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Microwave energy was demonstrated to be potentially beneficial for reducing the cost of several steps of the mining process. Significant literature was developed about this topic but few studies are focused on understanding the interaction between microwaves and minerals at a fundamental level in order to elucidate the underlying physical processes that control the observed phenomena. This is ascribed to the complexity of such phenomena, related to chemical and physical transformations, where electrical, thermal and mechanical forces play concurrent roles. In this work a new characterization method for the dielectric properties of mineral samples at microwave frequencies is presented. The method is based upon the scanning microwave microscopy technique that enables measurement of the dielectric constant, loss factor and conductivity with extremely high spatial resolution and accuracy. As opposed to conventional dielectric techniques, the scanning microwave microscope can then access and measure the dielectric properties of micrometric-sized mineral inclusions within a complex structure of natural rock. In this work two micrometric hematite inclusions were characterized at a microwave frequency of 3 GHz. Scanning electron microscopy/energy-dispersive x-ray spectroscopy and confocal micro-Raman spectroscopy were used to determine the structural details and chemical and elemental composition of mineral sample on similar scale. [ABSTRACT FROM AUTHOR]

Global demand for minerals and metals is increasing. It has been established that the impact of mining and mineral processing operations must be reduced to sustainably meet the demands of a low grade future. Successful incorporation of ore sorting in flow sheets has the potential to improve energy efficiency by rejecting non-economic material before grinding. Microwave heating combined with infra-red temperature measurement has been shown to distinguish low and high grade ore fragments from each other. In this work, experimentally validated 2-D finite difference models of a theoretical two phase ore, representing typical fragment textures and grades, are constructed. Microwave heating is applied at economically viable energy inputs and the resultant surface thermal profiles analysed up to 2 min after microwave heating. It is shown that the size and location of grains can dramatically alter surface temperature rise at short thermal measurement delay times and that the range of temperatures increases with increasing fragment grade. For the first time, it is suggested that increasing the delay time between microwave heating and thermal measurement can reduce the variation seen for fragments of the same grade but different textures, improving overall differentiation between high and low grade fragments. [ABSTRACT FROM AUTHOR]

Background: Major surgery is frequently associated with postoperative cognitive dysfunction (POCD) in elderly patients. Type of surgery and hospitalization may be important prognostic factors. The aims of the study were to find the incidence and risk factors for POCD in elderly patients undergoing minor surgery.Methods: We enrolled 372 patients aged greater than 60 years scheduled for minor surgery under general anesthesia. According to local practice, patients were allocated to either in- (199) or out-patient (173) care. Cognitive function was assessed using neuropsychological testing preoperatively and 7 days and 3 months postoperatively. Postoperative cognitive dysfunction was defined using Z-score analysis.Results: At 7 days, the incidence (confidence interval) of POCD in patients undergoing minor surgery was 6.8% (4.3-10.1). At 3 months the incidence of POCD was 6.6% (4.1-10.0). Logistic regression analysis identified the following significant risk factors: age greater than 70 years (odds ratio [OR]: 3.8 [1.7-8.7], P = 0.01) and in- vs. out-patient surgery (OR: 2.8 [1.2-6.3], P = 0.04).Conclusions: Our finding of less cognitive dysfunction in the first postoperative week in elderly patients undergoing minor surgery on an out-patient basis supports a strategy of avoiding hospitalization of older patients when possible. [ABSTRACT FROM AUTHOR]

Background: Postoperative cognitive dysfunction (POCD) is a common complication after cardiac and major non-cardiac surgery with general anaesthesia in the elderly. We hypothesized that the incidence of POCD would be less with regional anaesthesia rather than general.Methods: We included patients aged over 60 years undergoing major non-cardiac surgery. After giving written informed consent, patients were randomly allocated to general or regional anaesthesia. Cognitive function was assessed using four neuropsychological tests undertaken preoperatively and at 7 days and 3 months postoperatively. POCD was defined as a combined Z score >1.96 or a Z score >1.96 in two or more test parameters.Results: At 7 days, POCD was found in 37/188 patients (19.7%, [14.3-26.1%]) after general anaesthesia and in 22/176 (12.5%, [8.0-18.3%]) after regional anaesthesia, P = 0.06. After 3 months, POCD was present in 25/175 patients (14.3%, [9.5-20.4%]) after general anaesthesia vs. 23/165 (13.9%, [9.0-20.2%]) after regional anaesthesia, P = 0.93. The incidence of POCD after 1 week was significantly greater after general anaesthesia when we excluded patients who did not receive the allocated anaesthetic: 33/156 (21.2%[15.0-28.4%]) vs. 20/158 (12.7%[7.9-18.9%]) (P = 0.04). Mortality was significantly greater after general anaesthesia (4/217 vs. 0/211 (P < 0.05)).Conclusion: No significant difference was found in the incidence of cognitive dysfunction 3 months after either general or regional anaesthesia in elderly patients. Thus, there seems to be no causative relationship between general anaesthesia and long-term POCD. Regional anaesthesia may decrease mortality and the incidence of POCD early after surgery. [ABSTRACT FROM AUTHOR]

Background: The Neonatal Eating Outcome Assessment determines feeding performance based on the infant's postmenstrual age (PMA)., Objective: To examine item-level measurement properties of this assessment's rating scale., Methodology: In this retrospective study, Rasch analysis was completed on clinical data from the Neonatal Eating Outcome Assessment for 100 infants (52 preterm and 48 full-term) using Winsteps version 3.93.1. Instead of PMA-based scores, ordered letters converted to numerical scores were analyzed., Results: Analysis demonstrated that Section I (Pre-Feeding Skills) represents a separate construct from Sections II and III (Oral Feeding and End of Feeding, respectively). Sections II and III were adequately unidimensional to complete Rasch analysis. These sections fit the Rasch model overall, but rating scale category underuse was common, which may be attributed to sample characteristics., Implications: This analysis supports using validated ordered letter scoring of Sections II and III to measure oral feeding performance in preterm and full-term newborns., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RP is the author of the Neonatal Eating Outcome Assessment. The tool is available “at cost” to other clinicians with no direct financial benefit to Dr. RP.

Variations in political participation are linked to demographic factors, socioeconomic disparities, and cultural-ethnic diversity. Existing research has primarily explored reduced political involvement among individuals with disabilities, particularly in electoral politics. However, little research has attended the involvement of deaf people specifically. This is of interest because deaf youth are at an intersection of disability, language and cultural identity with their language affiliations and rejection or acceptance of disability evolving through childhood. This study draws from original data collected via an online survey, comprising 163 deaf young respondents aged 16-19 in Great Britain. We compare their levels of political participation with those of general population peers to explore how sociodemographic factors, alongside variations in self-identification as deaf, and meaningful interactions with other deaf people contribute to explain their political engagement. The results challenge conventional wisdom by demonstrating that deaf youth participate more actively in politics than their hearing peers in various forms of political involvement, including collective, contact, and institutional activism. We also recognize differences among deaf youth and propose that social aspects of identity formation, particularly embracing a deaf identity and having deaf friends, can boost certain forms of political engagement. In summary, this study underscores the importance of acknowledging the diversity of deaf youth in terms of affiliation with various forms of deaf identity, rendering their experience different from both disabled and hearing youth. By identifying the factors driving heightened political participation, policymakers and advocates can develop strategies to enhance political engagement among all young people, regardless of their hearing status., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Espinoza et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Women from socioeconomically deprived areas have lower breast cancer (BC) incidence rates for screen-detected oestrogen receptor (ER) + tumours and higher mortality for select tumour subtypes. We aimed to determine if ipsilateral breast cancer recurrence (IBR) differs by Scottish Index of Multiple Deprivation (SIMD) quintile and tumour subtype in Scotland., Methods: Patient data for primary invasive BC diagnosed in 2007-2008 in Scotland was analysed. Manual case-note review for 3495 patients from 10 years post-diagnosis was used. To determine the probability of IBR while accounting for the competing risk of death from any cause, cumulative incidence functions stratified by ER subtype and surgery were plotted. Multivariable Cox Proportional Hazards models were used to estimate the association of SIMD accounting for other predictors of IBR., Results: Among 2819 ER + tumours, 423 patients had a recurrence and 438 died. SIMD was related to death (p = 0.018) with the most deprived more likely to have died in the 10-year period (17.7% vs. 12.9%). We found no significant differences by SIMD in prognostic tumour characteristics (grade, TNM stage, treatment, screen-detection) or risk of IBR. Among 676 patients diagnosed with ER- tumours, 105 died and 185 had a recurrence. We found no significant differences in prognostic tumour characteristics by SIMD except screen detection with the most deprived more likely than the least to have their tumours detected from screening (46.9% vs. 28%, p = 0.03). Among patients with ER- tumours, 50% had mastectomy and the most deprived had increased 5-year IBR risk compared to the least deprived (HR 3.03 [1.41-6.53])., Conclusions: IBR is not a major contributor to mortality differences by SIMD for the majority of BC patients in our study. The lack of inequities in IBR are likely due to standardised treatment protocols and access to healthcare. The association with socioeconomic deprivation and recurrence for ER- tumours requires further study., (© 2023. BioMed Central Ltd., part of Springer Nature.)

With a focus on children with multiple disabilities (CMD), the purpose of this quality improvement project was to elevate educational measurement and practices involving CMD. Using the goal attainment scaling (GAS) methodology, this project was conducted within a public charter school, Pattison's Academy for Comprehensive Education (PACE), focusing on 31 CMD and measuring student improvement and program effectiveness. For 2010-2011 and 2011-2012, improvements were demonstrated for the majority of CMD by meeting or exceeding their goals. Goal attainment scaling was able to capture improvement in educational and rehabilitation goals in the majority of CMD. Goal attainment scaling can provide an indication of a program's effectiveness. The use of GAS in CMD has potential to maximize participation across the school setting where all children in the United States commonly develop and learn skills as well as find meaning.

READY is a self-report prospective longitudinal study of deaf and hard of hearing (DHH) young people aged 16 to 19 years on entry. Its overarching aim is to explore the risk and protective factors for successful transition to adulthood. This article introduces the cohort of 163 DHH young people, background characteristics and study design. Focusing on self-determination and subjective well-being only, those who completed the assessments in written English (n = 133) score significantly lower than general population comparators. Sociodemographic variables explain very little of the variance in well-being scores; higher levels of self-determination are a predictor of higher levels of well-being, outweighing the influence of any background characteristics. Although women and those who are LGBTQ+ have statistically significantly lower well-being scores, these aspects of their identity are not predictive risk factors. These results add to the case for self-determination interventions to support better well-being amongst DHH young people., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Pediatric stroke is a condition that often results in life-long motor, cognitive, or sensory deficits for children. The purpose of this focused review is to compile the most recent literature on pediatric stroke neuromotor interventions and summarize evidence for use by rehabilitation providers and researchers. Terms including stroke, pediatric, and neuromotor were searched with appropriate MeSH terms. Information was collected regarding interventions conducted and outcome measures used for each article. Interventions and outcome measures were organized based on ICF components (Body Structure and Function, Activity, Participation, and Environmental Factors). 16 articles were included after full-text screens. From these 16 articles, a large majority of them included some form of neuromodulation as a part of intervention. Results identified a potentially problematic gap between domains addressed by interventions and measured by outcomes, with a need to include more expansive outcome measures in research studies. There are several areas of potential growth in pediatric stroke literature. Research studies should be precise when describing included samples. As interventions for pediatric stroke shift toward neuromodulation and other neurologic treatments, there is a need for well-defined populations, both clinically in the community as well as in research studies. There is also a need for US guidelines for rehabilitation after pediatric stroke. Overall, the trend in the literature seems to suggest that combining some form of neuromodulatory technique with existing recommended rehabilitation technique (ex: CIMT) may promote overall recovery for children after stroke, though further research is needed., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Competing Interests: The authors declare no conflicts of interest.

Introduction: Cognitive impairments are a common and significant issue for young people with a severe mental illness. Young people with schizophrenia, bipolar disorder and major depression all experience significant cognitive problems that impede their ability to return to work or study. These neurocognitive problems are frequently exacerbated by social cognitive deficits that interfere with their ability to integrate into the community and understand the social and emotional nuances about them. This study aimed to assess if the addition of a social cognitive remediation treatment to a neurocognitive remediation therapy improved functional outcome., Methods: Five youth mental health services were trained in both the Neuropsychological Educational Approach to Remediation (NEAR) and the Social Cognition and Interaction Training (SCIT) treatments. Participants were randomised between receiving either NEAR + SCIT or NEAR + treatment as usual (TAU) over a 20-week period, with all participants receiving the NEAR treatment first. Symptoms, neurocognition, social cognition and functioning were examined at baseline, end of treatment and at 3 months follow-up and compared between the two arms of the study. The primary outcome was function., Results: Thirty-nine participants were randomised to treatment (Schizophrenia spectrum = 28, Bipolar disorder = 7, Major Depression = 2). The trial was curtailed by Covid-related service restrictions. There was an overall significant improvement in function over time with a trend towards a greater improvement in the NEAR + SCIT arm. No changes in symptoms, neurocognitive or social cognitive measures were seen. While 74% completed treatment only 49% agreed to follow up at 3 months affecting our ability to interpret the findings. Attrition did not differ by arm., Conclusions: In a pragmatic, service-based research project, treatment aimed at improving cognition enhanced functional outcome in young people with a range of severe mental illnesses. There was a trend towards improved function in young people who had a combined NEAR + SCIT approach., Clinical Trial Registration: Identifier: ACTRN12622000192785., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Harris, Kightley, Williams, Ma and Dodds.)

The significant increase in illegal use of the synthetic opioid fentanyl is leading to unintentional overdose fatalities. Spills of fentanyl where it is abused or prepared for illegal distribution can result in persistent contamination of areas. Remediation can be attempted through physical removal but may benefit greatly from application of decontamination solutions that provide in-situ degradation of fentanyl. This work investigates the efficacy of decontamination technologies for degradation of fentanyl-HCl on indoor surfaces. Decontamination studies were conducted to evaluate the oxidative degradation of fentanyl based on percarbonate, hydrogen peroxide, peracetic acid, and chlorine (bleach) chemistries. This study utilized an experimental design relevant to field operations to provide direct information to first or hazardous materials responders and providers of environmental fentanyl remediation services, who may otherwise rely on unverified approaches. Across a range of nonporous indoor surfaces, results suggest that water (with or without detergent) spraying alone can physically remove 70-90% of fentanyl (with all fentanyl recovered in runoff). In nearly all cases, the spray application of peracetic acid or acetified bleach oxidants resulted in statistically significant degradation of fentanyl (>95% reduction), with noticeably lower efficacy for other oxidants (e.g., pH neutral bleach and OxiClean™). The decontamination efficacy was significantly reduced upon the addition of cutting agents that competed for oxidant demand., (Published by Elsevier Ltd.)

In this paper, we contrast two emergences of the concept of 'uninfectious' (that pharmaceuticals can render someone living with HIV non-infectious) in HIV. First, using Novas' framing of 'political economies of hope', we describe the deployment of 'uninfectious' as part of global health campaigns. Second, we draw on Raffles' (International Social Science Journal, 2002, 54, 325) concept of 'intimate knowledge' to theorise our own account of 'uninfectious' through a re-analysis of qualitative data comprising the intimate experiences of people living with or around HIV collected at various points over the last 25 years. Framed as intimate knowledge, 'uninfectious' becomes known through people's multiple engagements with and developing understandings of HIV over a prolonged period. As contingent and specific, intimate knowledge does not register within the biomedical/scientific ontological system that underpins discourses of hope employed in global campaigns. The concept of intimate knowledge offers the potential to critique discourses of hope in biomedicine problematising claims to universality whilst enriching biomedical understandings with accounts of affective, embodied experience. Intimate knowledge may also provide a bridge between different epistemological traditions in the sociology of health and illness., (© 2021 The Authors. Sociology of Health & Illness published by John Wiley & Sons Ltd on behalf of Foundation for SHIL (SHIL).)

Measures of health care quality are produced from a variety of data sources, but often, physicians do not believe these measures reflect the quality of provided care. The aim was to assess the value to health system leaders (HSLs) and parents of benchmarking on health care quality measures using data mined from the electronic health record (EHR). Using in-context interviews with HSLs and parents, the authors investigated what new decisions and actions benchmarking using data mined from the EHR may enable and how benchmarking information should be presented to be most informative. Results demonstrate that although parents may have little experience using data on health care quality for decision making, they affirmed its potential value. HSLs expressed the need for high-confidence, validated metrics. They also perceived barriers to achieving meaningful metrics but recognized that mining data directly from the EHR could overcome those barriers. Parents and HSLs need high-confidence health care quality data to support decision making.

Background: Shared decision making (SDM) between families and physicians may facilitate informed, timely decisions to proceed with biologic therapy in children with inflammatory bowel disease (IBD). Our team previously developed an SDM tool to aid communication between physicians and families when considering biologic therapy for children with IBD., Objective: We are conducting a prospective, pre-post pilot trial of a new SDM tool. The primary aim of the study is to assess feasibility of both the intervention and trial procedures for a future large-scale trial., Methods: We are enrolling physicians with experience prescribing biologic therapy in the past year and families of children with IBD. Families in the intervention arm receive a 3-step intervention including a letter sent before trial consent or clinic appointment, an in-clinic decision tool and a follow-up phone call. Our primary trial outcome is a measure of feasibility, with measures of clinical and decision outcomes secondary. We seek to enroll 27 families in each of 2 arms (usual-care and intervention) and plan data collection at the time of the initial visit or hospital stay, and at 1 week, 3 months, and 6 months after the initial visit., Conclusion: This study protocol is designed to demonstrate that integrating novel consent procedures, including timing and multiple versions of written consent, may increase trial feasibility while maintaining scientific rigor and full protection of study participants.

Pediatric physical therapists use Goal Attainment Scaling (GAS) in a variety of clinical settings to objectively measure change in individual-, patient- and family-centered goals. Creating, recording, storing, scoring, and interpreting GAS goals have been manually completed. Recently developed GOALed, a GAS app, provides an improved, streamlined approach. The purpose of this special communication is to introduce the GOALed app and demonstrate its use with a case example.

Copper and zinc are routinely used in livestock antimicrobial footbaths in commercial farming. The footbath mix is a cost to farmers, and the disposal of spent footbath into slurry tanks leads to soil contamination, as well as the potential for antimicrobial metal resistance and co-selection. This study assesses the potential to mitigate a source of antimicrobial metal resistance in slurry tanks while recovering copper and zinc from spent cattle footbaths. This is the first study in literature to investigate the potential of recovering copper from cattle footbath solutions via any method. The sorbent, Ca 2 Al-EDTA Layered Double Hydroxides (LDH), were used to remove Cu 2+ from a Cu 2 SO 4 ·5H 2 0 solution at different temperatures. The maximum Cu 2+ uptake from the Cu 2 SO 4 ·5H 2 0 solution was 568 ± 88 mg g -1 . Faster and higher equilibrium uptake was achieved by increasing the temperature of the solution. The sorbent was found to be effective in removing copper and zinc from a commercially available cattle footbath solution (filtered footbath solution Cu 2+ uptake 283 ± 11.05 mg g -1 , Zn 2+ uptake 60 ± 0.05 mg g -1 ). Thus, this study demonstrates the opportunity for a completely novel and potentially economically beneficial method of mitigating antimicrobial resistance in agriculture and the environment, while also providing a new valuable copper and zinc waste stream for secondary metal production., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

To understand how parents and physicians make decisions regarding antibiotics and whether a potential associated risk of obesity would alter decisions, we conducted a qualitative study of parents and physicians who care for children. Parent focus groups and physician interviews used a guide focused on experience with antibiotics and perceptions of risks and benefits, including obesity. Content analysis was used to understand how a risk of obesity would influence antibiotic decisions. Most parents (n = 59) and physicians (n = 22) reported limited discussion about any risks at the time of antibiotic prescriptions. With an acute illness, most parents prioritized symptomatic improvement and chose to start antibiotics. Physicians' treatment preferences were varied. An obesity risk did not change most parents' or physicians' preferences. Given that parent-physician discussion at the time of acute illness is unlikely to change preferences, public health messaging may be a more successful approach to counter obesity and antibiotics overuse.

Background: There is no validated measure of positive mental well-being that is suitable for Deaf people who use a signed language such as British Sign Language (BSL). This impedes inclusion of this population in a range of research designed to evaluate effectiveness of interventions. The study aims were: (i) to translate the original English version of SWEMWBS into BSL and to test the SWEMWBS BSL with the Deaf population in the UK who use BSL; (ii) to examine its psychometric properties; and (iii) to establish the validity and reliability of the SWEMWBS BSL., Methods: The SWEMWBS was translated into BSL following a six stage translation procedure and in consultation with the originators. The draft version was piloted with Deaf BSL users (n = 96) who also completed the CORE-OM BSL well-being subscale and the EQ-5D VAS BSL. Reliability was explored using Cronbach's alpha for internal consistency and ICC for test-retest reliability. Validity was explored by using Kendall's tau correction for convergent validity and an exploratory factor analysis for construct validity., Results: The internal consistency for the reliability of the SWEMWBS BSL was found to be good and the test-retest one week apart showed an acceptable reliability. There was good convergent validity of the SWEMWBS BSL with the well-being subscale of the CORE-OM BSL and the EQ-5D VAS BSL., Conclusions: The SWEMWBS BSL can be used with a Deaf population of BSL users. This is the first validated version of a BSL instrument that focuses solely on positively phrased questions for measuring mental well-being.

It has been highlighted that in the original article [1] there is a typesetting mistake in the name of I. Fakoya. This was incorrectly captured as F. Fakoya. This correction article clarifies the correct name of the author.

Background: Increasing routine HIV testing among key populations is a public health imperative, so improving access to acceptable testing options for those in need is a priority. Despite increasing targeted distribution and uptake of HIV self-sampling kits (SSKs) among men who have sex with men in the UK, little is known about why targeted SSK interventions for black African users are not as wide-spread or well-used. This paper addresses this key gap, offering insight into why some groups may be less likely than others to adopt certain types of SSK interventions in particular contexts. These data were collected during the development phase of a larger study to explore the feasibility and acceptability of targeted distribution of SSKs to black African people., Methods: We undertook 6 focus groups with members of the public who self-identified as black African (n = 48), 6 groups with specialists providing HIV and social services to black African people (n = 53), and interviews with HIV specialist consultants and policy-makers (n = 9). Framework analysis was undertaken, using inductive and deductive analysis to develop and check themes., Results: We found three valuable components of targeted SSK interventions for this population: the use of settings and technologies that increase choice and autonomy; targeted offers of HIV testing that preserve privacy and do not exacerbate HIV stigma; and ensuring that the specific kit being used (in this case, the TINY vial) is perceived as simple and reliable., Conclusions: This unique and rigorous research offers insights into participants' views on SSK interventions, offering key considerations when targeting this population.. Given the plethora of HIV testing options, our work demonstrates that those commissioning and delivering SSK interventions will need to clarify (for users and providers) how each kit type and intervention design adds value. Most significantly, these findings demonstrate that without a strong locus of control over their own circumstances and personal information, black African people are less likely to feel that they can pursue an HIV test that is safe and secure. Thus, where profound social inequalities persist, so will inequalities in HIV testing uptake - by any means.

Background: Timely diagnosis of human immunodeficiency virus (HIV) enables access to antiretroviral treatment, which reduces mortality, morbidity and further transmission in people living with HIV. In the UK, late diagnosis among black African people persists. Novel methods to enhance HIV testing in this population are needed., Objectives: To develop a self-sampling kit (SSK) intervention to increase HIV testing among black Africans, using existing community and health-care settings (stage 1) and to assess the feasibility for a Phase III evaluation (stage 2)., Design: A two-stage, mixed-methods design. Stage 1 involved a systematic literature review, focus groups and interviews with key stakeholders and black Africans. Data obtained provided the theoretical base for intervention development and operationalisation. Stage 2 was a prospective, non-randomised study of a provider-initiated, HIV SSK distribution intervention targeted at black Africans. The intervention was assessed for cost-effectiveness. A process evaluation explored feasibility, acceptability and fidelity., Setting: Twelve general practices and three community settings in London., Main Outcome Measure: HIV SSK return rate., Results: Stage 1 - the systematic review revealed support for HIV SSKs, but with scant evidence on their use and clinical effectiveness among black Africans. Although the qualitative findings supported SSK distribution in settings already used by black Africans, concerns were raised about the complexity of the SSK and the acceptability of targeting. These findings were used to develop a theoretically informed intervention. Stage 2 - of the 349 eligible people approached, 125 (35.8%) agreed to participate. Data from 119 were included in the analysis; 54.5% (65/119) of those who took a kit returned a sample; 83.1% of tests returned were HIV negative; and 16.9% were not processed, because of insufficient samples. Process evaluation showed the time pressures of the research process to be a significant barrier to feasibility. Other major barriers were difficulties with the SSK itself and ethnic targeting in general practice settings. The convenience and privacy associated with the SSK were described as beneficial aspects, and those who used the kit mostly found the intervention to be acceptable. Research governance delays prevented implementation in Glasgow., Limitations: Owing to the study failing to recruit adequate numbers (the intended sample was 1200 participants), we were unable to evaluate the clinical effectiveness of SSKs in increasing HIV testing in black African people. No samples were reactive, so we were unable to assess pathways to confirmatory testing and linkage to care., Conclusions: Our findings indicate that, although aspects of the intervention were acceptable, ethnic targeting and the SSK itself were problematic, and scale-up of the intervention to a Phase III trial was not feasible. The preliminary economic model suggests that, for the acceptance rate and test return seen in the trial, the SSK is potentially a cost-effective way to identify new infections of HIV., Future Work: Sexual and public health services are increasingly utilising self-sampling technologies. However, alternative, user-friendly SSKs that meet user and provider preferences and UK regulatory requirements are needed, and additional research is required to understand clinical effectiveness and cost-effectiveness for black African communities., Study Registration: This study is registered as PROSPERO CRD42014010698 and Integrated Research Application System project identification 184223., Funding: The National Institute for Health Research Health Technology Assessment programme and the BHA for Equality in Health and Social Care., Competing Interests: Fiona Burns reports grants from the National Institute for Health Research (NIHR) for other projects during the conduct of the study, and personal fees and other from Gilead Sciences Ltd (London, UK), outside the submitted work. Rachael Hunter reports grants from the NIHR Health Technology Assessment (HTA) programme for other projects, during the conduct of the study. Ibidun Fakoya reports a grant from NIHR for another project, during the conduct of the study. Eleni Nastouli reports personal fees from Roche (Burgess Hill, UK), grants from Viiv Healthcare (London, UK), grants from the European Union (H2020) and personal fees from NIHR, outside the submitted work. Lisa McDaid reports grants from the NIHR HTA programme for other projects, during the conduct of the study. Jane Anderson reports grants and personal fees from Gilead Sciences Ltd, and personal fees from ViiV Healthcare, Merck Sharp & Dohme Limited (Hoddesdon, UK), Bristol-Myers Squibb (Uxbridge, UK), Jansen-Cilag Limited (High Wycombe, UK) and AbbVie (Maidenhead, UK), outside the submitted work.

This corrects the article DOI: 10.1038/npp.2016.60.

Current methodologies for the extraction of tantalum and niobium pose a serious threat to human beings and the environment due to the use of hydrofluoric acid (HF). Niobium and tantalum metal powders and pentoxides are widely used for energy efficient devices and components. However, the current processing methods for niobium and tantalum metals and oxides are energy inefficient. This dichotomy between materials use for energy applications and their inefficient processing is the main motivation for exploring a new methodology for the extraction of these two oxides, investigating the microwave absorption properties of the reaction products formed during the alkali roasting of niobium-tantalum bearing minerals with sodium bicarbonate. The experimental findings from dielectric measurement at elevated temperatures demonstrate an exponential increase in the values of the dielectric properties as a result of the formation of NaNbO 3 -NaTaO 3 solid solutions at temperatures above 700 °C. The investigation of the evolution of the dielectric properties during the roasting reaction is a key feature in underpinning the mechanism for designing a new microwave assisted high-temperature process for the selective separation of niobium and tantalum oxides from the remainder mineral crystalline lattice.

Introduction: Ductal Carcinoma in situ (DCIS) represents 5% of symptomatic and 20-30% of screen detected cancers. Breast conserving surgery (BCS) ± radiotherapy is performed in over 70% of women with DCIS. What constitutes an adequate margin for BCS remains unclear., Methods: A single institution follow up study has been conducted of 466 patients with pure DCIS treated by BCS between 2000 and 2010 of whom 292 received whole breast radiotherapy and 167 did not. Patients were selected for radiotherapy based on perceived risk of in breast tumour recurrence (IBTR). Distance to nearest radial margin was measured; 10 patients had a margin width of <1 mm, 94 had widths of 1-2 mm and 362 had widths of >2 mm. There was no association of margin width and the use of radiotherapy., Results: At a median follow up of 7.2 years there were 44 IBTR (27 DCIS and 17 invasive). There was no evidence that margin widths >2 mm resulted in a lower rate of IBTR than margin widths of 1-2 mm. The actuarial IBTR rates at 5 and 10 years for margins of 1-2 mm were 9.0% (95% CI ± 5.9%) and 9.0% (95% CI ± 5.9%) respectively and for margins of >2 mm were 8.0% (95% CI ± 3.9%) and 13.0% (95% CI ± 3.9%) respectively. Odds Ratio for IBTR 1-2 mm vs >2 mm was 0.839 (95% CI 0.392-1.827) p = 0.846. In a multivariate analysis only DCIS size predicted for IBTR (HR 2.73 p < 0.0001)., Conclusion: 1 mm appears a sufficient margin width for BCS in DCIS irrespective of whether patients receive radiotherapy., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Microwave annealing has emerged as an alternative to traditional thermal annealing approaches for optimising block copolymer self-assembly. A novel sample environment enabling small angle X-ray scattering to be performed in situ during microwave annealing is demonstrated, which has enabled, for the first time, the direct study of the effects of microwave annealing upon the self-assembly behavior of a model, commercial triblock copolymer system [polystyrene-block-poly(ethylene-co-butylene)-block-polystyrene]. Results show that the block copolymer is a poor microwave absorber, resulting in no change in the block copolymer morphology upon application of microwave energy. The block copolymer species may only indirectly interact with the microwave energy when a small molecule microwave-interactive species [diethylene glycol dibenzoate (DEGDB)] is incorporated directly into the polymer matrix. Then significant morphological development is observed at DEGDB loadings ≥6 wt%. Through spatial localisation of the microwave-interactive species, we demonstrate targeted annealing of specific regions of a multi-component system, opening routes for the development of "smart" manufacturing methodologies.

Gay men with diagnosed HIV can adopt a number of strategies to reduce the risk of transmitting HIV to others, although research has typically focussed on condom use. Interviews with 42 HIV-positive gay men who reported recent engagement in anal intercourse without condoms explored their awareness of sexual risk and their perceptions of non-condom-related strategies to reduce it. In articulating men's ambivalence for strategies that can only reduce the risk of transmission, rather than eliminating, the findings have implications for the consideration and integration of new biomedical interventions to reduce the likelihood of HIV transmission.

The A118G single-nucleotide polymorphism (SNP rs1799971) in the μ-opioid receptor gene, OPRM1, has been much studied in relation to alcohol use disorders. The reported effects of allelic variation at this SNP on alcohol-related behaviors, and on opioid receptor antagonist treatments, have been inconsistent. We investigated the pharmacogenetic interaction between A118G variation and the effects of two μ-opioid receptor antagonists in a clinical lab setting. Fifty-six overweight and moderate-heavy drinkers were prospectively stratified by genotype (29 AA homozygotes, 27 carriers of at least 1 G allele) in a double-blind placebo-controlled, three-period crossover design with naltrexone (NTX; 25 mg OD for 2 days, then 50 mg OD for 3 days) and GSK1521498 (10 mg OD for 5 days). The primary end point was regional brain activation by the contrast between alcohol and neutral tastes measured using functional magnetic resonance imaging (fMRI). Secondary end points included other fMRI contrasts, subjective responses to intravenous alcohol challenge, and food intake. GSK1521498 (but not NTX) significantly attenuated fMRI activation by appetitive tastes in the midbrain and amygdala. GSK1521498 (and NTX to a lesser extent) significantly affected self-reported responses to alcohol infusion. Both drugs reduced food intake. Across all end points, there was less robust evidence for significant effects of OPRM1 allelic variation, or for pharmacogenetic interactions between genotype and drug treatment. These results do not support strong modulatory effects of OPRM1 genetic variation on opioid receptor antagonist attenuation of alcohol- and food-related behaviors. However, they do support further investigation of GSK1521498 as a potential therapeutic for alcohol use and eating disorders.

Purpose: This quality improvement project aimed to improve parental experiences with healthcare delivery and collaborative health care offered at a school serving children with medical complexity (CMC) by implementing telehealth services., Methods: Parents of students at an urban public charter school for CMC were surveyed before and after telehealth was implemented at the school for two months, and again one year later, using the Measure of Processes of Care (MPOC-20)., Results: Parental scores on the MPOC-20 were generally high both before and after the implementation of telehealth. There were no significant differences in the scores. Anecdotally, parent satisfaction with telehealth services was high. A review of the utilization of school-based telehealth during the 2015-2016 school year among 13 schools, including this unique school for CMC, revealed that the odds of having a telehealth visit at the school for CMC vs the other 12 schools was 23.8 (p value < 0.001; CL:11.2 to 50.6)., Conclusion: Parental experiences with healthcare delivery were high both before and after the implementation of telehealth at an urban public charter school for CMC. Utilization of telehealth at the school for CMC was significantly higher than that of children enrolled in the program at 12 other schools. Further research is needed to evaluate parental experiences with school-based telehealth services.

Background: Completeness of excision is the most important factor influencing local recurrence after breast-conserving surgery (BCS). The aim of this case-control study was to determine factors influencing incomplete excision in patients undergoing BCS., Methods: Women with invasive breast cancer treated by BCS between 1 June 2008 and 31 December 2009 were identified from a prospectively collected database in the Edinburgh Breast Unit. The maximum size of the tumour, measured microscopically, was compared with the size estimated before operation by mammography and ultrasound imaging. A multivariable analysis was performed to investigate factors associated with incomplete excision., Results: The cohort comprised 311 women, of whom 193 (62·1 per cent) had a complete (CE group) and 118 (40·7 per cent) an incomplete (IE group) excision. Mammography underestimated tumour size in 75·0 per cent of the IE group compared with 40·7 per cent of the CE group (P < 0·001). Ultrasound imaging underestimated tumour size in 82·5 per cent of the IE group compared with 56·5 per cent of the CE group (P < 0·001). The risk of an incomplete excision was greater when mammography or ultrasonography underestimated pathological size: odds ratio (OR) 4·38 (95 per cent c.i. 2·59 to 7·41; P < 0·001) for mammography, and OR 3·64 (2·03 to 6·54; P < 0·001) for ultrasound imaging. For every 1-mm underestimation of size by mammography and ultrasonography, the relative odds of incomplete excision rose by 10 and 14 per cent respectively., Conclusion: Underestimation of tumour size by current imaging techniques is a major factor associated with incomplete excision in women undergoing BCS., (© 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Purpose: Debate continues on what is an adequate margin width to define a clear margin and whether there is a need to excise pectoral fascia or remove skin in breast conserving surgery. This study set out to provide answers to these questions., Patients and Methods: 1411 patients with invasive breast cancer were treated by breast conserving surgery and post-operative whole breast radiotherapy from January 2000 to December 2005. Distance from each margin to any in situ or invasive cancer was measured and recorded. If full thickness of breast tissue was removed no re excision of anterior and posterior margins was performed even if disease was <1 mm from a margin. Patients ≤50 years of age and those with anterior or posterior margins <1 mm to invasive cancer had a radiation boost. Median follow-up time was 6.4 years., Results: Local in breast tumour relapse (IBTR) occurred in 50 patients. The overall actuarial IBTR rate at 5 years was 2.2%. There was no difference in IBTR when comparing patients with radial margins of 1-5 mm or 5-10 mm. Anterior and posterior margins <1 mm or with ink on tumour cells were not associated with an increase in IBTR., Conclusion: There is no justification for radial margins of greater than 1 mm. If the anterior or posterior margin is <1 mm and full thickness of breast tissue has been removed, then re excision of these margins is unnecessary if boost radiotherapy is delivered., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Internationally, few clinical trials have involved Deaf people who use a signed language and none have involved BSL (British Sign Language) users. Appropriate terminology in BSL for key concepts in clinical trials that are relevant to recruitment and participant information materials, to support informed consent, do not exist. Barriers to conceptual understanding of trial participation and sources of misunderstanding relevant to the Deaf community are undocumented., Methods: A qualitative, community participatory exploration of trial terminology including conceptual understanding of 'randomisation', 'trial', 'informed choice' and 'consent' was facilitated in BSL involving 19 participants in five focus groups. Data were video-recorded and analysed in source language (BSL) using a phenomenological approach., Results and Discussion: Six necessary conditions for developing trial information to support comprehension were identified. These included: developing appropriate expressions and terminology from a community basis, rather than testing out previously derived translations from a different language; paying attention to language-specific features which support best means of expression (in the case of BSL expectations of specificity, verb directionality, handshape); bilingual influences on comprehension; deliberate orientation of information to avoid misunderstanding not just to promote accessibility; sensitivity to barriers to discussion about intelligibility of information that are cultural and social in origin, rather than linguistic; the importance of using contemporary language-in-use, rather than jargon-free or plain language, to support meaningful understanding., Conclusions: The study reinforces the ethical imperative to ensure trial participants who are Deaf are provided with optimum resources to understand the implications of participation and to make an informed choice. Results are relevant to the development of trial information in other signed languages as well as in spoken/written languages when participants' language use is different from the dominant language of the country.

Background: There is evidence of executive function impairment in obsessive compulsive disorder (OCD) that potentially contributes to symptom development and maintenance. Nevertheless, the precise nature of these executive impairments and their neural basis remains to be defined., Method: We compared stopping and shifting, two key executive functions previously implicated in OCD, in the same task using functional magnetic resonance imaging, in patients with virtually no co-morbidities and age-, verbal IQ- and gender-matched healthy volunteers. The combined task allowed direct comparison of neural activity in stopping and shifting independent of patient sample characteristics and state variables such as arousal, learning, or current symptom expression., Results: Both OCD patients and controls exhibited right inferior frontal cortex activation during stopping, and left inferior parietal cortex activation during shifting. However, widespread under-activation across frontal-parietal areas was found in OCD patients compared to controls for shifting but not stopping. Conservative, whole-brain analyses also indicated marked divergent abnormal activation in OCD in the caudate and thalamus for these two cognitive functions, with stopping-related over-activation contrasting with shift-related under-activation., Conclusions: OCD is associated with selective components of executive function, which engage similar common elements of cortico-striatal regions in different abnormal ways. The results implicate altered neural activation of subcortical origin in executive function abnormalities in OCD that are dependent on the precise cognitive and contextual requirements, informing current theories of symptom expression.

We present qualitative research findings about how perceptions of criminal prosecutions for the transmission of HIV interact with the provision of high-quality HIV health and social care in England and Wales. Seven focus groups were undertaken with a total of 75 diverse professionals working in clinical and community-based services for people with HIV. Participants' understanding of the law in this area was varied, with many knowing the basic requirements for a prosecution, yet lacking confidence in the best way to communicate key details with those using their service. Prosecutions for HIV transmission have influenced, and in some instances, disrupted the provision of HIV services, creating ambivalence and concern among many providers about their new role as providers of legal information. The way that participants approached the topic with service users was influenced by their personal views on individual and shared responsibility for health, their concerns about professional liability and their degree of trust in non-coercive health promotion approaches to managing public health. These findings reveal an underlying ambivalence among many providers about how they regard the interface between criminal law, coercion and public health. It is also apparent that in most HIV service environments, meaningful exploration of practical ethical issues is relatively rare. The data presented here will additionally be of use to managers and providers of HIV services in order that they can provide consistent and confident support and advice to people with HIV.

The development of pharmaceutical HIV prevention technologies (PPTs) over the last five years has generated intense interest from a range of stakeholders. There are concerns that these clinical and pharmaceutical interventions are proceeding with insufficient input of the social sciences. Hence key questions around implementation and evaluation remain unexplored whilst biomedical HIV prevention remains insufficiently critiqued or theorised from sociological as well as other social science perspectives. This paper presents the results of an expert symposium held in the UK to explore and build consensus on the role of the social sciences in researching and evaluating PPTs in this context. The symposium brought together UK social scientists from a variety of backgrounds. A position paper was produced and distributed in advance of the symposium and revised in the light this consultation phase. These exchanges and the emerging structure of this paper formed the basis for symposium panel presentations and break-out sessions. Recordings of all sessions were used to further refine the document which was also redrafted in light of ongoing comments from symposium participants. Six domains of enquiry for the social sciences were identified and discussed: self, identity and personal narrative; intimacy, risk and sex; communities, resistance and activism; systems, structures and institutions; economic considerations and analyses; and evaluation and outcomes. These are discussed in depth alongside overarching consensus points for social science research in this area as it moves forward.

Objective: Laser surface modification of platinum (Pt) electrodes was investigated for use in neuroprosthetics. Surface modification was applied to increase the surface area of the electrode and improve its ability to transfer charge within safe electrochemical stimulation limits., Approach: Electrode arrays were laser micromachined to produce Pt electrodes with smooth surfaces, which were then modified with four laser patterning techniques to produce surface structures which were nanosecond patterned, square profile, triangular profile and roughened on the micron scale through structured laser interference patterning (SLIP). Improvements in charge transfer were shown through electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and biphasic stimulation at clinically relevant levels. A new method was investigated and validated which enabled the assessment of in vivo electrochemically safe charge injection limits., Main Results: All of the modified surfaces provided electrical advantage over the smooth Pt. The SLIP surface provided the greatest benefit both in vitro and in vivo, and this surface was the only type which had injection limits above the threshold for neural stimulation, at a level shown to produce a response in the feline visual cortex when using an electrode array implanted in the suprachoroidal space of the eye. This surface was found to be stable when stimulated with more than 150 million clinically relevant pulses in physiological saline., Significance: Critical to the assessment of implant devices is accurate determination of safe usage limits in an in vivo environment. Laser patterning, in particular SLIP, is a superior technique for improving the performance of implant electrodes without altering the interfacial electrode chemistry through coating. Future work will require chronic in vivo assessment of these electrode patterns.

Adult ADHD has been linked to impaired motor response inhibition and reduced associated activation in the right inferior frontal cortex (IFC). However, it is unclear whether abnormal inferior frontal activation in adult ADHD is specifically related to a response inhibition deficit or reflects a more general deficit in attentional processing. Using functional magnetic resonance imaging, we tested a group of 19 ADHD patients with no comorbidities and a group of 19 healthy control volunteers on a modified go/no-go task that has been shown previously to distinguish between cortical responses related to response inhibition and attentional shifting. Relative to the healthy controls, ADHD patients showed increased commission errors and reduced activation in inferior frontal cortex during response inhibition. Crucially, this reduced activation was observed when controlling for attentional processing, suggesting that hypoactivation in right IFC in ADHD is specifically related to impaired response inhibition. The results are consistent with the notion of a selective neurocognitive deficit in response inhibition in adult ADHD associated with abnormal functional activation in the prefrontal cortex, whilst ruling out likely group differences in attentional orienting, arousal and motivation., (Copyright © 2014 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.)

The brain-derived neurotropic factor (BDNF) Val66Met polymorphism has been associated with abnormalities of synaptic plasticity in animal models, and abnormalities in motor cortical plasticity have also been described in humans using transcranial direct current stimulation. No study has yet been done on plasticity in non-motor regions, and the effect of two Met alleles (i.e. 'Met dose') is not well understood. We studied the effect of the BDNF Val66Met polymorphism on the after-effects of transcranial direct current stimulation and tetanic auditory stimulation in 65 subjects (23; Val66Val, 22; Val66Met and 20; Met66Met genotypes). In the first session, motor evoked potentials (MEP) were recorded under stereotaxic guidance for 90 min after 9 min of anodal transcranial direct current stimulation (TDCS). In the second session, auditory-evoked potentials (AEP) were recorded before and after 2 min of auditory 13 Hz tetanic stimulation. There was a difference in MEP facilitation post-TDCS comparing Met carriers with non-Met carriers, with Met carriers having a modest late facilitation at 30-90 min. There was no difference in responses between Val66Met genotype and Met66Met genotype subjects. Tetanic auditory stimulation also produced late facilitation of N1-P2 AEP at 25 min, but there was no apparent effect of genetic status. This study indicates that Met66Met carriers behave like Val66Met carriers for TDCS-induced plasticity, and produce a late facilitation of MEPs. Auditory cortical plasticity was not affected by the BDNF Val66Met polymorphism. This study sheds light on the differences between auditory and motor cortical plasticity and the role of the BDNF Val66Met polymorphism.

Purpose: Extubation may be delayed after spine surgery mainly for the concerns of airway safety. Risk factors for delayed extubation in cervical spine surgery have been described to include prolonged surgery time and amount of crystalloids or blood transfused. To date, risk factors for delayed extubation in thoracic or lumbar spine surgery have not been investigated. We retrospectively reviewed 135 consecutive patients from 2006 to 2009 who underwent thoracic or lumbar spine surgery by one particular surgeon to identify risk factors for delayed extubation., Methods: Data including patient factors, surgical time, anesthetic technique, blood loss, crystalloid and colloid administration, transfusion requirements, time to transfusion, and time to extubation were collected and analyzed. Delayed extubation was defined as the patient was not extubated in the operating room at completion of the surgery., Results: One hundred and eight patients were extubated in the OR. Delayed extubation occurred in 27 patients. Delayed extubation was significantly related to total operative time (6.6 ± 0.4 vs. 5.2 ± 0.1 h), volume of crystalloid replacement (6,018 ± 408 vs. 4,186 ± 130 cm3), volume of total colloids infused (787 ± 93 vs. 442 ± 36 cm3), intraoperative blood transfused (3.7 ± 0.5 vs. 0.7 ± 0.1 units); blood loss (2,137 ± 286 vs. 832 ± 50 cm3), and time to starting blood transfusion (106 ± 12 vs. 199 ± 9 min)., Conclusions: Our study suggests that intraoperative factors including prolonged surgical time, significant blood loss, larger volume of crystalloid and colloid infusion, and blood transfusion may be risk factors for delayed extubation following thoracic or lumbar spine surgery. Early blood transfusion may also increase the risk of delayed extubation. Patient factors did not affect extubation time.

Background: Impairments in mismatch negativity (MMN) generation have been consistently reported in patients with schizophrenia. However, underlying oscillatory activity of MMN deficits in schizophrenia and the relationship with cognitive impairments have not been investigated in detail. Time-frequency power and phase analyses can provide more detailed measures of brain dynamics of MMN deficits in schizophrenia., Method: 21 patients with schizophrenia and 21 healthy controls were tested with a roving frequency paradigm to generate MMN. Time-frequency domain power and phase-locking (PL) analysis was performed on all trials using short-time Fourier transforms with Hanning window tapering. A comprehensive battery (CANTAB) was used to assess neurocognitive functioning., Results: Mean MMN amplitude was significantly lower in patients with schizophrenia (95% CI 0.18 - 0.77). Patients showed significantly lower EEG power (95% CI -1.02 - -0.014) in the ~4-7 Hz frequency range (theta band) between 170 and 210 ms. Patients with schizophrenia showed cognitive impairment in multiple domains of CANTAB. However, MMN impairments in amplitude and power were not correlated with clinical measures, medication dose, social functioning or neurocognitive performance., Conclusion: The findings from this study suggested that while MMN may be a useful marker to probe NMDA receptor mediated mechanisms and associated impairments in gain control and perceptual changes, it may not be a useful marker in association with clinical or cognitive changes. Trial-by-trial EEG power analysis can be used as a measure of brain dynamics underlying MMN deficits which also can have implications for the use of MMN as a biomarker for drug discovery.

We demonstrate the use of surface acoustic wave nebulization (SAWN) to load optical traps. We show that the droplets sizes produced can be tuned by altering the RF frequency applied to the devices, which leads to more control over the sizes of trapped particles. Typically the size distribution of the liquid aerosols delivered using SAWN is smaller than via a standard commercial nebulization device. The ability to trap a range of liquids or small solid particles, not readily accessible using other ultrasonic devices, is also demonstrated both in optical tweezers and dual beam fiber traps.

The mu-opioid system has a key role in hedonic and motivational processes critical to substance addiction. However, existing mu-opioid antagonists have had limited success as anti-addiction treatments. GSK1521498 is a selective and potent mu-opioid antagonist being developed for the treatment of overeating and substance addictions. In this study, 28 healthy participants were administered single doses of GSK1521498 20 mg, ethanol 0.5 g/kg body weight, or both in combination, in a double blind placebo controlled four-way crossover design. The primary objective was to determine the risk of significant adverse pharmacodynamic and pharmacokinetic (PK) interactions. The effects of GSK1521498 on hedonic and consummatory responses to alcohol and the attentional processing of alcohol-related stimuli, and their modulation by the OPRM1 A118G polymorphism were also explored. GSK1521498 20 mg was well tolerated alone and in combination with ethanol. There were mild transient effects of GSK1521498 on alertness and mood that were greater when it was combined with ethanol. These effects were not of clinical significance. There were no effects of GSK1521498 on reaction time, hedonic or consummatory responses. These findings provide encouraging safety and PK data to support continued development of GSK1521498 for the treatment of alcohol addiction., (© The Authors 2013. The Journal of Clinical Pharmacology. Published by Wiley Periodicals, Inc.)