Postfledging Survival, Movements, and Dispersal of Ring Ouzels (Turdus torquatus)

We thank Invercauld Estate for cooperation with access to Glen Clunie. S. Redpath, J. Wilson, and S. Roos provided valuable comments on the manuscript. This study was funded by the Royal Society for the Protection of Birds, Scottish Natural Heritage, and the Cairngorms National Park Authority. J.L.L. was supported by the Natural Environment Research Council.Peer reviewedPublisher PD

Immune-derived PD-L1 gene expression defines a subgroup of stage II/III colorectal cancer patients with favorable prognosis that may be harmed by adjuvant chemotherapy

Abstract A recent phase II study of patients with metastatic colorectal carcinoma showed that mismatch repair gene status was predictive of clinical response to PD-1–targeting immune checkpoint blockade. Further examination revealed strong correlation between PD-L1 protein expression and microsatellite instability (MSI) in stage IV colorectal carcinoma, suggesting that the amount of PD-L1 protein expression could identify late-stage patients who might benefit from immunotherapy. To assess whether the clinical associations between PD-L1 gene expression and MSI identified in metastatic colorectal carcinoma are also present in stage II/III colorectal carcinoma, we used in silico analysis to elucidate the cell types expressing the PD-L1 gene. We found a statistically significant association of PD-L1 gene expression with MSI in early-stage colorectal carcinoma (P &amp;lt; 0.001) and show that, unlike in non–colorectal carcinoma tumors, PD-L1 is derived predominantly from the immune infiltrate. We demonstrate that PD-L1 gene expression has positive prognostic value in the adjuvant disease setting (PD-L1low vs. PD-L1high HR = 9.09; CI, 2.11–39.10). PD-L1 gene expression had predictive value, as patients with high PD-L1 expression appear to be harmed by standard-of-care treatment (HR = 4.95; CI, 1.10–22.35). Building on the promising results from the metastatic colorectal carcinoma PD-1–targeting trial, we provide compelling evidence that patients with PD-L1high/MSI/immunehigh stage II/III colorectal carcinoma should not receive standard chemotherapy. This conclusion supports the rationale to clinically evaluate this patient subgroup for PD-1 blockade treatment. Cancer Immunol Res; 4(7); 582–91. ©2016 AACR.</jats:p

Back to the future: routine morphological assessment of the tumour microenvironment is prognostic in stage II/III colon cancer in a large population-based study

AimsBoth morphological and molecular approaches have highlighted the biological and prognostic importance of the tumour microenvironment in colorectal cancer (CRC). Despite this, microscopic assessment of tumour microenvironment has not been adopted into routine practice.Methods and ResultsBased on existing evidence, we selected specific morphological features relating to peritumoral inflammatory and stromal responses, agreed criteria for scoring, and assessed these in representative H&amp;E-stained whole tumour sections, from a population-based cohort of 445 stage II/III colon cancer cases. Moderate/severe peritumoral diffuse lymphoid inflammation and Crohn's disease-like reaction were associated with significantly reduced risks of CRC-specific death (adjusted HR 0.48, 95% CI 0.31-0.76, and HR 0.60, 95% CI 0.42-0.84, respectively). The presence of &gt;50% tumour stromal percentage, assessed by global evaluation of tumour area, was associated with a significantly increased risk of CRC-specific death (HR 1.60 95% CI 1.06-2.41). A composite, “fibroinflammatory score” (0-3), combining dichotomised scores of these three features, showed a highly significant association in relation to survival outcomes. Those with a score ≥2 had an almost 2.5 fold increased risk of CRC-specific death (HR 2.44, 95% CI: 1.56-3.81), compared with those scoring zero. These associations were stronger in MSI-high tumours, potentially identifying a subset of MSI-high colon cancers which lack characteristic morphological features and have an associated worse prognosis.ConclusionsIn summary, reporting on H&amp;E staining of selected microscopic features of the tumour microenvironment, independently or in combination, offers valuable prognostic information in stage II/III colon cancer and may allow morphological correlation with developing molecular classifications of prognostic and predictive relevance.</p

Anti-epileptic effect of Ganoderma lucidum polysaccharides by inhibition of intracellular calcium accumulation and stimulation of expression of CaMKII a in epileptic hippocampal neurons

Purpose: To investigate the mechanism of the anti-epileptic effect of Ganoderma lucidum polysaccharides (GLP), the changes of intracellular calcium and CaMK II a expression in a model of epileptic neurons were investigated. Method: Primary hippocampal neurons were divided into: 1) Control group, neurons were cultured with Neurobasal medium, for 3 hours; 2) Model group I: neurons were incubated with Mg2+ free medium for 3 hours; 3) Model group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with the normal medium for a further 3 hours; 4) GLP group I: neurons were incubated with Mg2+ free medium containing GLP (0.375 mg/ml) for 3 hours; 5) GLP group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with a normal culture medium containing GLP for a further 3 hours. The CaMK II a protein expression was assessed by Western-blot. Ca2+ turnover in neurons was assessed using Fluo-3/AM which was added into the replacement medium and Ca2+ turnover was observed under a laser scanning confocal microscope. Results: The CaMK II a expression in the model groups was less than in the control groups, however, in the GLP groups, it was higher than that observed in the model group. Ca2+ fluorescence intensity in GLP group I was significantly lower than that in model group I after 30 seconds, while in GLP group II, it was reduced significantly compared to model group II after 5 minutes. Conclusion: GLP may inhibit calcium overload and promote CaMK II a expression to protect epileptic neuron

Detecting colorectal cancer using electrical impedance spectroscopy: an ex vivo feasibility study

Objective: Colorectal cancer is the fourth most common cancer worldwide, with a lifetime risk of around 20%. Current solutions do not allow clinicians to objectively assess tissue abnormality during endoscopy and perioperatively. A solution capable of objectively assessing samples in real time could greatly improve the treatment process. A solution that can be integrated in minimally invasive diagnostics and management strategies to provide real-time point-of-care information would be greatly transformative. Electrical impedance spectroscopy (EIS) may provide such a solution. In this paper, we present a feasibility study on using EIS in assessing colorectal tissue. Approach: We performed tetrapolar EIS using ZedScan on excised human colorectal tumour tissue and the matched normal colonic mucosa in 22 freshly resected specimens following elective surgery for colorectal cancer. Histopathological examination was used to confirm the final diagnosis. Statistical significance was assessed with Wilcoxon signed rank test. Main results: Tetrapolar EIS could discriminate cancer with statistically significant results when applying frequencies between 305 Hz – 625 kHz (p < 0.05). 300 Ω was set as the transfer impedance threshold to detect cancer. Thus, the area under the corresponding receiver operating characteristic curve for this threshold was 0.7105. Significance: This feasibility study demonstrates that impedance spectra changes in colorectal cancer tissue are detectable and may be statistically significant, suggesting that EIS has the potential to be the core technology in a novel non-invasive point of care test for detecting colorectal cancer. These results warrant further development and increasing the size of the study with a device specificity designed for colorectal cancer

Molecular profiling of signet ring cell colorectal cancer provides a strong rationale for genomic targeted and immune checkpoint inhibitor therapies

We would like to thank all patients whose samples were used in this study. We are also thankful to the Northern Ireland Biobank and Grampian Biorepository for providing us with tissue blocks and patient data; and Dr HG Coleman (Queen’s University Belfast) for her advice on statistical analyses. This work has been carried out with financial support from Cancer Research UK (grant: C11512/A18067), Experimental Cancer Medicine Centre Network (grant: C36697/A15590 from Cancer Research UK and the NI Health and Social Care Research and Development Division), the Sean Crummey Memorial Fund and the Tom Simms Memorial Fund. The Northern Ireland Biobank is funded by HSC Research and Development Division of the Public Health Agency in Northern Ireland and Cancer Research UK through the Belfast CRUK Centre and the Northern Ireland Experimental Cancer Medicine Centre; additional support was received from Friends of the Cancer Centre. The Northern Ireland Molecular Pathology Laboratory which is responsible for creating resources for the Northern Ireland Biobank has received funding from Cancer Research UK, Friends of the Cancer Centre and Sean Crummey Foundation.Peer reviewedPublisher PD

Beyond Antagonism? The Discursive Construction of ‘New’ Teachers in the United Arab Emirates

The UAE, which celebrated independence in 1971, is a rapidly changing environment where aspects of traditional Bedouin culture co-exist with the immense changes being wrought by the forces of globalization and the wealth brought about by the development of the oil industry. Emirati nationals are a minority within the UAE, comprising approximately 20% of the population, and the majority of the schoolteachers are expatriates drawn from other Arabic speaking countries. Within this context, the Higher Colleges of Technology's Bachelor of Education degree in Teaching English to Young Learners prepares young UAE national women for English language teaching positions in local government schools. The research presented in this paper is drawn from this two-year study of student teachers and explores the discursive construction of the students' systems of knowledge and belief. The paper concludes with a critical consideration of the study's implications and some possible recommendations for teacher education in the UAE that may also have resonance for teacher education programs in other contexts

Non-invasive or minimally invasive autopsy compared to conventional autopsy of suspected natural deaths in adults: a systematic review

Objectives: Autopsies are used for healthcare quality control and improving medical knowledge. Because autopsy rates are declining worldwide, various non-invasive or minimally invasive autopsy methods are now being developed. To investigate whether these might replace the invasive autopsies conventionally performed in naturally deceased adults, we systematically reviewed original prospective validation studies. Materials and methods: We searched six databases. Two reviewers independently selected articles and extracted data. Methods and patient groups were too heterogeneous for meaningful meta-analysis of outcomes. Results: Sixteen of 1538 articles met our inclusion criteria. Eight studies used a blinded comparison; ten included less than 30 appropriate cases. Thirteen studies used radiological imaging (seven dealt solely with non-invasive procedures), two thoracoscopy and laparoscopy, and one sampling without imaging. Combining CT and MR was the best non-invasive method (agreement for cause of death: 70 %, 95%CI: 62.6; 76.4), but minimally invasive methods surpassed non-invasive methods. The highest sensitivity for cause of death (90.9 %, 95%CI: 74.5; 97.6, suspected duplicates excluded) was achieved in recent studies combining CT, CT-angiography and biopsies. Conclusion: Minimally invasive autopsies including biopsies performed best. To establish a feasible alternative to conventional autopsy and to increase consent to post-mortem investigations, further research in larger study groups is needed. Key points: • Health care quality control benefits from clinical feedback provided by (alternative) autopsies. • So far, sixteen studies investigated alternative autopsy methods for naturally deceased adults. • Thirteen studies used radiological imaging modalities, eight tissue biopsies, and three CT-angiography. • Combined CT, CT-angiography and biopsies were most sensitive diagnosing cause of death