Cr[Formula: see text]AlN and the search for the highest temperature superconductor in the M[Formula: see text]AX family.

We have developed a high-throughput computational method to predict the superconducting transition temperature in stable hexagonal M[Formula: see text]AX phases, and applied it to all the known possible choices for M (M: Sc, Ti, V, Cr, Mn, Fe, Y, Zr, Nb, Mo, Lu, Hf and Ta). We combine this with the best candidates for A (A: Al, Cu, Ge and Sn ) and X (X: C and N) from our previous work, and predict T[Formula: see text] for 60 M[Formula: see text]AX-phase materials, 53 of which have never been studied before. From all of these, we identify Cr[Formula: see text]AlN as the best candidate for the highest T[Formula: see text], and confirm its high T[Formula: see text] with more detailed density functional theory electron-phonon coupling calculations. Our detailed calculations predict [Formula: see text] = 14.8 K for Cr[Formula: see text]AlN, which is significantly higher than any [Formula: see text] value known or predicted for any material in the M[Formula: see text]AX family to date.

Prediction of phonon-mediated superconductivity in new Ti-based M[Formula: see text]AX phases.

A high-throughput computational method is used to predict 39 new superconductors in the Ti-based M[Formula: see text]AX phases, and the best candidates are then studied in more detail using density functional theory electron-phonon coupling calculations. The detailed calculations agree with the simple predictions, and Ti[Formula: see text]AlX (X: B, C and N) materials are predicted to have higher values of [Formula: see text] than any currently known hexagonal M[Formula: see text]AX phases. The electronic states at the Fermi level are dominated by the Ti 3d states. The choice of X (X: B, C and N) has a significant impact on the electronic density of states but not on the phonon characteristics. The electron-phonon coupling parameter for Ti[Formula: see text]AlX (X: B, C and N) was determined to be 0.685, 0.743 and 0.775 with a predicted [Formula: see text] of 7.8 K, 10.8 K and 13.0 K, respectively.

Growing Old in the Emergency Department.

The research team were concerned that older patients requiring emergency admission seemed to wait longer for a hospital bed, and as such were disproportionately affected by Emergency Department overcrowding. To investigate this theory and explore any changes over time, a ten year dataset (2005-2014 inclusive) was extracted from the information systems at Beaumont Hospital, Dublin. This research examines the changing age profile of ED patients, identifies the relationship between age and the total time spent in the Emergency Department (Patient Experience Time (PET)), and examines the public belief that EDs are busiest in winter when reports of overcrowding and elderly patients waiting on trolleys get most media attention. The results highlight that the ED is busy all year round (but for different seasonal reasons) and point to an overdue need to plan for the current and future healthcare of older patients within and beyond acute hospitals.

In situ "artificial plasma" calibration of tokamak magnetic sensors.

A unique in situ calibration technique has been used to spatially calibrate and characterize the extensive new magnetic diagnostic set and close-fitting conducting wall of the High Beta Tokamak-Extended Pulse (HBT-EP) experiment. A new set of 216 Mirnov coils has recently been installed inside the vacuum chamber of the device for high-resolution measurements of magnetohydrodynamic phenomena including the effects of eddy currents in the nearby conducting wall. The spatial positions of these sensors are calibrated by energizing several large in situ calibration coils in turn, and using measurements of the magnetic fields produced by the various coils to solve for each sensor's position. Since the calibration coils are built near the nominal location of the plasma current centroid, the technique is referred to as an "artificial plasma" calibration. The fitting procedure for the sensor positions is described, and results of the spatial calibration are compared with those based on metrology. The time response of the sensors is compared with the evolution of the artificial plasma current to deduce the eddy current contribution to each signal. This is compared with simulations using the VALEN electromagnetic code, and the modeled copper thickness profiles of the HBT-EP conducting wall are adjusted to better match experimental measurements of the eddy current decay. Finally, the multiple coils of the artificial plasma system are also used to directly calibrate a non-uniformly wound Fourier Rogowski coil on HBT-EP.

Pilot translational study of dietary vitamin C supplementation in Barrett's esophagus.

The transcription factor Nuclear factor kappa B (NF-kappaB) is central to the regulation of genes encoding for mediators of inflammation and carcinogenesis. In the esophagus, NF-kappaB is progressively activated from inflammation to Barrett's metaplasia and adenocarcinoma. Vitamin C, an antioxidant, can inhibit NF-kappaB in in vitro models, and the aim of this study was to prospectively assess the effect of supplemental vitamin C on NF-kappaB and associated cytokines in patients with Barrett's esophagus. Twenty-five patients with long-segment Barrett's and specialized intestinal metaplasia received dietary vitamin C (1000 mg/day) orally for four weeks, and had pre- and post-vitamin C endoscopic biopsies. NF-kappaB activity (activated p50 and p65 subunits) of nuclear extracts was assessed using the Active Motif NF-kappaB assay, and cytokines and growth factors were measured using the Evidence Investigator biochip array. NF-kappaB and related pro-inflammatory cytokines and growth factors (IL-8, VEGF, IL-10) were activated in all Barrett's tissue pre-treatment. Down-regulation in activated NF-kappaB and cytokines was observed in 8/25 (35%) patients. Dietary vitamin C supplementation may down-regulate pro-inflammatory markers in a subset of Barrett's patients. Further studies with larger numbers of endpoints will be needed to further evaluate this effect.

Health-related quality of life assessment at presentation may predict complications and early relapse in patients with localized cancer of the esophagus.

SUMMARY: Health-related quality of life (HR-QOL) assessment in esophageal cancer is increasingly performed. However, the association of baseline HR-QOL in predicting outcome is unclear. This study aimed to assess the impact of HR-QOL scores at diagnosis with major morbidity, mortality, failure to progress to surgery, recurrence within 1 year, and survival in patients with localized esophageal cancer. The European Organization for Research and Treatment of Cancer's quality of life questionnaire was completed at diagnosis. Univariate and multivariate logistic regression were used to investigate the relationship between baseline HR-QOL and outcomes adjusting for confounding variables. A total of 185 patients with localized esophageal cancer were included, 89 undergoing multimodal therapy and 96 surgery alone. Global QOL scores were significantly associated with in-hospital mortality (P = 0.020) but not with major morbidity (P = 0.709) or 1-year survival (P = 0.247). Symptoms of fatigue and dyspnea at baseline were significantly (P < 0.05) associated with major morbidity, in-hospital mortality, and survival in univariate analysis. After adjusting for known confounding variables in multivariate analysis, only worse dyspnea score remained predictive of in-hospital mortality and a worse fatigue score remained predictive of 1-year survival. HR-QOL was of no benefit in predicting survival in multivariate analysis that identified pathological nodal status as the most significant factor. HR-QOL questionnaires may be helpful in preoperative assessment of risk. It is possible that patients with unrecognized micrometastatic disease at the time of surgery may report worse systemic symptoms at diagnosis, in particular fatigue and dyspnea, and these and global QOL scores may also identify poorer reserves that may increase in-hospital morbidity and mortality postoperatively.

The Rossetti-Nissen fundoplication--effective in managing gastro-oesophageal reflux disease.

BACKGROUND: The report herein details a prospective audit of a unit's eight-year experience of the Rossetti-Nissen fundoplication using a predominantly laparoscopic technique, selective hiatal repair, no bougie and a standardised protocol of pre- and post-operative functional endoscopic and symptom assessment. METHODS: Three hundred and seventy-eight patients underwent the Rossetti-Nissen fundoplication. All patients had documented data on endoscopy, health related quality of life (HR-QoL), surgical details and complications pre-operatively and at six months post-operatively. Repeat physiological testing was performed at six months. RESULTS: At a median follow-up of six (range 3-13) months there was improved symptom scoring and HR-QoL after fundoplication with an 89% patient satisfaction rate. Ninety-five patients (25%) reported some early dysphagia, and 91 of these reported the outcome of surgery to be excellent or good. Thirty-eight patients (10%) had recurrent heartburn and 28 (7%) were back on medication at six months post-operatively. At follow-up pH study at a median of six months, 89% of patients had normalised acid reflux scores. CONCLUSIONS: Rossetti-Nissen fundoplication, with no use of an oesophageal bougie and no division of short gastric vessels, is an effective procedure giving 89% patient satisfaction and significant improvement in QoL parameters and physiological measurements.

Superiority of anti-reflux stent compared with conventional stents in the palliative management of patients with cancer of the lower esophagus and esophago-gastric junction: results of a randomized clinical trial.

Palliation of inoperable esophageal cancer with covered stents aims to relieve progressive dysphagia and improve health-related quality of life (HRQoL). Introducing a stent across the esophagogastric junction in lower third tumors may predispose to unchecked gastro-esophageal reflux (GER). Esophageal stents incorporating an anti-reflux valve have been introduced to address this problem. We prospectively compared an anti-reflux stent with a standard stent in the palliation of inoperable lower third esophageal tumors. Forty-nine consecutive patients with malignant dysphagia were randomized to receive a standard (n = 25, group 1) or an anti-reflux stent (n = 24, group 2). HRQoL was assessed before stenting, at 1 week and at 2 months, utilizing European Organization for Research and Treatment of Cancer questionnaires QLQ-C30, QLQ-OES24 and reflux questionnaires. Esophageal pH testing was performed within 1 week of the stent insertion. Detailed statistical analysis was employed to assess general QoL, symptoms and pH scores in both groups. Both groups reported significantly improved QoL, health and dysphagia scores at 1 week and 2 months after stenting. Group 2 patients reported significantly (P < 0.05) better DeMeester symptom, general reflux scores, and normal pH profile at 1 week. At 2 months DeMeester symptom scores were significantly (P < 0.05) better in group 2 compared with group 1. Standard and anti-reflux stents afford comparable relief from dysphagia and improved quality of life in patients with inoperable lower third esophageal cancer. Anti-reflux stents, however, controlled symptomatic and physiologically relevant reflux and should therefore be considered as optimal palliation in this cohort.

Management of gastrointestinal stromal tumours: a single-centre experience.

BACKGROUND: Gastrointestinal stromal tumours (GISTs), although rare, are increasingly recognized, characterized immuno-phenotypically in most cases by a mutation in C-Kit. The advent of imatinib, a tyrosine kinase inhibitor, has presented a novel and effective therapy in advanced disease. The aim of this study was to present the experience and outcomes of a single centre. METHODS: Review of prospective GIST database at St James Hospital from 1997 to 2005. Survival data were analysed using Kaplan-Meier methods. RESULTS: A total of 32 patients (19 males/13 females) with a median age of 61 years (10-84) were treated. The stomach (n = 20) was the dominant site. Surgery was the first line of treatment for all these tumours, and in seven cases this was performed laparoscopically. C-Kit was positive in 81% of cases. The median survival was 78 months with a 5-year survival of 71%. CONCLUSION: GISTs are rare and surgical resection, increasingly with minimally invasive approaches, is associated with high cure rates, particularly in gastric tumours.

Laryngopharyngeal reflux in patients with symptoms of gastroesophageal reflux disease.

Laryngopharyngeal reflux (LPR) has been extensively studied in patients with laryngeal signs and symptoms, gastroesophageal reflux being identified in approximately 50%. Few studies have investigated the incidence and significance of LPR in GERD patients. Two-hundred and seventy-six consecutive patients referred with symptoms of gastroesophageal reflux had dual probe 24 h pH, esophageal manometry, GERD and ENT questionnaires. LPR was defined as at least three pharyngeal reflux events less than pH 5.0 with corresponding esophageal reflux, but excluding meal periods. Fourty-two percent of patients were positive for LPR on 24 h pH monitoring and 91.3% corresponded with an abnormal esophageal acid score. Distal esophageal acid exposure was significantly greater (P < 0.001) in patients with LPR but symptoms of GERD and regurgitation scores showed no significant differences between patients with positive and negative LPR on 24 h pH. There was no significant difference between the incidence of LPR in patients with or without laryngeal symptoms. There is a high incidence of LPR in patients with GERD but its significance for laryngeal symptoms is tenuous. Fixed distance dual probe pH monitoring allows documentation of conventional esophageal reflux and LPR.

Clinicopathologic factors predicting complete pathological response to neoadjuvant chemoradiotherapy in esophageal cancer.

Multimodal therapy comprising neoadjuvant chemotherapy and radiation therapy prior to radical resection is increasingly utilized in gastroesophageal cancer. The achievement of a complete pathological response (pCR) or a major response is associated with an improved survival. However, up to 70% of patients show an incomplete or no response to the neoadjuvant regimen, and the identification of factors which predict a response would be of considerable clinical benefit. A retrospective analysis of a prospectively updated esophageal cancer database was performed. The predictive values of the following clinicopathological factors were investigated: age, sex, tobacco, alcohol, weight, clinical history, tumor type, site, length, width, morphology and differentiation. Statistical analysis was performed using Chi-square test with Pearson's test or Kruskal-Wallis test. One hundred and seventy-six patients were identified who had undergone neo-adjuvant chemoradiotherapy at St James's Hospital Dublin, between January 1990 and June 2003. A complete pathological response was seen in 40 cases (23%). There was a significant (P < 0.05) relationship between response to chemoradiotherapy and pretreatment tumor length. The median tumor length in the pCR group was 2 cm (1-5 cm) compared with 3 cm (2-7 cm) in non-responders (P < 0.05). Body weight, sex, tobacco or alcohol usage, tumor site, or differentiation were not predictive of response, although a trend (P = 0.08) was observed for squamous cell cancer compared with adenocarcinoma. Smaller tumor length was predictive of a greater response to chemotherapy and radiation therapy. This may reflect different tumor biology, perhaps with acquired resistance to treatment-induced apoptosis in the larger tumors. A simpler explanation is that the existing dose and treatment schedule for combination chemoradiotherapy is suboptimal in patients with larger tumors.

Seeing baby: women's experience of prenatal ultrasound examination and unexpected fetal diagnosis.

OBJECTIVE: Although prenatal ultrasound (US) is a common clinical undertaking today, little information is available about women's experience of the procedure from the perspective of women themselves. The objective of this study was to explore women's experience of undergoing a routine prenatal US examination associated with an unexpected fetal diagnosis. STUDY DESIGN: Qualitative methods were used to explore the prenatal US experience of 13 women. Five women were given unexpected news of multiple pregnancy and eight women were given unexpected news of congenital fetal abnormality. One in-depth audio-taped interview was conducted with each woman. Content analysis of interview data identified themes common to women's experience of US. RESULTS: Identified themes of women's experience of routine prenatal US examination associated with an unexpected fetal diagnosis are: experiencing the setting, sensing information, feeling connected/disconnected, the power of the image, and communication rules. CONCLUSIONS: Women's experience of prenatal US examination is influenced by physical and environmental factors and by the behaviors of the US examiner. Behaviors of the examiner contribute to a woman's labeling of the US experience as positive or negative. Women identify being objectified by the examination and experience poor communication patterns after a fetal US diagnosis. Women's description of the US screen image as a baby suggests it is a powerful influence on subsequent clinical and ethical decision-making about the pregnancy.

Prospective evaluation of quality of life in patients with localized oesophageal cancer treated by multimodality therapy or surgery alone.

BACKGROUND: Health-related quality of life (HRQL) outcomes are important in assessing new approaches to the treatment of cancer. Neoadjuvant therapy is being used increasingly before surgery in patients with localized oesophageal cancer. This prospective non-randomized study evaluated HRQL in patients treated by preoperative chemotherapy and radiation therapy followed by surgery (multimodal therapy) or by surgery alone. METHODS: Data from European Organization for Research and Treatment of Cancer quality of life questionnaires QLQ-30 and QLQ-OES24 were collected prospectively. Questionnaires were completed at diagnosis, after chemoradiotherapy where applicable, and at 3, 6 and 12 months after surgery. RESULTS: The study included 202 consecutive patients with oesophageal cancer considered suitable for curative (R0) resection at the time of staging. Eighty-seven patients received chemotherapy combined with external-beam radiotherapy before surgery. At baseline, 75 (86 percent) of 87 patients in the multimodal group completed questionnaires, compared with 72 (62.6 percent) of 115 in the surgery-alone group. There were no significant differences in baseline global HRQL scores between groups. Preoperative chemoradiotherapy significantly reduced physical (P=0.004) and role (P=0.007) functioning before surgery, despite a significant (P=0.043) improvement in the dysphagia score. Oesophageal resection had a negative impact on global, functional and symptom HRQL scores at 3 months in both groups. Most variables had recovered by 6 months in the two groups, but at 12 months physical and role functioning remained impaired in the surgery-alone group, and social functioning and financial worries in the multimodal group. CONCLUSION: Although the multimodal regimen had a negative impact on HRQL before surgery, postoperative quality of life in patients who had multimodal therapy was similar to that in those who had surgery alone.

Effect of physical exercise on esophageal motility in patients with esophageal disease.

The most common type of esophageal dysfunction associated with chest pain is gastroesophageal reflux, which may be induced by exercise. The effect of exercise on esophageal function has mainly been investigated in normal subjects or trained athletes. Few studies have investigated exercise and esophageal motility disorders. One hundred and thirty-five patients underwent ambulatory esophageal manometry and pH monitoring, before, during and immediately after moderate exercise. Patients were divided into four groups: Normal, nutcracker, diffuse spasm and gastroesophageal reflux disease (GERD). Ambulatory manometry and pH were monitored while exercising on a treadmill during which standardized boluses of water were administered. Nutcracker and diffuse spasm patients demonstrated a significant fall in esophageal wave amplitude during exercise compared to controls, which returned rapidly to pre exercise values after resting. There was no evidence of acid reflux in the non-reflux groups during exercise. Reflux was noted in 13 patients with GERD during exercise, none of whom had evidence of reflux at the onset of exercise. When these patients were classified by reflux type, the majority, 11 patients, were found to come from the combined or supine reflux group. Esophageal amplitude in nutcracker esophagus does not increase during moderate exercise. Moderate exercise provokes reflux in GERD patients with combined or supine reflux.

Proinflammatory cytokine and nuclear factor kappa-B expression along the inflammation-metaplasia-dysplasia-adenocarcinoma sequence in the esophagus.

BACKGROUND: The incidence of esophageal adenocarcinoma has increased significantly in the western world over the last 20 yr. Most cases arise in a background of chronic gastroesophageal reflux, and specialized intestinal metaplasia in Barrett's esophagus is frequently an antecedent phenotype or evident in association with adenocarcinoma. The molecular events that characterize the pathway from inflammation to metaplasia to dysplasia and adenocarcinoma are poorly understood. AIMS: To examine the expression of the proinflammatory cytokines IL-8 and IL-1beta along the esophagitis, metaplasia, dysplasia, and adenocarcinoma pathway, and to correlate this with histological changes and expression of the transcription factor NF-kappaB. PATIENTS AND METHODS: Fresh biopsy specimens were collected from patients with reflux esophagitis (n=15), Barrett's esophagus (n=35), Barrett's adjacent to adenocarcinoma (n=8), and esophageal adenocarcinoma (n=35). IL-8 and IL-1beta expression were measured using enzyme-linked immunosorbent assay. NF-kappaB expression was measured by electrophoretic mobility shift assay. RESULTS: Elevated expression of NF-kappaB was found in 2 (13%) out of 15 patients with reflux esophagitis, 21 (60%) out of 35 patients with Barrett's esophagus, and 28 (80%) out of 35 patients with esophageal adenocarcinoma. All 5 patients with Barrett's esophagus and high-grade dysplasia showed elevated expression of NF-kappaB. IL-8 and IL-1beta were significantly increased in esophagitis, Barrett's, and adenocarcinoma compared with squamous epithelium, and in adenocarcinoma compared with all other groups. There was a stepwise increase in the expression of IL-8, IL-1beta, and NF-kappaB from normal through Barrett's epithelium to adenocarcinoma in eight cases of esophageal adenocarcinoma. The levels of both IL-8 and IL-1beta in adenocarcinoma patients correlated with stage of disease. Patients with adenocarcinoma who were NF-kappaB positive had significantly higher levels of both IL-8 (p=0.04) and IL-1beta (p=0.03) compared to adenocarcinoma patients who were NF-kappaB negative. CONCLUSIONS: The proinflammatory cytokines IL-8 and IL-1beta are elevated in esophagitis and Barrett's epithelium, and markedly elevated in adenocarcinoma. NF-kappaB activation is infrequent in esophagitis, but is increased in Barrett's epithelium and adenocarcinoma. The association of NF-kappaB activation with cytokine upregulation was only evident in patients with adenocarcinoma. These patterns may play an important role in Barrett's inflammation and tumourigenesis, and inhibition of the NF-kappaB/proinflammatory cytokine pathway may be an important target for future chemoprevention strategies.

Gastric myoelectrical activity post-chemoradiotherapy and esophagectomy: a prospective study using subscapular surface recording.

The aims of this study were to prospectively evaluate gastric function in esophageal cancer patients after chemoradiotherapy and following surgery, using cutaneous electrogastrography (EGG). Twenty-three patients with esophageal adenocarcinoma were recruited to the study. A subset of patients (n = 11) underwent neoadjuvant chemoradiotherapy and were also studied at 14 days after treatment. All patients underwent EGG studies prior to and following surgery, at 3 months postoperatively. Ten of these patients were also studied at medians of 6 months and 12 months after surgery. Twenty normal volunteers were used as controls. Post-operative EGG studies were monitored with a modified technique; the electrodes being placed in the subscapular region in the area of the transposed stomach. Following neoadjuvant treatment there was a significant increase in abnormal gastric myoelectrical activity involving changes in tachygastrias and decreased motility as measured by power ratio. Post-operatively there was a significant increase in bradygastria which persisted at 6 months but not at 12 months. There was a corresponding decrease in normogastria which persisted at 6 months and to a lesser extent at 12 months. Dominant frequency remained significantly depressed at 3, 6 and 12 months. Gastric myoelectrical activity is normal in untreated esophageal cancer. Neoadjuvant chemoradiotherapy causes a disruption to normal myoelectrical activity involving reduced motility and tachygastrias. Surgery causes a depression in dominant frequency with a reduced incidence of normogastria at 3 months and 6 months but with a tendency towards normality at 12 months.