Search

Background: Intimate partner violence (IPV) and violence against children are global issues with severe consequences. Intersections shared by the 2 forms of violence have led to calls for joint programming efforts to prevent both IPV and violence against children. Parenting programs have been identified as a key entry point for addressing multiple forms of family violence. Building on the IPV prevention material that has been integrated into the parenting program ParentText, a digital parenting chatbot, this pilot study seeks to explore parents' engagement with the IPV prevention content in ParentText and explore preliminary changes in IPV., Objective: This study aimed to assess parents' and caregivers' level of engagement with the IPV prevention material in the ParentText chatbot and explore preliminary changes in experiences and perpetration of IPV, attitudes toward IPV, and gender-equitable behaviors following the intervention., Methods: Caregivers of children aged between 0 and 18 years were recruited through convenience sampling by research assistants in Cape Town, South Africa, and by UNICEF (United Nations Children's Fund) Jamaica staff in 3 parishes of Jamaica. Quantitative data from women in Jamaica (n=28) and South Africa (n=19) and men in South Africa (n=21) were collected electronically via weblinks sent to caregivers' phones using Open Data Kit. The primary outcome was IPV experience (women) and perpetration (men), with secondary outcomes including gender-equitable behaviors and attitudes toward IPV. Descriptive statistics were used to report sociodemographic characteristics and engagement outcomes. Chi-square tests and 2-tailed paired dependent-sample t tests were used to investigate potential changes in IPV outcomes between pretest and posttest., Results: The average daily interaction rate with the program was 0.57 and 0.59 interactions per day for women and men in South Africa, and 0.21 for women in Jamaica. The rate of completion of at least 1 IPV prevention topic was 25% (5/20) for women and 5% (1/20) for men in South Africa, and 21% (6/28) for women in Jamaica. Exploratory analyses indicated significant pre-post reductions in overall IPV experience among women in South Africa (P=.01) and Jamaica (P=.01) and in men's overall harmful IPV attitudes (P=.01) and increases in men's overall gender-equitable behaviors (P=.02) in South Africa., Conclusions: To the best of our knowledge, this is the first pilot study to investigate user engagement with and indicative outcomes of a digital parenting intervention with integrated IPV prevention content. Study findings provide valuable insights into user interactions with the chatbot and shed light on challenges related to low levels of chatbot engagement. Indicative results suggest promising yet modest reductions in IPV and improvements in attitudes after the program. Further research using a randomized controlled trial is warranted to establish causality., (©Moa Schafer, Jamie Lachman, Paula Zinser, Francisco Antonio Calderón Alfaro, Qing Han, Chiara Facciola, Lily Clements, Frances Gardner, Genevieve Haupt Ronnie, Ross Sheil. Originally published in JMIR Formative Research (https://formative.jmir.org), 03.01.2025.)

Objectives: Clinical and imaging examinations frequently have indeterminate results during cancer surveillance, which can lead to overtreatment and cause psychological and financial harm to the patient. This study addresses the critical need to enhance diagnostic precision and decision-making in the management of HPV-associated oropharyngeal cancer. This study evaluated the utility of tumor tissue-modified viral (TTMV)-HPV DNA to resolve indeterminate disease status following definitive treatment for HPV-associated oropharyngeal cancer., Materials and Methods: In this retrospective cohort, patients treated for HPV-associated oropharyngeal cancer at eight U.S. institutions and who received one or more TTMV-HPV DNA tests during post-treatment surveillance between February 2020 and January 2022 were included., Results: Among 543 patients, 210 patients (38.7%; 210/543) experienced one or more clinically indeterminate findings (CIFs) during surveillance, with 503 CIFs recorded. Of those patients with an "indeterminate" disease status at a point during surveillance, 79 were associated with contemporaneous TTMV-HPV DNA testing. TTMV-HPV DNA testing demonstrated high accuracy (97.5%; 77/79) in correctly determining recurrence status. Patients whose disease status was "indeterminate" at the time of a positive TTMV-HPV DNA test were clinically confirmed to recur faster than those whose disease status was "no evidence of disease." Only 3% of patients (17/543) experienced indeterminate TTMV-HPV DNA tests during surveillance. Discordance between TTMV-HPV DNA tests and clinical results was minimal, with only 0.6% (3/543) of patients showing positive tests without recurrence., Conclusion: Our findings support the utility of circulating TTMV-HPV DNA in resolving indeterminate disease status and informing the subsequent clinical course., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Evidence-based parenting programmes have strong evidence in preventing and mitigating violence, but in-person programmes are challenging to deliver at scale. ParentApp is an open-source, offline-first app-based adaptation of the Parenting for Lifelong Health for Parents and Teens programme to promote playful and positive parenting, reduce risks for sexual violence victimisation, and prevent violence against adolescents. This study aims to evaluate the effectiveness and cost-effectiveness of ParentApp compared to an attention-control group., Methods: This study is a two-arm pragmatic cluster-randomised controlled trial to test whether ParentApp reduces adolescent physical abuse, emotional abuse, and sexual violence risks and victimisation at 1 month and 12 months post-intervention. Caregivers of adolescents aged 10-17 years and their adolescent children (N = 2400 caregiver-adolescent dyads) will be recruited in urban and peri-urban communities in the Mwanza region of Tanzania. A total of 80 study clusters will be stratified and randomised (1:1) to the intervention group, who will receive ParentApp with support through a WhatsApp group, or to an attention-control group, who will receive a water, sanitation, and hygiene app. Quantitative data will be collected through outcomes questionnaires with caregivers and adolescents, administered at baseline, 4 months post-baseline, and 16 months post-baseline, as well as through routine implementation data and ParentApp engagement data. Qualitative data will be collected through individual interviews and focus groups with caregivers, adolescents, and implementing partner staff., Discussion: App-based interventions have the potential to expand access to evidence-based parenting support, but currently lack rigorous evidence in low- and middle-income countries. This is the first known randomised control trial of a hybrid digital parenting programme to prevent the abuse of adolescents in low- and middle-income settings., Trial Registration: The trial was registered on the Open Science Framework on 14 March 2023, registration: OSF.IO/T9FXZ ., (© 2024. The Author(s).)

Purpose: Human papillomavirus (HPV) is causally linked to oropharyngeal squamous cell carcinoma (OPSCC). Consensus guidelines recommend clinical exams and imaging in decreasing frequency as part of posttreatment surveillance for recurrence. Plasma tumor tissue modified viral (TTMV)-HPV DNA testing has emerged as a biomarker which can inform disease status during surveillance., Experimental Design: This retrospective observational cohort study involved 543 patients who completed curative-intent therapy for HPV-associated OPSCC between February 2020 and January 2022 at eight U.S. cancer care institutions. We determined the negative predictive value (NPV) of TTMV-HPV DNA for recurrence when matched to physician-reported clinical outcome data (median follow-up time: 27.9 months; range: 4.5-154)., Results: The cohort included mostly men with a median age of 61 who had locoregionally advanced disease. HPV status was determined by p16 positivity in 87% of patients, with a positive HPV PCR/ISH among 55%; while pretreatment TTMV-HPV DNA status was unknown for most (79%) patients. Patients had a mean of 2.6 tests and almost half had three or more TTMV-HPV DNA results during surveillance. The per-test and per-patient sensitivity of the assay was 92.5% [95% confidence interval (CI): 87.5-97.5] and 87.3% (95% CI: 79.1-95.5), respectively. The NPV for the assay was 99.4% (95% CI: 98.9-99.8) and 98.4% (95% CI: 97.3-99.5), respectively., Conclusions: TTMV-HPV DNA surveillance testing yields few false negative results and few missed recurrences. These data could inform decisions on when to pursue reimaging following first disease restaging and could inform future surveillance practice. Additional study of how pretreatment TTMV-HPV DNA status impacts sensitivity for recurrence is needed., (©2023 The Authors; Published by the American Association for Cancer Research.)

Background: Intimate partner violence (IPV) is a serious public health issue which experienced a sharp incline during the onset of COVID-19. Increases in other forms of violence, such as violence against children (VAC), have also been linked to the pandemic, and there have been calls for greater prevention efforts that tackle both forms of violence concurrently. The COVID-19 crisis has highlighted the urgent need for evidence-based and scalable violence prevention interventions that target multiple forms of family violence. Parenting programmes have shown promising results in preventing various forms of family violence, including IPV and VAC, and have recently experienced an expansion in delivery, with digital intervention formats growing. This paper describes the development and evaluation of the IPV prevention content designed and integrated into ParentText, a chatbot parenting intervention adapted from Parenting for Lifelong Health programmes., Methods: The ParentText IPV prevention content was developed using the Six Steps in Quality Intervention Development (6SQuID) framework. This involved targeted literature searches for key studies to identify causal factors associated with IPV and determining those with greatest scope for change. Findings were used to develop the intervention content and theory of change. Consultations were held with academic researchers (n = 5), practitioners (n = 5), and local community organisations (n = 7), who reviewed the content. A formative evaluation was conducted with parents in relationships (n = 96) in Jamaica to better understand patterns in user engagement with the intervention and identify strategies to further improve engagement., Results: Using the 6SQuID model, five topics on IPV prevention were integrated into the ParentText chatbot. Text-messages covering each topic, including additional materials such as cartoons and videos, were also developed. The formative evaluation revealed an average user-engagement length of 14 days, 0.50 chatbot interactions per day, and over half of participants selected to view additional relationship content., Conclusions: This article provides a unique contribution as the first to integrate IPV prevention content into a remotely delivered, digital parenting intervention for low-resource settings. The findings from this research and formative evaluation shed light on the promising potential of chatbots as scalable and accessible forms of violence prevention, targeting multiple types of family violence., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: Patient and public involvement (PPI) in clinical research has a well-established infrastructure in the UK, and while there has been good progress within pharmaceutical-industry-sponsored research, further improvements are still needed. This review aims to share learnings from quality assessments of historical PPI projects within Pfizer UK to inform future projects and drive PPI progress in the pharmaceutical industry., Design and Setting: Internal assessments of Pfizer UK PPI projects were conducted to identify all relevant projects across the medicines development continuum between 2017 and 2021. Five sample projects were developed into case studies., Outcome Measure: Retrospective quality assessments were performed using the Patient Focused Medicines Development (PFMD) Patient Engagement Quality Guidance (PEQG) tool. Recommendations for improvement were developed., Results: Retrospective case study analysis and quality framework assessment revealed benefits of PPI to both Pfizer UK and to external partners, as well as challenges and learnings to improve future practice. Recommendations for improvement based on these findings focused on processes and procedures for PPI, group dynamics and diversity for PPI activities, sharing of expertise, the importance of bidirectional and timely feedback, and the use of understandable language in materials., Conclusions: PPI in medicines development is impactful and beneficial but is still being optimised in the pharmaceutical industry. Using the PFMD PEQG tool to define gaps, share learnings and devise recommendations for improvement helps to ensure that PPI is genuine and empowering, rather than tokenistic. Ultimately, these recommendations should be acted on to further embed PPI as an integral part of medicines development and health research within the pharmaceutical industry. This article includes a plain language summary in the supplement., Competing Interests: Competing interests: S-AD, SB, LC, SE, SH, BP and NB are employees of Pfizer and hold Pfizer stock. AB, RD, AD, EK, GP, JP and KS have no competing interests to report., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Violence against adolescents is a universal reality, with severe individual and societal costs. There is a critical need for scalable and effective violence prevention strategies such as parenting programmes, particularly in low- and middle-income countries where rates of maltreatment are highest. Digital interventions may be a scalable and cost-effective alternative to in-person delivery, yet maximising caregiver engagement is a substantial challenge. This trial employs a cluster randomised factorial experiment and a novel mixed-methods analytic approach to assess the effectiveness, cost-effectiveness, and feasibility of intervention components designed to optimise engagement in an open-source parenting app, ParentApp for Teens. The app is based on the evidence-based Parenting for Lifelong Health for Teens programme, developed collaboratively by academic institutions in the Global South and North, the WHO, and UNICEF., Methods/design: Sixteen neighbourhoods, i.e., clusters, will be randomised to one of eight experimental conditions which consist of any combination of three components (Support: self-guided/moderated WhatsApp groups; App Design: sequential workshops/non-sequential modules; Digital Literacy Training: on/off). The study will be conducted in low-income communities in Tanzania, targeting socioeconomically vulnerable caregivers of adolescents aged 10 to 17 years (16 clusters, 8 conditions, 640 caregivers, 80 per condition). The primary objective of this trial is to estimate the main effects of the three components on engagement. Secondary objectives are to explore the interactions between components, the effects of the components on caregiver behavioural outcomes, moderators and mediators of programme engagement and impact, and the cost-effectiveness of components. The study will also assess enablers and barriers to engagement qualitatively via interviews with a subset of low, medium, and high engaging participants. We will combine quantitative and qualitative data to develop an optimised ParentApp for Teens delivery package., Discussion: This is the first known cluster randomised factorial trial for the optimisation of engagement in a digital parenting intervention in a low- and middle-income country. Findings will be used to inform the evaluation of the optimised app in a subsequent randomised controlled trial., Trial Registration: Pan African Clinical Trial Registry, PACTR202210657553944. Registered 11 October 2022, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=24051 ., (© 2023. The Author(s).)

Caregivers support heart failure (HF) self-care with little HF education. The purpose of this study was to evaluate the effectiveness of a caregiver-only educational intervention aimed at improving caregiver self-efficacy, perceived control, and HF knowledge, as well as patient self-care and 30-day cardiac readmission. In total, 37 patients and their caregivers were randomly assigned to a control condition or a caregiver-only educational intervention with telephone follow-up. Outcomes included patient 30-day cardiac readmission, patient self-care, caregiver self-efficacy, caregiver perceived control, and caregiver HF knowledge. Linear mixed model, Kaplan-Meier, and Cox regression analyses were used to determine the effects of the intervention on outcomes. Self-care maintenance ( p = 0.002), self-care management ( p = 0.005), 30-day cardiac readmission ( p = 0.003), and caregiver perceived control ( p < 0.001) were significantly better in the intervention group. The results suggest that interventions targeting caregiver HF education could be effective in improving HF patients' 30-day cardiac readmissions, patient self-care, and caregiver perceived control.

It is well documented that 17β estradiol (E2) regulates excitatory synaptic transmission at hippocampal Shaffer-collateral (SC)-CA1 synapses, via activation of the classical estrogen receptors (ERα and ERβ). Hippocampal CA1 pyramidal neurons are also innervated by the temporoammonic (TA) pathway, and excitatory TA-CA1 synapses are reported to be regulated by E2. Recent studies suggest a role for the novel G-protein coupled estrogen receptor (GPER1) at SC-CA1 synapses, however, the role of GPER1 in mediating the effects of E2 at juvenile TA-CA1 synapses is unclear. Here we demonstrate that the GPER1 agonist, G1 induces a persistent, concentration-dependent (1-10 nM) increase in excitatory synaptic transmission at TA-CA1 synapses and this effect is blocked by selective GPER1 antagonists. The ability of GPER1 to induce this novel form of chemical long-term potentiation (cLTP) was prevented following blockade of N-methyl-D-aspartate (NMDA) receptors, and it was not accompanied by any change in paired pulse facilitation ratio (PPR). GPER1-induced cLTP involved activation of ERK but was independent of phosphoinositide 3-kinase (PI3K) signalling. Prior treatment with philanthotoxin prevented the effects of G1, indicating that synaptic insertion of GluA2-lacking α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors underlies GPER1-induced cLTP. Furthermore, activity-dependent LTP occluded G1-induced cLTP and vice versa, indicating that these processes have overlapping expression mechanisms. Activity-dependent LTP was blocked by the GPER1 antagonist, G15, suggesting that GPER1 plays a role in NMDA-dependent LTP at juvenile TA-CA1 synapses. These findings add a new dimension to our understanding of GPER1 in modulating neuronal plasticity with relevance to age-related neurodegenerative conditions., (© 2023. The Author(s).)

Competing Interests: The authors declare no conflicts of interest.

Background: The COVID-19 pandemic caused significant disruptions in cancer care, and preliminary research suggests that these disruptions are associated with increased levels of psychosocial distress among cancer survivors. The purpose of this study was to offer a descriptive report of the psychosocial functioning, perceived risk and fear of cancer progression, and COVID-19 pandemic impact and experiences in a unique, high-risk patient cohort: breast cancer survivors whose cancer treatment was delayed and/or changed due to the COVID-19 pandemic. Methods: This cross-sectional study included 50 women with dual carcinoma in situ , lobular carcinoma in situ , or invasive breast cancer whose cancer surgery was postponed due to the pandemic. As they awaited delayed surgery or shortly after they received delayed surgery, participants completed questionnaires on psychosocial functioning (depression, anxiety, sleep, and quality of life), their perceived risk and fear of cancer progression, patient-provider communication about disruptions in their care, personal impact of the pandemic, worry/threat about COVID-19, and COVID-19 symptoms/diagnoses. Descriptive statistics and bivariate correlations were computed among continuous study variables. Independent samples t -tests explored group differences in psychosocial functioning between survivors who were still awaiting delayed surgery and those who had recently received it. Results: Overall, the sample denied that the pandemic seriously negatively impacted their finances or resource access and reported low-to-moderate levels of psychosocial distress and fear about COVID-19. Twenty-six percent had clinically significant levels of fear of cancer progression, with levels comparable to other recent work. About a third were still awaiting delayed cancer surgery and this group reported lower satisfaction with communication from oncology providers but overall did not seem to report more psychosocial difficulties than those who already had surgery. Conclusion: Shortly before or after primary breast cancer surgery that was delayed due to the COVID-19 pandemic, this sample of survivors appears to be generally managing well psychosocially. However, many psychosocial difficulties (e.g., fear of cancer recurrence/progression) typically have an onset after the completion of treatment, therefore, research should continue to follow this cohort of cancer survivors as the pandemic's direct impact on their care likely increases their risk for these difficulties later in survivorship., 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 © 2021 Soriano, Perndorfer, Otto, Fenech, Siegel, Dickson-Witmer, Clements and Laurenceau.)

Background: Caregivers of patients with heart failure (HF) report depressive symptoms and poor quality of life (QOL) related to caregiving and poor family functioning, placing them at risk for poor health., Objectives: The purpose of this study was to examine the effect of depressive symptoms on the relationship between family functioning and quality of life in the HF caregiver., Methods: A sample of 92 HF caregivers were enrolled from an ambulatory clinic at a large academic medical center. A mediation analysis was used to analyze data obtained from the Family Assessment Device (FAD), the Patient Health Questionaire-9 (PHQ-9), and the Short Form-12 Health Survey Version 2 (SF-12v2)., Results: Depressive symptoms were found to be a significant mediator in the relationship between family functioning and caregiver quality of life., Conclusions: The results of this study suggest that interventions targeting caregiver depression and family functioning could be effective in enhancing HF caregivers' physical and mental QOL., (Copyright © 2020. Published by Elsevier Inc.)

Background and Purpose: 17β estradiol (E2) rapidly regulates excitatory synaptic transmission at the classical Schaffer collateral (SC) input to hippocampal CA1 neurons. However, the impact of E2 on excitatory synaptic transmission at the distinct temporoammonic (TA) input to CA1 neurons and the oestrogen receptors involved is less clear., Experimental Approach: Extracellular recordings were used to monitor excitatory synaptic transmission in hippocampal slices from juvenile male (P11-24) Sprague Dawley rats. Immunocytochemistry combined with confocal microscopy was used to monitor the surface expression of the AMPA receptor (AMPAR) subunit, GluA1 in hippocampal neurons cultured from neonatal (P0-3) rats., Key Results: Here, we show that E2 induces a novel form of LTP at TA-CA1 synapses, an effect mirrored by the ERα agonist, PPT, and blocked by an ERα antagonist. ERα-induced LTP is NMDA receptor (NMDAR)-dependent and involves a postsynaptic expression mechanism that requires PI 3-kinase signalling and synaptic insertion of GluA2-lacking AMPARs. ERα-induced LTP has overlapping expression mechanisms with classical Hebbian LTP, as HFS-induced LTP occluded PPT-induced LTP and vice versa. In addition, activity-dependent LTP was blocked by the ERα antagonist, suggesting that ERα activation is involved in NMDA-LTP at TA-CA1 synapses., Conclusion and Implications: ERα induces a novel form of LTP at juvenile male hippocampal TA-CA1 synapses. As TA-CA1 synapses are implicated in episodic memory processes and are an early target for neurodegeneration, these findings have important implications for the role of oestrogens in CNS health and neurodegenerative disease., (© 2019 The British Pharmacological Society.)

A validation study was conducted for an immunochromatographic method (BetaStar ® Advanced for Tetracyclines) for detection of tetracycline antibiotic residues in raw, commingled bovine milk. The assay was demonstrated to detect tetracycline, chlortetracycline, and oxytetracycline at levels below the FDA tolerance levels but above the maximum sensitivity thresholds established by the National Conference on Interstate Milk Shipments. Results of internal and independent laboratory dose-response studies employing spiked samples were in agreement. All three drugs at the approximate 90/95% sensitivity levels were detected in milk collected from cows that had been treated with the specific drug. Selectivity of the assay was 100%, as no false-positive results were obtained in testing 881 control milk samples. Testing the estimated 90/95 sensitivity level for tetracycline (213 ppb), chlortetracycline (272 ppb), and oxytetracycline (180 ppb) and at 1000 ppb for each antibiotic resulted in 100% positive tests for each tetracycline. Results of ruggedness experiments established the operating parameter tolerances for the test. Results of cross-reactivity testing established that the assay detects certain other tetracycline drugs but does not cross-react with any of 32 drugs belonging to seven different drug classes. Abnormally high bacterial or somatic cell counts (SCC) in raw milk produced no assay interference.

The hippocampus is a key target for the hormone leptin and leptin regulation of excitatory synaptic transmission at Schaffer-collateral-CA1 synapses during aging are well documented. However, little is known about the age-dependent actions of leptin at the temporoammonic (TA) input to CA1 neurons. Here we show that leptin induces a novel form of N-methyl-D-aspartate receptor-dependent long-term depression (LTD) at adult (12-24 weeks old) TA-CA1 synapses. Leptin-induced LTD requires activation of canonical Janus tyrosine kinase 2- signal transducer and activator of transcription signaling and removal of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors from synapses. Moreover, leptin-induced LTD is occluded by activity-dependent LTD at TA-CA1 synapses. By contrast, leptin has no effect on excitatory synaptic transmission at aged (12-14 months old) TA-CA1 synapses, and low-frequency stimulation also fails to induce LTD at this age. These findings demonstrate clear age-related alterations in the leptin sensitivity of TA-CA1 synapses and provide valuable information on how the leptin system alters with age. As leptin has been linked to Alzheimer's disease, these findings have important implications for understanding of age-related disorders such as Alzheimer's disease., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

In contemporary dance, experts evaluate creativity in competitions, auditions, and performances, typically through ratings of choreography or improvisation. Audiences also implicitly evaluate choreographic creativity, so dancers' livelihoods also hinge upon the opinions of non-expert observers. However, some argue that the abstract and often pedestrian nature of contemporary dance confuses non-expert audiences. Therefore, agreement regarding creativity and appreciation amongst experts and non-experts may be low. Finding appropriate methodologies for reliable and real-world creativity evaluation remains the subject of considerable debate within the psychology creativity research field. Although considerably variant in methodological operationalisation, the Consensual Assessment Technique (CAT) asks individuals to use an implicit definition to assess creativity in others' work. This study aimed to investigate the role of experience and expertise in the evaluation of choreographic creativity, with a secondary aim of testing the feasibility of an online snowballing methodology for large-scale dance-specific research, informed by the methodology of the CAT. We filmed 23 Contemporary Dance students each performing a 3-min peer-choreographed solo and then recruited 850 online evaluators with varying degrees of expertise and experience in dance and creativity. Evaluators viewed at least one randomly selected video and rated creativity, technical ability, appreciation and understanding of the work, each using a seven-point Likert scale. A one-way ANOVA showed a significant difference in creativity ratings across the 23 videos, and creativity correlated significantly with the other variables. We then categorized evaluators on nine aspects of their dance and creative experience and entered the data into a repeated-measures linear mixed model. Two of the fixed effects yielded differences in creativity evaluations: (i) contemporary choreographic experience and (ii) self-reported creative expertise, as did the random effect of the video. The results indicate that personal experience of the choreographic process impacts creativity assessment, above and beyond experience in dance class participation. Implications for creativity assessment within creativity research and practice are discussed.

Objectives: To compare radiologists' performance reading CTs independently with their performance using radiographers as concurrent readers in lung cancer screening., Methods: 369 consecutive baseline CTs performed for the UK Lung Cancer Screening (UKLS) trial were double-read by radiologists reading either independently or concurrently with a radiographer. In concurrent reading, the radiologist reviewed radiographer-identified nodules and then detected any additional nodules. Radiologists recorded their independent and concurrent reading times. For each radiologist, sensitivity, average false-positive detections (FPs) per case and mean reading times for each method were calculated., Results: 694 nodules in 246/369 (66.7%) studies comprised the reference standard. Radiologists' mean sensitivity and average FPs per case both increased with concurrent reading compared to independent reading (90.8 ± 5.6% vs. 77.5 ± 11.2%, and 0.60 ± 0.53 vs. 0.33 ± 0.20, respectively; p < 0.05 for 3/4 and 2/4 radiologists, respectively). The mean reading times per case decreased from 9.1 ± 2.3 min with independent reading to 7.2 ± 1.0 min with concurrent reading, decreasing significantly for 3/4 radiologists (p < 0.05)., Conclusions: The majority of radiologists demonstrated improved sensitivity, a small increase in FP detections and a statistically significantly reduced reading time using radiographers as concurrent readers., Key Points: • Radiographers as concurrent readers could improve radiologists' sensitivity in lung nodule detection. • An increase in false-positive detections with radiographer-assisted concurrent reading occurred. • The false-positive detection rate was still lower than reported for computer-aided detection. • Concurrent reading with radiographers was also faster than single reading. • The time saved per case using concurrently reading radiographers was relatively modest.

Objective: To compare the performance of radiographers against that of radiologists for CT lung nodule detection in the UK Lung Cancer Screening (UKLS) pilot trial., Methods: Four radiographers, trained in CT nodule detection, and three radiologists were prospectively evaluated. 290 CTs performed for the UKLS were independently read by 2 radiologists and 2 radiographers. The reference standard comprised all radiologist-identified positive nodules after arbitration of discrepancies. For each radiographer and radiologist, relative sensitivity and average false positives (FPs) per case were compared for all cases read, as well as for subsets of cases read by each radiographer-radiologist combination (10 combinations)., Results: 599 nodules in 209/290 (72.1%) CT studies comprised the reference standard. The relative mean (±standard deviation) sensitivity of the four radiographers was 71.6 ± 8.5% compared with 83.3 ± 8.1% for the three radiologists. Radiographers were less sensitive and detected more FPs per case than radiologists in 7/10 and 8/10 radiographer-radiologist combinations, respectively (ranges of difference 11.2-33.8% and 0.4-2.6; p < 0.05). In 3/10 and 2/10 combinations, there was no difference in sensitivity and FPs per case between radiographers and radiologists. For nodules ≥100 mm(3) in volume or ≥5 mm in maximum diameter, radiographers were relatively less sensitive than radiologists in only 5/10 radiographer-radiologist combinations (range of difference 16.1-30.6%; p < 0.05) and not significantly different in the remaining 5/10 combinations., Conclusion: Although overall radiographer performance was lower than that of experienced radiologists in this study, some radiographer performances were comparable with that of radiologists., Advances in Knowledge: Overall, radiographers were less sensitive than radiologists reading the same CTs and also displayed higher average FP detections per case when compared with a reference standard derived from radiologist readings. However, some radiographers compared favourably with radiologists, especially when considering larger potentially clinically relevant nodules. Thus, while probably not sensitive enough to function as first readers, radiographers may still be able to fulfil the role of an assistant reader-that is, as a first or concurrent reader, who presents detected nodules for verification to a reading radiologist.

The American Heart Association recommends therapeutic hypothermia for comatose patients with return of spontaneous circulation after out-of-hospital ventricular fibrillation cardiac arrest. While there is a growing body of evidence for the general efficacy of therapeutic hypothermia, the individualized benefit of therapy is not currently predictable. Ninety-one consecutive patients, from April 2011 to July 2014, were treated at the University of Kentucky Medical Center with the therapeutic hypothermia protocol. Medical records were reviewed retrospectively. Data, such as preexisting comorbidities, cardiac arrest characteristics, and hospital course, were used to compose a multivariate logistic regression with mortality serving as the primary endpoint. The overall in-hospital mortality was 64% (n = 58) in this group. The arrest was considered cardiac etiology in 84% (n = 76) of patients, of which 49% (n = 45) were classed as ventricular fibrillation and 9% (n = 8) as ventricular tachycardia. The presence of a shockable rhythm, as well as shorter duration of cardiac arrest, was associated with increased survival, whereas time to target temperature was not. The presence of a preexisting neurologic disease was associated with a 10-fold increase in estimated odds of mortality. Age, serum lactate, ionized calcium, arterial pH, estimated glomerular filtration rate, and APACHE score were all predictors of mortality. Cardiac arrest is a devastating condition with a high mortality rate. Given the limited resources of the resuscitation community, the ability to predict survivors based on routinely obtained measures upon admission would be of tremendous value. In this study, we show a series of admission parameters that demonstrate predictive ability in identifying patients more likely to survive with therapeutic hypothermia.

Background: Unnecessary antibiotic prescribing contributes to antimicrobial resistance. In this trial, we aimed to reduce unnecessary prescriptions of antibiotics by general practitioners (GPs) in England., Methods: In this randomised, 2 × 2 factorial trial, publicly available databases were used to identify GP practices whose prescribing rate for antibiotics was in the top 20% for their National Health Service (NHS) Local Area Team. Eligible practices were randomly assigned (1:1) into two groups by computer-generated allocation sequence, stratified by NHS Local Area Team. Participants, but not investigators, were blinded to group assignment. On Sept 29, 2014, every GP in the feedback intervention group was sent a letter from England's Chief Medical Officer and a leaflet on antibiotics for use with patients. The letter stated that the practice was prescribing antibiotics at a higher rate than 80% of practices in its NHS Local Area Team. GPs in the control group received no communication. The sample was re-randomised into two groups, and in December, 2014, GP practices were either sent patient-focused information that promoted reduced use of antibiotics or received no communication. The primary outcome measure was the rate of antibiotic items dispensed per 1000 weighted population, controlling for past prescribing. Analysis was by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN32349954, and has been completed., Findings: Between Sept 8 and Sept 26, 2014, we recruited and assigned 1581 GP practices to feedback intervention (n=791) or control (n=790) groups. Letters were sent to 3227 GPs in the intervention group. Between October, 2014, and March, 2015, the rate of antibiotic items dispensed per 1000 population was 126.98 (95% CI 125.68-128.27) in the feedback intervention group and 131.25 (130.33-132.16) in the control group, a difference of 4.27 (3.3%; incidence rate ratio [IRR] 0.967 [95% CI 0.957-0.977]; p<0.0001), representing an estimated 73,406 fewer antibiotic items dispensed. In December, 2014, GP practices were re-assigned to patient-focused intervention (n=777) or control (n=804) groups. The patient-focused intervention did not significantly affect the primary outcome measure between December, 2014, and March, 2015 (antibiotic items dispensed per 1000 population: 135.00 [95% CI 133.77-136.22] in the patient-focused intervention group and 133.98 [133.06-134.90] in the control group; IRR for difference between groups 1.01, 95% CI 1.00-1.02; p=0.105)., Interpretation: Social norm feedback from a high-profile messenger can substantially reduce antibiotic prescribing at low cost and at national scale; this outcome makes it a worthwhile addition to antimicrobial stewardship programmes., Funding: Public Health England., (Copyright © 2016 Hallsworth et al. Open Access article distributed under the terms of CC BY-NC-ND. Published by Elsevier Ltd.. All rights reserved.)

This article describes three strategies a cardiovascular-thoracic intensive care unit implemented to decrease the rate of hospital-acquired pressure ulcers in patients on extracorporeal membranous oxygenation support. These strategies include increased staff awareness of physiologic factors placing a critically ill patient on extracorporeal support at increased risk for development of pressure ulcers, development of a turning guideline and a skin care bundle, and use of coaching by a clinical nurse specialist to promote pressure ulcer prevention., (Copyright © 2014 Elsevier Inc. All rights reserved.)

What is the cellular origin of melanoma? What role do melanocyte stem cells (MSC) and other melanocyte precursors play in the development of melanoma? Are MSCs and other latent melanocyte precursors more susceptible to solar radiation? These and many other questions can be very effectively addressed using the zebrafish model. Zebrafish have a robust regenerative capability, permitting the study of how MSCs are regulated and recruited at specific times and places to generate the pigment pattern following fin amputation or melanocyte ablation. They can be used to determine the effects of environmental radiation on the proliferation, survival, repair, and differentiation of MSCs. Our lab is using zebrafish to investigate how UVA- (320-400 nm) and UVB- (290-320 nm) induced damage to MSCs may contribute to the development of melanoma. A review is given of MSCs in zebrafish as well as experimental techniques and drugs for manipulating MSC populations. These techniques can be used to design experiments to help answer many questions regarding the role of MSCs or melanocyte precursors in the formation of melanoma stem cells and tumors following exposure to UVA/UVB radiation.

Chronic kidney disease is fast becoming a worldwide epidemic. There is an estimated annual increase of 8% with an associated economical and clinical burden. Recent research into lifestyle factors has confirmed different dietary attributes play a part in slowing the progression of chronic nephropathies. This has important implications and a potentially cost-saving way, to help reduce the progression of the disease. The roles of obesity, lipids, protein, diabetes and blood pressure are discussed to show how the current literature reflects how to modify the dietary aspects of these. The mechanisms behind these are not fully understood, but the message remains the same that there is an increased need for dietary advice in the pre-dialysis population.

The src homology 2 domain-containing tyrosine phosphatase 2 (SHP2) plays an important role in development and in growth factor receptor signaling pathways, yet little is known of its role in the immune system. We generated mice expressing a dominant-negative version of the protein, SHP2(CS), specifically in T cells. In SHP2(CS) mice, T cell development appears normal with regard to both negative and positive selection. However, SHP2(CS) T cells express higher levels of activation markers, and aged mice have elevated serum Abs. This is associated with a marked increase in IL-4, IL-5, and IL-10 secretion by SHP2(CS) T cells in vitro. In addition, primary thymus-dependent B cell responses are deficient in SHP2(CS) mice. We show that whereas TCR-induced linker for activation of T cells phosphorylation is defective, CTLA-4 and programmed death-1 signaling are not affected by SHP2(CS) expression. Our results suggest that a key action of wild-type SHP2 is to suppress differentiation of T cells to the Th2 phenotype.

Aim: To evaluate the whether screening for cerebral metastases in neurologically intact patients with potentially resectable non-small cell lung cancer patients is both worthwhile and cost-effective., Methods: We prospectively performed computed tomography (CT) of the head in 105 consecutive patients with potentially resectable lung cancer over an 18-month period. None of these patients had neurological symptoms or signs., Results: Five patients (4.8%) with cerebral metastases were identified using CT. At our institution the financial saving of avoiding five thoracotomies was pound sterling 45,000, whilst the cost of performing 105 head CTs was pound sterling 16,000. This represented a substantial saving for the healthcare provider and preserved the quality of life in five patients., Conclusions: We conclude that screening for cerebral metastases in neurologically intact patients with potentially resectable non small cell lung cancer patients is both worthwhile and cost effective.

X-linked Emery-Dreifuss muscular dystrophy is usually caused by absence of the nuclear membrane protein, emerin, due to nonsense mutations or deletions, but a few missense mutations also exist. A pathogenic g993t mutation causes a Q133H change in the nuclear targeting region of emerin, but it may also reduce emerin levels by affecting mRNA splicing. We have introduced the g993t mutation by in vitro mutagenesis and studied the effect of Q133H on nuclear targeting by transfection of COS-7 cells. No qualitative or quantitative differences in nuclear targeting were observed between normal and mutant emerin. Quantitative BIAcore analysis showed no significant change in lamin A binding to emerin when the mutation was present. We conclude that Q133 is not essential for nuclear targeting of emerin or its interaction with lamin A. Reduced emerin levels due to altered splicing or defective interaction with an unidentified binding partner remain possible pathogenic mechanisms., (Copyright 2001 Academic Press.)

Most pathogenic missense mutations in the lamin A/C gene identified so far cause autosomal-dominant dilated cardiomyopathy and/or Emery-Dreifuss muscular dystrophy. A few specific mutations, however, cause a disease with remarkably different clinical features: FPLD, or familial partial lipodystrophy (Dunnigan-type), which mainly affects adipose tissue. We have prepared lamin A with a known FPLD mutation (R482Q) by in vitro mutagenesis. Nuclear targeting of lamin A in transfected COS cells, human skeletal muscle cells or mouse adipocyte cell cultures (pre- and post-differentiation) was not detectably affected by the mutation. Quantitative in vitro measurements of lamin A interaction with emerin using a biosensor also showed no effect of the mutation. The results show that the loss of function of R482 in lamin A/C in FPLD does not involve loss of ability to form a nuclear lamina or to interact with the nuclear membrane protein, emerin.

Emerin is the protein of the inner nuclear membrane that is affected by mutation in X-linked Emery-Dreifuss muscular dystrophy. The autosomal dominant form of the disease is caused by mutations in the lamin A/C gene. Several lines of circumstantial evidence have suggested an interaction of emerin with lamins in the nuclear lamina but direct interaction between the two proteins has not yet been demonstrated. We now demonstrate direct interaction between recombinant emerin and lamin A molecules using biomolecular interaction analysis (BIA) and monoclonal antibodies. An emerin-lamin A interaction system may be related in function to the LAP2-lamin B system at the inner nuclear rim., (Copyright 2000 Academic Press.)

Helicobacter pylori, an infectious agent of worldwide public health importance, has higher seroprevalence in developing countries than in developed countries. We investigated whether Bangladeshi women, born in Bangladesh, have a greater H. pylori seroprevalence than Bangladeshi women born in the U.K. and, in addition, whether there is an association between H. pylori seropositivity and age of migration to the U.K. amongst Bangladeshi women. Women attending antenatal clinics at the Royal London Hospital were screened using ELISA for anti-H. pylori IgG. In Bangladeshi individuals born in the U.K., 13/16 (81%, 95% confidence interval (CI) 54%-96%) and, in Bangladeshi individuals born in Bangladesh 91/137 (66%, 95% CI 59%-74%) had antibodies to H. pylori. No significant association was found between H. pylori seropositivity and country of birth, or age at migration to the U.K. Public health strategies concerning H. pylori should consider migrant populations with high seroprevalence of H. pylori.

The relationship between relative force, electromyogram (EMG) and time to fatigue was examined in seven male and seven female subjects [mean (SD) age, 21.7 (3.2) years] during isometric handgrip exercise. Subjects performed sustained submaximal contractions of the right handgrip at three different intensities: 30%, 50%, and 75% of the pretrial maximum voluntary contraction (MVC). EMG was sampled in 1-s epochs every 15 s during the contractions, and the integrated EMG (IEMG) values were then normalized to that of the pretrial MVC. As expected, time to fatigue was longest at 30% MVC and shortest at 75% MVC, but women performed consistently longer than men at each of the three intensities [woman vs men; 400.7 (35.8) vs 364.3 (34.4) s, 205.1 (15.6) vs 139.4 (13) s, and 89.9 (11.4) vs 66.4 (6.4) s, for 30%, 50%, and 75% MVC, respectively; P < 0.05)]. IEMG increased in a non-linear fashion over time during each trial, with the magnitude of IEMG being proportional to the intensity of the contraction. At the endurance limit, IEMG was greatest in the 75% MVC trial, however, no IEMG values reached those obtained in the related MVC [30%, 57.2 (6.9)%, 50%, 84.6 (5.7)%; 75%, 92.8 (7.4)%]. In conclusion, endurance time during sustained submaximal isometric handgrip exercise is dependent up on the intensity of the effort, with women having significantly larger endurance times than men. The related increase in IEMG is also proportional to the intensity of effort, however, the factors causing force to fail prior to the final IEMG reaching its predicted maximum remain to be elucidated.

To test the null hypothesis that frequent and multiple salivary exposure is not a risk factor for developing H. pylori infection, serum anti-H. pylori IgG from 179 dentists and dental students and 179 age-, sex- and socioeconomic-matched controls were assayed using an ELISA. Seroprevalence in dentists was 16% (11/70); clinical dental students 6% (3/47); and pre-clinical dental students 10% (6/62). There were no differences in H. pylori seropositivity between cases and controls. There was an increase in H. pylori seropositivity with age (chi (trend)2 9.04, p = 0.003). These data provide evidence that adults are not at high risk of developing H. pylori infection as a result of exposures to saliva from multiple sources.

A high prevalence of metronidazole resistance in Helicobacter pylori is reported in developing countries. This study examined whether migrants referred for diagnostic gastroscopy at a United Kingdom centre (n = 54), had a higher prevalence of metronidazole resistance than subjects born in the United Kingdom attending endoscopy (n = 46). Records of nitroimidazole treatment prescribed in the United Kingdom was obtained in 83 patients to find out if there was an association between H pylori metronidazole resistance and previous ingestion of either metronidazole or tinidazole. The prevalence of metronidazole resistant isolates varied according to country of birth: Bangladesh (90%, 27 of 30), other countries (67%, 16 of 24), and United Kingdom (37%, 17 of 46) (p < 0.001). Among those born in the United Kingdom, women were more likely to harbour resistant H pylori than men (54% v 18% respectively, p = 0.01) and more likely to have a history of previous nitroimidazole ingestion (41% v 11% respectively, p = 0.02). Patients previously exposed to either metronidazole or tinidazole were more likely to harbour resistant strains (84% (27 of 32) v 41% (21 or 51), p < 0.0001). The distribution of gastroduodenal disease, assessed endoscopically, was not affected by metronidazole resistance status.

Helicobacter pylori infection has been associated with stimulation of gastric mucosal reactive oxygen metabolite production. To provide further evidence of a causal relationship we looked for a dose-response relationship. We studied antral biopsy material from 110 patients. Quantitative H. pylori assessments were made using histologic and microbiologic methods. Reactive oxygen metabolite production was measured by luminol-dependent chemiluminescence. The usefulness of timed urease test colour changes as a guide to infective load was assessed. There was a positive association between mucosal reactive oxygen metabolite production and histologic (p = 0.002, n = 69) and microbiologic (Spearman's R = +0.6, p = 0.05, n = 18) quantitative H. pylori assessments. H. pylori infective load varied markedly over small areas (coefficient of repeatability of paired cultures (in colony-forming units/mg) = 1.9 x 10(6). Urease test timing correlated with histologic (p = 0.01) and microbiologic (p = 0.03) H. pylori quantitation. Histologically assessed mucosal damage was related to quantitative H. pylori assessment and to mucosal reactive oxygen metabolite production (p = 0.0001). These results support the hypothesis that H. pylori stimulates gastric mucosal reactive oxygen metabolite production and that this phenomenon is of pathogenic importance.

The use and quality of computed tomography (CT) in the evaluation of blunt abdominal trauma has been assessed by a retrospective review of 122 patients referred in the first 8 years following the installation of CT of the body. The referral patterns were analysed, and the quality of the images was assessed, with particular reference to unsatisfactory (unacceptable or poor) images. Referrals increased over the 8 years following installation. A large proportion of these examinations were performed outside normal working hours (58/122, 48%). In 64 out of 122 (52%) of examinations the images were considered of unsatisfactory quality with inadequate use of intravenous contrast medium cited as the most common cause for unsatisfactory examinations. Image quality did not improve with time. Image quality was unsatisfactory in a larger proportion of those examinations performed outside normal working hours (35/58, 60%) than those during the routine working day (29/64, 45%), although this difference did not reach statistical significance (0.1 greater than p greater than 0.05). Fewer unsatisfactory examinations were produced by a system dedicated to body CT (31/74, 42%) than by a neuroradiological system (33/48, 69%) (p less than 0.01). The proportion of unsatisfactory abdominal examinations was lower when the CT study concentrated on the abdomen (26/65, 40%) than when multiple regions (head, chest, abdomen, etc.) were examined (38/57, 67%) (p less than 0.01). This audit revealed many unsatisfactory examinations. In order to complete the audit loop we have addressed many of the contributory factors. A new CT system now provides images of high quality and is used for all abdominal work. Guidelines, which describe an optimized technique, have been issued to radiographers and radiologists. In particular, we have emphasized that there is no place for a poorly supervised "quick look" at the abdomen following a cranial or thoracic study.

Human gastrointestinal cancer xenografts were established in the nude mouse. Grafts were accomplished with gastric adenocarcinomas, gastric leiomyosarcoma, histiocytic lymphoma of the stomach and gallbladder, pancreatic tumors, colonic cancers and cell lines of duodenal (HUTU-80) and pancreatic (HS-766-T) cancers, melanoma (SK-Mel-5), and murine metastasizing Lewis lung carcinoma. The rate of successful xenografting of these tumors varied from virtually 100% with colon and duodenal cancer, 50% for a pancreatic cancer (P-1), to only 17% for gastric adenocarcinoma. Pancreas and colon adenocarcinomas have been maintained by successive xenotransplantation over 16 and 19 months, respectively. Human xenografts retained morphological identity with tissues of origin through several transplant generations and shared some of their ultrastructural characteristics but did not metastasize. Rodent xenografts, of heterogenous origin were characterized by differences in the duration of the latent period and in the rate of their initial development as described by the average doubling times and average slopes (B) of their growth curves. Differences between B of the Lewis lung carcinoma and all of the human xenografts and between B of a pancreatic adenocarcinoma and three other neoplasms were significant (P less than 0.05 to 0.04). Labeling indices determined for 14 cancer transplants were in the range of previously reported data for similar neoplasms in patients or other xenograft systems. These findings suggest that the nude mouse model can be used to evaluate endogenous properties of gastrointestinal cancers and their responses to exogenous agents.

This paper presents a description of the Canadian Back Education Units (CBEU) which was formed in 1974. It presently has three programmes; hospital, community and industry. The authors describe the basic philosophy and objectives of the CBEU with specific emphasis on the role of occupational therapy. The paper illustrates how occupational therapy is particularly essential in the community and industrial settings. The authors mention recommendations for expansion of the role of occupational therapy in community and industrial settings.