Reflection on Practice, in Practice: The Discipline of Noticing

This paper outlines the use of John Mason’s Discipline of Noticing by a group of university level mathematics lecturers. We describe the aims that motivated the study, the challenges we faced in using the Discipline of Noticing to reflect on our teaching, and the progress that we have made

Gastric IgG4-Related Autoimmune Fibrosclerosing Pseudotumour: A Novel Location

We describe the first reported case of an IgG4-related autoimmune fibrosclerosing pseudotumour located in the stomach of a 75-year old woman presenting with weight loss and vomiting. A lesion was detected in the gastric body at endoscopy. Subsequent characterisation by CT was suggestive of a gastrointestinal stromal tumour. Following laparoscopic resection, the patient recovered uneventfully. Histological examination of the resected specimen revealed an IgG4-related fibrosclerosing pseudotumour, a novel location for this histopathological entity

Effects of Feeding Bt Maize to Sows during Gestation and Lactation on Maternal and Offspring Immunity and Fate of Transgenic Material

peer-reviewedBackground: We aimed to determine the effect of feeding transgenic maize to sows during gestation and lactation on maternal and offspring immunity and to assess the fate of transgenic material. Methodology/Principal Findings: On the day of insemination, sows were assigned to one of two treatments (n = 12/treatment); 1) non-Bt control maize diet or 2) Bt-MON810 maize diet, which were fed for ~143 days throughout gestation and lactation. Immune function was assessed by leukocyte phenotyping, haematology and Cry1Ab-specific antibody presence in blood on days 0, 28 and 110 of gestation and at the end of lactation. Peripheral-blood mononuclear cell cytokine production was investigated on days 28 and 110 of gestation. Haematological analysis was performed on offspring at birth (n = 12/treatment). Presence of the cry1Ab transgene was assessed in sows' blood and faeces on day 110 of gestation and in blood and tissues of offspring at birth. Cry1Ab protein presence was assessed in sows' blood during gestation and lactation and in tissues of offspring at birth. Blood monocyte count and percentage were higher (P<0.05), while granulocyte percentage was lower (P<0.05) in Bt maize-fed sows on day 110 of gestation. Leukocyte count and granulocyte count and percentage were lower (P<0.05), while lymphocyte percentage was higher (P<0.05) in offspring of Bt maize-fed sows. Bt maize-fed sows had a lower percentage of monocytes on day 28 of lactation and of CD4+CD8+ lymphocytes on day 110 of gestation, day 28 of lactation and overall (P<0.05). Cytokine production was similar between treatments. Transgenic material or Cry1Ab-specific antibodies were not detected in sows or offspring. Conclusions/Significance: Treatment differences observed following feeding of Bt maize to sows did not indicate inflammation or allergy and are unlikely to be of major importance. These results provide additional data for Bt maize safety assessment.The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007–2013) under grant agreement number 211820 and the Teagasc Walsh Fellowship Programme

Evaluation of the Efficacy and Safety of a Marine-Derived Bacillus Strain for Use as an In-Feed Probiotic for Newly Weaned Pigs

peer-reviewedForty eight individual pigs (8.7±0.26 kg) weaned at 28±1 d of age were used in a 22-d study to evaluate the effect of oral administration of a Bacillus pumilus spore suspension on growth performance and health indicators. Treatments (n = 16) were: (1) non-medicated diet; (2) medicated diet with apramycin (200 mg/kg) and pharmacological levels of zinc oxide (2,500 mg zinc/kg) and (3) B. pumilus diet (non-medicated diet + 1010 spores/day B. pumilus). Final body weight and average daily gain tended to be lower (P = 0.07) and feed conversion ratio was worsened (P<0.05) for the medicated treatment compared to the B. pumilus treatment. Ileal E. coli counts were lower for the B. pumilus and medicated treatments compared to the non-medicated treatment (P<0.05), perhaps as a result of increased ileal propionic acid concentrations (P<0.001). However, the medicated treatment reduced fecal (P<0.001) and cecal (P<0.05) Lactobacillus counts and tended to reduce the total cecal short chain fatty acid (SCFA) concentration (P = 0.10). Liver weights were lighter and concentrations of liver enzymes higher (P<0.05) in pigs on the medicated treatment compared to those on the non-medicated or B. pumilus treatments. Pigs on the B. pumilus treatment had lower overall lymphocyte and higher granulocyte percentages (P<0.001) and higher numbers of jejunal goblet cells (P<0.01) than pigs on either of the other two treatments or the non-medicated treatment, respectively. However, histopathological examination of the small intestine, kidneys and liver revealed no abnormalities. Overall, the B. pumilus treatment decreased ileal E. coli counts in a manner similar to the medicated treatment but without the adverse effects on growth performance, Lactobacillus counts, cecal SCFA concentration and possible liver toxicity experienced with the medicated treatment.The study was funded by the Higher Education Authority/Institutes of Technology Ireland Technological Sector Research Strand III Programme

Active Inspiration Playmakers final report

Final Report the the 'Playmakers' project; a programme within the Virgin Active 'Active Inspiration' initiative.

"There is people like us and there is people like them, and we are not like them." Understating social exclusion - a qualitative study

Social exclusion is a complex concept that is relevant in terms of the health of vulnerable groups. Attempts have been made in the past to measure it, both at the population and the individual level. The aim of this research was to engage with a broad range of relevant stakeholders in Ireland in order to learn how they defined and conceptualised social exclusion. Semi-structured interviews were carried out with 24 participants selected using maximum variation sampling. One quarter of the interviewees were experts by experience. Participants included academic experts, the heads of organisations working nationally with socially excluded groups, politicians, clinicians, support workers and health service managers all with experience of working with socially excluded groups. The resulting definition of social exclusion was "the experience of lack of opportunity, or the inability to make use of available opportunities, thereby preventing full participation in society."From this, we developed a new model of the concept comprising three elements; Opportunities, Influencing factors and Social outcomes. Opportunities are the fundamental needs that are required to be met for a person to begin leaving social exclusion. Influencing factors are a mixture of the personal characteristics and more complex problems such as the intergenerational effects of disadvantage. Social outcomes include a person being accepted by wider society, and subsequently being able to participate. The conceptual framework we developed can contribute to a better understanding of the concept of social exclusion. The traditional policy focus on improving the needs of excluded people at the Opportunities level must continue, but must be complemented by tackling the problems at the levels of the Influencing factors and Social outcomes also. In terms of changes to practice, the measurement of the social exclusion status of people engaging with primary care and other services would be an important start in order to better understand the magnitude of the work required.</p

A non-endoscopic device to sample the oesophageal microbiota: a case-control study.

BACKGROUND: The strongest risk factor for oesophageal adenocarcinoma is reflux disease, and the rising incidence of this coincides with the eradication of Helicobacter pylori, both of which might alter the oesophageal microbiota. We aimed to profile the microbiota at different stages of Barrett's carcinogenesis and investigate the Cytosponge as a minimally invasive tool for sampling the oesophageal microbiota. METHODS: In this case-control study, 16S rRNA gene amplicon sequencing was done on 210 oesophageal samples from 86 patients representing the Barrett's oesophagus progression sequence (normal squamous controls [n=20], non-dysplastic [n=24] and dysplastic Barrett's oesophagus [n=23], and oesophageal adenocarcinoma [n=19]), relevant negative controls, and replicates on the Illumina MiSeq platform. Samples were taken from patients enrolled in the BEST2 study at five UK hospitals and the OCCAMS study at six UK hospitals. We compared fresh frozen tissue, fresh frozen endoscopic brushings, and the Cytosponge device for microbial DNA yield (qPCR), diversity, and community composition. FINDINGS: There was decreased microbial diversity in oesophageal adenocarcinoma tissue compared with tissue from healthy control patients as measured by the observed operational taxonomic unit (OTU) richness (p=0·0012), Chao estimated total richness (p=0·0004), and Shannon diversity index (p=0·0075). Lactobacillus fermentum was enriched in oesophageal adenocarcinoma (p=0·028), and lactic acid bacteria dominated the microenvironment in seven (47%) of 15 cases of oesophageal adenocarcinoma. Comparison of oesophageal sampling methods showed that the Cytosponge yielded more than ten-times higher quantities of microbial DNA than did endoscopic brushes or biopsies using quantitative PCR (p<0·0001). The Cytosponge samples contained the majority of taxa detected in biopsy and brush samples, but were enriched for genera from the oral cavity and stomach, including Fusobacterium, Megasphaera, Campylobacter, Capnocytophaga, and Dialister. The Cytosponge detected decreased microbial diversity in patients with high-grade dysplasia in comparison to control patients, as measured by the observed OTU richness (p=0·0147), Chao estimated total richness (p=0·023), and Shannon diversity index (p=0·0085). INTERPRETATION: Alterations in microbial communities occur in the lower oesophagus in Barrett's carcinogenesis, which can be detected at the pre-invasive stage of high-grade dysplasia with the novel Cytosponge device. Our findings are potentially applicable to early disease detection, and future test development should focus on longitudinal sampling of the microbiota to monitor for changes in microbial diversity in a larger cohort of patients. FUNDING: Cancer Research UK, National Institute for Health Research, Medical Research Council, Wellcome Trust, The Scottish Government (RESAS).Cancer Research UK, National Institute for Health Research, Medical Research Council, and Wellcome Trust.This is the author accepted manuscript. The final version is available from Elsevier via https://doi.org/10.1016/S2468-1253(16)30086-

Pilot randomized crossover study comparing the efficacy of transnasal disposable endosheath with standard endoscopy to detect Barrett's esophagus.

BACKGROUND AND STUDY AIMS: The transnasal endosheath endoscope is a new disposable technology with potential applicability to the primary care setting. The aim of this study was to evaluate the efficacy of transnasal endosheath endoscopy (TEE) for the detection of Barrett's esophagus, by comparing the diagnostic accuracy of TEE with that of standard endoscopy. PATIENTS AND METHODS: This was a prospective, randomized, crossover study performed in a single tertiary referral center. Consecutive patients undergoing surveillance for Barrett's esophagus or referred for diagnostic assessment were recruited. All patients were randomized to undergo TEE followed by standard endoscopy or the reverse. Endoscopy experiences and patient preferences were evaluated using a questionnaire. Endoscopic and histologic diagnosis of Barrett's esophagus, and optical image quality of both endoscopic procedures, were compared. RESULTS: A total of 21 of 25 patients completed the study. TEE had sensitivity and specificity of 100 % for an endoscopic diagnosis of Barrett's esophagus, and of 66.7 % and 100 %, respectively, for the histologic diagnosis of Barrett's esophagus. The mean optical quality of standard endoscopy was significantly better than that of TEE (7.11 ± 0.42 vs. 4.06 ± 0.27; P < 0.0001). However, following endoscopy, patients reported a significantly better experience with TEE compared with standard endoscopy (7.05 ± 0.49 vs. 4.35 ± 0.53; P = 0.0006), with 60 % preferring TEE and 25 % preferring sedated standard endoscopy. CONCLUSIONS: In this study, TEE had equal accuracy for an endoscopic diagnosis of Barrett's esophagus compared with standard endoscopy, at the expense of reduced image quality and a lower yield of intestinal metaplasia on biopsy. TEE was better tolerated and preferred by patients. Hence, TEE needs further evaluation in primary care as an initial diagnostic tool.This study was supported by funding from Cambridge Experimental Cancer Medicine Centre, NIHR Cambridge Biomedical Research Centre, and a core grant for RCF from the Medical Research Council. M.K.S. was supported by the BUPA Foundation.This is the author accepted manuscript. The final version is available from Thieme Publishing Group via http://dx.doi.org/10.1055/s-0034-139331

Effects of feeding Bt MON810 maize to sows during first gestation and lactation on maternal and offspring health indicators

A total of twenty-four sows and their offspring were used in a 20-week study to investigate the effects of feeding GM maize on maternal and offspring health. Sows were fed diets containing GM or non-GM maize from service to the end of lactation. GM maize-fed sows were heavier on day 56 of gestation (P< 0·05). Offspring from sows fed GM maize tended to be lighter at weaning (P= 0·08). Sows fed GM maize tended to have decreased serum total protein (P= 0·08), and increased serum creatinine (P< 0·05) and γ-glutamyltransferase activity (P= 0·07) on day 28 of lactation. Serum urea tended to be decreased on day 110 of gestation in GM maize-fed sows (P= 0·10) and in offspring at birth (P= 0·08). Both platelet count (P= 0·07) and mean cell Hb concentration (MCHC; P= 0·05) were decreased on day 110 of gestation in GM maize-fed sows; however, MCHC tended to be increased in offspring at birth (P= 0·08). There was a minimal effect of feeding GM maize to sows during gestation and lactation on maternal and offspring serum biochemistry and haematology at birth and body weight at weaning

Molecular effects of Lapatinib in the treatment of HER2 overexpressing oesophago-gastric adenocarcinoma.

BACKGROUND: Lapatinib, a dual EGFR and HER2 inhibitor has shown disappointing results in clinical trials of metastatic oesophago-gastric adenocarcinomas (OGAs), and in vitro studies suggest that MET, IGFR, and HER3 confer resistance. This trial applied Lapatinib in the curative neoadjuvant setting and investigated the feasibility and utility of additional endoscopy and biopsy for assessment of resistance mechanisms ex vivo and in vivo. METHODS: Patients with HER2 overexpressing OGA were treated for 10 days with Lapatinib monotherapy, and then in combination with three cycles of Oxaliplatin and Capecitabine before surgery. Endoscopic samples were taken for molecular analysis at: baseline including for ex vivo culture +/- Lapatinib to predict in vivo response, post-Lapatinib monotherapy and at surgery. Immunohistochemistry (IHC) and proteomic analysis was performed to assess cell kinetics and signalling activity. RESULTS: The trial closed early (n=10) due to an anastomotic leak in two patients for which a causative effect of Lapatinib could not be excluded. The reduction in Phosphorylated-HER2 (P-HER2) and P-EGFR in the ex vivo-treated biopsy demonstrated good correlation with the in vivo response at day 10. Proteomic analysis pre and post-Lapatinib demonstrated target inhibition (P-ERBB2, P-EGFR, P-PI3K, P-AKT, and P-ERK) that persisted until surgery. There was also significant correlation between the activation of MET with the level of P-Erk (P=0.0005) and P-PI3K : T-PI3K (total PI3K) ratio (P=0.0037). There was no significant correlation between the activation status of IGFR and HER3 with downstream signalling molecules. CONCLUSIONS: Additional endoscopy and biopsy sampling for multiple biomarker endpoints was feasible and confirmed in vitro data that MET is likely to be a significant mechanism of Lapatinib resistance in vivo.This research was funded by the Medical Research Council [Grant SK002].This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/bjc.2015.34