Return to Activities of Daily Living after Breast Cancer Surgery: An Observational Prospective Questionnaire-Based Study of Patients Undergoing Mastectomy with or without Immediate Reconstruction.

Background: Patients often ask about the time taken to return to activities of daily living (ADLs) after breast surgery, but there is a lack of data to give accurate guidance. We aimed to assess the feasibility of a study to determine the time taken to return to ADLs after mastectomy with or without breast reconstruction. Materials and Methods: A prospective multicentre, self-reported questionnaire-based feasibility study of women who had undergone mastectomy ± reconstruction was performed, between Jan 2017 and Dec 2019. Women were asked to self-report when they returned to 15 ADLs with a 5-option time scale for "return to activity." Results: The questionnaire was returned by 42 patients (median [range] age: 64 [31-84]). Of these, 22 had simple mastectomy, seven mastectomy and implant reconstruction, seven mastectomy and autologous reconstruction (DIEP), and six did not specify. Overall, over 90% could manage stairs and brush hair by two weeks and 84% could get in and out of the bath by four weeks. By 1-2 months, 92% could do their own shopping and 86% could drive. 68% of women employed returned to work within four months. Compared to simple mastectomy, patients undergoing reconstruction took a longer time to return to getting in/out of bath (<2 vs. 2-4 weeks), vacuuming (2-4 weeks vs. 1-2 months), and fitness (1-2 vs. 3-4 months). There was a slower return to shopping (1-2 months vs. 2-4 weeks), driving and work (both 3-4 vs. 1-2 months), and sports (3-4 vs. 1-2 months) in autologous reconstruction compared to implant reconstruction. Conclusion: This study is feasible. It highlights slower return to specific activities (particularly strength-based) in reconstruction patients, slower in autologous compared with implant reconstruction. The impact on return to ADLs should be discussed as part of the preoperative counselling as it will inform patients and help guide their decision making. A larger study is required to confirm these results.

Transition between Instability and Seeded Self-Modulation of a Relativistic Particle Bunch in Plasma.

We use a relativistic ionization front to provide various initial transverse wakefield amplitudes for the self-modulation of a long proton bunch in plasma. We show experimentally that, with sufficient initial amplitude [≥(4.1±0.4) MV/m], the phase of the modulation along the bunch is reproducible from event to event, with 3%-7% (of 2π) rms variations all along the bunch. The phase is not reproducible for lower initial amplitudes. We observe the transition between these two regimes. Phase reproducibility is essential for deterministic external injection of particles to be accelerated.

Proton Bunch Self-Modulation in Plasma with Density Gradient.

We study experimentally the effect of linear plasma density gradients on the self-modulation of a 400 GeV proton bunch. Results show that a positive or negative gradient increases or decreases the number of microbunches and the relative charge per microbunch observed after 10 m of plasma. The measured modulation frequency also increases or decreases. With the largest positive gradient we observe two frequencies in the modulation power spectrum. Results are consistent with changes in wakefields' phase velocity due to plasma density gradients adding to the slow wakefields' phase velocity during self-modulation growth predicted by linear theory.

Proton-driven plasma wakefield acceleration in AWAKE.

In this article, we briefly summarize the experiments performed during the first run of the Advanced Wakefield Experiment, AWAKE, at CERN (European Organization for Nuclear Research). The final goal of AWAKE Run 1 (2013-2018) was to demonstrate that 10-20 MeV electrons can be accelerated to GeV energies in a plasma wakefield driven by a highly relativistic self-modulated proton bunch. We describe the experiment, outline the measurement concept and present first results. Last, we outline our plans for the future. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

Experimental Observation of Proton Bunch Modulation in a Plasma at Varying Plasma Densities.

We give direct experimental evidence for the observation of the full transverse self-modulation of a long, relativistic proton bunch propagating through a dense plasma. The bunch exits the plasma with a periodic density modulation resulting from radial wakefield effects. We show that the modulation is seeded by a relativistic ionization front created using an intense laser pulse copropagating with the proton bunch. The modulation extends over the length of the proton bunch following the seed point. By varying the plasma density over one order of magnitude, we show that the modulation frequency scales with the expected dependence on the plasma density, i.e., it is equal to the plasma frequency, as expected from theory.

Acceleration of electrons in the plasma wakefield of a proton bunch.

High-energy particle accelerators have been crucial in providing a deeper understanding of fundamental particles and the forces that govern their interactions. To increase the energy of the particles or to reduce the size of the accelerator, new acceleration schemes need to be developed. Plasma wakefield acceleration1-5, in which the electrons in a plasma are excited, leading to strong electric fields (so called 'wakefields'), is one such promising acceleration technique. Experiments have shown that an intense laser pulse6-9 or electron bunch10,11 traversing a plasma can drive electric fields of tens of gigavolts per metre and above-well beyond those achieved in conventional radio-frequency accelerators (about 0.1 gigavolt per metre). However, the low stored energy of laser pulses and electron bunches means that multiple acceleration stages are needed to reach very high particle energies5,12. The use of proton bunches is compelling because they have the potential to drive wakefields and to accelerate electrons to high energy in a single acceleration stage13. Long, thin proton bunches can be used because they undergo a process called self-modulation14-16, a particle-plasma interaction that splits the bunch longitudinally into a series of high-density microbunches, which then act resonantly to create large wakefields. The Advanced Wakefield (AWAKE) experiment at CERN17-19 uses high-intensity proton bunches-in which each proton has an energy of 400 gigaelectronvolts, resulting in a total bunch energy of 19 kilojoules-to drive a wakefield in a ten-metre-long plasma. Electron bunches are then injected into this wakefield. Here we present measurements of electrons accelerated up to two gigaelectronvolts at the AWAKE experiment, in a demonstration of proton-driven plasma wakefield acceleration. Measurements were conducted under various plasma conditions and the acceleration was found to be consistent and reliable. The potential for this scheme to produce very high-energy electron bunches in a single accelerating stage20 means that our results are an important step towards the development of future high-energy particle accelerators21,22.

Simulation study of the disjoining pressure profile through a three-phase contact line.

Computer simulations are performed to measure the disjoining pressure profile Pi(y) across the three-phase contact line formed by a liquid-vapor interface intersecting a planar substrate wall lying in the xy plane. The method makes use of an exact expression for the disjoining pressure in terms of the density profile and the wall-fluid interaction. Pi(y) is reported for three distinct values of the wall-fluid attractive potential, representing differing levels of partial wetting by macroscopic adsorbed drops. Mechanical force-balance normal to the substrate is confirmed by direct evaluation of the required analog to Young's equation. For the model system under study, the disjoining pressure profiles are well-fitted by inverted Gaussians. The fitted results are used with an extension (to large values of Young's contact angle theta) of the interface Hamiltonian theory of Indekeu, thereby enabling us to report the line tension tau(theta).

Linear aggregation beyond isodesmic symmetry.

Exactly solvable models of linear aggregation have been known since Ising's seminal one-dimensional model. This model is defined by a unique nearest-neighbor bond strength that is independent of the length of the cluster; known as isodesmic symmetry. Linear aggregation in real systems has often been associated with broken isodesmic symmetry. Here we show that important examples can be mapped to a class of one-dimensional models that are also exactly solvable.

Pair correlation function decay in models of simple fluids that contain dispersion interactions.

We investigate the intermediate-and longest-range decay of the total pair correlation function h(r) in model fluids where the inter-particle potential decays as -r(-6), as is appropriate to real fluids in which dispersion forces govern the attraction between particles. It is well-known that such interactions give rise to a term in q(3) in the expansion of [Formula: see text], the Fourier transform of the direct correlation function. Here we show that the presence of the r(-6) tail changes significantly the analytic structure of [Formula: see text] from that found in models where the inter-particle potential is short ranged. In particular the pure imaginary pole at q = iα(0), which generates monotonic-exponential decay of rh(r) in the short-ranged case, is replaced by a complex (pseudo-exponential) pole at q = iα(0)+α(1) whose real part α(1) is negative and generally very small in magnitude. Near the critical point α(1)∼-α(0)(2) and we show how classical Ornstein-Zernike behaviour of the pair correlation function is recovered on approaching the mean-field critical point. Explicit calculations, based on the random phase approximation, enable us to demonstrate the accuracy of asymptotic formulae for h(r) in all regions of the phase diagram and to determine a pseudo-Fisher-Widom (pFW) line. On the high density side of this line, intermediate-range decay of rh(r) is exponentially damped-oscillatory and the ultimate long-range decay is power-law, proportional to r(-6), whereas on the low density side this damped-oscillatory decay is sub-dominant to both monotonic-exponential and power-law decay. Earlier analyses did not identify the pseudo-exponential pole and therefore the existence of the pFW line. Our results enable us to write down the generic wetting potential for a 'real' fluid exhibiting both short-ranged and dispersion interactions. The monotonic-exponential decay of correlations associated with the pseudo-exponential pole introduces additional terms into the wetting potential that are important in determining the existence and order of wetting transitions.

Linear self-assembly under confinement.

An exactly solvable model is used to obtain the response to confinement of the cluster distribution of linear aggregation. A direct relevance to simulation studies of linear self-assembly in discotic solutions and in peptide tape formation is proposed. The mapping predicts, for typical simulation procedures, that a finite reservoir of solute leads to a dramatic departure from isodesmic chemical equilibria for solute-solute interaction strengths higher than only a few k(B)T .

Direct monitoring of UV-induced free radical generation in HaCaT keratinocytes.

BACKGROUND: Ultraviolet radiation (UVR) is one of the most important aetiological factors in the development of skin cancer, with an estimated 100,000 new cases of nonmelanoma skin cancer (NMSC) diagnosed each year in the UK. To date, little work has been carried out to investigate the role of UVR in the increased production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) following exposure of skin cells to simulated solar UVR. AIM: To monitor directly the effects of simulated solar UVR on ROS and RNS generation in HaCaT keratinocytes. METHODS: This study reports the use of electrochemical monitoring techniques for the direct, real-time detection of two highly reactive free radical species, superoxide (O2-) and nitric oxide (NO), from HaCaT keratinocyte cells that had been exposed to a source of UVR designed to simulate the doses of UVA and UVB found in solar light. RESULTS: An increase in both O2- and NO generation was observed in HaCaT cells that had been exposed to UVR. No detectable increase in either species was observed in cells that had not been exposed to UVR. The specificity of the electrochemical methods for O2- or NO was confirmed through the scavenging or inhibition of these species. CONCLUSION: The findings of this study demonstrated that exposure of HaCaT cells to relatively low doses of UVR resulted in the immediate generation of both O2- and NO, therefore potentially leading to the downstream generation of highly damaging metabolites and the development of a number of pathologies, including cancer.

Hard-sphere fluid adsorbed in an annular wedge: the depletion force of hard-body colloidal physics.

Many important issues of colloidal physics can be expressed in the context of inhomogeneous fluid phenomena. When two large colloids approach one another in solvent, they interact at least partly by the response of the solvent to finding itself adsorbed in the annular wedge formed between the two colloids. At shortest range, this fluid mediated interaction is known as the depletion force/interaction because solvent is squeezed out of the wedge when the colloids approach closer than the diameter of a solvent molecule. An equivalent situation arises when a single colloid approaches a substrate/wall. Accurate treatment of this interaction is essential for any theory developed to model the phase diagrams of homogeneous and inhomogeneous colloidal systems. The aim of our paper is a test of whether or not we possess sufficient knowledge of statistical mechanics that can be trusted when applied to systems of large size asymmetry and the depletion force in particular. When the colloid particles are much larger than a solvent diameter, the depletion force is dominated by the effective two-body interaction experienced by a pair of solvated colloids. This low concentration limit of the depletion force has therefore received considerable attention. One route, which can be rigorously based on statistical mechanical sum rules, leads to an analytic result for the depletion force when evaluated by a key theoretical tool of colloidal science known as the Derjaguin approximation. A rival approach has been based on the assumption that modern density functional theories (DFT) can be trusted for systems of large size asymmetry. Unfortunately, these two theoretical predictions differ qualitatively for hard sphere models, as soon as the solvent density is higher than about 23 that at freezing. Recent theoretical attempts to understand this dramatic disagreement have led to the proposal that the Derjaguin and DFT routes represent opposite limiting behavior, for very large size asymmetry and molecular sized mixtures, respectively. This proposal implies that nanocolloidal systems lie in between the two limits, so that the depletion force no longer scales linearly with the colloid radius. That is, by decreasing the size ratio from mesoscopic to molecular sized solutes, one moves smoothly between the Derjaguin and the DFT predictions for the depletion force scaled by the colloid radius. We describe the results of a simulation study designed specifically as a test of compatibility with this complex scenario. Grand canonical simulation procedures applied to hard-sphere fluid adsorbed in a series of annular wedges, representing the depletion regime of hard-body colloidal physics, confirm that neither the Derjaguin approximation, nor advanced formulations of DFT, apply at moderate to high solvent density when the geometry is appropriate to nanosized colloids. Our simulations also allow us to report structural characteristics of hard-body solvent adsorbed in hard annular wedges. Both these aspects are key ingredients in the proposal that unifies the disparate predictions, via the introduction of new physics. Our data are consistent with this proposed physics, although as yet limited to a single colloidal size asymmetry.

Simulation test of hard-body colloidal physics.

Recent work has raised serious doubts as to whether widely used current statistical mechanical methods are applicable to model colloidal systems. This Letter reports a simulation test strongly supporting a complex scenario that has important implications for the future development of theoretical colloidal physics.

Geometric thermodynamic fields and the generalized ensemble in colloidal physics.

The statistical geometry of hard-sphere mixtures, as defined by Speedy and Reiss, is found to lead to a sum rule that is identical in form to the fundamental equation of the generalized ensemble. This leads one to conjecture the specific form of a set of thermodynamic fields entirely defined by ensemble averages of geometric properties of the configurations. The potential for a direct physical understanding of these quantities is discussed and it is noted that they could, therefore, be of crucial significance to our future understanding of colloidal physics. In the presence of an ideal wall, an analogous sum rule is obtained in terms of interfacial geometric properties (the available surface area for insertions at the wall). For this case, which generalizes beyond hard-sphere models, there exists an obvious physical interpretation involving complete wetting at the ideal wall.

An elegant advance in the physics of wetting.

The non-local interfacial Hamiltonian for short-ranged models of wetting phenomena proposed by Parry and co-authors is discussed in the context of the history of wetting transitions.

Statistical mechanics of the disjoining pressure of a planar film.

The physics of wetting transitions (stability of fluid films adsorbed at planar substrates) is reassessed in the context of the original theory of wetting known as Frumkin-Derjaguin theory [A. Frumkin, Zh. Fiz. Khim. 12, 337 (1938)]. In particular, the Russian School classify wetting phenomena in terms of the mean-field disjoining pressure. The integral of the mean-field disjoining pressure, with respect to film thickness, defines the interface potential accessible from density-functional theory (DFT). For wall-fluid models (substrate defined as an external field), the exact disjoining pressure of an adsorbed film can be expressed as a one-body sum rule. One of the aims of this work is to verify the internal consistency of the statistical thermodynamics of Frumkin-Derjaguin theory, by direct evaluation of the disjoining pressure sum rule, using DFT. For short-range models, the form of the interface potential (and hence disjoining pressure) is directly obtainable from liquid-state asymptotics. The second aim of this work is to verify from DFT that for standard short-range models there are three qualitatively different regimes, arising from competition between the correlation lengths predicted by asymptotic theory. A variety of related issues are also considered, including (i) crossover between the various regimes, (ii) incorporation of capillary-wave fluctuations (beyond mean-field), and (iii) qualitative changes induced by power-law dispersion interactions and the related prediction of two-stage wetting.

Ellipsometric study of adsorption on nanopatterned block copolymer substrates.

We report ellipsometrically obtained adsorption isotherms for a carefully chosen test liquid on block copolymer films of Kraton G1650, compared with adsorption isotherms on homogeneous films of the constituent polymers. Standard atomic force microscopy images imply the outer surface of Kraton G1650 is chemically patterned on the nanoscale, but this could instead be a reflection of structure buried beneath a 10 nm layer of the lower energy component. Our test liquid was chosen on the basis that it did not dissolve in either component and in addition that it was nonwetting on the lower energy polymer while forming thick adsorbed films on pure substrates of the higher energy component. Our ellipsometry data for Kraton G1650 rule out the presence of segregation by the lower energy constituent to the outer surface, implying a mixed surface consistent with Cassie's law. We discuss implications of our findings and related work for the outer surface structures of block copolymer films.

Interfacial statistical geometry: fluids adsorbed in wedges and at edges.

An exact sum rule is derived that links the structure of fluids adsorbed in wedges and at edges to the interfacial free energy far from the wedge apex. By focusing on hard-wall models, one observes a correspondence between interfacial statistical mechanics and geometry. The physical necessity of this correspondence can be argued from the presence of complete drying at a hard wall. Invoking the potential distribution theorem generates yet another class of geometric results, this time concerning the excluded volume generated by a sphere rolling along the surface of the wedge. Direct proof of these latter geometric theorems is straightforward in two-dimensions. Acute wedges and the right-angled wedge, provide examples of models for which comparison with simulation data and density functional theory are available.

Wetting of nanopatterned surfaces: the hexagonal disk surface.

Metropolis Monte Carlo simulations are used to investigate the wetting of chemically nanopatterned surfaces, for the case of hexagonal disk patterns where liquid wishes to wet high-energy circular patches but not wet the background surface. We calculate the density profiles of saturated liquid adsorbed on a variety of such substrates, spanning the nanoscale to atomic scale patterns. In addition, statistical mechanical sum rules are used to obtain interfacial order parameters and interfacial free energies. We observe that Cassie's law is typically obeyed, together with an associated breakdown of the mechanical interpretation of Young's equation, for pattern wavelengths greater than 15 molecular diameters. Here, the adsorbed fluid exists as an array of hemi-drops. At about half this wavelength, the breakdown of Cassie's law lies within realistic energy scales and is associated with the unbending of the outer surface of adsorbed films. For atomic scale patterns, the usual interpretation of Young's equation is restored for films thicker than one monolayer. At high chemical contrast, when the monolayer in contact with high-energy regions would prefer to be crystalline, we observe a variety of exotic interfacial phenomena that may have technological significance.