Dynamics of HIV treatment and social contagion

Modern-day management of infectious diseases is critically linked to the use of mathematical models to understand and predict dynamics at many levels, from the mechanisms of pathogenesis to the patterns of population-wide transmission and evolution. This thesis describes the development and application of mathematical techniques for HIV infection and dynamics on social networks. Treatment of HIV infection has improved dramatically in the past few decades but is still limited by the development of drug resistance and the inability of current therapies to completely eradicate the virus from an individual. We begin with a synthesis of the important evolutionary principles governing the HIV epidemic, emphasizing the role of modeling. We then describe a modeling framework to study the emergence of drug-resistant HIV within a patient. Our model integrates laboratory data and patient behavior, with the goal of predicting outcomes of clinical trials. Current results demonstrate how pharmacologic properties of antiretroviral drugs affect selection for drug resistance, and can explain drug-class-specific resistance risks. Thirdly, we describe models for a new class of drugs that aim to eliminate cells with latent viral infection. We provide estimates for the required efficacy of these drugs and describe the potential challenges of future clinical trials. Finally, models and mechanisms for understanding viral dynamics are increasingly finding applications outside traditional virology. They can be used to study the dynamics of behaviors, to help predict and intervene in their spread. We describe techniques for applying infectious disease models to social contagion, drawing on techniques for network epidemiology. We use this framework to interpret data on the interpersonal spread of health-related behaviors

Antiretroviral dynamics determines HIV evolution and predicts therapy outcome

Despite the high inhibition of viral replication achieved by current anti-HIV drugs, many patients fail treatment, often with emergence of drug-resistant virus. Clinical observations show that the relationship between adherence and likelihood of resistance differs dramatically across drug class. We developed a mathematical model that explains these observations and makes novel predictions. Our model incorporates drug properties, fitness differences between susceptible and resistant strains, mutation, and adherence. We show that antiviral activity falls quickly for drugs with sharp dose-response curves and short half-lives, such as boosted protease inhibitors, limiting the time when resistance can be selected. We find that poor adherence to such drugs causes failure via growth of susceptible virus, explaining puzzling clinical observations. Furthermore, our model predicts that certain single-pill combination therapies can prevent resistance regardless of patient adherence. Our approach represents a first step for simulating clinical trials and may help select novel drug regimens for investigation.MathematicsPhysic

Barriers and facilitators to deprescribing in primary care: a systematic review

Background Managing polypharmacy is a challenge for healthcare systems globally. It is also a health inequality concern as it can expose some of the most vulnerable in society to unnecessary medications and adverse drug-related events. Care for most patients with multimorbidity and polypharmacy occurs in primary care. Safe deprescribing interventions can reduce exposure to inappropriate polypharmacy. However, these are not fully accepted or routinely implemented. Aim To identify barriers and facilitators to safe deprescribing interventions for adults with multimorbidity and polypharmacy in primary care. Design and setting Systematic review of studies published from 2000, examining safe deprescribing interventions for adults with multimorbidity and polypharmacy (PROSPERO: CRD42019121848). Method A search of electronic databases: Medline, Embase, CINHAL, Cochrane and HMIC (26.02.19) using an agreed search strategy; supplemented by handsearching of relevant journals, and screening of reference lists and citations of included studies. Results Forty studies from 14 countries were identified. Cultural and organisational barriers included a culture of diagnosis and prescribing; evidence-based guidance focused on single diseases; a lack of evidence-based guidance for the care of older people with multimorbidities; and a lack of shared communication, decision-making systems, tools and resources. Interpersonal and individual-level barriers included professional etiquette; fragmented care; prescribers’ and patients’ uncertainties; and gaps in tailored support. Facilitators included prudent prescribing; greater availability and acceptability of non-pharmacological alternatives; resources; improved communication, collaboration, knowledge and understanding; patient-centred care; and shared decision-making. Conclusion A whole systems patient-centred approach to safe deprescribing interventions is required, involving key decision-makers, healthcare professionals, patients and carers

Anderson's ethical vulnerability: animating feminist responses to sexual violence

Pamela Sue Anderson argues for an ethical vulnerability which “activates an openness to becoming changed” that “can make possible a relational accountability to one another on ethical matters”. In this essay I pursue Anderson’s solicitation that there is a positive politics to be developed from acknowledging and affirming vulnerability. I propose that this politics is one which has a specific relevance for animating the terms of feminist responses to sexual violence, something which has proved difficult for feminist theorists and activists alike. I will demonstrate the contribution of Anderson’s work to such questions by examining the way in which “ethical vulnerability” as a framework can illuminate the intersectional feminist character of Tarana Burke’s grassroots Me Too movement when compared with the mainstream, viral version of the movement. I conclude by arguing that Anderson’s “ethical vulnerability” contains ontological insights which can allay both activist and academic concerns regarding how to respond to sexual violence

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio

Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS

The chi_b(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb^-1, these states are reconstructed through their radiative decays to Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table, corrected author list, matches final version in Physical Review Letter

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13