Entropy, Ergodicity and Stem Cell Multipotency

Populations of mammalian stem cells commonly exhibit considerable cell-cell variability. However, the functional role of this diversity is unclear. Here, we analyze expression fluctuations of the stem cell surface marker Sca1 in mouse hematopoietic progenitor cells using a simple stochastic model and find that the observed dynamics naturally lie close to a critical state, thereby producing a diverse population that is able to respond rapidly to environmental changes. We propose an information-theoretic interpretation of these results that views cellular multipotency as an instance of maximum entropy statistical inference.Comment: 6 pages, 3 figure

Sample size calculations for cluster randomised controlled trials with a fixed number of clusters

Background\ud Cluster randomised controlled trials (CRCTs) are frequently used in health service evaluation. Assuming an average cluster size, required sample sizes are readily computed for both binary and continuous outcomes, by estimating a design effect or inflation factor. However, where the number of clusters are fixed in advance, but where it is possible to increase the number of individuals within each cluster, as is frequently the case in health service evaluation, sample size formulae have been less well studied. \ud \ud Methods\ud We systematically outline sample size formulae (including required number of randomisation units, detectable difference and power) for CRCTs with a fixed number of clusters, to provide a concise summary for both binary and continuous outcomes. Extensions to the case of unequal cluster sizes are provided. \ud \ud Results\ud For trials with a fixed number of equal sized clusters (k), the trial will be feasible provided the number of clusters is greater than the product of the number of individuals required under individual randomisation ($n_i$) and the estimated intra-cluster correlation ($\rho$). So, a simple rule is that the number of clusters ($\kappa$) will be sufficient provided: \ud \ud $\kappa$ > $n_i$ x $\rho$\ud \ud Where this is not the case, investigators can determine the maximum available power to detect the pre-specified difference, or the minimum detectable difference under the pre-specified value for power. \ud \ud Conclusions\ud Designing a CRCT with a fixed number of clusters might mean that the study will not be feasible, leading to the notion of a minimum detectable difference (or a maximum achievable power), irrespective of how many individuals are included within each cluster. \ud \u

Faecal incontinence persisting after childbirth : a 12 year longitudinal study

© 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.Peer reviewedPostprin

Experimental demonstration of coupled optical springs

Optical rigidity will play an important role in improving the sensitivity of future generations of gravitational wave (GW) interferometers, which employ high laser power in order to reach and exceed the standard quantum limit. Several experiments have demonstrated the combined effect of two optical springs on a single system for very low-weight mirror masses or membranes. In this paper we investigate the complex interactions between multiple optical springs and the surrounding apparatus in a system of comparable dynamics to a large-scale GW detector. Using three 100 g mirrors to form a coupled cavity system capable of sustaining two or more optical springs, we demonstrate a number of different regimes of opto-mechanical rigidity and measurement techniques. Our measurements reveal couplings between each optical spring and the control loops that can affect both the achievable increase in sensitivity and the stability of the system. Hence this work establishes a better understanding of the realisation of these techniques and paves the way to their application in future GW observatories, such as upgrades to Advanced LIGO

Experimental test of higher-order Laguerre–Gauss modes in the 10 m Glasgow prototype interferometer

Brownian noise of dielectric mirror coatings is expected to be one of the limiting noise sources, at the peak sensitivity, of next generation ground based interferometric gravitational wave (GW) detectors. The use of higher-order Laguerre–Gauss (LG) beams has been suggested to reduce the effect of coating thermal noise in future generations of gravitational wave detectors. In this paper we describe the first test of interferometry with higher-order LG beams in an environment similar to a full-scale gravitational wave detector. We compare the interferometric performance of higher-order LG modes and the fundamental mode beams, injected into a 10 m long suspended cavity that features a finesse of 612, a value chosen to be typical of future gravitational wave detectors. We found that the expected mode degeneracy of the injected LG3, 3 beam was resolved into a multiple peak structure, and that the cavity length control signal featured several nearby zero crossings. The break up of the mode degeneracy is due to an astigmatism (defined as |Rcy − Rcx|) of 5.25 ± 0.5 cm on one of our cavity mirrors with a radius of curvature (Rc) of 15 m. This observation agrees well with numerical simulations developed with the FINESSE software. We also report on how these higher-order mode beams respond to the misalignment and mode mismatch present in our 10 m cavity. In general we found the LG3, 3 beam to be considerably more susceptible to astigmatism and mode mismatch than a conventional fundamental mode beam. Therefore the potential application of higher-order Laguerre–Gauss beams in future gravitational wave detectors will impose much more stringent requirements on both mode matching and mirror astigmatism

Terrestrial Alteration Mineral Assemblages in the NWA 10416 Olivine Phyric Shergottite

We report on the alteration history of the olivine-phyric, highly depleted (HD) shergottite, Northwest Africa (NWA) 10416, paying particular attention to the origin of the aqueous alteration seen affecting the meteorite’s olivine megacrysts. The rock’s interior displays 1 mm, zoned, altered olivine megacrysts set in a groundmass of clinopyroxene, unzoned olivine, and interstitial plagioclase and maskelynite. Synchrotron micro X-ray diffraction (µ-XRD) and transmission electron microscopy (TEM) show that plagioclase and maskelynite have been partially replaced by kaolinite. The relict olivine megacryst cores display a unique concentric colouration for Martian meteorites, having central amber-coloured zones surrounded by a brown mantle zone, with the rims remaining clear and unaltered. This colouration is a result of fluid alteration and partial replacement, with hydration. TEM analysis revealed the ∼200 nm scale banded and largely amorphous nature of the alteration, but with some (∼ 20%) relict crystalline olivine patches. Although the coloured olivine zones show cation and anion site vacancies compared to stoichiometric olivine, a relict igneous compositional trend is preserved in the megacrysts, from Mg-rich altered cores (Mg# = 76) to unaltered stoichiometric rims (Fo53). Synchrotron Fe-K X-ray absorption near-edge structure (XANES) analysis revealed that the coloured zones of the megacryst have different Fe oxidation values. High ferric contents are present in the brown mantle zones (Fe3+/ΣFe ≤ 0.92) and the amber zones (Fe3+/ΣFe ≤ 0.30), whereas the clear rims are ferrous. This suggests alteration occurred in an oxidising environment and that the sharp contrast in colour of the megacryst (brown to clear) is a record of a relict fluid reaction front. In order to test the terrestrial or extraterrestrial origin of the alteration, olivine material from a shock-melt vein was analysed by TEM. The analysis revealed 0.952 nm curved d-spacing’s from clay alteration undisturbed by any shock effects, strongly suggesting a terrestrial origin. The d-spacing values most likely represent a collapsed saponite or vermiculite, showing that in some places olivine has been replaced by crystalline clay. Oxygen isotope analysis of bulk (Δ17O = 0.309 ± 0.009 (2σ) ‰) and amber-coloured megacryst material (= 0.271 ± 0.002 (2σ) ‰), are also consistent with terrestrial alteration. We propose a model in which, during the meteorite’s time in Northwest Africa, low-temperature, likely acidic, groundwater exploited fractures. The fluid altered the olivine megacrysts in a way that was controlled by the pre-existing, igneous compositional zonation, with Mg-rich olivine being more susceptible to alteration in this fluid environment. The plagioclase and maskelynite were also altered to a high degree. After the alteration event it is likely that NWA 10416 had a significant residence time in Northwest Africa, accounting for terrestrial calcite and the dehydration of some clay phases

A case study evaluation of implementation of a care pathway to support normal birth in one English birth centre: anticipated benefits and unintended consequences

Background: The policy drive for the UK National Health Service (NHS) has focused on the need for high quality services informed by evidence of best practice. The introduction of care pathways and protocols to standardise care and support implementation of evidence into practice has taken place across the NHS with limited evaluation of their impact. A multi-site case study evaluation was undertaken to assess the impact of use of care pathways and protocols on clinicians, service users and service delivery. One of the five sites was a midwifery-led Birth Centre, where an adapted version of the All Wales Clinical Pathway for Normal Birth had been implemented. Methods: The overarching framework was realistic evaluation. A case study design enabled the capture of data on use of the pathway in the clinical setting, use of multiple methods of data collection and opportunity to study and understand the experiences of clinicians and service users whose care was informed by the pathway. Women attending the Birth Centre were recruited at their 36 week antenatal visit. Episodes of care during labour were observed, following which the woman and the midwife who cared for her were interviewed about use of the pathway. Interviews were also held with other key stakeholders from the study site. Qualitative data were content analysed. Results: Observations were undertaken of four women during labour. Eighteen interviews were conducted with clinicians and women, including the women whose care was observed and the midwives who cared for them, senior midwifery managers and obstetricians. The implementation of the pathway resulted in a number of anticipated benefits, including increased midwifery confidence in skills to support normal birth and promotion of team working. There were also unintended consequences, including concerns about a lack of documentation of labour care and negative impact on working relationships with obstetric and other midwifery colleagues. Women were unaware their care was informed by a care pathway. Conclusion: Care pathways are complex interventions which generate a number of consequences for practice. Those considering introduction of pathways need to ensure all relevant stakeholders are engaged with this and develop robust evaluation strategies to accompany implementation

“Are you doing your pelvic floors?” An ethnographic exploration of discussions between women and health professionals about pelvic floor muscle exercises during pregnancy

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordICS 2019: International Continence Society 49th Annual Meeting, 3-6 September 2019, Gothenburg, SwedenNational Institute for Health Research (NIHR