Dynamics beyond dynamic jam; unfolding the Painlev\'e paradox singularity

This paper analyses in detail the dynamics in a neighbourhood of a G\'enot-Brogliato point, colloquially termed the G-spot, which physically represents so-called dynamic jam in rigid body mechanics with unilateral contact and Coulomb friction. Such singular points arise in planar rigid body problems with slipping point contacts at the intersection between the conditions for onset of lift-off and for the Painlev\'e paradox. The G-spot can be approached in finite time by an open set of initial conditions in a general class of problems. The key question addressed is what happens next. In principle trajectories could, at least instantaneously, lift off, continue in slip, or undergo a so-called impact without collision. Such impacts are non-local in momentum space and depend on properties evaluated away from the G-spot. The results are illustrated on a particular physical example, namely the a frictional impact oscillator first studied by Leine et al. The answer is obtained via an analysis that involves a consistent contact regularisation with a stiffness proportional to $1/\varepsilon^2$. Taking a singular limit as $\varepsilon \to 0$, one finds an inner and an outer asymptotic zone in the neighbourhood of the G-spot. Two distinct cases are found according to whether the contact force becomes infinite or remains finite as the G-spot is approached. In the former case it is argued that there can be no such canards and so an impact without collision must occur. In the latter case, the canard trajectory acts as a dividing surface between trajectories that momentarily lift off and those that do not before taking the impact. The orientation of the initial condition set leading to each eventuality is shown to change each time a certain positive parameter $\beta$ passes through an integer

Setting up and initiating patient public involvement (PPI) as a collaborative process benefits research in its early stages

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Advancing tree genomics to future proof next generation orchard production

The challenges facing tree orchard production in the coming years will be largely driven by changes in the climate affecting the sustainability of farming practices in specific geographical regions. Identifying key traits that enable tree crops to modify their growth to varying environmental conditions and taking advantage of new crop improvement opportunities and technologies will ensure the tree crop industry remains viable and profitable into the future. In this review article we 1) outline climate and sustainability challenges relevant to horticultural tree crop industries, 2) describe key tree crop traits targeted for improvement in agroecosystem productivity and resilience to environmental change, and 3) discuss existing and emerging genomic technologies that provide opportunities for industries to future proof the next generation of orchards

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin