Practical considerations for measuring the effective reproductive number, Rt.

Estimation of the effective reproductive number Rt is important for detecting changes in disease transmission over time. During the Coronavirus Disease 2019 (COVID-19) pandemic, policy makers and public health officials are using Rt to assess the effectiveness of interventions and to inform policy. However, estimation of Rt from available data presents several challenges, with critical implications for the interpretation of the course of the pandemic. The purpose of this document is to summarize these challenges, illustrate them with examples from synthetic data, and, where possible, make recommendations. For near real-time estimation of Rt, we recommend the approach of Cori and colleagues, which uses data from before time t and empirical estimates of the distribution of time between infections. Methods that require data from after time t, such as Wallinga and Teunis, are conceptually and methodologically less suited for near real-time estimation, but may be appropriate for retrospective analyses of how individuals infected at different time points contributed to the spread. We advise caution when using methods derived from the approach of Bettencourt and Ribeiro, as the resulting Rt estimates may be biased if the underlying structural assumptions are not met. Two key challenges common to all approaches are accurate specification of the generation interval and reconstruction of the time series of new infections from observations occurring long after the moment of transmission. Naive approaches for dealing with observation delays, such as subtracting delays sampled from a distribution, can introduce bias. We provide suggestions for how to mitigate this and other technical challenges and highlight open problems in Rt estimation

'Keeping up to date with the Old Way of Doing Things': Competence Management in the UK Heritage Railway Industry

There are over 200 heritage railways throughout the UK, operated primarily by volunteers. To address recent accidents, the Heritage Railway Association has provided guidance on the management of competence, complementing that of the Office of Rail and Road. However, each heritage railway has its own bespoke approach to this issue. Aspects such as the volunteer culture, the prevailing language, the diversity of skills, qualifications and learning abilities, are all factors to be addressed in managing competence effectively. Here, qualitative research methods have been used in the form of eighteen in-depth interviews conducted with workers at four UK heritage railways. Analysis of this data revealed issues such as the need to transfer knowledge from an aging volunteer workforce to new recruits and the importance of ensuring that competences are portable to maintain the viability of the industry, whilst recognising the special needs of volunteers in this unique working environment. Future work will determine the gap between how volunteers ‘see’ competence and how it is managed today, with the aim of developing a new approach to competence management for the UK heritage railway industry

Origin and Implication of Ellipticity in High-order Harmonic Generation from Aligned Molecules

We address theoretically and numerically the possibility of observing ellipticity in high-order harmonic generation (HHG) from aligned molecules driven by linearly polarized fields—a subject of controversy in the recent literature with significant implications. To that end we develop a numerical method for solution of the electronic dynamics and extend a recently developed theory of HHG from aligned molecules. Our numerical results are in good agreement with recent experimental data. The theory explains analytically several observations of polarization experiments. We note the conditions under which ellipticity can be observed and the information content of elliptically polarized harmonics regarding the molecular system

Saturation of Penicillin-Binding Protein 1 by Beta-Lactam Antibiotics in Growing Cells of Bacillus Licheniformis

With the help of a new highly sensitive method allowing the quantification of free penicillin-binding proteins (PBPs) and of an integrated mathematical model, the progressive saturation of PBP1 by various beta-lactam antibiotics in growing cells of Bacillus licheniformis was studied. Although the results confirmed PBP1 as a major lethal target for these compounds, they also underlined several weaknesses in our present understanding of this phenomenon. In growing cells, but not in resting cells, the penicillin target(s) appeared to be somewhat protected from the action of the inactivators. In vitro experiments indicated that amino acids, peptides and depsipeptides mimicking the peptide moiety of the nascent peptidoglycan significantly interfered with the acylation of PBP1 by the antibiotics. In addition, the level of PBP1 saturation at antibiotic concentrations corresponding to the minimum inhibitory concentrations was not constant, suggesting that additional, presently undiscovered, factors might be necessary to account for the experimental observations