The peritoneal tumour microenvironment of high-grade serous ovarian cancer

High-grade serous ovarian cancer (HGSC) disseminates early and extensively throughout the peritoneal space, causing multiple lesions that are a major clinical problem. The aim of this study was to investigate the cellular composition of peritoneal tumour deposits in patient biopsies and their evolution in mouse models using immunohistochemistry, intravital microscopy, confocal microscopy, and 3D modelling. Tumour deposits from the omentum of HGSC patients contained a prominent leukocyte infiltrate of CD3(+) T cells and CD68(+) macrophages, with occasional neutrophils. Alpha-smooth muscle actin(+) (α-SMA(+) ) pericytes and/or fibroblasts surrounded these well-vascularized tumour deposits. Using the murine bowel mesentery as an accessible mouse peritoneal tissue that could be easily imaged, and two different transplantable models, we found multiple microscopic tumour deposits after i.p. injection of malignant cells. Attachment to the peritoneal surface was rapid (6-48 h) with an extensive CD45(+) leukocyte infiltrate visible by 48 h. This infiltrate persisted until end point and in the syngeneic murine ID8 model, it primarily consisted of CD3(+) T lymphocytes and CD68(+) macrophages with α-SMA(+) cells also involved from the earliest stages. A majority of tumour deposits developed above existing mesenteric blood vessels, but in avascular spaces new blood vessels tracked towards the tumour deposits by 2-3 weeks in the IGROV-1 xenografts and 6 weeks in the ID8 syngeneic model; a vigorous convoluted blood supply was established by end point. Inhibition of tumour cell cytokine production by stable expression of shRNA to CXCR4 in IGROV-1 cells did not influence the attachment of cells to the mesentery but delayed neovascularization and reduced tumour deposit size. We conclude that the multiple peritoneal tumour deposits found in HGSC patients can be modelled in the mouse. The techniques described here may be useful for assessing treatments that target the disseminated stage of this disease

What is the contribution of physician associates in hospital care in England? A mixed methods, multiple case study.

OBJECTIVES: To investigate the deployment of physician associates (PAs); the factors supporting and inhibiting their employment and their contribution and impact on patients' experience and outcomes and the organisation of services. DESIGN: Mixed methods within a case study design, using interviews, observations, work diaries and documentary analysis. SETTING: Six acute care hospitals in three regions of England in 2016-2017. PARTICIPANTS: 43 PAs, 77 other health professionals, 28 managers, 28 patients and relatives. RESULTS: A key influencing factor supporting the employment of PAs in all settings was a shortage of doctors. PAs were found to be acceptable, appropriate and safe members of the medical/surgical teams by the majority of doctors, managers and nurses. They were mainly deployed to undertake inpatient ward work in the medical/surgical team during core weekday hours. They were reported to positively contribute to: continuity within their medical/surgical team, patient experience and flow, inducting new junior doctors, supporting the medical/surgical teams' workload, which released doctors for more complex patients and their training. The lack of regulation and attendant lack of authority to prescribe was seen as a problem in many but not all specialties. The contribution of PAs to productivity and patient outcomes was not quantifiable separately from other members of the team and wider service organisation. Patients and relatives described PAs positively but most did not understand who and what a PA was, often mistaking them for doctors. CONCLUSIONS: This study offers new insights concerning the deployment and contribution of PAs in medical and surgical specialties in English hospitals. PAs provided a flexible addition to the secondary care workforce without drawing from existing professions. Their utility in the hospital setting is unlikely to be completely realised without the appropriate level of regulation and authority to prescribe medicines and order ionising radiation within their scope of practice

The Behavior of Granular Materials under Cyclic Shear

The design and development of a parallel plate shear cell for the study of large scale shear flows in granular materials is presented. The parallel plate geometry allows for shear studies without the effects of curvature found in the more common Couette experiments. A system of independently movable slats creates a well with side walls that deform in response to the motions of grains within the pack. This allows for true parallel plate shear with minimal interference from the containing geometry. The motions of the side walls also allow for a direct measurement of the velocity profile across the granular pack. Results are presented for applying this system to the study of transients in granular shear and for shear-induced crystallization. Initial shear profiles are found to vary from packing to packing, ranging from a linear profile across the entire system to an exponential decay with a width of approximately 6 bead diameters. As the system is sheared, the velocity profile becomes much sharper, resembling an exponential decay with a width of roughly 3 bead diameters. Further shearing produces velocity profiles which can no longer be fit to an exponential decay, but are better represented as a Gaussian decay or error function profile. Cyclic shear is found to produce large scale ordering of the granular pack, which has a profound impact on the shear profile. There exist periods of time in which there is slipping between layers as well as periods of time in which the layered particles lock together resulting in very little relative motion.Comment: 10 pages including 12 figure

Experienced tutors' deployment of thinking skills and what might be entailed in enhancing such skills

In the context of research that reports weaknesses in adults' critical thinking skills, the primary aim was to examine adults' use of critical thinking skills that are described in taxonomies and to identify areas for development. Position papers written by an opportunity sample of 32 experienced adult educators formed the data for a descriptive sample survey design intended to reveal participants' use of critical thinking skills. Each 6000-word paper was written during a development programme that supported such skills. A content analysis of the papers revealed that when participants drew on personal and published ideas about learning to derive their proposals for change, they accepted the ideas uncritically, thereby implying that they might find it difficult to help learners to examine ideas critically. The evidence supports research that implies that critical thinking skills are unlikely to develop unless overall course design privileges the development of epistemological understanding (King and Kitchener 1994, Kuhn 1999). A fundamental assumption underlying the study is that this understanding influences effective citizenship and personal development, as well as employability. A proposition that merits attention in future research is that the development of epistemological understanding is largely neglected in current curricula in formal post-16 education

Density Fluctuations in an Electrolyte from Generalized Debye-Hueckel Theory

Near-critical thermodynamics in the hard-sphere (1,1) electrolyte is well described, at a classical level, by Debye-Hueckel (DH) theory with (+,-) ion pairing and dipolar-pair-ionic-fluid coupling. But DH-based theories do not address density fluctuations. Here density correlations are obtained by functional differentiation of DH theory generalized to {\it non}-uniform densities of various species. The correlation length $\xi$ diverges universally at low density $\rho$ as $(T\rho)^{-1/4}$ (correcting GMSA theory). When $\rho=\rho_c$ one has $\xi\approx\xi_0^+/t^{1/2}$ as $t\equiv(T-T_c)/T_c\to 0+$ where the amplitudes $\xi_0^+$ compare informatively with experimental data.Comment: 5 pages, REVTeX, 1 ps figure included with epsf. Minor changes, references added. Accepted for publication in Phys. Rev. Let

Near-infrared Observations of Nova V574 Puppis (2004)

We present results obtained from extensive near-infrared spectroscopic and photometric observations of nova V574 Pup during its 2004 outburst. The observations were obtained over four months, starting from 2004 November 25 (four days after the nova outburst) to 2005 March 20. The near-IR JHK light curve is presented - no evidence is seen from it for dust formation to have occurred during our observations. In the early decline phase, the JHK spectra of the nova are dominated by emission lines of hydrogen Brackett and Paschen series, OI, CI and HeI. We also detect the fairly uncommon Fe II line at 1.6872 micron in the early part of our observations. The strengths of the HeI lines at 1.0830 micron and 2.0585 micron are found to become very strong towards the end of the observations indicating a progression towards higher excitation conditions in the nova ejecta. The width of the emission lines do not show any significant change during the course of our observations. The slope of the continuum spectrum was found to have a lambda^{-2.75} dependence in the early stages which gradually becomes flatter with time and changes to a free-free spectral dependence towards the later stages. Recombination analysis of the HI lines shows deviations from Case B conditions during the initial stages. However, towards the end of our observations, the line strengths are well simulated with case B model values with electron density n_e = 10^{9-10} cm^{-3} and a temperature equal to 10^4 K. Based on our distance estimate to the nova of 5.5 kpc and the observed free-free continuum emission in the later part of the observations, we estimate the ionized mass of the ejecta to be between 10^{-5} and 10^{-6} solar-mass.Comment: 10 pages, 8 figures, Accepted for publication in MNRA

Physician associates in England's hospitals: a survey of medical directors exploring current usage and factors affecting recruitment.

In the UK secondary care setting, the case for physician associates is based on the cover and stability they might offer to medical teams. We assessed the extent of their adoption and deployment - that is, their current usage and the factors supporting or inhibiting their inclusion in medical teams - using an electronic, self-report survey of medical directors of acute and mental health NHS trusts in England. Physician associates - employed in small numbers, in a range of specialties, in 20 of the responding trusts - were reported to have been employed to fill gaps in medical staffing and support medical specialty trainees. Inhibiting factors were commonly a shortage of physician associates to recruit and lack of authority to prescribe, as well as a lack of evidence and colleague resistance. Our data suggest there is an appetite for employment of physician associates while practical and attitudinal barriers are yet to be fully overcome

Dragging a polymer chain into a nanotube and subsequent release

We present a scaling theory and Monte Carlo (MC) simulation results for a flexible polymer chain slowly dragged by one end into a nanotube. We also describe the situation when the completely confined chain is released and gradually leaves the tube. MC simulations were performed for a self-avoiding lattice model with a biased chain growth algorithm, the pruned-enriched Rosenbluth method. The nanotube is a long channel opened at one end and its diameter $D$ is much smaller than the size of the polymer coil in solution. We analyze the following characteristics as functions of the chain end position $x$ inside the tube: the free energy of confinement, the average end-to-end distance, the average number of imprisoned monomers, and the average stretching of the confined part of the chain for various values of $D$ and for the number of monomers in the chain, $N$. We show that when the chain end is dragged by a certain critical distance $x^*$ into the tube, the polymer undergoes a first-order phase transition whereby the remaining free tail is abruptly sucked into the tube. This is accompanied by jumps in the average size, the number of imprisoned segments, and in the average stretching parameter. The critical distance scales as $x^*\sim ND^{1-1/\nu}$. The transition takes place when approximately 3/4 of the chain units are dragged into the tube. The theory presented is based on constructing the Landau free energy as a function of an order parameter that provides a complete description of equilibrium and metastable states. We argue that if the trapped chain is released with all monomers allowed to fluctuate, the reverse process in which the chain leaves the confinement occurs smoothly without any jumps. Finally, we apply the theory to estimate the lifetime of confined DNA in metastable states in nanotubes.Comment: 13pages, 14figure

The Middle Way: East Asian masters students’ perceptions of critical argumentation in U.K. universities.

The paper explores the learning experiences of East Asian masters students in dealing with Western academic norms of critical thinking in classroom debate and assignment writing. The research takes a cultural approach, and employs grounded theory and case study methodology, the aims being for students to explain their perceptions of their personal learning journeys. The data suggest that the majority of students interviewed rejected full academic acculturation into Western norms of argumentation. They instead opted for a ‘Middle Way’ that synergizes the traditional cultural academic values held by many East Asian students with those elements of Western academic norms that are perceived to be aligned with these. This is a relatively new area of research which represents a challenge for British lecturers and students

Threats to the validity of the Collegiate Learning Assessment (CLA+) as a measure of critical thinking skills and implications for Learning Gain

The University of Reading Learning Gain project is a three-year longitudinal project to test and evaluate a range of available methodologies and to draw conclusions on what might be the right combination of instruments for the measurement of Learning Gain in higher education. This paper analyses the validity of a measure of critical thinking skills, the Collegiate Learning Assessment (CLA+) and the implications of using this standardised test as a proxy for Learning Gain. The paper reviews five inferences regarding the interpretations and use of test scores: construct representation, scoring, generalisation, extrapolation and decision-making. Each section reviews some of the available evidence in support of the claims the CLA+ makes and the threats to their validity. The possible impact of these issues on Learning Gain in the UK is considered