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Abstract A whiplash injury can alter neck muscle function, which remains years after the injury and may explain why symptoms such as persistent pain and disability occur. There is currently limited knowledge about dynamic neck muscle function in chronic whiplash-associated disorders (WAD), and about the extent to which altered muscle function can improve after rehabilitation. Ultrasound can detect mechanical neck muscle function by measuring real-time deformation and deformation rate in the muscles. This method was used for five dorsal neck muscles in participants with chronic WAD versus matched controls in resistant neck rotation. We obtained real-time, non-invasive ultrasound measurements using speckle tracking, multivariate analyses, and mixed-design ANOVA analyses. The results showed altered deformation in the three deepest neck muscle layers, with less deformation area in the WAD group compared to controls in rotation to the most painful side at baseline. Participants in the WAD group performed three months of neck-specific exercises, resulting in improved deformation in the deep neck muscles in WAD and with a similar deformation pattern to controls, and the significant group differences ceased. We reveal new and important insights into the capability of ultrasound to diagnose altered neck muscle function and evaluate an exercise intervention.

Abstract Background Distinguishing benign from malignant pancreaticobiliary disease is challenging because of the absence of reliable biomarkers. Circulating extracellular vesicles (EVs) have emerged as functional mediators between cells. Their cargos, including microRNAs (miRNAs), are increasingly acknowledged as an important source of potential biomarkers. This multicentric, prospective study aimed to establish a diagnostic plasma EV-derived miRNA signature to discriminate pancreatic ductal adenocarcinoma (PDAC) from benign pancreaticobiliary disease. Methods Plasma EVs were isolated using size exclusion chromatography (SEC) and characterised using nanoparticle tracking analysis, electron microscopy and Western blotting. EV-RNAs underwent small RNA sequencing to discover differentially expressed markers for PDAC (n = 10 benign vs. 10 PDAC). Candidate EV-miRNAs were then validated in a cohort of 61 patients (n = 31 benign vs. 30 PDAC) by RT-qPCR. Logistic regression and optimal thresholds (Youden Index) were used to develop an EV-miR-200 family model to detect cancer. This model was tested in an independent cohort of 95 patients (n = 30 benign, 33 PDAC, and 32 cholangiocarcinoma). Results Small RNA sequencing and RT-qPCR showed that EV-miR-200 family members were significantly overexpressed in PDAC vs. benign disease. Combined expression of the EV-miR-200 family showed an AUC of 0.823. In an independent validation cohort, application of this model showed a sensitivity, specificity and AUC of 100%, 88%, and 0.97, respectively, for diagnosing PDAC. Conclusions This is the first study to validate plasma EV-miR-200 members as a clinically-useful diagnostic biomarker for PDAC. Further validation in larger cohorts and clinical trials is essential. These findings also suggest the potential utility in monitoring response and/or recurrence. Graphical Abstract

Abstract There has been concern about adolescent mental health during the pandemic. The current study examined adolescent mental health during the initial phase of the COVID-19 pandemic in the UK. Using indicator of psychological distress, wellbeing and resilience, latent profile analysis was used to identify homogeneous mental health groups among young people aged 13–24 (N = 1971). Multinomial logistic regression was then used to examine which sociodemographic and psychosocial variables predicted latent class membership. Four classes were found. The largest class (Class 1, 37.2%) was characterised by moderate symptomology and moderate wellbeing. Class 2 (34.2%) was characterised by low symptomology and high wellbeing, while Class 3 (25.4%) was characterised by moderate symptomology and high wellbeing. Finally, Class 4 was the smallest (3.2%) and was characterised by high symptomology and low wellbeing. Compared to the low symptomology, high wellbeing class, all other classes were associated with less social engagement with friends, poorer family functioning, greater somatic symptoms, and a less positive model of self. A number of unique associations between the classes and predictor variables were identified. Although around two-thirds of adolescents reported moderate-to-high symptomology, most of these individuals also reported concurrent moderate-to-high levels of wellbeing, reflecting resilience. Furthermore, these findings demonstrate how a more comprehensive picture of mental health can be gained through adopting a dual-continua conceptualisation of mental health that incorporates both pathology and well-being. In this way, at-risk youth can be identified and interventions and resources targeted appropriately.

Abstract Background Use of bystander video livestreaming from scene to Emergency Medical Services (EMS) is becoming increasingly common to aid decision making about the resources required. Possible benefits include earlier, more appropriate dispatch and clinical and financial gains, but evidence is sparse. Methods A feasibility randomised controlled trial with an embedded process evaluation and exploratory economic evaluation where working shifts during six trial weeks were randomised 1:1 to use video livestreaming during eligible trauma incidents (using GoodSAM Instant-On-Scene) or standard care only. Pre-defined progression criteria were: (1) ≥ 70% callers (bystanders) with smartphones agreeing and able to activate live stream; (2) ≥ 50% requests to activate resulting in footage being viewed; (3) Helicopter Emergency Medical Services (HEMS) stand-down rate reducing by ≥ 10% as a result of live footage; (4) no evidence of psychological harm in callers or staff/dispatchers. Observational sub-studies included (i) an inner-city EMS who routinely use video livestreaming to explore acceptability in a diverse population; and (ii) staff wellbeing in an EMS not using video livestreaming for comparison to the trial site. Results Sixty-two shifts were randomised, including 240 incidents (132 control; 108 intervention). Livestreaming was successful in 53 incidents in the intervention arm. Patient recruitment (to determine appropriateness of dispatch), and caller recruitment (to measure potential harm) were low (58/269, 22% of patients; 4/244, 2% of callers). Two progression criteria were met: (1) 86% of callers with smartphones agreed and were able to activate livestreaming; (2) 85% of requests to activate livestreaming resulted in footage being obtained; and two were indeterminate due to insufficient data: (3) 2/6 (33%) HEMS stand down due to livestreaming; (4) no evidence of psychological harm from survey, observations or interviews, but insufficient survey data from callers or comparison EMS site to be confident. Language barriers and older age were reported in interviews as potential challenges to video livestreaming by dispatchers in the inner-city EMS. Conclusions Progression to a definitive RCT is supported by these findings. Bystander video livestreaming from scene is feasible to implement, acceptable to both 999 callers and dispatchers, and may aid dispatch decision-making. Further assessment of unintended consequences, benefits and harm is required. Trial registration. ISRCTN 11449333 (22 March 2022). https://www.isrctn.com/ISRCTN11449333

Introduction Accurate and timely dispatch of emergency medical services (EMS) is vital due to limited resources and patients’ risk of mortality and morbidity increasing with time. Currently, most UK emergency operations centres (EOCs) rely on audio calls and accurate descriptions of the incident and patients’ injuries from lay 999 callers. If dispatchers in the EOCs could see the scene via live video streaming from the caller’s smartphone, this may enhance their decision making and enable quicker and more accurate dispatch of EMS. The main aim of this feasibility randomised controlled trial (RCT) is to assess the feasibility of conducting a definitive RCT to assess the clinical and cost effectiveness of using live streaming to improve targeting of EMS.Methods and analysis The SEE-IT Trial is a feasibility RCT with a nested process evaluation. The study also has two observational substudies: (1) in an EOC that routinely uses live streaming to assess the acceptability and feasibility of live streaming in a diverse inner-city population and (2) in an EOC that does not currently use live streaming to act as a comparator site regarding the psychological well-being of EOC staff using versus not using live streaming.Ethics and dissemination The study was approved by the Health Research Authority on 23 March 2022 (ref: 21/LO/0912), which included NHS Confidentiality Advisory Group approval received on 22 March 2022 (ref: 22/CAG/0003). This manuscript refers to V.0.8 of the protocol (7 November 2022). The trial is registered with the ISRCTN (ISRCTN11449333). The first participant was recruited on 18 June 2022.The main output of this feasibility trial will be the knowledge gained to help inform the development of a large multicentre RCT to evaluate the clinical and cost effectiveness of the use of live streaming to aid EMS dispatch for trauma incidents.Trial registration number ISRCTN11449333.

Bariatric surgery is an effective treatment for obesity. However, around one in five people experience significant weight regain. Acceptance and Commitment Therapy (ACT) teaches acceptance of and defusion from thoughts and feelings which influence behaviour, and commitment to act in line with personal values. To test the feasibility and acceptability of ACT following bariatric surgery a randomised controlled trial of 10 sessions of group ACT or Usual Care Support Group control (SGC) was delivered 15–18 months post bariatric surgery (ISRCTN registry ID: ISRCTN52074801). Participants were compared at baseline, 3, 6 and 12 months using validated questionnaires to assess weight, wellbeing, and healthcare use. A nested, semi-structured interview study was conducted to understand acceptability of the trial and group processes. 80 participants were consented and randomised. Attendance was low for both groups. Only 9 (29%) ACT participants completed > = half of the sessions, this was the case for 13 (35%) SGC participants. Forty-six (57.5%) did not attend the first session. At 12 months, outcome data were available from 19 of the 38 receiving SGC, and from 13 of the 42 receiving ACT. Full datasets were collected for those who remained in the trial. Nine participants from each arm were interviewed. The main barriers to group attendance were travel difficulties and scheduling. Poor initial attendance led to reduced motivation to return. Participants reported a motivation to help others as a reason to join the trial; lack of attendance by peers removed this opportunity and led to further drop out. Participants who attended the ACT groups reported a range of benefits including behaviour change. We conclude that the trial processes were feasible, but that the ACT intervention was not acceptable as delivered. Our data suggest changes to recruitment and intervention delivery that would address this.

Abstract The COVID-19 pandemic has brought about unprecedented global changes in individual and collective behaviour. To reduce the spread of the virus, public health bodies have promoted social distancing measures while attempting to mitigate their mental health consequences. The current study aimed to identify cognitive predictors of social distancing adherence and mental health symptoms, using computational models derived from delay discounting (the preference for smaller, immediate rewards over larger, delayed rewards) and patch foraging (the ability to trade-off between exploiting a known resource and exploring an unknown one). In a representative sample of the UK population (N = 442), we find that steeper delay discounting predicted poorer adherence to social distancing measures and greater sensitivity to reward magnitude during delay discounting predicted higher levels of anxiety symptoms. Furthermore, under-valuing recently sampled information during foraging independently predicted greater violation of lockdown guidance. Our results suggest that those who show greater discounting of delayed rewards struggle to maintain social distancing. Further, those who adapt faster to new information are better equipped to change their behaviour in response to public health measures. These findings can inform interventions that seek to increase compliance with social distancing measures whilst minimising negative repercussions for mental health.

Infection with SARS-CoV2 and the development of Coronavirus disease 2019 (COVID-19) has been linked to induction of autoimmunity and autoantibody production. Here the authors characterise the new-onset IgG autoantibody response in hospitalised patients with COVID-19 which they correlate to the magnitude of the SARS-CoV2 response.

Hesitancy and resistance towards vaccination is a challenge for public health. Here the authors determine psychological characteristics associated with COVID-19 vaccine hesitancy or resistance attitudes in the UK and Ireland.

This paper serves to alert IJPDS readers to the availability of a major new longitudinal survey data resource, the COVID-19 Psychological Research Consortium (C19PRC) Study, which is being released for secondary use via the Open Science Framework. The C19PRC Study is a rich and detailed dataset that provides a convenient and valuable foundation from which to study the social, political, and health status of European adults during an unprecedented time of change as a direct result of the COVID-19 pandemic and Brexit. Here, we provide an overview of the C19PRC Study design, with the purpose of stimulating interest about the study among social scientists and maximising use of this resource.

COVID-19 conspiracy theories have proliferated during the global pandemic, and their rapid spread among certain groups may jeopardize the public health response (e.g., undermining motivation to engage in social distancing and willingness to vaccinate against the virus). Using survey data from two waves of a nationally representative, longitudinal study of life in lockdown in the United Kingdom (N = 1,406), we analyze the factors associated with belief in three origin theories related to COVID-19, namely that it 1) originated in a meat market in Wuhan, China; 2) was developed in a lab in Wuhan, China; and 3) is caused by 5G mobile networks. Our findings suggest that political-psychological predispositions are strongly associated with belief in conspiracy theories about the virus, though the direction and effect sizes of these predictors vary depending on the specific content of each origin theory. For instance, belief in the Chinese lab conspiracy theory is strongly associated with right-wing authoritarianism (RWA), social dominance orientation (SDO), and general conspiracy ideation, as well as less reliable news sources, distrust in scientists, and anxiety about the pandemic. Belief in the 5G network conspiracy theory is strongly associated with SDO, distrust in scientists, while less strongly with conspiracy ideation and information from social networks/media; RWA is strongly negatively associated with belief in the 5G conspiracy theory, with older and more wealthy individuals somewhat less likely to endorse it. The meat market origin theory is predicted by intolerance of uncertainty, ethnocentrism, COVID-19 anxiety, and less so by higher income, while distrust in scientists is negatively associated with this origin story. Finally, belief in COVID-19 conspiracy theories is associated with negative public health behaviors such as unwillingness to social distance and vaccinate against the virus. Crucially, our findings suggest that the specific content of COVID-19 conspiracy theories likely determines which individuals may be most likely to endorse them.

Background: Cataract surgery is one of the most common operations. Femtosecond laser-assisted cataract surgery (FLACS) is a technique that automates a number of operative steps. Objectives: To compare FLACS with phacoemulsification cataract surgery (PCS). Design: Multicentre, outcome-masked, randomised controlled non-inferiority trial. Setting: Three collaborating NHS hospitals. Participants: A total of 785 patients with age-related cataract in one or both eyes were randomised between May 2015 and September 2017. Intervention: FLACS (n = 392 participants) or PCS (n = 393 participants). Main outcome measures: The primary outcome was uncorrected distance visual acuity in the study eye after 3 months, expressed as the logarithm of the minimum angle of resolution (logMAR): 0.00 logMAR (or 6/6 if expressed in Snellen) is normal (good visual acuity). Secondary outcomes included corrected distance visual acuity, refractive outcomes (within 0.5 dioptre and 1.0 dioptre of target), safety and patient-reported outcome measures at 3 and 12 months, and resource use. All trial follow-ups were performed by optometrists who were masked to the trial intervention. Results: A total of 353 (90%) participants allocated to the FLACS arm and 317 (81%) participants allocated to the PCS arm attended follow-up at 3 months. The mean uncorrected distance visual acuity was similar in both treatment arms [0.13 logMAR, standard deviation 0.23 logMAR, for FLACS, vs. 0.14 logMAR, standard deviation 0.27 logMAR, for PCS, with a difference of –0.01 logMAR (95% confidence interval –0.05 to 0.03 logMAR; p = 0.63)]. The mean corrected distance visual acuity values were again similar in both treatment arms (–0.01 logMAR, standard deviation 0.19 logMAR FLACS vs. 0.01 logMAR, standard deviation 0.21 logMAR PCS; p = 0.34). There were two posterior capsule tears in the PCS arm. There were no significant differences between the treatment arms for any secondary outcome at 3 months. At 12 months, the mean uncorrected distance visual acuity was 0.14 logMAR (standard deviation 0.22 logMAR) for FLACS and 0.17 logMAR (standard deviation 0.25 logMAR) for PCS, with a difference between the treatment arms of –0.03 logMAR (95% confidence interval –0.06 to 0.01 logMAR; p = 0.17). The mean corrected distance visual acuity was 0.003 logMAR (standard deviation 0.18 logMAR) for FLACS and 0.03 logMAR (standard deviation 0.23 logMAR) for PCS, with a difference of –0.03 logMAR (95% confidence interval –0.06 to 0.01 logMAR; p = 0.11). There were no significant differences between the arms for any other outcomes, with the exception of the mean binocular corrected distance visual acuity with a difference of –0.02 logMAR (95% confidence interval –0.05 to 0.00 logMAR) (p = 0.036), which favoured FLACS. There were no significant differences between the arms for any health, social care or societal costs. For the economic evaluation, the mean cost difference was £167.62 per patient higher for FLACS (95% of iterations between –£14.12 and £341.67) than for PCS. The mean QALY difference (FLACS minus PCS) was 0.001 (95% of iterations between –0.011 and 0.015), which equates to an incremental cost-effectiveness ratio (cost difference divided by QALY difference) of £167,620. Limitations: Although the measurement of outcomes was carried out by optometrists who were masked to the treatment arm, the participants were not masked. Conclusions: The evidence suggests that FLACS is not inferior to PCS in terms of vision after 3 months’ follow-up, and there were no significant differences in patient-reported health and safety outcomes after 12 months’ follow-up. In addition, the statistically significant difference in binocular corrected distance visual acuity was not clinically significant. FLACS is not cost-effective. Future work: To explore the possible differences in vision in patients without ocular co-pathology. Trial registration: Current Controlled Trials ISRCTN77602616. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 6. See the NIHR Journals Library website for further project information. Moorfields Eye Charity (grant references GR000233 and GR000449 for the endothelial cell counter and femtosecond laser used).

Background The COVID-19 pandemic has had a major impact on delivery of social support services. This might be expected to particularly affect older adults and people living with dementia (PLWD), and to reduce their well-being.Aims To explore how social support service use by older adults, carers and PLWD, and their mental well-being changed over the first 3 months since the pandemic outbreak.Methods Unpaid dementia carers, PLWD and older adults took part in a longitudinal online or telephone survey collected between April and May 2020, and at two subsequent timepoints 6 and 12 weeks after baseline. Participants were asked about their social support service usage in a typical week prior to the pandemic (at baseline), and in the past week at each of the three timepoints. They also completed measures of levels of depression, anxiety and mental well-being.Results 377 participants had complete data at all three timepoints. Social support service usage dropped shortly after lockdown measures were imposed at timepoint 1 (T1), to then increase again by T3. The access to paid care was least affected by COVID-19. Cases of anxiety dropped significantly across the study period, while cases of depression rose. Well-being increased significantly for older adults and PLWD from T1 to T3.Conclusions Access to social support services has been significantly affected by the pandemic, which is starting to recover slowly. With mental well-being differently affected across groups, support needs to be put in place to maintain better well-being across those vulnerable groups during the ongoing pandemic.

The over-purchasing and hoarding of necessities is a common response to crises, especially in developed economies where there is normally an expectation of plentiful supply. This behaviour was observed internationally during the early stages of the Covid-19 pandemic. In the absence of actual scarcity, this behaviour can be described as 'panic buying' and can lead to temporary shortages. However, there have been few psychological studies of this phenomenon. Here we propose a psychological model of over-purchasing informed by animal foraging theory and make predictions about variables that predict over-purchasing by either exacerbating or mitigating the anticipation of future scarcity. These variables include additional scarcity cues (e.g. loss of income), distress (e.g. depression), psychological factors that draw attention to these cues (e.g. neuroticism) or to reassuring messages (eg. analytical reasoning) or which facilitate over-purchasing (e.g. income). We tested our model in parallel nationally representative internet surveys of the adult general population conducted in the United Kingdom (UK: N = 2025) and the Republic of Ireland (RoI: N = 1041) 52 and 31 days after the first confirmed cases of COVID-19 were detected in the UK and RoI, respectively. About three quarters of participants reported minimal over-purchasing. There was more over-purchasing in RoI vs UK and in urban vs rural areas. When over-purchasing occurred, in both countries it was observed across a wide range of product categories and was accounted for by a single latent factor. It was positively predicted by household income, the presence of children at home, psychological distress (depression, death anxiety), threat sensitivity (right wing authoritarianism) and mistrust of others (paranoia). Analytic reasoning ability had an inhibitory effect. Predictor variables accounted for 36% and 34% of the variance in over-purchasing in the UK and RoI respectively. With some caveats, the data supported our model and points to strategies to mitigate over-purchasing in future crises.

COVID-19 continues to pose a threat to global public health. Multiple safe and effective vaccines against COVID-19 are available with one-third of the global population now vaccinated. Achieving a sufficient level of vaccine coverage to suppress COVID-19 requires, in part, sufficient acceptance among the public. However, relatively high rates of hesitance and resistance to COVID-19 vaccination persists, threating public health efforts to achieve vaccine-induced population protection. In this study, we examined longitudinal changes in COVID-19 vaccine acceptance, hesitance, and resistance in two nations (the United Kingdom and the Republic of Ireland) during the first nine months of the pandemic, and identified individual and psychological factors associated with consistent non-acceptance of COVID-19 vaccination. Using nationally representative, longitudinal data from the United Kingdom (UK; N = 2025) and Ireland (N = 1041), we found that (1) COVID-19 vaccine acceptance declined in the UK and remained unchanged in Ireland following the emergence of approved vaccines; (2) multiple subgroups existed reflecting people who were consistently willing to be vaccinated (‘Accepters’: 68% in the UK and 61% in Ireland), consistently unwilling to be vaccinated (‘Deniers’: 12% in the UK and 16% in Ireland), and who fluctuated over time (‘Moveable Middle’: 20% in the UK and 23% in Ireland); and (3) the ‘deniers’ and ‘moveable middle’ were distinguishable from the ‘accepters’ on a range of individual (e.g., younger, low income, living alone) and psychological (e.g., distrust of scientists and doctors, conspiracy mindedness) factors. The use of two high-income, Western European nations limits the generalizability of these findings. Nevertheless, understanding how receptibility to COVID-19 vaccination changes as the pandemic unfolds, and the factors that distinguish and characterise those that are hesitant and resistant to vaccination is helpful for public health efforts to achieve vaccine-induced population protection against COVID-19.

Background: The comparative efficacy, and cost-effectiveness, of imiquimod or podophyllotoxin cream, either alone or in combination with the quadrivalent HPV vaccine (Gardasil®, Merck Sharp & Dohme Corp., Merck & Co., Inc., Whitehouse Station, NJ, USA) in the treatment and prevention of recurrence of anogenital warts is not known. Objective: The objective was to compare the efficacy of imiquimod and podophyllotoxin creams to treat anogenital warts and to assess whether or not the addition of quadrivalent human papillomavirus vaccine increases wart clearance or prevention of recurrence. Design: A randomised, controlled, multicentre, partially blinded factorial trial. Participants were randomised equally to four groups, combining either topical treatment with quadrivalent human papillomavirus vaccine or placebo. Randomisation was stratified by gender, a history of previous warts and human immunodeficiency virus status. There was an accompanying economic evaluation, conducted from the provider perspective over the trial duration. Setting: The setting was 22 sexual health clinics in England and Wales. Participants: Participants were patients with a first or repeat episode of anogenital warts who had not been treated in the previous 3 months and had not previously received quadrivalent human papillomavirus vaccine. Interventions: Participants were randomised to 5% imiquimod cream (Aldara®; Meda Pharmaceuticals, Takeley, UK) for up to 16 weeks or 0.15% podophyllotoxin cream (Warticon®; GlaxoSmithKlein plc, Brentford, UK) for 4 weeks, which was extended to up to 16 weeks if warts persisted. Participants were simultaneously randomised to quadrivalent human papillomavirus vaccine (Gardasil) or saline control at 0, 8 and 24 weeks. Cryotherapy was permitted after week 4 at the discretion of the investigator. Main outcome measures: The main outcome measures were a combined primary outcome of wart clearance at week 16 and remaining wart free at week 48. Efficacy analysis was by logistic regression with multiple imputation for missing follow-up values; economic evaluation considered the costs per quality-adjusted life-year. Results: A total of 503 participants were enrolled and attended at least one follow-up visit. The mean age was 31 years, 66% of participants were male (24% of males were men who have sex with men), 50% had a previous history of warts and 2% were living with human immunodeficiency virus. For the primary outcome, the adjusted odds ratio for imiquimod cream versus podophyllotoxin cream was 0.81 (95% confidence interval 0.54 to 1.23), and for quadrivalent human papillomavirus vaccine versus placebo, the adjusted odds ratio was 1.46 (95% confidence interval 0.97 to 2.20). For the components of the primary outcome, the adjusted odds ratio for wart free at week 16 for imiquimod versus podophyllotoxin was 0.77 (95% confidence interval 0.52 to 1.14) and for quadrivalent human papillomavirus vaccine versus placebo was 1.30 (95% confidence interval 0.89 to 1.91). The adjusted odds ratio for remaining wart free at 48 weeks (in those who were wart free at week 16) for imiquimod versus podophyllotoxin was 0.98 (95% confidence interval 0.54 to 1.78) and for quadrivalent human papillomavirus vaccine versus placebo was 1.39 (95% confidence interval 0.73 to 2.63). Podophyllotoxin plus quadrivalent human papillomavirus vaccine had inconclusive cost-effectiveness compared with podophyllotoxin alone. Limitations: Hepatitis A vaccine as control was replaced by a saline placebo in a non-identical syringe, administered by someone outside the research team, for logistical reasons. Sample size was reduced from 1000 to 500 because of slow recruitment and other delays. Conclusions: A benefit of the vaccine was not demonstrated in this trial. The odds of clearance at week 16 and remaining clear at week 48 were 46% higher with vaccine, and consistent effects were seen for both wart clearance and recurrence separately, but these differences were not statistically significant. Imiquimod and podophyllotoxin creams had similar efficacy for wart clearance, but with a wide confidence interval. The trial results do not support earlier evidence of a lower recurrence with use of imiquimod than with use of podophyllotoxin. Podophyllotoxin without quadrivalent human papillomavirus vaccine is the most cost-effective strategy at the current vaccine list price. A further larger trial is needed to definitively investigate the effect of the vaccine; studies of the immune response in vaccine recipients are needed to investigate the mechanism of action. Trial registration: Current Controlled Trials. Current Controlled Trials ISRCTN32729817 and EudraCT 2013-002951-14. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 47. See the NIHR Journals Library website for further project information.

Abstract Background Anogenital warts are the second most common sexually transmitted infection diagnosed in sexual health services in England. About 90% of genital warts are caused by human papillomavirus (HPV) types 6 or 11, and half of episodes diagnosed are recurrences. The best and most cost-effective treatment for patients with anogenital warts is unknown. The commonly used treatments are self-administered topical agents, podophyllotoxin (0.15% cream) or imiquimod (5% cream), or cryotherapy with liquid nitrogen. Quadrivalent HPV (qHPV) vaccination is effective in preventing infection, and disease, but whether it has any therapeutic effect is not known. Methods and design To investigate the efficacy of clearance and prevention of recurrence of external anogenital warts by topical treatments, podophyllotoxin 0.15% cream or imiquimod 5% cream, in combination with a three-dose regimen of qHPV or control vaccination. 500 adult patients presenting with external anogenital warts with either a first or subsequent episode of anogenital warts will be entered into this randomised, controlled partially blinded 2 × 2 factorial trial. Discussion The trial is expected to provide the first high-quality evidence of the comparative efficacy and cost-effectiveness of the two topical treatments in current use, as well as investigate the potential benefit of HPV vaccination, in the management of anogenital warts. Trial registration The trial was registered prior to starting recruitment under the following reference numbers: International Standard Randomized Controlled Trial Number (ISRCTN) Registry - ISRCTN32729817 (registered 25 July 2014); European Union Clinical Trials Register (EudraCT) - 2013-002951-14 (registered 26 June 2013).

The zebrafish embryo is a popular model for drug screening, disease modelling and molecular genetics. In this study, samples were obtained from zebrafish at different developmental stages. The stages that were chosen were 3/4, 4/5, 24, 48, 72 and 96 hours post fertilization (hpf). Each sample included fifty embryos. The samples were analysed using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). Principle component analysis (PCA) was applied to get an overview of the data and orthogonal projection to latent structure discriminant analysis (OPLS-DA) was utilised to discriminate between the developmental stages. In this way, changes in metabolite profiles during vertebrate development could be identified. Using a GC-TOF-MS metabolomics approach it was found that nucleotides and metabolic fuel (glucose) were elevated at early stages of embryogenesis, whereas at later stages amino acids and intermediates in the Krebs cycle were abundant. This agrees with zebrafish developmental biology, as organs such as the liver and pancreas develop at later stages. Thus, metabolomics of zebrafish embryos offers a unique opportunity to investigate large scale changes in metabolic processes during important developmental stages in vertebrate development. In terms of stability of the metabolic profile and viability of the embryos, it was concluded at 72 hpf was a suitable time point for the use of zebrafish as a model system in numerous scientific applications.

As children continue their preschool years, they learn many new things and develop their own opinions and ideas. During this time, people inside and outside of the home may greatly influence them. As preschoolers continue to learn and grow, caregivers can take many steps to guide their children in a healthy and positive direction. This 3-page fact sheet is a minor revision written by Kate Bennett, Gail Kauwell, and Karla P. Shelnutt, and published by the Department of Family, Youth and Community Sciences, April 2017.

This is a Spanish language version of Chronic Kidney Disease: Phosphorus and Your Diet.

Phosphorous is an essential mineral necessary for the formation of bones and teeth, but also for kidney function and the regulation of muscle contractions, heartbeat, and nerve transmission. High blood levels of phosphorus may lead to adverse effects on bone, kidney, and heart health. When there is too much phosphorus in the blood, the body reacts by leaching calcium from the bones. This can be especially dangerous for those with Chronic Kidney Disease. This 4-page fact sheet discusses the relationship between Chronic Kidney Disease and Phosphorous intake, examining foods that are high in phosphorous and ways to manage phosphorous levels. Written by Nancy J. Gal, Lauren Headrick, Kate Bennett, and Wendy J. Dahl, and published by the Food Science and Human Nutrition Department, December 2015. FSHN15-10/FS273: Chronic Kidney Disease: Phosphorus and Your Diet (ufl.edu)

Exposure of the brain to general anesthesia during early infancy may adversely affect its neural and cognitive development. The mechanisms mediating this are complex, incompletely understood and may be sexually dimorphic, but include developmentally inappropriate apoptosis, inflammation and a disruption to cognitively salient gene expression. We investigated the effects of a 6h isoflurane exposure on cell death, microglial activation and gene expression in the male neonatal piglet brain. Piglets (n = 6) were randomised to: (i) naive controls or (ii) 6h isoflurane. Cell death (TUNEL and caspase-3) and microglial activation were recorded in 7 brain regions. Changes in gene expression (microarray and qPCR) were assessed in the cingulate cortex. Electroencephalography (EEG) was recorded throughout. Isoflurane anesthesia induced significant increases in cell death in the cingulate and insular cortices, caudate nucleus, thalamus, putamen, internal capsule, periventricular white matter and hippocampus. Dying cells included both neurons and oligodendrocytes. Significantly, microglial activation was observed in the insula, pyriform, hippocampus, internal capsule, caudate and thalamus. Isoflurane induced significant disruption to the expression of 79 gene transcripts, of these 26 are important for the control of transcription and 23 are important for the mediation of neural plasticity, memory formation and recall. Our observations confirm that isoflurane increases apoptosis and inflammatory responses in the neonatal piglet brain but also suggests novel additional mechanisms by which isoflurane may induce adverse neural and cognitive development by disrupting the expression of genes mediating activity dependent development of neural circuits, the predictive adaptive responses of the brain, memory formation and recall.

Hierarchical modelling was applied in order to identify the organs that contribute to the levels of metabolites in plasma. Plasma and organ samples from gut, kidney, liver, muscle and pancreas were obtained from mice. The samples were analysed using gas chromatography time-of-flight mass spectrometry (GC TOF-MS) at the Swedish Metabolomics centre, Umeå University, Sweden. The multivariate analysis was performed by means of principal component analysis (PCA) and orthogonal projections to latent structures (OPLS). The main goal of this study was to investigate how each organ contributes to the metabolic plasma profile. This was performed using hierarchical modelling. Each organ was found to have a unique metabolic profile. The hierarchical modelling showed that the gut, kidney and liver demonstrated the greatest contribution to the metabolic pattern of plasma. For example, we found that metabolites were absorbed in the gut and transported to the plasma. The kidneys excrete branched chain amino acids (BCAAs) and fatty acids are transported in the plasma to the muscles and liver. Lactic acid was also found to be transported from the pancreas to plasma. The results indicated that hierarchical modelling can be utilized to identify the organ contribution of unknown metabolites to the metabolic profile of plasma.

As children continue their preschool years, they learn many new things and develop their own opinions and ideas. During this time, people inside and outside of the home may greatly influence them. As preschoolers continue to learn and grow, caregivers can take many steps to guide their children in a healthy and positive direction. This 4-page fact sheet was written by Kate Bennet, Gail Kauwell, and Karla P. Shelnutt, and published by the UF Department of Family, Youth and Community Sciences, April 2014.

Learning that your child has a shellfish allergy can be scary. But having a plan and knowing how to treat and avoid a reaction to shellfish can ease this fear and keep your child safe. This publication explains shellfish allergies and provides information on the symptoms and how to respond if a reaction occurs. There are also tips to make it easier to manage your child’s shellfish allergy at home and away from home.This 4-page fact sheet was written by Kate Bennett, Karla P. Shelnutt, and Gail P. A. Kauwell, and published by the UF Department of Family Youth and Community Sciences, November 2013. http://edis.ifas.ufl.edu/fy1402