells: requirements for intranuclear crystallogenesis, structural and functional analysis
Intranuclear crystalline inclusions have been observed in the nucleus of epithelial cells infected with Adenovirus serotype 5 (Ad5) at late steps of the virus life cycle. Using immuno-electron microscopy and confocal microscopy of cells infected with various Ad5 recombinants modified in their penton base or fiber domains, we found that these inclusions represented crystals of penton capsomers, the heteromeric capsid protein formed of penton base and fiber subunits. The occurrence of protein crystals within the nucleus of infected cells required the integrity of the fiber knob and part of the shaft domain. In the knob domain, the region overlapping residues 489–492 in the FG loop was found to be essential for crystal formation. In the shaft, a large deletion of repeats 4 to 16 had no detrimental effect on crystal inclusions, whereas deletion of repeats 8 to 21 abolished crystal formation without altering the level of fiber protein expression. This suggested a crucial role of the five penultimate repeats in the crystallisation process. Chimeric pentons made of Ad5 penton base and fiber domains from different serotypes were analyzed with respect to crystal formation. No crystal was found when fiber consisted of shaft (S) from Ad5 and knob (K) from Ad3 (heterotypic S5-K3 fiber), but occurred with homotypic S3K3 fiber. However, less regular crystals were observed with homotypic S35-K35 fiber. TB5, a monoclonal antibody directed against the Ad5 fiber knob was found by immunofluorescence microscopy to react with high efficiency with the intranuclear protein crystals in situ. Data obtained with Ad fiber mutants indicated that the absence of crystalline inclusions correlated with a lower infectivity and/or lower yields of virus progeny, suggesting that the protein crystals might be involved in virion assembly. Thus, we propose that TB5 staining of Ad-infected 293 cells can be used as a prognostic assay for the viability and productivity of fiber-modified Ad5 vectors
The demand for sports and exercise: Results from an illustrative survey
Funding from the Department of Health policy research programme was used in this study.There is a paucity of empirical evidence on the extent to which price and perceived benefits affect the level of participation in sports and exercise. Using an illustrative sample of 60 adults at Brunel University, West London, we investigate the determinants of demand for sports and exercise. The data were collected through face-to-face interviews that covered indicators of sports and exercise behaviour; money/time price and perceived benefits of participation; and socio- economic/demographic details. Count, linear and probit regression models were fitted as appropriate. Seventy eight per cent of the sample participated in sports and exercise and spent an average of £27 per month and an average of 20 min travelling per occasion of sports and exercise. The demand for sport and exercise was negatively associated with time (travel or access time) and ‘variable’ price and positively correlated with ‘fixed’ price. Demand was price inelastic, except in the case of meeting the UK government’s recommended level of participation, which is time price elastic (elasticity = −2.2). The implications of data from a larger nationally representative sample as well as the role of economic incentives in influencing uptake of sports and exercise are discussed.This article is available through the Brunel Open Access Publishing Fund
Predicting the safety and efficacy of butter therapy to raise tumour pHe: an integrative modelling study
Background: Clinical positron emission tomography imaging has demonstrated the vast majority of human cancers exhibit significantly increased glucose metabolism when compared with adjacent normal tissue, resulting in an acidic tumour microenvironment. Recent studies demonstrated reducing this acidity through systemic buffers significantly inhibits development and growth of metastases in mouse xenografts.\ud
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Methods: We apply and extend a previously developed mathematical model of blood and tumour buffering to examine the impact of oral administration of bicarbonate buffer in mice, and the potential impact in humans. We recapitulate the experimentally observed tumour pHe effect of buffer therapy, testing a model prediction in vivo in mice. We parameterise the model to humans to determine the translational safety and efficacy, and predict patient subgroups who could have enhanced treatment response, and the most promising combination or alternative buffer therapies.\ud
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Results: The model predicts a previously unseen potentially dangerous elevation in blood pHe resulting from bicarbonate therapy in mice, which is confirmed by our in vivo experiments. Simulations predict limited efficacy of bicarbonate, especially in humans with more aggressive cancers. We predict buffer therapy would be most effectual: in elderly patients or individuals with renal impairments; in combination with proton production inhibitors (such as dichloroacetate), renal glomular filtration rate inhibitors (such as non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors), or with an alternative buffer reagent possessing an optimal pK of 7.1–7.2.\ud
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Conclusion: Our mathematical model confirms bicarbonate acts as an effective agent to raise tumour pHe, but potentially induces metabolic alkalosis at the high doses necessary for tumour pHe normalisation. We predict use in elderly patients or in combination with proton production inhibitors or buffers with a pK of 7.1–7.2 is most promising
Holographic current correlators at finite coupling and scattering off a supersymmetric plasma
By studying the effect of the order(\alpha'^3) string theory corrections to
type IIB supergravity, including those corrections involving the Ramond-Ramond
five-form field strength, we obtain the corrected equations of motion of an
Abelian perturbation of the AdS_5-Schwarzschild black hole. We then use the
gauge theory/string theory duality to examine the coupling-constant dependence
of vector current correlators associated to a gauged U(1) sub-group of the
global R-symmetry group of strongly-coupled N=4 supersymmetric Yang-Mills
theory at finite temperature. The corrections induce a set of higher-derivative
operators for the U(1) gauge field, but their effect is highly suppressed. We
thus find that the order(\alpha'^3) corrections affect the vector correlators
only indirectly, through the corrected metric. We apply our results to
investigate scattering off a supersymmetric Yang-Mills plasma at low and high
energy. In the latter regime, where Deep Inelastic Scattering is expected to
occur, we find an enhancement of the plasma structure functions in comparison
with the infinite 't Hooft coupling result.Comment: 38 pages, 6 figures, minor clarifications added, typos corrected,
references adde
An instability of higher-dimensional rotating black holes
We present the first example of a linearized gravitational instability of an
asymptotically flat vacuum black hole. We study perturbations of a Myers-Perry
black hole with equal angular momenta in an odd number of dimensions. We find
no evidence of any instability in five or seven dimensions, but in nine
dimensions, for sufficiently rapid rotation, we find perturbations that grow
exponentially in time. The onset of instability is associated with the
appearance of time-independent perturbations which generically break all but
one of the rotational symmetries. This is interpreted as evidence for the
existence of a new 70-parameter family of black hole solutions with only a
single rotational symmetry. We also present results for the Gregory-Laflamme
instability of rotating black strings, demonstrating that rotation makes black
strings more unstable.Comment: 38 pages, 13 figure
Towards strange metallic holography
We initiate a holographic model building approach to `strange metallic'
phenomenology. Our model couples a neutral Lifshitz-invariant quantum critical
theory, dual to a bulk gravitational background, to a finite density of gapped
probe charge carriers, dually described by D-branes. In the physical regime of
temperature much lower than the charge density and gap, we exhibit anomalous
scalings of the temperature and frequency dependent conductivity. Choosing the
dynamical critical exponent appropriately we can match the non-Fermi liquid
scalings, such as linear resistivity, observed in strange metal regimes. As
part of our investigation we outline three distinct string theory realizations
of Lifshitz geometries: from F theory, from polarised branes, and from a
gravitating charged Fermi gas. We also identify general features of
renormalisation group flow in Lifshitz theories, such as the appearance of
relevant charge-charge interactions when . We outline a program to
extend this model building approach to other anomalous observables of interest
such as the Hall conductivity.Comment: 71 pages, 8 figure
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