Effects of neo-adjuvant chemotherapy for oesophago-gastric cancer on neuro-muscular gastric function

Delayed gastric emptying symptoms are often reported after chemotherapy. This study aims to characterise the effects of chemotherapy on gastric neuro-muscular function. Patients undergoing elective surgery for oesophago-gastric cancer were recruited. Acetylcholinesterase, nNOS, ghrelin receptor and motilin expressions were studied in gastric sections from patients receiving no chemotherapy (n = 3) or oesophageal (n = 2) or gastric (n = 2) chemotherapy. A scoring system quantified staining intensity (0–3; no staining to strong). Stomach sections were separately suspended in tissue baths for electrical field stimulation (EFS) and exposure to erythromycin or carbachol; three patients had no chemotherapy; four completed cisplatin-based chemotherapy within 6 weeks prior to surgery. AChE expression was markedly decreased after chemotherapy (scores 2.3 ± 0.7, 0.5 ± 0.2 and 0 ± 0 in non-chemotherapy, oesophageal- and gastric-chemotherapy groups (p < 0.03 each) respectively. Ghrelin receptor and motilin expression tended to increase (ghrelin: 0.7 ± 0.4 vs 2.0 ± 0.4 and 1.2 ± 0.2 respectively; p = 0.04 and p = 0.2; motilin: 0.7 ± 0.5 vs 2.2 ± 0.5 and 2.0 ± 0.7; p = 0.06 and p = 0.16). Maximal contraction to carbachol was 3.7 ± 0.7 g and 1.9 ± 0.8 g (longitudinal muscle) and 3.4 ± 0.4 g and 1.6 ± 0.6 (circular) in non-chemotherapy and chemotherapy tissues respectively (p < 0.05 each). There were loss of AChE and reduction in contractility to carbachol. The tendency for ghrelin receptors to increase suggests an attempt to upregulate compensating systems. Our study offers a mechanism by which chemotherapy markedly alters neuro-muscular gastric function

Dynamics of ions in the selectivity filter of the KcsA channel

The statistical and dynamical properties of ions in the selectivity filter of the KcsA ion channel are considered on the basis of molecular dynamics (MD) simulations of the KcsA protein embedded in a lipid membrane surrounded by an ionic solution. A new approach to the derivation of a Brownian dynamics (BD) model of ion permeation through the filter is discussed, based on unbiased MD simulations. It is shown that depending on additional assumptions, ion’s dynamics can be described either by under-damped Langevin equation with constant damping and white noise or by Langevin equation with a fractional memory kernel. A comparison of the potential of the mean force derived from unbiased MD simulations with the potential produced by the umbrella sampling method demonstrates significant differences in these potentials. The origin of these differences is an open question that requires further clarifications

Social media and teacher professional learning communities

peer-reviewed.Background: An extensive and international evidence base positions professional learning communities (PLCs) as an effective continued professional development (CPD) mechanism that can impact on teachers’ practices and, in turn, students’ learning. The landscape of teacher PLCs is continuously developing; notably through teachers’ uses of social media. Yet, there is limited robust evidence identifying the characteristics of social media PLCs that impact on teachers’ learning and practice. Purpose: This exploratory study examined the characteristics of a specific Twitter-based professional learning community – #pechat. The research questions were: (i) what is the nature of a Twitter-based professional learning community? and (ii) what characteristics of a Twitter-based professional learning community develop learning and practice? Methods: Data were generated from 901 tweets between 100 participants; and 18 in-depth semi-structured elicitation interviews with participants and moderators of the Twitter-based professional learning community. Data were analysed through a process of deliberation, and a relativist approach informed quality. Findings: Two themes are reported to explain the nature of the Twitter-based professional learning community and the different types of characteristics of #pechat that developed learning and practice. The first theme engagement shows how different participants of #pechat engaged with discussions and how moderators played a key role in facilitating discussions between participants. The second theme shared practices shows how discussions between participants of #pechat led to the development of new practices that some teachers were able to use to accomplish particular objectives in their physical education lessons. Conclusion: The analysis of the data provided evidence to suggest that #pechat is a PLC and is representative of an established group of practitioners. These characteristics should be considered in the design of future online professional development experiences. Facilitator or moderator training could support the development of social media based PLCs that subsequently and positively impact on teachers’ practices.ACCEPTEDpeer-reviewe

Randomly Crosslinked Macromolecular Systems: Vulcanisation Transition to and Properties of the Amorphous Solid State

As Charles Goodyear discovered in 1839, when he first vulcanised rubber, a macromolecular liquid is transformed into a solid when a sufficient density of permanent crosslinks is introduced at random. At this continuous equi- librium phase transition, the liquid state, in which all macromolecules are delocalised, is transformed into a solid state, in which a nonzero fraction of macromolecules have spontaneously become localised. This solid state is a most unusual one: localisation occurs about mean positions that are distributed homogeneously and randomly, and to an extent that varies randomly from monomer to monomer. Thus, the solid state emerging at the vulcanisation transition is an equilibrium amorphous solid state: it is properly viewed as a solid state that bears the same relationship to the liquid and crystalline states as the spin glass state of certain magnetic systems bears to the paramagnetic and ferromagnetic states, in the sense that, like the spin glass state, it is diagnosed by a subtle order parameter. In this review we give a detailed exposition of a theoretical approach to the physical properties of systems of randomly, permanently crosslinked macromolecules. Our primary focus is on the equilibrium properties of such systems, especially in the regime of Goodyear's vulcanisation transition.Comment: Review Article, REVTEX, 58 pages, 3 PostScript figure

Networked learning, stepping beyond the net generation and digital natives

This chapter critically examines the idea that young people have undergone a change in which exposure to digital and networked technologies has caused a step change in the character of a whole generation. The empirical and theoretical basis for this argument is reviewed and critical theoretical perspectives are assessed. Evidence from earlier research is compared and contrasted with evidence gathered from students who are said to be part of the new generation. The chapter explores the consequences of these ideas from the standpoint of networked learning. One aim of the chapter is to suggest ways in which the changes that have taken can be more adequately theorized in relation to the idea of networked learning. Arguments used to support generational change rely on a technological determinism and alternative accounts understand young people as active agents. I suggest ex-panding the notion of the agent to include persons enacting roles in collective or-ganizations. Overall the importance of the debate is that determinist arguments can close down debate and networked learning would be impoverished if this occurs

Temporal trends in mode, site and stage of presentation with the introduction of colorectal cancer screening: a decade of experience from the West of Scotland

background:  Population colorectal cancer screening programmes have been introduced to reduce cancer-specific mortality through the detection of early-stage disease. The present study aimed to examine the impact of screening introduction in the West of Scotland. methods:  Data on all patients with a diagnosis of colorectal cancer between January 2003 and December 2012 were extracted from a prospectively maintained regional audit database. Changes in mode, site and stage of presentation before, during and after screening introduction were examined. results:  In a population of 2.4 million, over a 10-year period, 14 487 incident cases of colorectal cancer were noted. Of these, 7827 (54%) were males and 7727 (53%) were socioeconomically deprived. In the postscreening era, 18% were diagnosed via the screening programme. There was a reduction in both emergency presentation (20% prescreening vs 13% postscreening, P0.001) and the proportion of rectal cancers (34% prescreening vs 31% pos-screening, P0.001) over the timeframe. Within non-metastatic disease, an increase in the proportion of stage I tumours at diagnosis was noted (17% prescreening vs 28% postscreening, P0.001). conclusions:  Within non-metastatic disease, a shift towards earlier stage at diagnosis has accompanied the introduction of a national screening programme. Such a change should lead to improved outcomes in patients with colorectal cancer

Association of Thalamic Dysconnectivity and Conversion to Psychosis in Youth and Young Adults at Elevated Clinical Risk

IMPORTANCE: Severe neuropsychiatric conditions, such as schizophrenia, affect distributed neural computations. One candidate system profoundly altered in chronic schizophrenia involves the thalamocortical networks. It is widely acknowledged that schizophrenia is a neurodevelopmental disorder that likely affects the brain before onset of clinical symptoms. However, no investigation has tested whether thalamocortical connectivity is altered in individuals at risk for psychosis or whether this pattern is more severe in individuals who later develop full-blown illness. OBJECTIVES: To determine whether baseline thalamocortical connectivity differs between individuals at clinical high risk for psychosis and healthy controls, whether this pattern is more severe in those who later convert to full-blown illness, and whether magnitude of thalamocortical dysconnectivity is associated with baseline prodromal symptom severity. DESIGN, SETTING, AND PARTICIPANTS: In this multicenter, 2-year follow-up, case-control study, we examined 397 participants aged 12-35 years of age (243 individuals at clinical high risk of psychosis, of whom 21 converted to full-blown illness, and 154 healthy controls). The baseline scan dates were January 15, 2010, to April 30, 2012. MAIN OUTCOMES AND MEASURES: Whole-brain thalamic functional connectivity maps were generated using individuals\u27 anatomically defined thalamic seeds, measured using resting-state functional connectivity magnetic resonance imaging. RESULTS: Using baseline magnetic resonance images, we identified thalamocortical dysconnectivity in the 243 individuals at clinical high risk for psychosis, which was particularly pronounced in the 21 participants who converted to full-blown illness. The pattern involved widespread hypoconnectivity between the thalamus and prefrontal and cerebellar areas, which was more prominent in those who converted to full-blown illness (t(173) = 3.77, P \u3c .001, Hedge g = 0.88). Conversely, there was marked thalamic hyperconnectivity with sensory motor areas, again most pronounced in those who converted to full-blown illness (t(173) = 2.85, P \u3c .001, Hedge g = 0.66). Both patterns were significantly correlated with concurrent prodromal symptom severity (r = 0.27, P \u3c 3.6 x 10(-8), Spearman rho = 0.27, P \u3c 4.75 x 10(-5), 2-tailed). CONCLUSIONS AND RELEVANCE: Thalamic dysconnectivity, resembling that seen in schizophrenia, was evident in individuals at clinical high risk for psychosis and more prominently in those who later converted to psychosis. Dysconnectivity correlated with symptom severity, supporting the idea that thalamic connectivity may have prognostic implications for risk of conversion to full-blown illness