Shifts in growth strategies reflect tradeoffs in cellular economics

The growth rate-dependent regulation of cell size, ribosomal content, and metabolic efficiency follows a common pattern in unicellular organisms: with increasing growth rates, cell size and ribosomal content increase and a shift to energetically inefficient metabolism takes place. The latter two phenomena are also observed in fast growing tumour cells and cell lines. These patterns suggest a fundamental principle of design. In biology such designs can often be understood as the result of the optimization of fitness. Here we show that in basic models of self-replicating systems these patterns are the consequence of maximizing the growth rate. Whereas most models of cellular growth consider a part of physiology, for instance only metabolism, the approach presented here integrates several subsystems to a complete self-replicating system. Such models can yield fundamentally different optimal strategies. In particular, it is shown how the shift in metabolic efficiency originates from a tradeoff between investments in enzyme synthesis and metabolic yields for alternative catabolic pathways. The models elucidate how the optimization of growth by natural selection shapes growth strategies

Next-to-leading order predictions for Z gamma+jet and Z gamma gamma final states at the LHC

We present next-to-leading order predictions for final states containing leptons produced through the decay of a Z boson in association with either a photon and a jet, or a pair of photons. The effect of photon radiation from the final state leptons is included and we also allow for contributions arising from fragmentation processes. Phenomenological studies are presented for the LHC in the case of final states containing charged leptons and in the case of neutrinos. We also use the procedure introduced by Stewart and Tackmann to provide a reliable estimate of the scale uncertainty inherent in our theoretical calculations of jet-binned Z gamma cross sections. These computations have been implemented in the public code MCFM.Comment: 30 pages, 10 figure

Scattering AMplitudes from Unitarity-based Reduction Algorithm at the Integrand-level

SAMURAI is a tool for the automated numerical evaluation of one-loop corrections to any scattering amplitudes within the dimensional-regularization scheme. It is based on the decomposition of the integrand according to the OPP-approach, extended to accommodate an implementation of the generalized d-dimensional unitarity-cuts technique, and uses a polynomial interpolation exploiting the Discrete Fourier Transform. SAMURAI can process integrands written either as numerator of Feynman diagrams or as product of tree-level amplitudes. We discuss some applications, among which the 6- and 8-photon scattering in QED, and the 6-quark scattering in QCD. SAMURAI has been implemented as a Fortran90 library, publicly available, and it could be a useful module for the systematic evaluation of the virtual corrections oriented towards automating next-to-leading order calculations relevant for the LHC phenomenology.Comment: 35 pages, 7 figure

Patient risk profiles and practice variation in nonadherence to antidepressants, antihypertensives and oral hypoglycemics

BACKGROUND: Many patients experience difficulties in following treatment recommendations. This study's objective is to identify nonadherence risk profiles regarding medication (antidepressants, antihypertensives, and oral hypoglycemics) from a combination of patients' socio-demographic characteristics, morbidity presented within general practice and medication characteristics. An additional objective is to explore differences in nonadherence among patients from different general practices. METHODS: Data were obtained by linkage of a Dutch general practice registration database to a dispensing registration database from the year 2001. Subjects included in the analyses were users of antidepressants (n = 4,877), antihypertensives (n = 14,219), or oral hypoglycemics (n = 2,428) and their GPs. Outcome variables were: 1) early dropout i.e., a maximum of two prescriptions and 2) refill nonadherence (in patients with 3+ prescriptions); refill adherence < 80% was considered as nonadherence. Multilevel modeling was used for analyses. RESULTS: Both early dropout and refill nonadherence were highest for antidepressants, followed by antihypertensives. Risk factors appeared medication specific and included: 1) non-western immigrants being more vulnerable for nonadherence to antihypertensives and antidepressants; 2) type of medication influencing nonadherence in both antihypertensives and antidepressants, 3) GP consultations contributing positively to adherence to antihypertensives and 4) somatic co-morbidity influencing adherence to antidepressants negatively. There was a considerable range between general practices in the proportion of patients who were nonadherent. CONCLUSION: No clear risk profiles for nonadherence could be constructed. Characteristics that are correlated with nonadherence vary across different types of medication. Moreover, both patient and prescriber influence adherence. Especially non-western immigrants need more attention with regard to nonadherence, for example by better monitoring or communication. Since it is not clear which prescriber characteristics influence adherence levels of their patients, there is need for further research into the role of the prescriber

Teaching Feedback to First-year Medical Students: Long-term Skill Retention and Accuracy of Student Self-assessment

Giving and receiving feedback are critical skills and should be taught early in the process of medical education, yet few studies discuss the effect of feedback curricula for first-year medical students. To study short-term and long-term skills and attitudes of first-year medical students after a multidisciplinary feedback curriculum. Prospective pre- vs. post-course evaluation using mixed-methods data analysis. First-year students at a public university medical school. We collected anonymous student feedback to faculty before, immediately after, and 8 months after the curriculum and classified comments by recommendation (reinforcing/corrective) and specificity (global/specific). Students also self-rated their comfort with and quality of feedback. We assessed changes in comments (skills) and self-rated abilities (attitudes) across the three time points. Across the three time points, students’ evaluation contained more corrective specific comments per evaluation [pre-curriculum mean (SD) 0.48 (0.99); post-curriculum 1.20 (1.7); year-end 0.95 (1.5); p = 0.006]. Students reported increased skill and comfort in giving and receiving feedback and at providing constructive feedback (p &lt; 0.001). However, the number of specific comments on year-end evaluations declined [pre 3.35 (2.0); post 3.49 (2.3); year-end 2.8 (2.1)]; p = 0.008], as did students’ self-rated ability to give specific comments. Teaching feedback to early medical students resulted in improved skills of delivering corrective specific feedback and enhanced comfort with feedback. However, students’ overall ability to deliver specific feedback decreased over time

Barriers to the uptake and use of feedback in the context of summative assessment

Despite calls for feedback to be incorporated in all assessments, a dichotomy exists between formative and summative assessments. When feedback is provided in a summative context, it is not always used effectively by learners. In this study we explored the reasons for this. We conducted individual interviews with 17 students who had recently received web based feedback following a summative assessment. Constant comparative analysis was conducted for recurring themes. The summative assessment culture, with a focus on avoiding failure, was a dominant and negative influence on the use of feedback. Strong emotions were prevalent throughout the period of assessment and feedback, which reinforced the focus on the need to pass, rather than excel. These affective factors were heightened by interactions with others. The influence of prior learning experiences affected expectations about achievement and the need to use feedback. The summative assessment and subsequent feedback appeared disconnected from future clinical workplace learning. Socio-cultural influences and barriers to feedback need to be understood before attempting to provide feedback after all assessments. A move away from the summative assessment culture may be needed in order to maximise the learning potential of assessments

A novel design process for selection of attributes for inclusion in discrete choice experiments:Case study exploring variation in clinical decision-making about thrombolysis in the treatment of acute ischaemic stroke

On-line structured prioritisation exercise (SPE). Full survey used to collect data. (DOCX 42 kb