Author Correction: Superconductivity mediated by polar modes in ferroelectric metals.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Superconductivity mediated by polar modes in ferroelectric metals.

The occurrence of superconductivity in doped SrTiO3 at low carrier densities points to the presence of an unusually strong pairing interaction that has eluded understanding for several decades. We report experimental results showing the pressure dependence of the superconducting transition temperature, Tc, near to optimal doping that sheds light on the nature of this interaction. We find that Tc increases dramatically when the energy gap of the ferroelectric critical modes is suppressed, i.e., as the ferroelectric quantum critical point is approached in a way reminiscent to behaviour observed in magnetic counterparts. However, in contrast to the latter, the coupling of the carriers to the critical modes in ferroelectrics is predicted to be small. We present a quantitative model involving the dynamical screening of the Coulomb interaction and show that an enhancement of Tc near to a ferroelectric quantum critical point can arise due to the virtual exchange of longitudinal hybrid-polar-modes, even in the absence of a strong coupling to the transverse critical modes.

Quality assurance of surgery in the randomized ST03 trial of perioperative chemotherapy in carcinoma of the stomach and gastro-oesophageal junction.

BACKGROUND: The UK Medical Research Council ST03 trial compared perioperative epirubicin, cisplatin and capecitabine (ECX) chemotherapy with or without bevacizumab (B) in gastric and oesophagogastric junctional cancer. No difference in survival was noted between the arms of the trial. The present study reviewed the standards and performance of surgery in the context of the protocol-specified surgical criteria. METHODS: Surgical and pathological clinical report forms were reviewed to determine adherence to the surgical protocols, perioperative morbidity and mortality, and final histopathological stage for all patients treated in the study. RESULTS: Of 1063 patients randomized, 895 (84·2 per cent) underwent resection; surgical details were available for 880 (98·3 per cent). Postoperative assessment data were available for 873 patients; complications occurred in 458 (52·5 per cent) overall, of whom 71 (8·1 per cent) developed complications deemed to be life-threatening by the responsible clinician. The most common complications were respiratory (211 patients, 24·2 per cent). The anastomotic leak rate was 118 of 873 (13·5 per cent) overall; among those who underwent oesophagogastrectomy, the rate was higher in the group receiving ECX-B (23·6 per cent versus 9·9 per cent in the ECX group). Pathological assessment data were available for 845 patients. At least 15 nodes were removed in 82·5 per cent of resections and the median lymph node harvest was 24 (i.q.r. 17-34). Twenty-five or more nodes were removed in 49·0 per cent of patients. Histopathologically, the R1 rate was 24·9 per cent (208 of 834 patients). An R1 resection was more common for proximal tumours. CONCLUSION: In the ST03 trial, the performance of surgery met the protocol-stipulated criteria. Registration number: NCT00450203 ( http://www.clinicaltrials.gov).

Synergistic activity and heterogeneous acquired resistance of combined MDM2 and MEK inhibition in KRAS mutant cancers.

There are currently no effective targeted therapies for KRAS mutant cancers. Therapeutic strategies that combine MEK inhibitors with agents that target apoptotic pathways may be a promising therapeutic approach. We investigated combining MEK and MDM2 inhibitors as a potential treatment strategy for KRAS mutant non-small cell lung cancers (NSCLC) and colorectal carcinomas that harbor wild-type TP53. The combination of pimasertib (MEK inhibitor) and SAR405838 (MDM2 inhibitor) was synergistic and induced the expression of PUMA and BIM, led to apoptosis and growth inhibition in vitro, and tumor regression in vivo. Acquired resistance to the combination commonly resulted from the acquisition of TP53 mutations, conferring complete resistance to MDM2 inhibition. In contrast, resistant clones exhibited marked variability in sensitivity to MEK inhibition, which significantly impacted sensitivity to subsequent treatment with alternative MEK inhibitor-based combination therapies. These results highlight both the potential promise and limitations of combining MEK and MDM2 inhibitors for treatment of KRAS mutant NSCLC and colorectal cancers.

Prospects and applications near ferroelectric quantum phase transitions: a key issues review.

The emergence of complex and fascinating states of quantum matter in the neighborhood of zero temperature phase transitions suggests that such quantum phenomena should be studied in a variety of settings. Advanced technologies of the future may be fabricated from materials where the cooperative behavior of charge, spin and current can be manipulated at cryogenic temperatures. The progagating lattice dynamics of displacive ferroelectrics make them appealing for the study of quantum critical phenomena that is characterized by both space- and time-dependent quantities. In this key issues article we aim to provide a self-contained overview of ferroelectrics near quantum phase transitions. Unlike most magnetic cases, the ferroelectric quantum critical point can be tuned experimentally to reside at, above or below its upper critical dimension; this feature allows for detailed interplay between experiment and theory using both scaling and self-consistent field models. Empirically the sensitivity of the ferroelectric T c's to external and to chemical pressure gives practical access to a broad range of temperature behavior over several hundreds of Kelvin. Additional degrees of freedom like charge and spin can be added and characterized systematically. Satellite memories, electrocaloric cooling and low-loss phased-array radar are among possible applications of low-temperature ferroelectrics. We end with open questions for future research that include textured polarization states and unusual forms of superconductivity that remain to be understood theoretically.

Co-enrolment of Participants into Multiple Cancer Trials: Benefits and Challenges.

Opportunities to enter patients into more than one clinical trial are not routinely considered in cancer research and experiences with co-enrolment are rarely reported. Potential benefits of allowing appropriate co-enrolment have been identified in other settings but there is a lack of evidence base or guidance to inform these decisions in oncology. Here, we discuss the benefits and challenges associated with co-enrolment based on experiences in the Add-Aspirin trial - a large, multicentre trial recruiting across a number of tumour types, where opportunities to co-enrol patients have been proactively explored and managed. The potential benefits of co-enrolment include: improving recruitment feasibility; increased opportunities for patients to participate in trials; and collection of robust data on combinations of interventions, which will ensure the ongoing relevance of individual trials and provide more cohesive evidence to guide the management of future patients. There are a number of perceived barriers to co-enrolment in terms of scientific, safety and ethical issues, which warrant consideration on a trial-by-trial basis. In many cases, any potential effect on the results of the trials will be negligible - limited by a number of factors, including the overlap in trial cohorts. Participant representatives stress the importance of autonomy to decide about trial enrolment, providing a compelling argument for offering co-enrolment where there are multiple trials that are relevant to a patient and no concerns regarding safety or the integrity of the trials. A number of measures are proposed for managing and monitoring co-enrolment. Ensuring acceptability to (potential) participants is paramount. Opportunities to enter patients into more than one cancer trial should be considered more routinely. Where planned and managed appropriately, co-enrolment can offer a number of benefits in terms of both scientific value and efficiency of study conduct, and will increase the opportunities for patients to participate in, and benefit from, clinical research.

A multicenter trial of myeloablative clofarabine and busulfan conditioning for relapsed or primary induction failure AML not in remission at the time of allogeneic hematopoietic stem cell transplantation.

Allogeneic hematopoietic cell transplantation (HCT) may produce long-term survival in AML after relapse or primary induction failure (PIF). However, outcomes of HCT performed for AML not in remission are historically poor given high relapse rates and transplant-related mortality. Preliminary studies suggest conditioning with clofarabine and myeloablative busulfan (CloBu4) may exert significant anti-leukemic effects without excessive toxicity in refractory hematologic malignancies. A prospective multicenter phase II trial was conducted to determine the efficacy of CloBu4 for patients proceeding directly to HCT with AML not in remission. Seventy-one patients (median age: 56 years) received CloBu4. At day 30 after HCT, 90% achieved morphologic remission. The incidence of non-relapse mortality and relapse at 2 years was 25% and 55%, respectively. The 2-year overall survival (OS) and event-free survival (EFS) were 26% and 20%, respectively. Patients entering HCT in PIF had significantly greater EFS than those in relapse (34% vs 8%; P<0.01). Multivariate analysis comparing CloBu4 with a contemporaneous cohort (Center for International Blood and Marrow Transplantation Research) of AML not in remission receiving other myeloablative conditioning (n=105) demonstrated similar OS (HR: 1.33, 95% confidence interval: 0.92-1.92; P=0.12). HCT with myeloablative CloBu4 is associated with high early response rates and may produce durable remissions in select patients with AML not in remission.

Uniaxial ferroelectric quantum criticality in multiferroic hexaferrites BaFe12O19 and SrFe12O19.

BaFe12O19 is a popular M-type hexaferrite with a Néel temperature of 720 K and is of enormous commercial value ($3 billion/year). It is an incipient ferroelectric with an expected ferroelectric phase transition extrapolated to lie at 6 K but suppressed due to quantum fluctuations. The theory of quantum criticality for such uniaxial ferroelectrics predicts that the temperature dependence of the electric susceptibility χ diverges as 1/T(3), in contrast to the 1/T(2) dependence found in pseudo-cubic materials such as SrTiO3 or KTaO3. In this paper we present evidence of the susceptibility varying as 1/T(3), i.e. with a critical exponent γ = 3. In general γ = (d + z - 2)/z, where the dynamical exponent for a ferroelectric z = 1 and the dimension is increased by 1 from deff = 3 + z to deff = 4 + z due to the effect of long-range dipole interactions in uniaxial as opposed to multiaxial ferroelectrics. The electric susceptibility of the incipient ferroelectric SrFe12O19, which is slightly further from the quantum phase transition is also found to vary as 1/T(3).

Quantum criticality in a uniaxial organic ferroelectric.

Tris-sarcosine calcium chloride (TSCC) is a highly uniaxial ferroelectric with a Curie temperature of approximately 130 K. By suppressing ferroelectricity with bromine substitution on the chlorine sites, pure single crystals were tuned through a ferroelectric quantum phase transition. The resulting quantum critical regime was investigated in detail and was found to persist up to temperatures of at least 30-40 K. The nature of long-range dipole interactions in uniaxial materials, which lead to non-analytical terms in the free-energy expansion in the polarization, predict a dielectric susceptibility varying as 1/T(3)close to the quantum critical point. Rather than this, we find that the dielectric susceptibility varies as 1/T(2) as expected and observed in better known multi-axial systems. We explain this result by identifying the ultra-weak nature of the dipole moments in the TSCC family of crystals. Interestingly, we observe a shallow minimum in the inverse dielectric function at low temperatures close to the quantum critical point in paraelectric samples that may be attributed to the coupling of quantum polarization and strain fields. Finally, we present results of the heat capacity and electro-caloric effect and explain how the time dependence of the polarization in ferroelectrics and paraelectrics should be considered when making quantitative estimates of temperature changes induced by applied electric fields.

Impact of adolescent ethanol exposure and adult amphetamine self-administration on evoked striatal dopamine release in male rats.

RATIONALE: Adolescent binge drinking is common and associated with increased risk of substance use disorders. Transition from recreational to habitual ethanol consumption involves alterations in dorsal striatal function, but the long-term impact of adolescent ethanol exposure upon this region remains unclear. OBJECTIVES: This study aimed to characterise and describe relationships between adolescent ethanol exposure, amphetamine self-administration and adult dopamine dynamics in dorsal striatum, including response to amphetamine challenge, in male Wistar rats. METHODS: Ethanol (2 g/kg) or water was administered intragastrically in an episodic binge-like regimen (three continuous days/week) between 4 and 9 weeks of age (i.e. post-natal days 28-59). In adulthood, animals were divided into two groups. In the first, dorsal striatal potassium-evoked dopamine release was examined via chronoamperometry, in the basal state and after a single amphetamine challenge (2 mg/kg, i.v.). In the second, amphetamine self-administration behaviour was studied (i.e. fixed and progressive ratio) before chronoamperometric analysis was conducted as described above. RESULTS: Adolescent ethanol exposure suppressed locally evoked dopamine response after amphetamine challenge in adulthood, whereas in the basal state, no differences in dopamine dynamics were detected. Ethanol-exposed animals showed no differences in adult amphetamine self-administration behaviour but an abolished effect on dopamine removal in response to a single amphetamine challenge after self-administration. CONCLUSION: Amphetamine challenges in adult rats revealed differences in in vivo dopamine function after adolescent ethanol exposure. The attenuated drug response in ethanol-exposed animals may affect habit formation and contribute to increased risk for substance use disorders as a consequence of adolescent ethanol.

Some current problems in perovskite nano-ferroelectrics and multiferroics: kinetically-limited systems of finite lateral size.

We describe some unsolved problems of current interest; these involve quantum critical points in ferroelectrics and problems which are not amenable to the usual density functional theory, nor to classical Landau free energy approaches (they are kinetically limited), nor even to the Landau-Kittel relationship for domain size (they do not satisfy the assumption of infinite lateral diameter) because they are dominated by finite aperiodic boundary conditions.

Heavy-fermion quantum criticality and destruction of the Kondo effect in a nickel oxypnictide.

A quantum critical point arises at a continuous transformation between distinct phases of matter at zero temperature. Studies in antiferromagnetic heavy-fermion materials have revealed that quantum criticality has several classes, with an unconventional type that involves a critical destruction of the Kondo entanglement. To understand such varieties, it is important to extend the materials basis beyond the usual setting of intermetallic compounds. Here we show that a nickel oxypnictide, CeNiAsO, exhibits a heavy-fermion antiferromagnetic quantum critical point as a function of either pressure or P/As substitution. At the quantum critical point, non-Fermi-liquid behaviour appears, which is accompanied by a divergent effective carrier mass. Across the quantum critical point, the low-temperature Hall coefficient undergoes a rapid sign change, suggesting a sudden jump of the Fermi surface and a destruction of the Kondo effect. Our results imply that the enormous materials basis for the oxypnictides, which has been so crucial in the search for high-temperature superconductivity, will also play a vital role in the effort to establish the universality classes of quantum criticality in strongly correlated electron systems.

Enhancement of the magnetocaloric effect driven by changes in the crystal structure of Al-doped GGG, Gd3Ga5-xAlxO12 (0 ≤x ≤5).

The Gd3Ga5-xAlxO12 (0 ≤ x ≤ 5) solid solution has been prepared using ceramic synthesis routes and the structural and magnetic properties were investigated using x-ray diffraction, magnetic susceptibility, χ, and isothermal magnetisation, M(H), measurements. Our results indicate a contraction of the unit cell and more significant antiferromagnetic interactions as x increases. Despite the decrease in the magnetic polarisation on the application of a field and the corresponding decrease in the change in the magnetic entropy, ΔS, we find that Gd3Al5O12 has a significantly higher observed (17%) and theoretical (14%) ΔS per unit mass than Gd3Ga5O12. The theoretical increase in ΔS per unit volume (7%) is offset by the increased antiferromagnetic interactions in Gd3Al5O12. The differences in ΔS are driven by a decrease in both the mass and the density as Al ions replace Ga ions. These results highlight the importance of changes to the crystal structure when considering materials for solid state magnetic cooling.

Presentation and management of gastrointestinal stromal tumours.

Gastrointestinal stromal tumour (GIST) is the most common mesenchymal tumour of the gastrointestinal tract. The aim of this study was to present the experience of a single centre. A prospective GIST database from 1997 to 2011 in a tertiary referral centre wa reviewed. 78 patients (36 male/42 female) with a median age of 66 (range 10-93) were diagnosed with GIST during this period. Surgery was the primary treatment for 70 patients (90%); 19 (24%) resections were laparoscopic. Nineteen patients (24%) received Imatinib therapy. At a median follow up of 3 years, 10 patients (15%) had recurrence. Five-year survival was 89%. Surgery remains the mainstay of treatment. Minimally invasive approaches may be carried out with high cure rates. This study highlights the changing presentation and treatment approach, as well as the excellent outcomes achievable for GIST tumours.

Clinical laboratory markers of inflammation as determinants of chronic graft-versus-host disease activity and NIH global severity.

Chronic graft-versus-host disease (cGVHD) remains a major cause of non-relapse morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Currently there are no accepted measures of cGVHD activity to aid in clinical management and disease staging. We analyzed clinical markers of inflammation in the sera of patients with established cGVHD and correlated those with definitions of disease activity. In all, 189 adults with cGVHD (33% moderate and 66% severe according to National Institutes of Health (NIH) global scoring) were consecutively enrolled onto a cross-sectional prospective cGVHD natural history study. At the time of evaluation, 80% were receiving systemic immunosuppression and failed a median of four prior systemic therapies (PST) for their cGVHD. Lower albumin (P<0.0001), higher C-reactive protein (P = 0.043), higher platelets (P = 0.030) and higher number of PST (P<0.0001) were associated with active disease defined as clinician's intention to intensify or alter systemic therapy due to the lack of response. Higher platelet count (P = 0.021) and higher number of PST (P<0.0001) were associated with more severe diseased defined by NIH global score. This study identified common laboratory indicators of inflammation that can serve as markers of cGVHD activity and severity.

Stridor secondary to a bronchogenic cyst in a neonate.

We present the case of a female neonate with expiratory stridor that was caused by a bronchogenic cyst that led to tracheobronchomalacia. Rigid endoscopy revealed that a severe anterior compression of the tracheobronchial tree had caused tracheomalacia and right bronchomalacia. Computed tomography of the chest with intravenous contrast demonstrated the presence of a mediastinal mass anterior to the trachea and bronchus. Following a complete excision via a median sternotomy, histopathologic examination identified the mass as a bronchogenic cyst with respiratory epithelial lining and cartilage elements. The patient experienced a complete resolution of her respiratory symptoms postoperatively.

Red blood cell-incompatible allogeneic hematopoietic progenitor cell transplantation.

Transplantation of hematopoietic progenitor cells from red cell-incompatible donors occurs in 30-50% of patients. Immediate and delayed hemolytic transfusion reactions are expected complications of red cell-disparate transplantation and both ABO and other red cell systems such as Kidd and rhesus can be involved. The immunohematological consequences of red cell-incompatible transplantation include delayed red blood cell recovery, pure red cell aplasia and delayed hemolysis from viable lymphocytes carried in the graft ('passenger lymphocytes'). The risks of these reactions, which may be abrupt in onset and fatal, are ameliorated by graft processing and proper blood component support. Red blood cell antigens are expressed on endothelial and epithelial tissues in the body and could serve to increase the risk of GvHD. Mouse models indicate that blood cell antigens may function as minor histocompatibility antigens affecting engraftment. Similar observations have been found in early studies of human transplantation for transfused recipients, although current conditioning and immunosuppressive regimens appear to overcome this affect. No deleterious effects from the use of red cell-incompatible hematopoietic grafts on transplant outcomes, such as granulocyte and platelet engraftments, the incidences of acute or chronic GvHD, relapse risk or OS, have been consistently demonstrated. Most studies, however, include limited number of patients, varying diagnoses and differing treatment regimens, complicating the detection of an effect of ABO-incompatible transplantation. Classification of patients by ABO phenotype ignoring the allelic differences of these antigens also may obscure the effect of red cell-incompatible transplantation on transplant outcomes.

Complementary medicine use in patients with head and neck cancer in Ireland.

The objectives of the study were: first, to determine the prevalence of traditional medicine (TM) and complementary and alternative medicine (CAM) use in head and neck cancer patients in Ireland; second, to educate ourselves on the plethora of CAM/TM options available to patients outside the dominion of conventional medicine. The study design consisted of a cross-sectional survey carried out in three head and neck cancer centres. Self-administered questionnaires were distributed to 110 head and neck cancer patients attending the three cancer centres and data were collected for statistical analysis. A total of 106 patients completed the questionnaire; 21.7% of the participants used CAM/TM since their diagnosis with head and neck cancer. CAM/TM usage was higher in female (34.3%) than in male patients (16.2%). CAM/TM use was more common in the 41-50-year age group, in patients with higher educational levels and those holding strong religious beliefs, and also in married than single patients. The most common types of CAM/TM used were spiritual and laying on of hands. The most common reasons reported for using CAM/TM were to counteract the ill effects of treatment and increase the body's ability to fight cancer. Sources of information on CAM/TM were friends (65%), family (48%) and media (21%). This survey reveals a high prevalence of CAM/TM use in head and neck cancer patients, hence emphasising the need for otolaryngologists to educate themselves on the various therapies available to be able to provide informative advice. There is an urgent need for evidence-based investigation of various CAM/TM therapies currently offered to patients.

The impact of adenotonsillectomy on asthma in children.

OBJECTIVE: To investigate the impact of adenotonsillectomy on asthma in the pediatric population. STUDY DESIGN: Retrospective chart review. METHODS: All children who underwent adenotonsillectomy at our institution from 2002-2007 were identified from a medical records database. Of the 560 charts reviewed, 93 of the patients had the diagnosis of asthma from a pediatric pulmonologist. Outcome measures of asthma control were analyzed one year preoperatively and one year postoperatively and included: hospital visits, systemic steroid use, asthma medication use, and asthma control test scores. RESULTS: There was a statistically significant improvement in postoperative asthma severity in all measures including mean hospital visits, systemic steroid administration, asthma medication use, and childhood asthma control test scores (p<0.01). CONCLUSION: This study suggests that adenotonsillectomy, which provides improvement in the upper airway of children, may in turn lead to improvement of the lower airways of children, especially those with bronchial asthma.