Use of Bayesian networks to dissect the complexity of genetic disease: application to the Genetic Analysis Workshop 17 simulated data

Complex diseases are often the downstream event of a number of risk factors, including both environmental and genetic variables. To better understand the mechanism of disease onset, it is of great interest to systematically investigate the crosstalk among various risk factors. Bayesian networks provide an intuitive graphical interface that captures not only the association but also the conditional independence and dependence structures among the variables, resulting in sparser relationships between risk factors and the disease phenotype than traditional correlation-based methods. In this paper, we apply a Bayesian network to dissect the complex regulatory relationships among disease traits and various risk factors for the Genetic Analysis Workshop 17 simulated data. We use the Bayesian network as a tool for the risk prediction of disease outcome

Periprosthetic fractures of the femur after total knee arthroplasty

Periprosthetic fracture following total knee arthroplasty is a potentially serious complication. This injury can involve the distal femur, proximal tibia or the patella. This review article analyzes the prevalence, risk factors, classification and treatment options for periprosthetic fractures of the femur

Repeated successful surgical rescues of early and delayed multiple ruptures of ventricular septum, right ventricle and aneurysmal left ventricle following massive biventricular infarction

A 58 year old man underwent 6 surgical interventions for various complications of massive biventricular myocardial infarction over a period of 2 years following acute occlusion of a possibly "hyperdominant" left anterior descending coronary artery. These included concomitant repair of apicoanterior post-infarction VSD and right ventricular free wall rupture, repeat repair of recurrent VSD following inferoposterior extension of VSD in the infarcted septum 5 weeks later, repair of delayed right ventricular free wall rupture 4 weeks subsequently, repair of a bleeding left ventricular aneurysm eroding through left chest wall 16 months thereafter, repair of right upper lobe lung tear causing massive anterior mediastinal haemorrhage, mimicking yet another cardiac rupture, 2 months later, followed, at the same admission, 2 weeks later, by sternal reconstruction for dehisced and infected sternum using pedicled myocutaneous latissimus dorsi flap. 5 years after the latissimus myoplasty, the patient remains in NYHA class 1 and is leading a normal life

Normal tissue toxicity after small field hypofractionated stereotactic body radiation

Stereotactic body radiation (SBRT) is an emerging tool in radiation oncology in which the targeting accuracy is improved via the detection and processing of a three-dimensional coordinate system that is aligned to the target. With improved targeting accuracy, SBRT allows for the minimization of normal tissue volume exposed to high radiation dose as well as the escalation of fractional dose delivery. The goal of SBRT is to minimize toxicity while maximizing tumor control. This review will discuss the basic principles of SBRT, the radiobiology of hypofractionated radiation and the outcome from published clinical trials of SBRT, with a focus on late toxicity after SBRT. While clinical data has shown SBRT to be safe in most circumstances, more data is needed to refine the ideal dose-volume metrics

Illuminating the life of GPCRs

The investigation of biological systems highly depends on the possibilities that allow scientists to visualize and quantify biomolecules and their related activities in real-time and non-invasively. G-protein coupled receptors represent a family of very dynamic and highly regulated transmembrane proteins that are involved in various important physiological processes. Since their localization is not confined to the cell surface they have been a very attractive "moving target" and the understanding of their intracellular pathways as well as the identified protein-protein-interactions has had implications for therapeutic interventions. Recent and ongoing advances in both the establishment of a variety of labeling methods and the improvement of measuring and analyzing instrumentation, have made fluorescence techniques to an indispensable tool for GPCR imaging. The illumination of their complex life cycle, which includes receptor biosynthesis, membrane targeting, ligand binding, signaling, internalization, recycling and degradation, will provide new insights into the relationship between spatial receptor distribution and function. This review covers the existing technologies to track GPCRs in living cells. Fluorescent ligands, antibodies, auto-fluorescent proteins as well as the evolving technologies for chemical labeling with peptide- and protein-tags are described and their major applications concerning the GPCR life cycle are presented

Combined measurement of differential and total cross sections in the H → γγ and the H → ZZ* → 4ℓ decay channels at s=13 TeV with the ATLAS detector

A combined measurement of differential and inclusive total cross sections of Higgs boson production is performed using 36.1 fb−1 of 13 TeV proton–proton collision data produced by the LHC and recorded by the ATLAS detector in 2015 and 2016. Cross sections are obtained from measured H→γγ and H→ZZ*(→4ℓ event yields, which are combined taking into account detector efficiencies, resolution, acceptances and branching fractions. The total Higgs boson production cross section is measured to be 57.0−5.9 +6.0 (stat.) −3.3 +4.0 (syst.) pb, in agreement with the Standard Model prediction. Differential cross-section measurements are presented for the Higgs boson transverse momentum distribution, Higgs boson rapidity, number of jets produced together with the Higgs boson, and the transverse momentum of the leading jet. The results from the two decay channels are found to be compatible, and their combination agrees with the Standard Model predictions

Search for High-Mass Resonances Decaying to τν in pp Collisions at √s=13 TeV with the ATLAS Detector

A search for high-mass resonances decaying to τν using proton-proton collisions at √s=13 TeV produced by the Large Hadron Collider is presented. Only τ-lepton decays with hadrons in the final state are considered. The data were recorded with the ATLAS detector and correspond to an integrated luminosity of 36.1 fb−1. No statistically significant excess above the standard model expectation is observed; model-independent upper limits are set on the visible τν production cross section. Heavy W′ bosons with masses less than 3.7 TeV in the sequential standard model and masses less than 2.2–3.8 TeV depending on the coupling in the nonuniversal G(221) model are excluded at the 95% credibility level

Measurement of differential cross sections and W + /W − cross-section ratios for W boson production in association with jets at √s =8 TeV with the ATLAS detector

This paper presents a measurement of the W boson production cross section and the W + /W − cross-section ratio, both in association with jets, in proton--proton collisions at s √ =8 TeV with the ATLAS experiment at the Large Hadron Collider. The measurement is performed in final states containing one electron and missing transverse momentum using data corresponding to an integrated luminosity of 20.2 fb −1 . Differential cross sections for events with one or two jets are presented for a range of observables, including jet transverse momenta and rapidities, the scalar sum of transverse momenta of the visible particles and the missing transverse momentum in the event, and the transverse momentum of the W boson. For a subset of the observables, the differential cross sections of positively and negatively charged W bosons are measured separately. In the cross-section ratio of W + /W − the dominant systematic uncertainties cancel out, improving the measurement precision by up to a factor of nine. The observables and ratios selected for this paper provide valuable input for the up quark, down quark, and gluon parton distribution functions of the proto