Optimization of Time-Course Experiments for Kinetic Model Discrimination

Systems biology relies heavily on the construction of quantitative models of biochemical networks. These models must have predictive power to help unveiling the underlying molecular mechanisms of cellular physiology, but it is also paramount that they are consistent with the data resulting from key experiments. Often, it is possible to find several models that describe the data equally well, but provide significantly different quantitative predictions regarding particular variables of the network. In those cases, one is faced with a problem of model discrimination, the procedure of rejecting inappropriate models from a set of candidates in order to elect one as the best model to use for prediction

Prediction of absolute risk of fragility fracture at 10 years in a Spanish population: validation of the WHO FRAX ™ tool in Spain

<p>Abstract</p> <p>Background</p> <p>Age-related bone loss is asymptomatic, and the morbidity of osteoporosis is secondary to the fractures that occur. Common sites of fracture include the spine, hip, forearm and proximal humerus. Fractures at the hip incur the greatest morbidity and mortality and give rise to the highest direct costs for health services. Their incidence increases exponentially with age.</p> <p>Independently changes in population demography, the age - and sex- specific incidence of osteoporotic fractures appears to be increasing in developing and developed countries. This could mean more than double the expected burden of osteoporotic fractures in the next 50 years.</p> <p>Methods/Design</p> <p>To assess the predictive power of the WHO FRAX™ tool to identify the subjects with the highest absolute risk of fragility fracture at 10 years in a Spanish population, a predictive validation study of the tool will be carried out. For this purpose, the participants recruited by 1999 will be assessed. These were referred to scan-DXA Department from primary healthcare centres, non hospital and hospital consultations. Study population: Patients attended in the national health services integrated into a FRIDEX cohort with at least one Dual-energy X-ray absorptiometry (DXA) measurement and one extensive questionnaire related to fracture risk factors. Measurements: At baseline bone mineral density measurement using DXA, clinical fracture risk factors questionnaire, dietary calcium intake assessment, history of previous fractures, and related drugs. Follow up by telephone interview to know fragility fractures in the 10 years with verification in electronic medical records and also to know the number of falls in the last year. The absolute risk of fracture will be estimated using the FRAX™ tool from the official web site.</p> <p>Discussion</p> <p>Since more than 10 years ago numerous publications have recognised the importance of other risk factors for new osteoporotic fractures in addition to low BMD. The extension of a method for calculating the risk (probability) of fractures using the FRAX™ tool is foreseeable in Spain and this would justify a study such as this to allow the necessary adjustments in calibration of the parameters included in the logarithmic formula constituted by FRAX™.</p

Surgical site infection in critically ill patients with secondary and tertiary peritonitis: epidemiology, microbiology and influence in outcomes

BACKGROUND: Surgical site infection (SSI) remains a significant problem in the postoperative period that can negatively affect clinical outcomes. Microbiology findings are typically similar to other nosocomial infections, with differences dependent on microbiology selection due to antibiotic pressure or the resident flora. However, this is poorly understood in the critical care setting. We therefore aimed to assess the incidence, epidemiology and microbiology of SSI and its association with outcomes in patients with severe peritonitis in the intensive care unit (ICU). METHODS: We prospectively studied 305 consecutive patients admitted to our surgical ICU from 2010 to 2014 with a diagnosis of secondary or tertiary peritonitis. We collected the following data: SSI diagnosis, demographics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II score, type of surgery, microbiology, antibiotic treatment and outcomes. Microbiological sampling was done by means of swabs. RESULTS: We identified 269 episodes of SSI in 162 patients (53.1 %) aged 64.4 ± 14.3 years, of which 200 episodes occurred in men (64.6 %). The mean APACHE II and SAPS II scores were 19.7 ± 7.8 and 36.5 ± 16.1 respectively. The mean ICU and hospital stays were 19.8 ± 24.8 and 21.7 ± 30 days respectively. Pseudomonas spp. (n = 52, 19.3 %), Escherichia coli (n = 55, 20.4 %) and Candida spp. (n = 46, 17.1 %) were the most frequently isolated microorganisms, but gram-positive cocci (n = 80, 29.7 %) were also frequent. Microorganisms isolated from SSIs were associated with a higher incidence of antibiotic resistance (64.9 %) in ICU patients, but not with higher in-hospital mortality. However, patients who suffered from SSI had longer ICU admissions (odds ratio = 1.024, 95 % confidence interval 1.010–1.039, P = 0.001). CONCLUSIONS: The incidence of SSI in secondary or tertiary peritonitis requiring ICU admission is very high. Physicians may consider antibiotic-resistant pathogens, gram-positive cocci and fungi when choosing empiric antibiotic treatment for SSI, although more studies are needed to confirm our results due to the inherent limitations of the microbiological sampling with swabs performed in our research. The presence of SSI may be associated with prolonged ICU stays, but without any influence on overall mortality

Measurement of double-parton scattering in inclusive production of four jets with low transverse momentum in proton-proton collisions at root s=13 TeV

A measurement of inclusive four-jet production in proton-proton collisions at a center-of-mass energy of 13 TeV is presented. The transverse momenta of jets within vertical bar eta vertical bar 4.7 are required to exceed 35, 30, 25, and 20 GeV for the first-, second-, third-, and fourth-leading jet, respectively. Differential cross sections are measured as functions of the jet transverse momentum, jet pseudorapidity, and several other observables that describe the angular correlations between the jets. The measured distributions show sensitivity to different aspects of the underlying event, parton shower modeling, and matrix element calculations. In particular, the interplay between angular correlations caused by parton shower and double-parton scattering contributions is shown to be important. The double-parton scattering contribution is extracted by means of a template fit to the data, using distributions for single-parton scattering obtained from Monte Carlo event generators and a double-parton scattering distribution constructed from inclusive single-jet events in data. The effective double-parton scattering cross section is calculated and discussed in view of previous measurements and of its dependence on the models used to describe the single-parton scattering background

Measurement of the inclusive and differential t(t)over-bar gamma cross sections in the single-lepton channel and EFT interpretation at root s=13 TeV

Peer reviewe

Measurement of the Higgs boson width and evidence of its off-shell contributions to ZZ production

Since the discovery of the Higgs boson in 2012, detailed studies of its properties have been ongoing. Besides its mass, its width—related to its lifetime—is an important parameter. One way to determine this quantity is to measure its off-shell production, where the Higgs boson mass is far away from its nominal value, and relating it to its on-shell production, where the mass is close to the nominal value. Here we report evidence for such off-shell contributions to the production cross-section of two Z bosons with data from the CMS experiment at the CERN Large Hadron Collider. We constrain the total rate of the off-shell Higgs boson contribution beyond the Z boson pair production threshold, relative to its standard model expectation, to the interval [0.0061, 2.0] at the 95% confidence level. The scenario with no off-shell contribution is excluded at a p-value of 0.0003 (3.6 standard deviations). We measure the width of the Higgs boson as $\Gamma$$_H$=3.2$^{+2.4}_{−1.7}$MeV, in agreement with the standard model expectation of 4.1 MeV. In addition, we set constraints on anomalous Higgs boson couplings to W and Z boson pairs

Measurement of differential t(t)over-bar production cross sections in the full kinematic range using lepton plus jets events from proton-proton collisions at root s=13 TeV

Measurements of differential and double-differential cross sections of top-quark pair (t (t) over bar) production arc presented in the lepton + jets channels with a single electron or muon and jets in the final state. The analysis combines for the first time signatures of top quarks with low transverse momentum p(T), where the top-quark decay products can be identified as separated jets and isolated leptons, and with high p(T), where the decay products are collimated and overlap. The measurements arc based on proton-proton collision data at is - = 13 TeV collected by the CMS experiment at the LHC, corresponding to an integrated luminosity of 137 fb(-1). The cross sections are presented at the parton and particle levels, where the latter minimizes extrapolations based on theoretical assumptions. Most of the measured differential cross sections are well described by standard model predictions with the exception of some double-differential distributions. The inclusive t (t) over bar production cross section is measured to be sigma(t (t) over bar) = 791 +/- 25 pb, which constitutes the most precise measurement in the lepton + jets channel to date.Peer reviewe

Search for new particles in an extended Higgs sector with four b quarks in the final state at √s = 13 TeV

A search for a massive resonance X decaying to a pair of spin-0 bosons ϕ that themselves decay to pairs of bottom quarks, is presented. The analysis is restricted to the mass ranges from 25 to 100 GeV and from 1 to 3 TeV. For these mass ranges, the decay products of each ϕ boson are expected to merge into a single large-radius jet. Jet substructure and flavor identification techniques are used to identify these jets. The search is based on CERN LHC proton-proton collision data at , collected with the CMS detector in 2016–2018, corresponding to an integrated luminosity of 138 . Model-specific limits, where the two new particles arise from an extended Higgs sector, are set on the product of the production cross section and branching fraction for as a function of the resonances' masses, where both the and branching fractions are assumed to be 100%. These limits are the first of their kind on this process, ranging between 30 and 1 fb at 95% confidence level for the considered mass ranges

Search for a vector-like quark T′ → tH via the diphoton decay mode of the Higgs boson in proton-proton collisions at s \sqrt{s} = 13 TeV

A search for the electroweak production of a vector-like quark T′, decaying to a top quark and a Higgs boson is presented. The search is based on a sample of proton-proton collision events recorded at the LHC at = 13 TeV, corresponding to an integrated luminosity of 138 fb−1. This is the first T′ search that exploits the Higgs boson decay to a pair of photons. For narrow isospin singlet T′ states with masses up to 1.1 TeV, the excellent diphoton invariant mass resolution of 1–2% results in an increased sensitivity compared to previous searches based on the same production mechanism. The electroweak production of a T′ quark with mass up to 960 GeV is excluded at 95% confidence level, assuming a coupling strength κT = 0.25 and a relative decay width Γ/MT′ < 5%

Observation of the Bc+_\mathrm{c}^+ Meson in Pb-Pb and pp Collisions at sNN\sqrt{s_{\mathrm{NN}}} = 5.02 TeV and Measurement of its Nuclear Modification Factor

The B$_\mathrm{c}^+$ meson is observed for the first time in heavy ion collisions. Data from the CMS detector are used to study the production of the B$_\mathrm{c}^+$ meson in lead-lead (Pb-Pb) and proton-proton (pp) collisions at a center-of-mass energy per nucleon pair of $\sqrt{s_{\mathrm{NN}}}$ = 5.02 TeV , via the B$_\mathrm{c}^+$ → (J/ψ → μ$^+$μ$^−$)μ$^+$ν$_μ$ decay. The B$_\mathrm{c}^+$ nuclear modification factor, derived from the PbPb-to-pp ratio of production cross sections, is measured in two bins of the trimuon transverse momentum and of the PbPb collision centrality. The B$_\mathrm{c}^+$meson is shown to be less suppressed than quarkonia and most of the open heavy-flavor mesons, suggesting that effects of the hot and dense nuclear matter created in heavy ion collisions contribute to its production. This measurement sets forth a promising new probe of the interplay of suppression and enhancement mechanisms in the production of heavy-flavor mesons in the quark-gluon plasma