Two Examples of Circular Motion for Introductory Courses in Relativity

The circular twin paradox and Thomas Precession are presented in a way that makes both accessible to students in introductory relativity courses. Both are discussed by examining what happens during travel around a polygon and then in the limit as the polygon tends to a circle. Since relativistic predictions based on these examples can be verified in experiments with macroscopic objects such as atomic clocks and the gyroscopes on Gravity Probe B, they are particularly convincing to introductory students.Comment: Accepted by the American Journal of Physics This version includes revision

Anisotropy of weakly vibrated granular flows

We experimentally probe the anisotropy of the fabric of weakly vibrated, flowing granular media. Depending on the driving parameters --- flow rate and vibration strength --- this anisotropy varies significantly. We show how the anisotropy collapses when plotted as function of the driving stresses, uncovering a direct link between stresses and anisotropy. Moreover, our data suggests that for small anisotropies, the shear stresses vanish. Anisotropy of the fabric of granular media thus plays a crucial role in determining the rheology of granular flows

Whole-cell metabolic control analysis

Since its conception some fifty years ago, metabolic control analysis (MCA) aims to understand how cells control their metabolism by adjusting the activity of their enzymes. Here we extend its scope to a whole-cell context. We consider metabolism in the evolutionary context of growth-rate maximisation by optimisation of protein concentrations. This framework allows for the prediction of flux control coefficients from proteomics data or stoichiometric modelling. Since genes compete for finite biosynthetic resources, we treat all protein concentrations as interdependent. We show that elementary flux modes (EFMs) emerge naturally as the optimal metabolic networks in the whole-cell context and we derive their control properties. In the evolutionary optimum, the number of expressed EFMs is determined by the number of protein-concentration constraints that limit growth rate. We use published glucose-limited chemostat data of S. cerevisiae to illustrate that it uses only two EFMs prior to the onset of fermentation and that it uses four EFMs during fermentation. We discuss published enzyme-titration data to show that S. cerevisiae and E. coli indeed can express proteins at growth-rate maximising concentrations. Accordingly, we extend MCA to elementary flux modes operating at an optimal state. We find that the expression of growth-unassociated proteins changes results from classical metabolic control analysis. Finally, we show how flux control coefficients can be estimated from proteomics and ribosome-profiling data. We analyse published proteomics data of E. coli to provide a whole-cell perspective of the control of metabolic enzymes on growth rate. We hope that this paper stimulates a renewed interest in metabolic control analysis, so that it can serve again the purpose it once had: to identify general principles that emerge from the biochemistry of the cell and are conserved across biological species

Isometries of infinite dimensional Hilbert geometries

In this paper we extend two classical results concerning the isometries of strictly convex Hilbert geometries, and the characterisation of the isometry groups of Hilbert geometries on finite dimensional simplices, to infinite dimensions. The proofs rely on a mix of geometric and functional analytic methods

Neurovascular-Sparing MR-Guided Adaptive Radiotherapy in Prostate Cancer; Defining the Potential Population for Erectile Function-Sparing Treatment

BACKGROUND: Magnetic resonance-guided adaptive radiotherapy (MRgRT) enables neurovascular-sparing treatment for localized prostate cancer (PCa). The aim of this treatment is preservation of erectile function by sparing the neurovascular bundles, the internal pudendal arteries, the corpora cavernosa, and the penile bulb. Internal pudendal arteries, corpora cavernosa, and penile bulb sparing can generally be achieved in all patients, but NVB sparing can be challenging due to its proximity to the prostate and is therefore dependent on tumor location. PCa patients that have sufficient erectile function at baseline and favorable tumor characteristics might benefit from this treatment. Currently, it is unclear what proportion of patients are eligible for neurovascular-sparing treatment and to what extent this is technically feasible. AIM: To define the eligibility and technical feasibility for neurovascular-sparing MRgRT in intermediate-risk localized PCa patients. METHODS: A consecutive series of men that received 5 × 7.25 gray (Gy) MRgRT for localized PCa were included. Baseline erectile function was assessed using the International Index of Erectile Function (IIEF)-5 questionnaire. Additionally, the ability of sparing the neurovascular bundles was assessed in all patients. Per neurovascular-sparing protocol, the dominant intraprostatic lesion with a 4 mm isotropic margin should receive 34.44 Gy in ≥ 99% of the volume (i.e., high-dose area). When the high-dose area directly borders or overlaps the NVB because of a dorsolateral position of the dominant intraprostatic lesion, sparing of the NVB was considered not feasible on that side. OUTCOMES: Patient-reported IIEF-5 baseline questionnaires and the technical feasibility of NVB sparing were assessed. RESULTS: Of the 102 men that completed the IIEF-5 questionnaire at baseline, 49.0% of patients reported to have an IIEF-5 score of ≥ 17. In those patients, the NVB could technically have been spared bilaterally in 20.0% and unilaterally in 68.0%. CLINICAL IMPLICATIONS: Our findings define the potential population for neurovascular-sparing MRgRT for localized PCa and indicate the proportion in which the NVB can technically be spared. STRENGTH & LIMITATIONS: The major strength of this study is the prospective collection of data. The limitations include that the neurovascular-sparing feasibility definition is based on pre-clinical planning data. CONCLUSION: A substantial group of 49.0% of patients in our study had mild or no erectile dysfunction at baseline. Of these patients, the NVB could technically have been spared bilaterally in 20.0% and unilaterally in 68.0% during MRgRT. Trials need to assess the effect of neurovascular-sparing MRgRT on erectile function. Teunissen FR, van der Voort van Zyp JRN, Verkooijen HM, et al., Neurovascular-Sparing MR-Guided Adaptive Radiotherapy in Prostate Cancer; Defining the Potential Population for Erectile Function-Sparing Treatment. J Sex Med 2022;19:1196-1200

Differences in guideline-recommended heart failure medication between Dutch heart failure clinics: an analysis of the CHECK-HF registry

Background: Heart failure (HF) is associated with poor prognosis, high morbidity and mortality. The prognosis can be optimised by guideline adherence, which also can be used as a benchmark of quality of care. The purpose of this study was to evaluate differences in use of HF medication between Dutch HF clinics. Methods: The current analysis was part of a cross-sectional registry of 10,910 chronic HF patients at 34 Dutch outpatient clinics in the period of 2013 until 2016 (CHECK-HF), and focused on the differences in prescription rates between the participating clinics in patients with heart failure with reduced ejection fraction (HFrEF). Results: A total of 8,360 HFrEF patients were included with a mean age of 72.3 ± 11.8 years (ranging between 69.1 ± 11.9 and 76.6 ± 10.0 between the clinics), 63.9% were men (ranging between 54.3 and 78.1%), 27.3% were in New York Heart Association (NYHA) class III/IV (ranging between 8.8 and 62.1%) and the average estimated glomerular filtration rate (eGFR) was 59.6 ± 24.6 ml/min (ranging between 45.7 ± 23.5 and 97.1 ± 16.5). The prescription rates ranged from 58.9–97.4% for beta blockers (p < 0.01), 61.9–97.1% for renin-angiotensin system (RAS) inhibitors (p < 0.01), 29.9–86.8% for mineralocorticoid receptor antagonists (MRAs) (p < 0.01), 0.0–31.3% for ivabradine (p < 0.01) and 64.9–100.0% for diuretics (p < 0.01). Also, the percentage of patients who received the target dose differed significantly, 5.9–29.1% for beta blockers (p < 0.01), 18.4–56.1% for RAS inhibitors (p < 0.01) and 13.2–60.6% for MRAs (p < 0.01). Conclusions: The prescription rates and prescribed dosages of guideline-recommended medication differed significantly between HF outpatient clinics in the Netherlands, not fully explained by differences in patient profiles