A census of general surgery consultants in England and Wales: implications for the current and future surgical workforce.

INTRODUCTION: This study aimed to describe the composition of the current general surgical consultant body in England and Wales and quantify levels of inequality within it as well as describe future workforce challenges. METHODS: This is an observational study of all general surgical departments in England and Wales. Consultant general surgeons were identified and data regarding their gender, country of undergraduate medical education, subspecialty and private practice were recorded. RESULTS: Of the 2,682 consultant general surgeons in England and Wales identified for this study, just 17% are women, with gender inequality most marked in university teaching hospitals and among certain subspecialties. Almost 40% of consultants did not obtain their primary undergraduate degree in the United Kingdom and there are considerably fewer surgeons who studied abroad in university teaching hospitals. Over 40% of current general surgical consultants have been qualified for more than three decades and there is no equivalent sized group of younger consultants. CONCLUSIONS: There remains considerable gender and racial inequality in the consultant general surgical workforce, with pockets of a lack of diversity within university or teaching hospital surgical departments and some subspecialties. The proportion of surgeons in their fourth decade of clinical practice represents the largest group of current practising consultants, which points towards an impending workforce crisis should senior clinicians seek to reduce activity or consider taking early retirement.

Acute Toxicity of Hypofractionated and Conventionally Fractionated (Chemo)Radiotherapy Regimens for Bladder Cancer: An Exploratory Analysis from the RAIDER Trial.

AIMS: Adding concurrent (chemo)therapy to radiotherapy improves outcomes for muscle-invasive bladder cancer patients. A recent meta-analysis showed superior invasive locoregional disease control for a hypofractionated 55 Gy in 20 fractions schedule compared with 64 Gy in 32 fractions. In the RAIDER clinical trial, patients undergoing 20 or 32 fractions of radical radiotherapy were randomised (1:1:2) to standard radiotherapy or to standard-dose or escalated-dose adaptive radiotherapy. Neoadjuvant chemotherapy and concomitant therapy were permitted. We report exploratory analyses of acute toxicity by concomitant therapy-fractionation schedule combination. MATERIALS AND METHODS: Participants had unifocal bladder urothelial carcinoma staged T2-T4a N0 M0. Acute toxicity was assessed (Common Terminology Criteria for Adverse Events) weekly during radiotherapy and at 10 weeks after the start of treatment. Within each fractionation cohort, non-randomised comparisons of the proportion of patients reporting treatment emergent grade 2 or worse genitourinary, gastrointestinal or other adverse events at any point in the acute period were carried out using Fisher's exact tests. RESULTS: Between September 2015 and April 2020, 345 (163 receiving 20 fractions; 182 receiving 32 fractions) patients were recruited from 46 centres. The median age was 73 years; 49% received neoadjuvant chemotherapy; 71% received concomitant therapy, with 5-fluorouracil/mitomycin C most commonly used: 44/114 (39%) receiving 20 fractions; 94/130 (72%) receiving 32 fractions. The acute grade 2+ gastrointestinal toxicity rate was higher in those receiving concomitant therapy compared with radiotherapy alone in the 20-fraction cohort [54/111 (49%) versus 7/49 (14%), P < 0.001] but not in the 32-fraction cohort (P = 0.355). Grade 2+ gastrointestinal toxicity was highest for gemcitabine, with evidence of significant differences across therapies in the 32-fraction cohort (P = 0.006), with a similar pattern but no significant differences in the 20-fraction cohort (P = 0.099). There was no evidence of differences in grade 2+ genitourinary toxicity between concomitant therapies in either the 20- or 32-fraction cohorts. CONCLUSION: Grade 2+ acute adverse events are common. The toxicity profile varied by type of concomitant therapy; the gastrointestinal toxicity rate seemed to be higher in patients receiving gemcitabine.

Mandrax use, sexual risk, and opportunities for pre-exposure prophylaxis among out-of-school adolescent girls and young women in Cape Town, South Africa.

BACKGROUND: In South Africa (SA), adolescent girls and young women (AGYW) aged 15 - 24 years account for nearly 25% of all new HIV infections in the country. The intersection of substance use and sexual risk continues to drive the HIV epidemic among AGYW. For example, methaqualone, also known as Mandrax, has sedative effects that may affect women's ability to negotiate condom use during sex, refuse sex without a condom, or consent to sex, thereby increasing their risk for HIV. Consequently, it is critical to understand how Mandrax use affects HIV risk among AGYW and to assess awareness of and willingness to use biomedical HIV prevention methods, such as pre-exposure prophylaxis (PrEP), among AGYW who use Mandrax. OBJECTIVES: To examine the role of Mandrax use in sexual behaviours and investigate the extent to which AGYW who use Mandrax are aware of and willing to initiate PrEP. METHODS: Data for this report were derived from baseline and 6-month follow-up data provided by 500 AGYW participating in a cluster-randomised trial assessing the efficacy of a young woman-focused intervention to reduce substance use and HIV risk. AGYW who self-identified as black African or coloured, reported using substances, reported condomless sex in the past 3 months, and had discontinued school early were recruited from 24 community clusters across Cape Town, SA. Following consent/assent, participants provided biological specimens to test for recent drug use (including Mandrax) and completed the self-report questionnaire. RESULTS: Logistic regression analysis revealed that the AGYW who had a positive test result for Mandrax use were less likely to use a condom with their main partner (p=0.01), and almost three times more likely to use alcohol and/or other drugs before or during their last act of sexual intercourse (p<0.001), compared with the AGYW who had a negative Mandrax test result. Mandrax use was not significantly related to PrEP awareness (p>0.10) or willingness to use PrEP (p>0.10), but 70% of AGYW who used Mandrax were willing to initiate PrEP. CONCLUSION: The study findings highlight how Mandrax use may contribute to HIV risk among SA AGYW. Key decision-makers should consider incorporating substance use prevention efforts into existing HIV reduction programmes and equip youth-friendly clinics with the resources to identify AGYW who use Mandrax and offer them PrEP.

Main COVID-19 information sources in a culturally and linguistically diverse community in Sydney, Australia: A cross-sectional survey.

OBJECTIVE: Describe COVID-19 information-seeking experiences for culturally and linguistically diverse groups in Sydney, Australia. METHODS: Cross-sectional survey, translated into 11 languages; participants recruited from March 21 to July 9, 2021. Regression models identified factors associated with difficulty finding easy-to-understand COVID-19 information. RESULTS: Across 708 participants (88% born overseas, 31% poor English proficiency), difficulty finding easy-to-understand COVID-19 information was rated 4.13 for English (95%CI: 3.85-4.41) and 4.36 for non-English language materials (95%CI: 4.07-4.66) (1 easy to 10 hard). Participants who were older (p < 0.001), had inadequate health literacy (p < 0.001), or poor English proficiency (p < 0.001) found it harder to find easy-to-understand English-language COVID-19 information. Those who had greater difficulty finding easy-to-understand non-English COVID-19 information were younger (p = 0.004), had poor English proficiency (p < 0.001), were university-educated (p = 0.05), and had spent longer living in Australia (p = 0.001). They were more likely to rely on friends and family for COVID-19 information (p = 0.02). There was significant variation in information-seeking experiences across language groups (p's < 0.001). CONCLUSIONS: Easy-to-understand and accessible COVID-19 information is needed to meet the needs of people in culturally and linguistically diverse communities. PRACTICE IMPLICATIONS: COVID-19 communication efforts must involve working alongside these communities to leverage existing communication channels and tailor messages.

Substance use and depressive and anxiety symptoms among out-of-school adolescent girls and young women in Cape Town, South Africa.

BACKGROUND: There is a high prevalence of substance use among youth in South Africa (SA), and adolescent girls and young women (AGYW) experience high rates of depression and anxiety. Substance use behaviours and mental health are associated with other public health problems among AGYW such as HIV and unintended pregnancy. Therefore, understanding the relationship between substance use and mental health is imperative to improve AGYW's health. OBJECTIVES: To examine the association between heavy drinking, marijuana, methamphetamine and methaqualone (Mandrax) use and depressive and anxiety symptoms among AGYW aged 16 - 19 years who have dropped out of school in Cape Town, SA. METHODS: Data for this report come from the baseline data of 500 participants of an ongoing cluster-randomised trial assessing the efficacy of a young woman-focused intervention to reduce substance use and HIV risk. After AGYW consented/assented to participate, they completed a urine drug screen and a baseline questionnaire. RESULTS: Logistic and negative binomial regressions, controlling for clustering at the neighbourhood level, revealed that frequency of depressive symptoms was significantly and positively related to a positive drug screen for Mandrax (ß=0.07; p=0.03). All other associations between the frequency of depressive symptoms and substance use were not statistically significant (ps>0.05). The associations between frequency of anxiety symptoms and substance use were not statistically significant (ps>0.05). CONCLUSIONS: Our findings highlight the need to address substance use, especially Mandrax use and its associated risk, and depression in an integrated, youth-friendly setting.

Academic success plans in advanced pharmacy practice experiences to promote self-awareness and improve performance.

INTRODUCTION: Pharmacy schools should encourage self-awareness, provide exposure to the continuous professional development cycle, and intervene early when students exhibit performance deficiencies. Academic success plans (ASPs) have been shown in other disciplines to be successful intervention tools which encourage student reflection and self-awareness. This study evaluates the impact of ASPs used during the advanced pharmacy practice experience (APPE) curriculum at two schools. METHODS: ASPs were assigned to students who had either a "needs development" or lower documented for the same learning outcome during more than one APPE, for poor overall performance during an APPE, or for documented professionalism issues. Average scores were calculated by assigning point values to each learning outcome assessment score (exceeds expectations = 1; competent = 0; needs development, needs significant development, remediation required = -1). RESULTS: During AY2014-2015 and AY2015-2016, 104 ASPs were assigned to 75 students (13.5% of students). The majority (89.6%) were assigned due to repeated deficiencies in the same learning outcome(s), with the most frequent being "Develop, Implement, and Monitor Drug Therapy Plans." After completion of an ASP, average scores significantly improved (p < 0.05) in 9 out of 12 learning outcomes among all students who completed an ASP. Thirteen students completed 15 ASPs for professionalism reasons, most commonly punctuality. CONCLUSIONS: Prior to 2015, Experiential Education Office interventions were primarily grades-based, not necessarily based on achievement of specific learning outcomes. ASPs were successfully used to allow students to practice self-awareness skills, to engage in the CPD process, and to improve APPE performance.

A comparison of baseline professional attitudes and behaviors among student pharmacists to inform a co-curricular professional engagement program.

BACKGROUND: Professionalism in pharmacy students is an area of great focus with the release of Accreditation Council for Pharmacy Education (ACPE) Standards 2016. This study assessed and compared student pharmacists' professionalism at one college of pharmacy to inform the implementation of a co-curricular professional engagement program. METHODS: Two validated instruments (Behavioral Professionalism Assessment Instrument [BPAI] and Pharmacy Professionalism Instrument [PPI]) were administered to assess baseline professionalism. Kruskall-Wallis tests compared responses among the three pharmacy classes. Analysis was conducted using SPSS. This research was approved by the Mercer University's Institutional Review Board. RESULTS: A total of 362 students completed the survey (75% response rate), of which 131 were first-year, 139 were second-year, and 92 were third-year students. There were significant differences in agreement among these classes of students as to whether a program focused on professional engagement was important and helpful (p < 0.001). Seven BPAI statements and five PPI statements demonstrated significant differences in the level of agreement among the professional years. These behaviors include: completing assignments independently and without supervision (p = 0.004); commitment to helping others (p = 0.004); reporting a medication error (p = 0.005); using time efficiently (p = 0.02); and being respectful (p = 0.04). DISCUSSION: At baseline, 12 statements were significantly different in the level of agreement among the three pharmacy classes. Differences may be explained by perceived professionalism (in first-year students) versus actual professional behaviors (second- and third-year students), as well as breadth and depth of experience. A co-curricular professional engagement program could increase student awareness of professionalism and professional behaviors and be tailored to meet assessed student needs.

SGLT2 inhibition and glucagon secretion in humans.

With the increasing prevalence of type 2 diabetes (T2D), therapies aimed at delineating diabetes pathophysiology and understanding their mechanisms of action are of critical importance. As such, growing interest in the clinical pharmacology of sodium-glucose cotransporter 2 (SGLT2) and its inhibition by gliflozins in the treatment of T2D is becoming increasingly evident. SGLT2 inhibition results in urinary glucose excretion, thereby reducing blood glucose levels. The importance of this homoeostasis mechanism is evident from several clinical trials demonstrating that patients taking this class of compounds have reductions in glycaemia, body weight and blood pressure compared with other antidiabetic agents. Yet, while such outcomes are very encouraging, some studies have reported elevated plasma glucagon levels and endogenous glucose production (EGP), two traits that are already prevalent in T2D. However, these findings were later explained by the specific expression of SGLT2 by pancreatic alpha cells, where glucagon secretion is directly regulated. Although conflicting data are now emerging on SGLT2 regulation of glucagon secretion, as SGLT2 is not expressed in the intestines, circulating glucagon concentrations are most likely of pancreatic origin. Thus, the present review considers the mechanism of action of SGLT2 inhibitors in the regulation of glucagon secretion, and the discrepancies in data from mice compared with people. The pragmatic use of human islets to accurately decipher SGLT2 inhibition in the regulation of glucagon secretion is also discussed.

Purity of islet preparations and 5-year metabolic outcome of allogenic islet transplantation.

In allogenic islet transplantation (IT), high purity of islet preparations and low contamination by nonislet cells are generally favored. The aim of the present study was to analyze the relation between the purity of transplanted preparations and graft function during 5 years post-IT. Twenty-four patients with type 1 diabetes, followed for 5 years after IT, were enrolled. Metabolic parameters and daily insulin requirements were compared between patients who received islet preparations with a mean purity <50% (LOW purity) or ≥50% (HIGH purity). We also analyzed blood levels of carbohydrate antigen 19-9 (CA 19-9)-a biomarker of pancreatic ductal cells-and glucagon, before and after IT. At 5 years, mean hemoglobin A1c (HbA1c levels) (P = .01) and daily insulin requirements (P = .03) were lower in the LOW purity group. Insulin independence was more frequent in the LOW purity group (P < .05). CA19-9 and glucagon levels increased post-IT (P < .0001) and were inversely correlated with the degree of purity. Overall, our results suggest that nonislet cells have a beneficial effect on long-term islet graft function, possibly through ductal-to-endocrine cell differentiation. ClinicalTrial.gov NCT00446264 and NCT01123187.

A compliance assessment of midpoint formative assessments completed by APPE preceptors.

INTRODUCTION: Experiential pharmacy preceptors should provide formative and summative feedback during a learning experience. Preceptors are required to provide colleges and schools of pharmacy with assessments or evaluations of students' performance. Students and experiential programs value on-time completion of midpoint evaluations by preceptors. The objective of this study was to determine the number of on-time electronically documented formative midpoint evaluations completed by preceptors during advanced pharmacy practice experiences (APPEs). METHODS: Compliance rates of on-time electronically documented formative midpoint evaluations were reviewed by the Office of Experiential Education of a five-member consortium during the two-year study period prior to the adoption of Standards 2016. Pearson chi-square test and generalized linear models were used to determine if statistically significant differences were present. RESULTS: Average midpoint compliance rates for the two-year research period were 40.7% and 41% respectively. No statistical significance was noted comparing compliance rates for year one versus year two. However, statistical significance was present when comparing compliance rates between schools during year two. Feedback from students and preceptors pointed to the need for brief formal midpoint evaluations that require minimal time to complete, user friendly experiential management software, and methods for documenting verbal feedback through student self-reflection. CONCLUSIONS: Additional education and training to both affiliate and faculty preceptors on the importance of written formative feedback at midpoint is critical to remaining in compliance with Standards 2016.

Expanding Dress Code Requirements in the Doctor of Pharmacy Program.

Although the use of a professional dress code is standard practice across colleges and schools of pharmacy during introductory and advanced pharmacy practice experiences, requiring professional attire is not applied consistently during the didactic portion of students' education. There are arguments for and against the adoption of a professional dress code throughout the entire doctor of pharmacy program, including the classroom setting. Given uncertainty regarding the potential benefits and challenges that may arise from adopting a professional dress code in the didactic portion of a student pharmacist's education, it is perhaps not surprising that programs adopt disparate policies regarding its use. This exploration was conducted as part of a series of debates held in conjunction with the American Association of Colleges of Pharmacy's (AACP) Academic Leadership Fellows Program (ALFP) and was presented at the 2015 AACP Interim Meeting on February 7, 2015.

Evaluation of pharmacy resident alertness in an overnight on-call program.

PURPOSE: Results of a study to determine the impact of overnight on-call duty on pharmacy residents' alertness are presented. METHODS: A prospective single-site observational study was conducted to evaluate sleep patterns and alertness levels among pharmacy residents serving 24-hour on-call duty assignments at a large hospital. The study participants (n = 10) wore a wrist actigraph to allow continuous tracking of rest-activity patterns; in addition, study participants completed a validated three-minute psychomotor vigilance test (PVT) during designated time periods around the beginning and the end of each duty shift and several hours after the shift ended. Study participants also documented sleep quality and quantity in a sleep log and self-rated their level of alertness using the Karolinska sleepiness scale (KSS). RESULTS: Assessments were conducted for a total of 31 on-call duty shifts over one month. Paired comparisons of PVT data obtained at the three assessment periods indicated that on-call duty was not associated with significant changes in PVT performance measures (mean response speed and number of attention lapses). On average, on-call residents rated the quality of sleep during duty assignments as 5 on a 10-point Likert scale. CONCLUSION: On-call residents slept for a mean of six hours during overnight duty shifts, with half of the residents reporting sleep interruptions (a mean of 1.73 per shift). PVT results and KSS values indicated no overall decline in resident alertness during the study period.

Control of Förster energy transfer in the vicinity of metallic surfaces and hyperbolic metamaterials.

Optical cavities, plasmonic structures, photonic band crystals and interfaces, as well as, generally speaking, any photonic media with homogeneous or spatially inhomogeneous dielectric permittivity (including metamaterials) have local densities of photonic states, which are different from that in vacuum. These modified density of states environments are known to control both the rate and the angular distribution of spontaneous emission. In the present study, we question whether the proximity to metallic and metamaterial surfaces can affect other physical phenomena of fundamental and practical importance. We show that the same substrates and the same nonlocal dielectric environments that boost spontaneous emission, also inhibit Förster energy transfer between donor and acceptor molecules doped into a thin polymeric film. This finding correlates with the fact that in dielectric media, the rate of spontaneous emission is proportional to the index of refraction n, while the rate of the donor-acceptor energy transfer (in solid solutions with a random distribution of acceptors) is proportional to n(-1.5). This heuristic correspondence suggests that other classical and quantum phenomena, which in regular dielectric media depend on n, can also be controlled with custom-tailored metamaterials, plasmonic structures, and cavities.

Evaluation of models predicting insignificant prostate cancer to select men for active surveillance of prostate cancer.

BACKGROUND: In an era of personalized medicine, individualized risk assessment using easily available tools on the internet and the literature are appealing. However, uninformed use by clinicians and the public raises potential problems. Herein, we assess the performance of published models to predict insignificant prostate cancer (PCa), using a multi-national low-risk population that may be considered for active surveillance (AS) based on contemporary practice. METHODS: Data on men suitable for AS but undergoing upfront radical prostatectomy were pooled from three international academic institutions in Cambridge (UK), Toronto (Canada) and Melbourne (Australia). Four predictive models identified from literature review were assessed for their ability to predict the presence of four definitions of insignificant PCa. Evaluation was performed using area under the curve (AUC) of receiver operating characteristic curves and Brier scores for discrimination, calibration curves and decision curve analysis. RESULTS: A cohort of 460 men meeting the inclusion criteria of all four nomograms was identified. The highest AUCs calculated for any of the four models ranged from 0.618 to 0.664, suggesting weak positive discrimination at best. Models had best discriminative ability for a definition of insignificant disease characterized by organ-confined Gleason score ⩽6 with a total volume ⩽0.5 ml or 1.3 ml. Calibration plots showed moderate range of predictive ability for the Kattan model though this model did not perform well at decision curve analysis. CONCLUSIONS: External assessment of models predicting insignificant PCa showed moderate performance at best. Uninformed interpretation may cause undue anxiety or false reassurance and they should be used with caution.

Improving decision making about clinical trial participation - a randomised controlled trial of a decision aid for women considering participation in the IBIS-II breast cancer prevention trial.

BACKGROUND: Decision aids may improve informed consent in clinical trial recruitment, but have not been evaluated in this context. This study investigated whether decision aids (DAs) can reduce decisional difficulties among women considering participation in the International Breast Cancer Intervention Study-II (IBIS-II) trial. METHODS: The IBIS-II trial investigated breast cancer prevention with anastrazole in two cohorts: women with increased risk (Prevention), and women treated for ductal carcinoma in situ (DCIS). Australia, New Zealand and United Kingdom participants were randomised to receive a DA (DA group) or standard trial consent materials (control group). Questionnaires were completed after deciding about participation in IBIS-II (post decision) and 3 months later (follow-up). RESULTS: Data from 112 Prevention and 34 DCIS participants were analysed post decision (73 DA; 73 control); 95 Prevention and 24 DCIS participants were analysed at follow-up (58 DA; 61 control). There was no effect on the primary outcome of decisional conflict. The DCIS-DA group had higher knowledge post decision, and the Prevention-DA group had lower decisional regret at follow-up. CONCLUSIONS: This was the first study to evaluate a DA in the clinical trial setting. The results suggest DAs can potentially increase knowledge and reduce decisional regret about clinical trial participation.

Investigation of an association between onset of narcolepsy and vaccination with pandemic influenza vaccine, Ireland April 2009-December 2010.

In 2011, the Irish Medicines Board received reports of onset of narcolepsy following vaccination against influenza A(H1N1)pdm09 with Pandemrix. A national steering committee was convened to examine the association between narcolepsy and pandemic vaccination. We conducted a retrospective population-based cohort study. Narcolepsy cases with onset from 1 April 2009 to 31 December 2010 were identified through active case finding. Narcolepsy history was gathered from medical records. Pandemic vaccination status was obtained from vaccination databases. Two independent experts classified cases using the Brighton case definition. Date of onset was defined as date of first healthcare contact for narcolepsy symptoms. Incidence of narcolepsy in vaccinated and non-vaccinated individuals was compared. Of 32 narcolepsy cases identified, 28 occurred in children/adolescents and for 24 first healthcare contact was between April 2009 and December 2010. Narcolepsy incidence was 5.7 (95% confidence interval (CI): 3.4­8.9) per 100,000 children/adolescents vaccinated with Pandemrix and 0.4 (95% CI: 0.1­1.0) per 100,000 unvaccinated children/adolescents (relative risk: 13.9; absolute attributable risk: 5.3 cases per 100,000 vaccinated children/adolescents). This study confirms the crude association between Pandemrix vaccination and narcolepsy as observed in Finland and Sweden. The vaccine is no longer in use in Ireland. Further studies are needed to explore the immunogenetic mechanism of narcolepsy.

Identification of circulating microRNAs in HNF1A-MODY carriers.

AIMS/HYPOTHESIS: HNF1A-MODY is a monogenic form of diabetes caused by mutations in the HNF1A gene. Here we identify, for the first time, HNF1A-MODY-associated microRNAs (miRNAs) that can be detected in the serum of HNF1A-MODY carriers. METHODS: An miRNA array was carried out in rat INS-1 insulinoma cells inducibly expressing the common human Pro291fsinsC-HNF1A frame shift mutation. Differentially expressed miRNAs were validated by quantitative real-time PCR. Expression of miRNAs in the serum of HNF1A-MODY carriers (n = 31), MODY-negative family members (n = 10) and individuals with type 2 diabetes mellitus (n = 17) was quantified by absolute real-time PCR analysis. RESULTS: Inducible expression of Pro291fsinsC-HNF1A in INS-1 cells caused a significant upregulation of three miRNAs (miR-103, miR-224, miR-292-3p). The differential expression of two miRNAs (miR-103 and miR-224) was validated in vitro. Strongly elevated levels of miR-103 and miR-224 could be detected in the serum of HNF1A-MODY carriers compared with MODY-negative family controls. Serum levels of miR-103 distinguished HNF1A-MODY carriers from HbA1c-matched individuals with type 2 diabetes mellitus. CONCLUSIONS/INTERPRETATION: Our study demonstrates that the pathophysiology of HNF1A-MODY is associated with the overexpression of miR-103 and miR-224. Furthermore, our study demonstrates that these miRNAs can be readily detected in the serum of HNF1A-MODY carriers.

Controlling spontaneous emission with metamaterials.

We have observed, in metamaterial with hyperbolic dispersion (an array of silver nanowires in alumina membrane), a sixfold reduction of the emission lifetime of dye deposited onto the metamaterial's surface. This serves as evidence of an anomalously high density of photonic states in hyperbolic metamaterials, demonstrates the feasibility of an earlier-predicted single-photon gun, and paves the road for the use of metamaterials in quantum optics.

Early loss of mammalian target of rapamycin complex 1 (mTORC1) signalling and reduction in cell size during dominant-negative suppression of hepatic nuclear factor 1-alpha (HNF1A) function in INS-1 insulinoma cells.

AIMS/HYPOTHESIS: Mutations in the HNF1A (previously known as TCF1) gene encoding hepatocyte nuclear factor-1alpha (HNF1A) lead to the development of maturity-onset diabetes of the young, type 3 (HNF1A-MODY), characterised by impaired insulin secretion and a reduction in beta cell mass. HNF1A plays an important role in pancreatic beta cell differentiation and survival. The mammalian target of rapamycin (mTOR) is a central growth factor- and nutrient-activated protein kinase controlling cell metabolism, growth and survival. We investigated the role of mTOR inactivation in the decline in beta cell mass in a cellular model of HNF1A-MODY. METHODS: Previously we showed that suppression of HNF1A function via expression of a dominant-negative mutant (DN-HNF1A) decreases insulin gene transcription in insulinoma (INS-1) cells. We investigated the signalling of two distinct mTOR protein complexes, mTORC1 and mTORC2, in response to DN-HNF1A induction. RESULTS: We observed delayed inactivation of mTORC2 48 h after DN-HNF1A induction, evidenced by a reduction in serine 473 phosphorylation of thymoma viral proto-oncogene 1 (AKT1). We also observed an early inactivation of mTORC1 24 h after DN-HNF1A induction, which was detected by decreases in threonine 389 phosphorylation of p70 ribosomal protein S6 kinase (S6K1) and serine 65 phosphorylation of translational inhibitor eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1). Flow cytometry and gene expression analysis demonstrated a pre-apoptotic decrease in INS-1 cell size in response to DN-HNF1A induction, and an increase in the level of the mTORC1-regulated cell-cycle inhibitor, cyclin-dependent kinase inhibitor 1B p27. CONCLUSIONS/INTERPRETATION: Our data suggest that mTOR kinase and signalling through mTORC1 are highly sensitive to suppression of HNF1A function, and may contribute to disturbance of cell-size regulation and cell-cycle progression in HNF1A-MODY.

Influence of doping rate in Er3+:ZnO films on emission characteristics.

High-quality Er(3+):ZnO films were grown by the pulsed-laser deposition technique for 0.5 and 2 wt. % Er doping. Two peaks were observed at approximately 1.54 microm in the photoluminescence spectra of samples with 2 wt. % doping contrary to only one peak in the 0.5 wt. % doped sample. Both peaks were found to be strongly temperature dependent. The microscopic studies clearly illustrate that the appearance of the additional peak is attributed to the environment of Er(3+) ions in the form of ErO(6) clusters, which are optically active centers in the ZnO matrix. These results are very important for designing waveguides for telecommunications.