Body composition, gastrointestinal, and reproductive differences between broiler breeders fed using everyday or skip-a-day rearing programs.

Broiler breeder feed restriction practices have intensified as broiler feed efficiency has been improved. Skip-a-day (SAD) rearing regimen has controlled breeder growth, although this practice has become questionable for the modern breeder. We compared everyday (ED) and SAD programs and evaluated their impact on pullet growth performance, body composition, gastrointestinal tract development, and reproduction. At d 0, Ross 708 (Aviagen) pullet chicks (n = 1,778) were randomly assigned to 7 floor pens. Three pens were fed using the ED and 4 pens with SAD program through wk 21 using a chain-feeder system. ED and SAD grower diets were formulated to be isonutritious, with the only difference that ED diets had more crude fiber. Pullets (n = 44 per pen) were moved to 16 hen pens by treatment at wk 21 with 3 YP males (Aviagen) in each pen. All birds were fed common laying diets. In addition to BW data, sampled pullets and hens were scanned using dual energy X-ray absorptiometry (DEXA) to obtain body bone density and composition. Hen performance and hatchery metrics were recorded through wk 60. ED birds were heavier with similar nutrient intake from wk 10 to 45 (P ≤ 0.013). Pullet uniformity was unaffected by feeding method (P ≥ 0.443). SAD pullets had less body fat at wk 19 (P = 0.034) compared to ED pullets, likely as a metabolic consequence of intermittent feeding. SAD birds had lower bone density at wk 7, 15, and 19 (P ≤ 0.026). At 4 wk of age, SAD pullets had less intestinal villi goblet cells compared to ED pullets (P ≤ 0.050), possibly explained by the effect that feed removal has on cell migration rates. Overall egg-specific gravity (P = 0.057) and hatch of fertile % (P = 0.088) tended to be higher in eggs from ED hens. Altogether, ED feeding increased young pullet intestinal goblet cells and increased both bone density and body fat at wk 19. ED program improved pullet feed conversion (2.6% less feed) and increased eggshell quality and hatch of fertile.

Management of vagus nerve stimulation therapy in the peri-operative period: Guidelines from the Association of Anaesthetists: Guidelines from the Association of Anaesthetists.

Vagus nerve stimulation is a well-established treatment option for patients with drug-resistant epilepsy and has an expanding range of other clinical indications. Side effects of vagus nerve stimulation therapy include: cough; voice changes; vocal cord adduction; rarely, obstructive sleep apnoea; and arrhythmia. Patients with implanted vagus nerve stimulation devices may present for unrelated surgery and critical care to clinicians who are unfamiliar with their function and safe management. These guidelines have been formulated by multidisciplinary consensus based on case reports, case series and expert opinion to support clinicians in the management of patients with these devices. The aim is to provide specific guidance on the management of vagus nerve stimulation devices in the following scenarios: the peri-operative period; peripartum period; during critical illness; and in the MRI suite. Patients should be aware of the importance of carrying their personal vagus nerve stimulation device magnet with them at all times to facilitate urgent device deactivation if necessary. We advise that it is generally safer to formally deactivate vagus nerve stimulation devices before general and spinal anaesthesia. During periods of critical illness associated with haemodynamic instability, we also advise cessation of vagus nerve stimulation and early consultation with neurology services.

Identification, validation and biological characterisation of novel glioblastoma tumour microenvironment subtypes: implications for precision immunotherapy.

BACKGROUND: New precision medicine therapies are urgently required for glioblastoma (GBM). However, to date, efforts to subtype patients based on molecular profiles have failed to direct treatment strategies. We hypothesised that interrogation of the GBM tumour microenvironment (TME) and identification of novel TME-specific subtypes could inform new precision immunotherapy treatment strategies. MATERIALS AND METHODS: A refined and validated microenvironment cell population (MCP) counter method was applied to >800 GBM patient tumours (GBM-MCP-counter). Specifically, partition around medoids (PAM) clustering of GBM-MCP-counter scores in the GLIOTRAIN discovery cohort identified three novel patient clusters, uniquely characterised by TME composition, functional orientation markers and immune checkpoint proteins. Validation was carried out in three independent GBM-RNA-seq datasets. Neoantigen, mutational and gene ontology analysis identified mutations and uniquely altered pathways across subtypes. The longitudinal Glioma Longitudinal AnalySiS (GLASS) cohort and three immunotherapy clinical trial cohorts [treatment with neoadjuvant/adjuvant anti-programmed cell death protein 1 (PD-1) or PSVRIPO] were further interrogated to assess subtype alterations between primary and recurrent tumours and to assess the utility of TME classifiers as immunotherapy biomarkers. RESULTS: TMEHigh tumours (30%) displayed elevated lymphocyte, myeloid cell immune checkpoint, programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 transcripts. TMEHigh/mesenchymal+ patients featured tertiary lymphoid structures. TMEMed (46%) tumours were enriched for endothelial cell gene expression profiles and displayed heterogeneous immune populations. TMELow (24%) tumours were manifest as an 'immune-desert' group. TME subtype transitions upon recurrence were identified in the longitudinal GLASS cohort. Assessment of GBM immunotherapy trial datasets revealed that TMEHigh patients receiving neoadjuvant anti-PD-1 had significantly increased overall survival (P = 0.04). Moreover, TMEHigh patients treated with adjuvant anti-PD-1 or oncolytic virus (PVSRIPO) showed a trend towards improved survival. CONCLUSIONS: We have established a novel TME-based classification system for application in intracranial malignancies. TME subtypes represent canonical 'termini a quo' (starting points) to support an improved precision immunotherapy treatment approach.

Impact of every-day versus skip-a-day feeding of broiler breeder pullets during rearing on body weight uniformity and reproductive performance.

Genetic selection for increased growth rate in broilers makes feed restriction programs such as skip-a-day (SAD) feeding, for broiler breeders essential to managing body weight, flock uniformity, and reproductive performance. The objective of this experiment was to compare intestinal development, weight gain of breeder pullets, and reproductive performance (22-45 wk) when fed a high fiber diet (3.8% crude fiber) on either an every-day (ED) or SAD basis during rearing. The same developer ration and feed amounts were fed to both treatments. Day-old Ross 708 pullet chicks (n = 912) were randomly distributed into 4 floor pens (n = 228/pen, 2 pens/treatment). At 20 wk of age all birds were weighed, and the coefficient of variation (CV) and average body weight was calculated for each treatment. Birds were then distributed into 10 lay pens (n = 35 birds/pen, 5 pens/treatment) at 21.5 wk of age. Light was increased from 8 h to 15.25 h at move to the lay facility, and all birds were daily fed for the remainder of the study. Data were analyzed by SAS SLICE using a significance level of P ≤ 0.05. During lay, 25% of the birds from each treatment were weighed weekly to adjust feed and monitor body weight. At 21 wk the ED fed pullets were more uniform (P = 0.0007) than the SAD fed pullets. Eggs were collected daily and set for hatch every 4 wk from 28 to 42 wk of age. No significant difference in the hatch data were observed. The ED fed birds achieved first egg at 166 d of age while the SAD fed birds achieved first egg at 173 d of age. Specific gravity was measured every 2 wk from 30 to 40 wk, with ED reared birds having better overall eggshell quality (P = 0.02) and greater egg weight (P < 0.0001) than those fed SAD. Feeding a high fiber diet on an ED basis during rearing, improved body weight uniformity in rearing, encouraged early lay, improved eggshell quality and increased egg weight.

The impact of progesterone receptor negativity on oncological outcomes in oestrogen-receptor-positive breast cancer.

BACKGROUND: Oestrogen receptor (ER) status provides invaluable prognostic and therapeutic information in breast cancer (BC). When clinical decision making is driven by ER status, the value of progesterone receptor (PgR) status is less certain. The aim of this study was to describe clinicopathological features of ER-positive (ER+)/PgR-negative (PgR-) BC and to determine the effect of PgR negativity in ER+ disease. METHODS: Consecutive female patients with ER+ BC from a single institution were included. Factors associated with PgR- disease were assessed using binary logistic regression. Oncological outcome was assessed using Kaplan-Meier and Cox regression analysis. RESULTS: In total, 2660 patients were included with a mean(s.d.) age of 59.6(13.3) years (range 21-99 years). Median follow-up was 97.2 months (range 3.0-181.2). Some 2208 cases were PgR+ (83.0 per cent) and 452 were PgR- (17.0 per cent). Being postmenopausal (odds ratio (OR) 1.66, 95 per cent c.i. 1.25 to 2.20, P < 0.001), presenting with symptoms (OR 1.71, 95 per cent c.i. 1.30 to 2.25, P < 0.001), ductal subtype (OR 1.51, 95 per cent c.i. 1.17 to 1.97, P = 0.002) and grade 3 tumours (OR 2.20, 95 per cent c.i. 1.68 to 2.87, P < 0.001) were all associated with PgR negativity. In those receiving neoadjuvant chemotherapy (308 patients), pathological complete response rates were 10.1 per cent (25 of 247 patients) in patients with PgR+ disease versus 18.0 per cent in PgR- disease (11 of 61) (P = 0.050). PgR negativity independently predicted worse disease-free (hazard ratio (HR) 1.632, 95 per cent c.i. 1.209 to 2.204, P = 0.001) and overall survival (HR 1.774, 95 per cent c.i. 1.324 to 2.375, P < 0.001), as well as worse overall survival in ER+/HER2- disease (P = 0.004). CONCLUSIONS: In ER+ disease, PgR- tumours have more aggressive clinicopathological features and worse oncological outcomes. Neoadjuvant and adjuvant therapeutic strategies should be tailored according to PgR status.

Disease recurrence and oncological outcome of patients treated surgically with curative intent for estrogen receptor positive, lymph node negative breast cancer.

BACKGROUND: The molecular era has identified four breast cancer subtypes. Luminal A breast cancer (LABC) is defined by estrogen-receptor positive (ER+), progesterone-receptor positive (PgR+) and human epidermal growth factor receptor-2 negative (HER2-) tumours; these cancers are the most common and carry favourable prognoses. AIMS: To describe clinicopathologic features, oncological outcome and relapse patterns in LABC. METHODS: Consecutive female patients diagnosed with ER/PgR+/HER2-, lymph node negative (LN-) breast cancer between 2005 and 2015 were included. Clinicopathological and recurrence data was recorded using descriptive statistics. Oncological outcome was determined using Kaplan-Meier and Cox-regression analyses. RESULTS: Analysis was performed for 849 patients with median follow-up of 102.1 months. Mean disease-free (DFS) and overall survival (OS) were 85.8% and 91.8%. Seventy patients died during this study (8.2%), while 58 patients had recurrence; 7 had local recurrence (0.8%) and 51 had distant recurrence (DDR) (6.0%). Patients developing DDR were likely to be postmenopausal (P = 0.028), present symptomatically (P < 0.001) and have larger tumours (P < 0.001). The mean time to DDR was 65.7 months, with fatal recurrence occurring in 66.6% of patients with DDR (34/51). Systemic chemotherapy prescription did not influence DDR (P = 0.053). Age >65 (hazards ratio (HR):1.66, 95% Confidence Interval (CI):1.07-2.55, P = 0.022), presenting symptomatically (HR:2.28, 95%CI:1.21-4.29, P = 0.011) and tumour size >20 mm (HR:1.81, 95%CI:1.25-2.62, P = 0.002) predicted DFS, while age>65 (HR:2.60, 95%CI:1.49-4.53, P = 0.001) and being postmenopausal at diagnosis (HR:3.13, 95%CI:1.19-8.22, P = 0.020) predicted OS. CONCLUSION: Our series demonstrated excellent survival outcomes for patients diagnosed with LN- LABC after almost a decade of follow-up. However, following DDR, fatal progression is often imminent.

Characterization of sperm-associated antigen 6 expression in the reproductive tract of the domestic rooster (Gallus domesticus) and its impact on sperm mobility.

Sperm mobility is a major determinant of sperm quality in the domesticated chicken (Gallus domesticus) and is therefore an area of interest for improving fertility. Sperm-associated antigen 6 (SPAG6) is an important flagellar protein implicated to be necessary for flagellar function but negatively associated with rooster fertility. This study was aimed to characterize the expression of SPAG6 and investigate its utility as a protein biomarker of sperm mobility. By western analysis, relative SPAG6 abundances were compared between the testicular, epididymal, and vasal tissues and in sequentially maturing sperm. Immunocytochemistry techniques were used to detect localization of SPAG6 in chicken sperm. Last, western analysis was used to compare relative SPAG6 abundances in sperm of differing mobility. SPAG6 was found in higher abundance in epididymal tissues and in highest abundance in vasal tissues, relative to that of the testis. SPAG6 was also found to sequentially increase in abundance in maturing sperm. SPAG6 localizes between the axonemal central pair of microtubules in the sperm flagella, but it is also found in lower concentration in the acrosomal region. SPAG6 was not a significant predictor of sperm mobility. SPAG6 abundance, alone, is not a strong predictor of sperm mobility. Its impact on rooster fertility is likely unrelated to its impact on sperm mobility.

Does Mode of Surgical Intervention Based on Oncotype DX Score Influence Disease Recurrence in Early Breast Cancer?

Introduction Routine utilization of multigene assays to inform operative decision-making in early breast cancer (EBC) treatment is yet to be established. In this pilot study, we sought to establish the potential benefits of surgical intervention in EBC based on recurrence risk quantification using the Oncotype DX (ODX) assay. Materials and Methods Consecutive ODX tests performed over a 9-year period from October 2007 to May 2016 were evaluated. Oncotype scores were classified into high (≥31), medium (18-30), or low-risk (0-17) groups. The primary outcome was breast cancer recurrence. Subgroup analysis offered assessment of the recurrence effect of mode of surgical intervention for patient groups as defined by the oncotype score. Results In total 361 patients underwent ODX testing. The mean age and follow-up were 55.25 (± 10.58) years and 38.59 (± 29.1) months, respectively. The majority of patients underwent wide local excision (86.7%) with 8.9 and 4.4% patients having a mastectomy or wide local excision with completion mastectomy, respectively. Fifty-one percent of patients fell into the low risk ODX category with a further 40.2 and 8.5% deemed to be of intermediate and high risk. Five patients (1.38%) had disease recurrence. Comparative analysis of operative groups in each oncotype group revealed no difference in recurrence scores in the low- ( p = 0.84) and high-risk groups ( p = 0.92) with a statistically significant difference identified in the intermediate risk group ( p = 0.002). Conclusion To date we have been unable to definitively identify a role for ODX in guiding surgical approach in EBC. There is, however, a need for larger studies to examine this hypothesis.

Synchronous renal and para-aortic metastasis in a uterine serous carcinoma: A case review and clinical considerations.

•Serous endometrial carcinomas rarely involve the renal system.•Stage IVB serous endometrial carcinoma with confirmed renal metastasis.•Paclitaxel/carboplatin treating serous endometrial carcinoma with renal metastasis.

Natural cause mortality in persons with serious mental illness.

OBJECTIVE: To identify the determinants of natural cause mortality in a cohort of individuals with serious mental illness assessed prospectively. METHOD: Persons with schizophrenia (n = 789) and bipolar disorder (n = 498), mean age of 38 (s.d. 12.6) years, underwent an in-person clinical assessment. They also had a blood sample drawn from which infectious disease markers were measured. Mortality was subsequently determined utilizing data from the National Death Index following a period of up to 16.9 years. RESULTS: A total of 6.8% (87 of 1287) of persons died of natural causes. Mortality was predicted in a multivariate model by baseline cigarette smoking (RR = 6.29, 95% CI 1.41, 3.72, P = 0.00076); divorced or widowed status (RR = 1.90, CI 1.21, 2.99); reduced cognitive score (RR = 0.73, CI 0.61, 0.87); receipt of antidepressant medication (RR = 1.74, CI 1.12, 2.71); elevated levels of antibodies to Epstein-Barr virus (EBV) (RR = 1.29, CI 1.01, 1.66); and a genitourinary (RR = 1.82, CI 1.16, 2.86), respiratory (RR = 1.82, CI 1.16, 2.86), or cardiac (RR = 2.09, CI 1.33, 3.29) condition. There was an additive effect of smoking and both a cardiac and a respiratory condition but not elevated EBV antibody levels. CONCLUSION: Smoking is a modifiable behaviour which is associated with mortality in this population.

Re-Appraisal of Estrogen Receptor Negative/Progesterone Receptor Positive (ER-/PR+) Breast Cancer Phenotype: True Subtype or Technical Artefact?

Expression of the ER and PR receptors is routinely quantified in breast cancer as a predictive marker of response to hormonal therapy. Accurate determination of ER and PR status is critical to the optimal selection of patients for targeted therapy. The existence of an ER-/PR+ subtype is controversial, with debate centred on whether this represents a true phenotype or a technical artefact on immunohistochemistry (IHC). The aim of this study was to investigate the true incidence and clinico-pathological features of ER-/PR+ breast cancers in a tertiary referral symptomatic breast unit. Clinico-pathological data were collected on invasive breast cancers diagnosed between 1995 and 2005. IHC for ER and PR receptors was repeated on all cases which were ER-/PR+, with the same paraffin block used for the initial diagnostic testing. Concordance between the diagnostic and repeat IHC was determined using validated testing. Complete data, including ER and PR status were available for 697 patients diagnosed during the study period. On diagnostic IHC, the immunophenotype of the breast tumours was: ER+/PR+ in 396 (57%), ER-/PR- in 157 (23%), ER+/PR- in 88 (12%) and ER-/PR+ in 56 (8.6%) patients. On repeat IHC of 48/56 ER-/PR+ tumours 45.8% were ER+/PR+, 6% were ER+/PR- and 43.7% were ER-/PR- None of the cases were confirmed to be ER-/PR+. The ER-/PR+ phenotypic breast cancer is likely to be the result of technical artefact. Prompt reassessment of patients originally assigned to this subtype who re-present with symptoms should be considered to ensure appropriate clinical management.

Pathogen-mediated NMDA receptor autoimmunity and cellular barrier dysfunction in schizophrenia.

Autoantibodies that bind the N-methyl-D-aspartate receptor (NMDAR) may underlie glutamate receptor hypofunction and related cognitive impairment found in schizophrenia. Exposure to neurotropic pathogens can foster an autoimmune-prone environment and drive systemic inflammation leading to endothelial barrier defects. In mouse model cohorts, we demonstrate that infection with the protozoan parasite, Toxoplasma gondii, caused sustained elevations of IgG class antibodies to the NMDAR in conjunction with compromised blood-gut and blood-brain barriers. In human cohorts, NMDAR IgG and markers of barrier permeability were significantly associated with T. gondii exposure in schizophrenia compared with controls and independently of antipsychotic medication. Combined T. gondii and NMDAR antibody seropositivity in schizophrenia resulted in higher degrees of cognitive impairment as measured by tests of delayed memory. These data underscore the necessity of disentangling the heterogeneous pathophysiology of schizophrenia so that relevant subsets eligible for NMDAR-related treatment can be identified. Our data aid to reconcile conflicting reports regarding a role of pathological NMDAR autoantibodies in this disorder.

Population Pharmacokinetics, Pharmacodynamics, and Exploratory Exposure-Response Analyses of Apixaban in Subjects Treated for Venous Thromboembolism.

Apixaban is approved for treatment of venous thromboembolism (VTE) and prevention of recurrence. Population pharmacokinetics, pharmacokinetics-pharmacodynamics (anti-FXa activity), and exposure-response (binary bleeding and thromboembolic endpoints) of apixaban in VTE treatment subjects were characterized using data from phase I-III studies. Apixaban pharmacokinetics were adequately characterized by a two-compartment model with first-order absorption and elimination. Age, sex, and Asian race had less than 25% impact on exposure, while subjects with severe renal impairment were predicted to have 56% higher exposure than the reference subject (60-year-old non-Asian male weighing 85 kg with creatinine clearance of 100 mL/min). The relationship between apixaban concentration and anti-FXa activity was described by a linear model with a slope estimate of 0.0159 IU/ng. The number of subjects with either a bleeding or thromboembolic event was small, and no statistically significant relationship between apixaban exposure and clinical endpoints could be discerned with a logistic regression analysis.

Trends in breast reconstruction practices in a specialized breast tertiary referral centre.

BACKGROUND: Breast reconstruction is an important component of multidisciplinary breast cancer management. The practice of breast reconstruction after mastectomy has evolved significantly in the past decade as a result of both increasing mastectomy rates and advances in reconstructive strategy. These changes have significantly influenced the contemporary surgical management of breast cancer. The aim of this study was to examine trends in breast reconstruction after mastectomy in an Irish population. METHODS: Data were reviewed from a database of all patients who had mastectomy with or without breast reconstruction at Galway University Hospital, a tertiary breast cancer referral centre, between 2004 and 2014. Trends in breast reconstruction after mastectomy were explored with respect to patient demographics, clinicopathological features, and neoadjuvant and adjuvant therapy. RESULTS: Of 1303 patients who underwent mastectomy during interval studied, 706 (54.2 per cent) had breast reconstruction after mastectomy. In 629 patients (89·1 per cent), breast reconstruction was performed in the immediate setting. Reconstruction rates increased over time from 20·5 per cent in 2004 to 44·7 per cent in 2014. Reconstruction was more commonly performed in younger patients and those with benign, in situ and early-stage disease. A negative relationship between radiotherapy and reconstruction was observed. A pedicled flap with or without an implant was the most commonly used reconstructive approach in patients receiving radiotherapy. CONCLUSION: Breast reconstruction after mastectomy has become the standard of care in the surgical treatment of breast cancer. Recent trends show a transition favouring implant-based approaches.

A ZEB1-miR-375-YAP1 pathway regulates epithelial plasticity in prostate cancer.

MicroRNA-375 (miR-375) is frequently elevated in prostate tumors and cell-free fractions of patient blood, but its role in genesis and progression of prostate cancer is poorly understood. In this study, we demonstrated that miR-375 is inversely correlated with epithelial-mesenchymal transition signatures (EMT) in clinical samples and can drive mesenchymal-epithelial transition (MET) in model systems. Indeed, miR-375 potently inhibited invasion and migration of multiple prostate cancer lines. The transcription factor YAP1 was found to be a direct target of miR-375 in prostate cancer. Knockdown of YAP1 phenocopied miR-375 overexpression, and overexpression of YAP1 rescued anti-invasive effects mediated by miR-375. Furthermore, transcription of the miR-375 gene was shown to be directly repressed by the EMT transcription factor, ZEB1. Analysis of multiple patient cohorts provided evidence for this ZEB1-miR-375-YAP1 regulatory circuit in clinical samples. Despite its anti-invasive and anti-EMT capacities, plasma miR-375 was found to be correlated with circulating tumor cells in men with metastatic disease. Collectively, this study provides new insight into the function of miR-375 in prostate cancer, and more broadly identifies a novel pathway controlling epithelial plasticity and tumor cell invasion in this disease.

Influence of complications following immediate breast reconstruction on breast cancer recurrence rates.

BACKGROUND: The rate of immediate breast reconstruction is rising. Postoperative infections are more frequent in patients who undergo reconstruction. The inflammatory response to a postoperative infection can increase the risk of tumour recurrence in other forms of cancer through the release of proinflammatory mediators. The aim of this study was to assess the relationship between complications and breast cancer recurrence in patients undergoing immediate reconstruction. METHODS: This was a review of a prospectively maintained database of all patients who had immediate breast reconstruction between 2004 and 2009 at Galway University Hospital, a tertiary breast cancer referral centre serving the west of Ireland. All patients had a minimum follow-up of 5 years. Outcomes assessed included the development of wound complications and breast cancer recurrence. The data were evaluated by univariable and multivariable Cox regression analysis. RESULTS: A total of 229 patients who underwent immediate reconstruction were identified. The overall 5-year recurrence-free survival rate was 85·6 per cent. Fifty-three patients (23·1 per cent) had wound complications, of whom 44 (19·2 per cent) developed a wound infection. There was a significantly greater risk of developing systemic recurrence among patients who experienced a postoperative wound complication compared with those without a complication (hazard ratio 4·94, 95 per cent c.i. 2·72 to 8·95; P < 0·001). This remained significant after adjusting for Nottingham Prognostic Index group in the multivariable analysis. The 5-year recurrence-free survival rate for patients who had a wound complication was 64 per cent, compared with 89·2 per cent in patients without a complication (P < 0·001). CONCLUSION: This study has demonstrated that wound complications after immediate breast reconstructive surgery have significant implications for patients with breast cancer. Strategies are required to minimize the risk of postoperative wound complications in patients with breast cancer undergoing immediate reconstruction.

A qualitative analysis of the attitudes of Irish patients towards participation in genetic-based research.

BACKGROUND: Progress in diagnostic and therapeutic strategies in medicine is dependent upon high-quality biomedical research. Technological advances have facilitated improved understanding of disease aetiology, and rapidly emerging data promises further progress. Translating this potential into the clinic depends on patient participation in innovative clinical trials. We investigated attitudes to genetic research in Ireland, particularly with respect to commercial and financial implications. METHODS: A multi-centre, cross-sectional survey study was performed. Consecutive out-patients attending four clinics were asked to complete paper-based questionnaires. The same questionnaire was publicly available in electronic format on www.surveymonkey.com for 72 h. Data were analysed using SPSS. RESULTS: 351 questionnaires were completed (99 paper, 252 electronic). The majority of respondents were female (n = 288, 82 %), and highly educated, with 244 (70 %) attending college/university. Most participants supported genetic research (267, 76 %), more frequently for common diseases (274, 78 %) than rare disorders (204, 58 %, p < 0.001, χ 2). 103 (29 %) had participated in scientific research, and 57 (16 %) had donated material to a bio-bank. The majority (n = 213, 61 %) would not support research with potential financial/commercial gain. 106 (30 %) would decline to participate in research if researchers would benefit financially, compared to 49 (14 %) if the research was supported by a pharmaceutical company (p < 0.001, χ 2). Respondents would provide buccal samples (258, 74 %) more readily than tissue (225, 64 %) or blood (222, 63 %). CONCLUSIONS: A high level of support for genetic research exists among the Irish population, but active participation is dependent upon a number of factors, notably, type of biological material required, frequency of the disease in question, and commercial interest of the researchers.

Medicolegal implications of accuracy of GP referral letters to specialist breast clinic.

BACKGROUND: Referrals to symptomatic breast clinics have increased significantly in recent years with unchanged numbers of detected cancers. The general practitioner (GP) referral information relating to this increased patient volume causes anxiety and potentially creates confusion and future medicolegal issues if inaccurate. AIMS: To compare GP triage category requests and clinical findings with those determined by the breast centre. METHODS: 1,014 consecutive referrals to a symptomatic breast service were included. GP triage request category and clinical findings were prospectively recorded and compared to cancer centre surgeon triage category, clinical findings and cancer detection rates. RESULTS: GPs requested urgent appointments for 49 % of referrals, only 22 % were considered urgent on triage at the cancer centre. The triage category request was downgraded in 56 % of referrals from urgent to routine. Thirty-three cancers were detected, representing 3 % of referrals. Eighty-eight percent of cancers were identified in the group with positive clinical findings at the breast clinic. 24 % of the new referrals were for mastalgia alone. In the 55 % of referred cases where GPs reported a clinical abnormality, only 39 % of these had a clinical finding confirmed by the breast surgeon. CONCLUSIONS: There is poor correlation between GP triage category request and those assigned by the breast unit. GP referrals indicating patients with a clinical abnormality was discordant with specialist findings in 61% of cases. The frequency of overstating of clinical findings by GPs is such that subsequent cancer diagnosis does not imply failure of a preceding triple assessment process.

The future of UK/Irish surgery: A European solution.

The United Kingdom (UK) and Republic of Ireland (ROI) hospital systems are dependent on junior doctors for their functionality however it is increasingly difficult to recruit UK/ROI trained doctors to fill these posts. Directive 2005/36/EC, which came into force in 2007, is the principal European legislation on the recognition of equivalence of professional qualifications across Europe. European trained doctors are therefore attractive candidates for junior doctor posts. However, although their training is recognised as equivalent by the Irish Medical Council (IMC) and General Medical Council (GMC) they are not being appointed to equivalent posts by the Health Service Executive (HSE) or National Health Service (NHS). With the influence of European Union (EU) centralisation, modification of UK/ROI consultant grade is imminent, possibly to pyramidal structure of the Continental European model with clearer lines of corporate responsibility.

Analysis of subsequent publication and impact of abstracts presented at the Sir Peter Freyer Surgical Symposium: Focus on the Plenary Session.

BACKGROUND: The quality of abstracts presented at a conference reflects the academic activity and research productivity of the surgical/scientific association concerned. The abstract to publication rate (44.5 % internationally), is an important indicator of the quality of presented research. AIM: To evaluate the publication rate and impact of abstracts presented at the plenary session of the Sir Peter Freyer Surgical Symposium over a 25-year period (1989-2014), and identify factors influencing publication. METHODS: Plenary abstracts were identified from abstract books of the Symposium from 1989-2014. The authors, institution, subspecialty and research subject were recorded. A Medline search with name of the first and last author, key words and content of all abstracts was conducted to identify related publications. The impact factor (IF) of the journal and the time to publication was recorded. RESULTS: 298 presented abstracts resulted in 168 publications (publication rate: 56 %). Basic Science research accounted for 80 % (n = 237) of the total number of presentations with the remaining 20 % (n = 61) being categorised as clinical research. Overall, cancer research accounted for 48 % of presented work. The average time to publication was 2 ± 7 years, while 11 % of all published studies achieved publication in the year of the symposium. The median impact factor for published research was 3.558 (IF range 0-39). CONCLUSION: These results indicate that the quality of papers presented at the Sir Peter Freyer Surgical Symposium compares favourably with international equivalents, making this meeting an important forum for Irish Academic Surgery.