The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer

The prognosis of epithelial ovarian cancer is poor in part due to the high frequency of chemoresistance. Recent evidence points to the Toll-like receptor-4 (TLR4), and particularly its adaptor protein MyD88, as one potential mediator of this resistance. This study aims to provide further evidence that MyD88 positive cancer cells are clinically significant, stem-like and reproducibly detectable for the purposes of prognostic stratification. Expression of TLR4 and MyD88 was assessed immunohistochemically in 198 paraffin-embedded ovarian tissues and in an embryonal carcinoma model of cancer stemness. In parallel, expression of TLR4 and MyD88 mRNA and regulatory microRNAs (miR-21 and miR-146a) was assessed, as well as in a series of chemosensitive and resistant cancer cells lines. Functional analysis of the pathway was assessed in chemoresistant SKOV-3 ovarian cancer cells. TLR4 and MyD88 expression can be reproducibly assessed via immunohistochemistry using a semi-quantitative scoring system. TLR4 expression was present in all ovarian epithelium (normal and neoplastic), whereas MyD88 was restricted to neoplastic cells, independent of tumour grade and associated with reduced progression-free and overall survival, in an immunohistological specific subset of serous carcinomas, p<0.05. MiR-21 and miR-146a expression was significantly increased in MyD88 negative cancers (p<0.05), indicating their participation in regulation. Significant alterations in MyD88 mRNA expression were observed between chemosensitive and chemoresistant cells and tissue. Knockdown of TLR4 in SKOV-3 ovarian cells recovered chemosensitivity. Knockdown of MyD88 alone did not. MyD88 expression was down-regulated in differentiated embryonal carcinoma (NTera2) cells, supporting the MyD88+ cancer stem cell hypothesis. Our findings demonstrate that expression of MyD88 is associated with significantly reduced patient survival and altered microRNA levels and suggest an intact/functioning TLR4/MyD88 pathway is required for acquisition of the chemoresistant phenotype. Ex vivo manipulation of ovarian cancer stem cell (CSC) differentiation can decrease MyD88 expression, providing a potentially valuable CSC model for ovarian cancer

Be good, know the rules’: Children’s perspectives on starting school and self-regulation

Despite the importance of self-regulation for school readiness and success across the lifespan, little is known about children’s conceptions of this important ability. Using mixed-method interviews, this research examined kindergarten children’s (n = 57) perspectives on self-regulation in a disadvantaged area in Dublin, Ireland. Children depicted school as requiring regulation of their emotional, cognitive and behavioural responses. They characterised school as a dynamic setting, placing emphasis on the regulatory challenges of the outdoor environment. Children also described difficulties associated with navigating complex social interactions, often without assistance from external supports. The results inform strategies to support children’s emerging self-regulation abilities.Irish Research CouncilUpdate citation details during checkdate report - A

Exploring the position of curriculum studies across the continuum of teacher education in Ireland

Curriculum, while often narrowly defined, is a contested space that stimulates continuing international debate, yet the importance of curriculum studies is frequently overlooked across the continuum of teacher education. Within the Irish context a technicist interpretation of curriculum studies, focusing primarily of subject knowledge and development, has historically been adopted. More recent Teaching Council of Ireland policy documents have espoused a broader macro understanding of curriculum studies as a foundation discipline within initial teacher education. However, concerns have been raised regarding student teachers’ ability to fully engage with such material so early in their professional development. With the recently embraced continuum of teacher education in Ireland, this paper examines how curriculum studies is currently defined by Irish policy and problematises how it is addressed in practice. The paper proceeds to explore emerging opportunities to expand this area of study across the continuum. A case for the place of curriculum studies as central to the advancement of the profession through the promotion of teachers as change agents is presented

Riding the waves: the ongoing impact of COVID-19 on a national surgical training cohort

Background: The World Health Organisation declared a global pandemic on the 11 March 2020 resulting in implementation of methods to contain viral spread, including curtailment of all elective and non-emergent interventions. Many institutions have experienced changes in rostering practices and redeployment of trainees to non-surgical services. Examinations, study days, courses, and conferences have been cancelled. These changes have the potential to significantly impact the education and training of surgical trainees.Aim: To investigate the impact of the COVID-19 pandemic on training, educational, and operative experiences of Irish surgical trainees.Methods: Surgical trainees were surveyed anonymously regarding changes in working and educational practices since the declaration of the COVID-19 pandemic on 11 March 2020. The survey was circulated in May 2020 to both core and higher RCSI surgical trainees, when restrictions were at level five. Questions included previous and current access to operative sessions as well as operative cases, previous and current educational activities, access to senior-led training, and access to simulation-/practical-based training methods. A repeat survey was carried out in October 2020 when restrictions were at level two.Results: Overall, primary and secondary survey response rates were 29% (n = 98/340) and 19.1% (n = 65/340), respectively. At the time of circulation of the second survey, the number of operative sessions attended and cases performed had significantly improved to numbers experienced pre-pandemic (p Conclusion: Surgical training and education have been significantly impacted in light of COVID-19. This is likely to continue to fluctuate in line with subsequent waves. Significant efforts have to be made to enable trainees to meet educational and operative targets.</div

Plaque Structural Stress Estimations Improve Prediction of Future Major Adverse Cardiovascular Events After Intracoronary Imaging.

BACKGROUND: Although plaque rupture is responsible for most myocardial infarctions, few high-risk plaques identified by intracoronary imaging actually result in future major adverse cardiovascular events (MACE). Nonimaging markers of individual plaque behavior are therefore required. Rupture occurs when plaque structural stress (PSS) exceeds material strength. We therefore assessed whether PSS could predict future MACE in high-risk nonculprit lesions identified on virtual-histology intravascular ultrasound. METHODS AND RESULTS: Baseline nonculprit lesion features associated with MACE during long-term follow-up (median: 1115 days) were determined in 170 patients undergoing 3-vessel virtual-histology intravascular ultrasound. MACE was associated with plaque burden ≥70% (hazard ratio: 8.6; 95% confidence interval, 2.5-30.6; P<0.001) and minimal luminal area ≤4 mm(2) (hazard ratio: 6.6; 95% confidence interval, 2.1-20.1; P=0.036), although absolute event rates for high-risk lesions remained <10%. PSS derived from virtual-histology intravascular ultrasound was subsequently estimated in nonculprit lesions responsible for MACE (n=22) versus matched control lesions (n=22). PSS showed marked heterogeneity across and between similar lesions but was significantly increased in MACE lesions at high-risk regions, including plaque burden ≥70% (13.9±11.5 versus 10.2±4.7; P<0.001) and thin-cap fibroatheroma (14.0±8.9 versus 11.6±4.5; P=0.02). Furthermore, PSS improved the ability of virtual-histology intravascular ultrasound to predict MACE in plaques with plaque burden ≥70% (adjusted log-rank, P=0.003) and minimal luminal area ≤4 mm(2) (P=0.002). Plaques responsible for MACE had larger superficial calcium inclusions, which acted to increase PSS (P<0.05). CONCLUSIONS: Baseline PSS is increased in plaques responsible for MACE and improves the ability of intracoronary imaging to predict events. Biomechanical modeling may complement plaque imaging for risk stratification of coronary nonculprit lesions.British Heart Foundation (Grant ID: FS/13/33/30168)This is the author accepted manuscript. The final version is available from Wolters Kluwer via https://doi.org/10.1161/CIRCIMAGING.115.00417

An observational study of dose dense chemotherapy with lipegfilgrastim support in early breast cancer

Purpose Breast cancer is one of the most prevalent malignant diseases in women. The development of dose dense chemotherapy regimens has improved clinical outcomes but has been associated with increased hematological toxicity. Currently there is a paucity of data on the use of lipegfilgrastim in dose dense AC treatment in early breast cancer. The purpose of this study was to assess the use of lipegfilgrastim in the treatment of early breast cancer and to examine the incidence of treatment-related neutropenia during the dose dense AC phase and subsequent paclitaxel treatment. Methods This was a single arm, non-interventional, prospective study. The primary endpoint was to determine the rate of neutropenia defined as ANC of  38 °C and ANC  Results Forty-one participants were included in the study. Of the 160 planned dose dense AC treatments, 157 were administered, and 95% (152/160) of these were given on time. The rate of treatment delay was 5% (95% CI 2.2 to 9.9%) due to infection (4) and mucositis (1). Four (10%) patients developed febrile neutropenia. The most frequently occurring adverse event was grade 1 bone pain. Conclusion Lipegfilgrastim is an effective option in the prophylaxis of chemotherapy-induced neutropenia, and its use in everyday anti-cancer treatment can be considered.</p

Delivery of systemic anti-cancer therapy during the COVID-19 pandemic

Background: The first confirmed case of COVID-19 in Ireland was on February 29th 2020. From March until late April, the number of cases increased exponentially. The delivery of anti-cancer therapy during the COVID-19 pandemic was extremely challenging. In order to balance the benefits of continuing anti-cancer therapy with the associated increased hospital visits, combined with the risk of COVID-19 infection, we undertook a series of system changes in the delivery of cancer care.Methods: Patients who attended our dayward over a 4-month period were included. Data were obtained from patient and chemotherapy prescribing records. Patients were screened for symptoms of COVID-19 at two separate timepoints: prior to their visit via telephone, and using a symptom questionnaire on arrival at the hospital. If patients displayed COVID-19 symptoms, they were isolated and a viral swab arranged.Results: A total of 456 patients attended from January 1st to April 30th. The numbers of visits from January to April were 601, 586, 575, and 607, respectively. During this period, there were 2369 patient visits to the dayward and 1953 (82%) intravenous regimens administered. Of the 416 visits that did not lead to treatment, 114 (27%) were scheduled non-treatment review visits, 194 (47%) treatments were held due to disease-related illness, and 108 (26%) treatments were held due to treatment-related complications. Screening measurements were implemented on March 18th due to rising COVID-19 prevalence in the general population. Overall, 53 treatments were held due to the screening process: 19 patients (36%) elicited COVID-19 symptoms via telephone screening; 34 patients (64%) were symptomatic in our pre-assessment area and referred for swabs, of which 4 were positive. Those with a negative swab were rescheduled for chemotherapy the following week.Conclusions: With careful systematic changes, safe and continued delivery of systemic anti-cancer therapy during the COVID-19 pandemic is possible.</div

Legislative Documents

Also, variously referred to as: House bills; House documents; House legislative documents; legislative documents; General Court documents