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Background Announced in March 2016 and implemented in April 2018, the UK Soft Drinks Industry Levy (SDIL) aims to incentivise the reformulation of soft drinks. The SDIL has successfully decreased the amount of sugar in UK soft drinks, and purchased in soft drinks. Consequently, the SDIL has been widely applauded as a policy success. SSB taxation in other countries, however, has not been as successful and in some cases the policy was retracted. We aimed to develop an understanding of why the SDIL was deemed successful by analysing parliamentary debate two years before its announcement until two years post-implementation (2014–2020). Methods Searches of Hansard were conducted for parliamentary debate transcripts discussing the SDIL across three key time periods: Pre-Announcement (01/01/14–15/03/16), Announcement – Implementation (16/03/16–5/04/18), and Post-Implementation (6/04/18–16/03/20). 218 transcripts containing eligible search terms were identified, and 179 included in the analysis after screening for relevance. Applied thematic analysis was conducted in 5 stages: familiarisation and creation of initial codebooks, independent second coding, codebook finalisation through team consensus, final coding of the dataset to the complete codebook and theme finalisation through team consensus. Results Common issues raised in discussions across the timeline were: the ring-fencing of SDIL funds for pro-social causes, the scale of the health problems associated with excess sugar consumption, and the role of celebrities in making the SDIL a high profile issue. MPs acknowledged that the SDIL is not a ‘silver bullet’ for obesity prevention: it was positioned as either a ‘good start’ with other interventions required or that other interventions were needed instead. Distinct themes were that, due to early reformulation, the SDIL was discussed as ‘having worked’ one year prior to implementation. This notion persisted until the end of the timeline. These themes will be further refined to identify temporal patterns and trends. Additional results will be submitted before the June 28th deadline. Population Health Relevance The SDIL is unique: it is a flagship policy for the UK Childhood Obesity Strategy and has cross-party support. Understanding why and how the SDIL made it onto the statutes, and why it was politically successful is vital for using policy instruments to improve population health in future. This work will aid understanding of the parliamentary process surrounding the SDIL, and could provide insight for those wishing to extend the SDIL to other products or implement SSB taxes elsewhere.

OBJECTIVE Non–small cell lung cancer (NSCLC) is the most common primary tumor to develop brain metastasis. Prognostic markers are needed to better determine survival after neurosurgical resection of intracranial disease. Given the importance of mutation subtyping in determining systemic therapy and overall prognosis of NSCLC, the authors examined the prognostic value of mutation status for postresection survival of patients with NSCLC brain metastasis. METHODS The authors retrospectively analyzed all cases of NSCLC brain metastasis with available molecular testing data that were resected by a single surgeon at a single academic center from January 2009 to February 2019. Mutation status, demographic characteristics, clinical factors, and treatments were analyzed. Association between predictive variables and overall survival after neurosurgery was determined with Cox regression. RESULTS Of the included patients (n = 84), 40% were male, 76% were smokers, the mean ± SD Karnofsky Performance Status was 85 ± 14, and the mean ± SD age at surgery was 63 ± 11 years. In total, 23%, 26%, and 4% of patients had EGFR, KRAS, and ALK/ROS1 alterations, respectively. On multivariate analysis, survival of patients with EGFR (HR 0.495, p = 0.0672) and KRAS (HR 1.380, p = 0.3617) mutations were not significantly different from survival of patients with wild-type (WT) tumor. However, the subgroup of patients with EGFR mutation who also received tyrosine kinase inhibitor (TKI) therapy had significantly prolonged survival (HR 0.421, p = 0.0471). In addition, postoperative stereotactic radiosurgery (HR 0.409, p = 0.0177) and resected tumor diameter < 3 cm (HR 0.431, p = 0.0146) were also significantly associated with prolonged survival, but Graded Prognostic Assessment score ≤ 1.0 (HR 2.269, p = 0.0364) was significantly associated with shortened survival. CONCLUSIONS Patients with EGFR mutation who receive TKI therapy may have better survival after resection of brain metastasis than patients with WT tumor. These results may inform counseling and decision-making regarding the appropriateness of resection of NSCLC brain metastasis.

BACKGROUND Chronic oroantral fistulae (OAF) with secondary sinusitis can occur following repulsion of cheek teeth in horses. CASE REPORT An 8-year-old Andalusian cross gelding presented with an iatrogenic clinical crown fracture of tooth 209, which underwent repulsion of its apical portion (day 0). The horse was treated with intramuscular penicillin and intravenous gentamicin (5 days), followed by oral trimethoprim-sulphonamide (10 days) and then oral doxycycline (14 days). The acute iatrogenic OAF created during the initial repulsion persisted; a chronic OAF was identified on day 24. On day 48, septic sinusitis with multidrug-resistant (MDR) Escherichia coli was confirmed. Although susceptible to enrofloxacin in vitro, 30 days of therapy was unsuccessful. Subsequent serial cultures grew multiple MDR and extensively drug-resistant (XDR) gram-negative microorganisms. Whole-genome sequencing (WGS) revealed multiple sequence types of E. coli, with a range of resistance and virulence genes. The orientation of the OAF, regional osteomyelitis and septic sinusitis were confirmed with computed tomography on day 70. On day 74, enteral nutrition was provided through a cervical oesophagostomy tube for 3 months for prevention of oral feed contamination. The OAF was treated with various alternative therapeutics, including apple cider vinegar, propolis and amikacin impregnated products, until resolution on day 116. CONCLUSION These non-conventional therapeutics, antimicrobials and long-term oesophagostomy contributed to the successful treatment of a complicated OAF. In the future, WGS may be useful to inform antimicrobial selection when MDR or XDR organisms are identified.

Mesothelioma is a rare and fatal cancer with limited therapeutic options until the recent approval of combination immune checkpoint blockade. Here we report the results of the phase 2 PrE0505 trial (NCT02899195) of the anti-PD-L1 antibody durvalumab plus platinum-pemetrexed chemotherapy for 55 patients with previously untreated, unresectable pleural mesothelioma. The primary endpoint was overall survival compared to historical control with cisplatin and pemetrexed chemotherapy; secondary and exploratory endpoints included safety, progression-free survival and biomarkers of response. The combination of durvalumab with chemotherapy met the pre-specified primary endpoint, reaching a median survival of 20.4 months versus 12.1 months with historical control. Treatment-emergent adverse events were consistent with known side effects of chemotherapy, and all adverse events due to immunotherapy were grade 2 or lower. Integrated genomic and immune cell repertoire analyses revealed that a higher immunogenic mutation burden coupled with a more diverse T cell repertoire was linked to favorable clinical outcome. Structural genome-wide analyses showed a higher degree of genomic instability in responding tumors of epithelioid histology. Patients with germline alterations in cancer predisposing genes, especially those involved in DNA repair, were more likely to achieve long-term survival. Our findings indicate that concurrent durvalumab with platinum-based chemotherapy has promising clinical activity and that responses are driven by the complex genomic background of malignant pleural mesothelioma., In a phase 2 trial, the combination of chemotherapy with durvalumab, an anti-PD-L1 antibody, exhibited promising clinical activity in patients with previously untreated, unresectable mesothelioma, with additional analyses providing insights into genomic and immunologic features potentially associated with response.

This article outlines an attempt to use drawing and comics as an arts-based research methodology during an ethnographic project relating to sport and social change in South Africa. The use of drawi...

Purpose The aim of this paper is twofold. First, to understand the degree to which the intended outcomes of Saudi’s Nitaqat labour market policy corresponds to the actual responses from private companies. Second, to investigate how these gaps between policy intentions and actual outcomes have informed recent changes to Nitaqat policy. Design/methodology/approach This paper uses a qualitative approach with a case study design and thematic analysis procedures. Data were obtained from the following three sources: semi-structured interviews completed during the early stage of Nitaqat in 2013–2014 with nine policymakers and 44 key stakeholders from six private Saudi companies; policy documents and gray literature on the aims and effects of the Nitaqat program; and available peer-reviewed literature on the subject. Findings This paper sets out and analyses the following four main goals of Nitaqat: First, to increase the Saudi national employment rate, second, increase company efficiency, third, improve human resource capabilities, and fourth, increase female labour participation. This paper reveals that although Nitaqat has certainly resulted in a positive change in some of these areas, in other areas, there remain gaps between the intentions and the actual effects of Nitaqat. This paper analyses recent changes to Nitaqat and argues that further changes may be needed to achieve the full goals of Nitaqat. Originality/value This paper’s originality lies in its analysis of the aims of labour market policies and organisational responses. It highlights the reasons for disconnections between the policy aims and organisational practices and explores how policymakers react and respond to these implementation gaps.

Objectives Clinical studies have reported an inverse relationship between calcium and vitamin D intake and hypertensive disorders of pregnancy (HDP). The aim of this study was to investigate if there was an association between calcium/vitamin D intake, and vitamin D (25OHD) status, and maternal blood pressure (BP), during pregnancy and at 5-year follow-up. Study design This was an observational study of 415 women who participated in the ROLO (Randomised cOntrolled trial of LOw glycaemic index diet for the prevention of recurrence of macrosomia) study. Maternal BP measurements were taken during each trimester and at 5-year follow-up. Calcium and vitamin D intake were determined at each trimester and 25OHD was measured in early and late pregnancy. Results Over two-thirds of the cohort were vitamin D sufficient (25OHD > 30 nmol/L) and had adequate calcium intake (>750 mg/day). There was no correlation between calcium intake or vitamin D intake and maternal BP in trimester 1 to 3 or at 5-year follow-up. Vitamin D status at 13 weeks’ gestation negatively correlated with mean arterial pressure in trimester 1 (r = −0.152, p = 0.044). There was no correlation however between 25OHD at 28 weeks’ gestation and BP at 28 or 34 weeks’ gestation or 25OHD and BP at 5-year follow-up. Conclusions In a healthy population of women with adequate calcium and vitamin D intake, no clinically significant correlation existed between calcium and vitamin D and maternal BP.

Public education is not just a way to organise and fund education. It is also the expression of a particular ideal about education and of a particular way to conceive of the relationship between education and society. The ideal of public education sees education as an important dimension of the common good and as an important institution in securing the common good. The common good is never what individuals or particular groups want or desire, but always reaches beyond such particular desires towards that which societies as a whole should consider as desirable. This does, of course, put the common good in tension with the desires of individuals and groups. Neo-liberal modes of governance have, over the past decades, put this particular educational set up under pressure and have, according to some, eroded the very idea of the common good. This set of contributions reflects on this state of affairs, partly through an exploration of the idea of publicness itself – how it can be rearticulated and regained – and partly through reflections on the current state of education in the ‘north’ and the ‘south.’ Refereed/Peer-reviewed

The novel Coronavirus Disease 2019 (COVID-19) is a pandemic of great public health and clinical concern due to its high rate of infectivity, and subsequent morbidity and mortality. The objectives of the study were to 1) assess individual experiences with testing and symptoms of COVID-19 infection; 2) determine the extent to which individuals experienced COVID-19 post-exposure symptoms; and 3) determine if an association exists between pre-existing conditions and severity of COVID-19 symptoms with post-exposure symptoms. One hundred and twenty-one (N= 121) New York State residents who had COVID-19 symptoms and were tested positive for the virus participated in this study. The survey was created in Qualtrics, and the link was posted online (Facebook, Twitter, Snap Chat), and sent to New Yorkers via email and WhatsApp to gather data. Data were exported from Excel spreadsheet to Statistical Package for the Social Sciences (SPSS), version 25, where Chi-Square tests were conducted. Results indicated that most of the participants were between ages 18-35 (54.5%), African Americans (50.4%), non- Hispanic (65%), female (69.4%), had less than a college degree (51%), and made an income in 2019 of less than $55,000 per year (62%). Eighty-seven (approximately 73%) of the participants reported that getting access to testing was easy/very easy. More than one-half reported that they experienced fatigue (66.9%), lack of energy (61.2%), headache (57.9%), muscle ache (53.7%), cough (50.4%), and loss of smell (50.4%) while infected with COVID-19. Participants who experienced symptoms described their most bothersome symptom as severe (37%), followed by mild (33%), and moderate (27%). There was a statistically significant relationship between severity of symptoms and post-exposure problems experienced by participants (X2 = 13.69; df = 2; p = .001); as well as between pre-existing conditions and post-exposure problems experienced by participants (X2 = 10.53; df = 1; p = .001). Information from this study could benefit public health practitioners and clinicians by improving their knowledge about COVID-19 and its impacts on survivors.

Evidence-based adherence counseling interventions must be delivered with fidelity to ensure that their effectiveness is retained, but little is known regarding how counselors in biomedical HIV trials deliver these interventions. Forty-two counselors from the MTN-025/HOPE Study, which was conducted in 14 sites in sub-Saharan Africa, participated. They completed a quantitative assessment and consented for their HOPE counseling session ratings to be analyzed. Twenty-two (52%) self-identified as research nurses and 20 (48%) as counselors. Of 928 session ratings, 609 (66%) were classified as Good, 188 (20%) as Fair, and 131 (14%) as Poor, based on pre-established criteria. Overall mean ratings for session tasks and global components (each rated from 1 to 5) were 4.12 (SD = 0.45; range 2.46-4.73) and 4.02 (SD = 0.64; range 1.75-4.79), respectively. Twenty-six (62%) counselors attained Good or Fair ratings on at least 85% of their sessions, but 33% of counselors had more than 25% of their sessions rated as Poor; three counselors (7%) never met criteria for a Good session. Even after extensive training, counselors' fidelity to the intervention varied. Our findings highlight the value of fidelity monitoring using session audio-recordings, the importance of ongoing coaching and support, and the need to plan for counselors with consistently poor fidelity.Las intervenciones de consejería de adherencia basadas en la evidencia deben ser realizadas con fidelidad para asegurar que retengan su efectividad, pero se sabe poco sobre cómo los consejeros en ensayos biomédicos de VIH realizan estas intervenciones. Cuarenta y dos consejeros participaron del Estudio MTN-025/HOPE, el cual se llevó a cabo en 14 sitios en África subsahariana. Completaron un cuestionario cuantitativo y dieron su consentimiento para el análisis de las calificaciones de sus sesiones de consejería para HOPE. Veintidós (52%) se identificaron como enfermeras investigadoras y 20 (48%) como consejeros. De 928 sesiones calificadas, 609 (66%) fueron clasificadas como Buenas, 188 (20%) como Suficientes, y 131 (14%) como Mediocres, basado en criterios preestablecidos. Las calificaciones promedias de las tareas de las sesiones y de los componentes globales (calificados de 1 a 5) fueron de 4.12 (SD = 0.45; rango 2.46–4.73) y de 4.02 (SD = 0.64; rango 1.75–4.79), respectivamente. Veintiséis (62%) consejeros lograron calificaciones Buenas o Suficientes en al menos el 85% de sus sesiones, pero para el 33% de los consejeros, más del 25% de sus sesiones fueron calificadas como Mediocres; tres consejeros (7%) nunca cumplieron con los criterios de una Buena sesión. Aún después de una capacitación intensiva, la fidelidad a la intervención variaba. Nuestros hallazgos destacan el valor de monitorear para la fidelidad usando audio-grabaciones de las sesiones, la importancia de la instrucción y el apoyo continuo, y la necesidad de planear qué medidas tomar cuando hay consejeros que no son fieles a la intervención.

Media framing of social protests can influence public opinion and governmental response. An extensive line of scholarly work had pointed to the existence of two alternative news frames; public order and debate. We argue that prior work may have been limited by the reliance on deductive strategies using predefined, theoretically-driven frames. Using a data-driven computational method, the Analysis of Topic Model Networks (ANTMN), we examine mainstream news’ framing of two contentious protests that took place during Donald Trump’s presidency; Unite the Right rally in Charlottesville, VA ( n = 1231 news articles), and the Black Lives Matter protests ( n = 2810). In addition to the frames found in past research, we identify a prominent Politics frame, often focussing on the role of Trump in inciting and reacting to racial tensions. An in-depth analysis of the application of frames to each protest revealed a nuanced use of the Protest Paradigm. We suggest possible revisions to existing theories, and discuss the potential social and political implications of our findings.

Background Patients with non‐small cell lung cancer may develop pneumonitis after thoracic radiotherapy (RT) and immune checkpoint inhibitors (ICIs). We hypothesized that distinct morphologic features are associated with different pneumonitis etiologies. Materials and Methods We systematically compared computed tomography (CT) features of RT‐ versus ICI‐pneumonitis. Clinical and imaging features were tested for association with pneumonitis severity. Lastly, we constructed an exploratory radiomics‐based machine learning (ML) model to discern pneumonitis etiology. Results Between 2009 and 2019, 82 patients developed pneumonitis: 29 after thoracic RT, 23 after ICI, and 30 after RT + ICI. Fifty patients had grade 2 pneumonitis, 22 grade 3, and 7 grade 4. ICI‐pneumonitis was more likely bilateral (65% vs. 28%; p = .01) and involved more lobes (66% vs. 45% involving at least three lobes) and was less likely to have sharp border (17% vs. 59%; p = .004) compared with RT‐pneumonitis. Pneumonitis morphology after RT + ICI was heterogeneous, with 47% bilateral, 37% involving at least three lobes, and 40% sharp borders. Among all patients, risk factors for severe pneumonitis included poor performance status, smoking history, worse lung function, and bilateral and multifocal involvement on CT. An ML model based on seven radiomic features alone could distinguish ICI‐ from RT‐pneumonitis with an area under the receiver‐operating curve of 0.76 and identified the predominant etiology after RT + ICI concordant with multidisciplinary consensus. Conclusion RT‐ and ICI‐pneumonitis exhibit distinct spatial features on CT. Bilateral and multifocal lung involvement is associated with severe pneumonitis. Integrating these morphologic features in the clinical management of patients who develop pneumonitis after RT and ICIs may improve treatment decision‐making. Implications for Practice Patients with non‐small cell lung cancer often receive thoracic radiation and immune checkpoint inhibitors (ICIs), both of which can cause pneumonitis. This study identified similarities and differences in pneumonitis morphology on computed tomography (CT) scans among pneumonitis due to radiotherapy (RT) alone, ICI alone, and the combination of both. Patients who have bilateral CT changes involving at least three lobes are more likely to have ICI‐pneumonitis, whereas those with unilateral CT changes with sharp borders are more likely to have radiation pneumonitis. After RT and/or ICI, severe pneumonitis is associated with bilateral and multifocal CT changes. These results can help guide clinicians in triaging patients who develop pneumonitis after radiation and during ICI treatment., Patients with non‐small cell lung cancer often receive thoracic radiotherapy and immune checkpoint inhibitors (ICIs), both of which can cause pneumonitis. The results of this study can help guide clinicians in triaging patients who develop pneumonitis after receipt of radiation and/or immune checkpoint inhibitor treatment.

In a rapidly changing and unpredictable global environment, there is new impetus to draw on community development approaches in the face of complex practice challenges that include the long-term impacts of the COVID-19 pandemic. As social work and community development educators in Ireland and Australia, the question becomes how can we respond in a time of major 'disruption' where there are both opportunities and constraints? This paper settles on this pause and uncertainty to seek new approaches to prepare social work students for changing conditions. Long-standing questions re-surface in relation to social, economic, political and environmental structures and conditions that are located in a neoliberal framework. The paper explores challenges and opportunities facing educators and social work students through a core set of principles—critical, relational and connected—that underpin our community development pedagogy. Within these themes, we explore teaching practices which seek to create a 'Community of Learners', generate a process of collaborative critical inquiry, engage students in reflective praxis enriched by contemporary theory and research, and foster a deep, connected and adaptive perspective on global and local issues. This stimulates creativity and meets the need for critical and adaptable practitioners capable of practical action through this period of disruption and crises of governance, climate and technologies of the future. [ABSTRACT FROM AUTHOR] Copyright of Community Development Journal is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Racial/ethnic discrimination may contribute to the risk of type 2 diabetes mellitus (T2DM), but few studies have prospectively examined this relationship among racially/ethnically diverse populations. We analyzed prospective data from 33,833 eligible Sister Study participants enrolled from 2003 to 2009. In a follow-up questionnaire (2008–2012), participants reported their lifetime experiences of everyday and major forms of racial/ethnic discrimination. Self-reported physician diagnoses of T2DM were ascertained through September 2017. Hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards models, overall and by race/ethnicity. Mean age at enrollment was 54.9 (standard deviation, 8.8) years; 90% of participants self-identified as non-Hispanic (NH) White, 7% as NH Black, and 3% as Hispanic/Latina. Over an average of 7 years of follow-up, there were 1,167 incident cases of T2DM. NH Black women most frequently reported everyday (75%) and major (51%) racial/ethnic discrimination (vs. 4% and 2% of NH White women, respectively, and 32% and 16% of Hispanic/Latina women, respectively). While everyday discrimination was not associated with T2DM risk, experiencing major discrimination was marginally associated with higher T2DM risk overall (hazard ratio = 1.26, 95% confidence interval: 0.99, 1.61) after adjustment for sociodemographic characteristics and body mass index. Associations were similar across racial/ethnic groups; however, racial/ethnic discrimination was more frequently reported among racial/ethnic minority women. Antidiscrimination efforts may help mitigate racial/ethnic disparities in T2DM risk.

Single-molecule imaging is widely used to determine statistical distributions of molecular properties. One such characteristic is the bending flexibility of biological filaments, which can be parameterized via the persistence length. Quantitative extraction of persistence length from images of individual filaments requires both the ability to trace the backbone of the chains in the images and sufficient chain statistics to accurately assess the persistence length. Chain tracing can be a tedious task, performed manually or using algorithms that require user input and/or supervision. Such interventions have the potential to introduce user-dependent bias into the chain selection and tracing. Here, we introduce a fully automated algorithm for chain tracing and determination of persistence lengths. Dubbed “AutoSmarTrace”, the algorithm is built off a neural network, trained via machine learning to identify filaments within images recorded using atomic force microscopy (AFM). We validate the performance of AutoSmarTrace on simulated images with widely varying levels of noise, demonstrating its ability to return persistence lengths in agreement with the ground truth. Persistence lengths returned from analysis of experimental images of collagen and DNA agree with previous values obtained from these images with different chain-tracing approaches. While trained on AFM-like images, the algorithm also shows promise to identify chains in other single-molecule imaging approaches, such as rotary shadowing electron microscopy and fluorescence imaging.Statement of SignificanceMachine learning presents powerful capabilities to the analysis of large data sets. Here, we apply this approach to the determination of bending flexibility – described through persistence length – from single-molecule images of biological filaments. We present AutoSmarTrace, a tool for automated tracing and analysis of chain flexibility. Built on a neural network trained via machine learning, we show that AutoSmarTrace can determine persistence lengths from AFM images of a variety of biological macromolecules including collagen and DNA. While trained on AFM-like images, the algorithm works well to identify filaments in other types of images. This technique can free researchers from tedious tracing of chains in images, removing user bias and standardizing determination of chain mechanical parameters from single-molecule conformational images.

Patients are prioritized for liver transplantation (LT) under an "urgency-based" system using the Model for End-Stage Liver Disease score. This system focuses solely on waitlist mortality, without considerations of posttransplant morbidity, mortality, and health care use. We sought to develop and internally validate a continuous posttransplant risk score during 5-year and 10-year time horizons. This retrospective cohort study used national registry data of adult deceased donor LT (DDLT) recipients with ≥90 days of pretransplant waiting time from February 27, 2002 to December 31, 2018. We fit Cox regression models at 5 and 10 years to estimate beta coefficients for a risk score using manual variable selection and calculated the absolute predicted survival time. Among 21,103 adult DDLT recipients, 11 variables were selected for the final model. The area under the curves at 5 and 10 years were 0.63 (95% confidence interval [CI], 0.60-0.66) and 0.67 (95% CI, 0.64-0.70), respectively. The group with the highest ("best") scores had 5-year and 10-year survivals of 89.4% and 85.4%, respectively, compared with 45.9% and 22.2% for those with the lowest ("worst") scores. Our score was significantly better at predicting long-term survival compared with the existing scores. We developed and validated a risk score using nearly 17 years of data to prioritize patients with end-stage liver disease based on projected posttransplant survival. This score can serve as the building block by which the transplant field can change the entire approach to prioritizing patients to an approach that is based on considerations of maximizing benefits (ie, survival benefit-based allocation) rather than simply waitlist mortality.

Background & Aims Liver transplant priority in the US and Europe follows the ‘sickest-first’ principle. However, for patients with hepatocellular carcinoma (HCC), priority is based on binary tumor criteria to expedite transplant for patients with ‘acceptable’ post-transplant outcomes. Newer risk scores developed to overcome limitations of these binary criteria are insufficient to be used for waitlist priority as they focus solely on HCC-related pre-transplant variables. We sought to develop a risk score to predict post-transplant survival for patients using HCC- and non-HCC-related variables. Methods We performed a retrospective cohort study using national registry data on adult deceased-donor liver transplant (DDLT) recipients with HCC from 2/27/02-12/31/18. We fit Cox regression models focused on 5- and 10-year survival to estimate beta coefficients for a risk score using manual variable selection. We then calculated absolute predicted survival time and compared it to available risk scores. Results Among 6,502 adult DDLT recipients with HCC, 11 variables were selected in the final model. The AUCs at 5- and 10-years were: 0.62, 95% CI 0.57–0.67 and 0.65, 95% CI 0.58–0.72, which was not statistically significantly different to the Metroticket and HALT-HCC scores. The LiTES-HCC score was able to discriminate patients based on post-transplant survival among those meeting Milan and UCSF criteria. Conclusion We developed and validated a risk score to predict post-transplant survival for patients with HCC. By including HCC- and non-HCC-related variables (e.g., age, chronic kidney disease), this score could allow transplant professionals to prioritize patients with HCC in terms of predicted survival. In the future, this score could be integrated into survival benefit-based models to lead to meaningful improvements in life-years at the population level. Lay summary We created a risk score to predict how long patients with liver cancer will live if they get a liver transplant. In the future, this could be used to decide which waitlisted patients should get the next transplant.

PURPOSE To investigate the contribution of PALB2 pathogenic gene variants (PGVs, PALB2_PGV) and the CHEK2 c.1100delC (CHEK2_1100delC) PGV to familial breast and ovarian cancer, and PALB2_PGV associated breast cancer pathology. METHODS Outcomes of germline PALB2_PGV and CHEK2_1100delC testing were recorded in 3,127 women with histologically confirmed diagnoses of invasive breast cancer, carcinoma in situ, or epithelial nonmucinous ovarian cancer, and 1,567 female controls. Breast cancer pathology was recorded in PALB2_PGV cases from extended families. RESULTS Thirty-five PALB2 and 44 CHEK2_1100delC PGVs were detected in patients (odds ratio [OR] PALB2 breast-ovarian = 5.90 [95% CI: 1.92-18.36], CHEK2 breast-ovarian = 4.46 [95% CI: 1.86-10.46], PALB2 breast = 6.16 [95% CI: 1.98-19.21], CHEK2 breast = 4.89 [95% CI: 2.01-11.34]). Grade 3 ER-positive HER2-negative, grade 3 and triple negative (TN) tumors were enriched in cases with PALB2 PGVs compared with all breast cancers known to our service (respectively: 15/43, 254/1,843, P = 0.0005; 28/37, 562/1,381, P = 0.0001; 12/43, 204/1,639, P

BackgroundPremature infants and their parents experience significant stress related to separation and lifesaving procedures. While evidence suggests that skin-to-skin contact (SSC) is a stress-reducing intervention for both neonates and parents, the mechanisms that underlie its efficacy are not well understood.ObjectivePurpose of this systematic review is to summarize the current state of knowledge on changes in biomarkers (ie, oxytocin [OT], cortisol, hypoxanthine, xanthine, uric acid, and allantoin), associated with SSC in premature infants and parents, that may reflect physiologic responses to stress.MethodsA comprehensive literature search was conducted from 1990 to 2020. Studies were selected using prespecified inclusion and exclusion criteria.ResultsOf the 175 studies identified, only 19 are included in this review. Ten studies evaluated only infants, 2 evaluated only parents, and 7 evaluated for changes in biomarkers in both infants and parents. Cortisol was the most common biomarker evaluated. While changes in infants' cortisol levels were highly variable, in 55% of the parent studies, parent cortisol levels decreased following SSC. In both parents and infants, OT levels decreased following SSC. Only 1 study found that allantoin levels were significantly lower in infants who received SSC.Implications for practice and researchWhile evidence suggests the numerous benefits of SSC, additional research is needed to identify the optimal biomarker to determine the mechanisms that underlie these effects. The use of novel biomarkers (eg, gene expression changes microbiome) may provide new insights into the mechanisms that underlie the efficacy of SSC.Video Abstract available at:https://journals.lww.com/advancesinneonatalcare/Pages/videogallery.aspx?autoPlay=false&videoId=48.

Background Chronic respiratory diseases are responsible for significant patient morbidity, mortality, and healthcare use. Community virtual ward (CVW) models of care have been successfully implemented to manage patients with complex medical conditions. Aims To explore the feasibility and clinical outcomes of a CVW model of care in patients with chronic respiratory disease. Methods Patients known to specialist respiratory services with Chronic Obstructive Pulmonary Disease (COPD) and/or asthma were admitted to the CVW for disease optimisation and exacerbation management. Individualised management plans were delivered in the patients’ home by hospital-based respiratory and community nursing teams, incorporating remote technology to monitor vital signs. Symptoms and health status at admission and discharge were compared. Results Twenty patients were admitted. One-quarter of patients had asthma, 50% COPD, and 25% combined asthma/COPD. Patients had severe disease, mean (SD) FEV1 50(20) % predicted, and an average 6.4(5.7) exacerbations of disease in the previous 12 months. Patients received personalised disease and self-management education. All acute exacerbations (n = 11) were successfully treated in the community. The average length of CVW admission was 10(4) days. By discharge, 60% of COPD and 66% of asthma patients recorded improvements in symptoms score exceeding the minimal clinically important difference. Fifty percent had clinically meaningful improvements in health status. Conclusion A CVW model facilitates the delivery of combined specialist and generalist care to patients with chronic respiratory disease in the community and improves symptoms and health status. The principles of the model are transferable to other conditions to improve overall health and reduce emergency hospital care.

Background Afghanistan has one of the highest under-five mortality rates in South Asia, 70.4 per 1000 live births. Determinants need to be identified to reduce this rate. Knowledge of the existence of familial and community frailty will also assist in the reduction of under-five mortality. Methods The 2015 Afghanistan Demographic Health Survey, including 32,712 live births, was analysed. Under-five mortality was disaggregated into neonatal, post-neonatal and child mortality and piecewise traditional Cox proportional hazard, variance-corrected and frailty models were developed. All the models identified determinants and the two frailty models examined the existence of familial and community frailty for each age group. Results There was statistically significant evidence of community frailty. Breastfeeding status was a highly significant determinant under univariable and multivariable analysis for neonatal and post-neonatal mortality. Post-neonates of employed mothers also experienced increased mortality, particularly those whose mother worked in agriculture where the hazard ratio was 2.77 (95% CI 2.10, 3.65). Birth order 5+ was associated with increased mortality for all three age groups. Conclusion The Afghanistan Ministry of Public Health should identify frail communities. Support, such as daycare facilities, should be provided and early initiation of breastfeeding and breastfeeding throughout the post-neonatal period should also be encouraged. Impact The study identified determinants of neonatal, post-neonatal and child mortality. The study also established the presence of community frailty with respect to under-five mortality in Afghanistan. The study shows that the association of not breastfeeding and mortality is more acute in the early neonatal age group and it extends into the post-neonatal age group. The study identified the association of high birth order and mortality in the neonatal, post-neonatal and child age groups in Afghanistan. Policies should be implemented that encourage early initiation of breastfeeding to continue throughout the post-neonatal period and support for vulnerable families should be provided.

Informed consent is an integral part of the process prior to any surgical procedure [1]. Flexible cystoscopy is a common day case urological procedure and it is the gold standard investigation for visible haematuria [2]. To assess if postal consent is a suitable form of gaining informed consent for flexible cystoscopy. Patients booked for a flexible cystoscopy are initially reviewed in clinic. An information leaflet with an attached consent form is then posted to their home 2 weeks prior to their procedure. We designed a short questionnaire, to assess patient’s satisfaction and understanding of the literature, given to them after the procedure. Sixty-seven questionnaires were completed. The mean age was 54. Sixty patients (93%) think that postal consent is of benefit to the patient. Sixty-one patients (91%) read the information sheet and felt that there was enough information regarding the procedure on it. Fifty-four patients (81%) had no difficulty understanding the consent form. Forty patients (60%) signed the form prior to arrival in the hospital. Postal consent is commonly used for gastro-intestinal endoscopy procedures. Postal consent for flexible cystoscopy is not well reported in the literature. Our study shows postal consent to be a suitable form of gaining informed consent for flexible cystoscopy.

Rezum technology uses heat from radiofrequency-generated water vapour to ablate prostate tissue. We evaluate the introduction of this thermal therapy to an Irish teaching hospital for the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia. A pilot study of men with moderate to severe lower urinary tract symptoms who underwent Rezum treatment to the prostate was performed. Perioperative efficacy was evaluated using international prostate symptom score (IPSS), quality of life score (IPSS-QOL), uroflowmetry and post-void residual (PVR) volumes. Costs were evaluated and compared against matched patients undergoing the standard of care, transurethral resection of the prostate (TURP). Ten patients with a mean age of 70 ± 9 years who met the inclusion criteria underwent Rezum treatment. Mean PSA was 4.73 ± 4 ng/mL and mean prostate volume 72 ± 30 cc. Rezum therapy significantly improved both IPSS by 74% from mean baseline score of 20.8 ± 4 to 5.3 ± 1.49 (p

This article explores how headteachers/principals engage in social justice leadership practice using data gathered from the Scottish and American contributions to the International School Leadership Development Network’s (ISLDN) research on social justice leadership. While the literature focuses on high-level strategies to address issues of equity there is limited discussion of the day-to-day practice of social justice leadership. In fostering inclusive cultures, the day-to-day practice of headteachers/principals is critical in challenging low-level forms of discrimination, micro-aggressions, which create hostile environments for diverse groups of learners. The article considers the concept of ‘leadership practice’ by examining the notion of relational leadership to highlight the social processes of ‘organising activities’ of leadership. In this, we focus on caring practices and explore these through four case studies of headteachers/principals recognised for their social justice leadership. A framework of Noddings’ caring practices of modelling, dialogue and confirmation as relational organising activities, is used to begin to capture the day-to-day practice of social justice leadership.

OBJECTIVES: To report changes in practice brought about by COVID-19 and the implementation of new guidelines, and to explore factors relating to unscheduled re-presentations for patients discharged from the emergency department (ED). DESIGN: Prospective multicentre national audit over 12 weeks from 6th April 2020. SETTING: UK secondary care ENT departments. PARTICIPANTS: Adult patients with acute epistaxis. MAIN OUTCOME MEASURES: Re-presentation within 10 days for patients discharged from the ED. RESULTS: Eighty three centres from all four UK nations submitted 2631 valid cases. The majority of cases were ED referrals (89.7%, n = 2358/2631). 54.6% were discharged from the ED following ENT review (n = 1267/2322), of whom 19.5% re-presented within 10 days (n = 245/1259) and 6.8% were ultimately admitted (n = 86/1259). 46.7% of patients had a non-dissolvable pack inserted by ED prior to referral to ENT (n = 1099/2355). The discharge rates for ED patients and their subsequent re-presentation rates were as follows: non-dissolvable packs, 29.5% discharged (n = 332/1125), 18.2% re-presented (n = 60/330); dissolvable products, 71.1% discharged (n = 488/686), 21.8% re-presented (n = 106/486); cautery only, 89.2% discharged (n = 247/277), 20.0% re-presented (n = 49/245); and no intranasal intervention, 85.5% discharged (n = 200/234), 15.2% re-presented (n = 30/198). Univariable logistic regression showed that not being packed by ED, antiplatelet medications, failed cautery and recent epistaxis treatment were significant predictors of re-presentation within 10 days. CONCLUSIONS: Management of acute epistaxis was notably affected during the initial peak of the pandemic, with a shift towards reduced admissions. This national audit highlights that many patients who may previously have been admitted to hospital may be safely discharged from the ED following acute epistaxis.

Blood cultures should be performed in non‐specifically unwell older adults following nonspecific presentations. Prompt diagnosis and commencement of targeted antimicrobial therapy are essential in older patients with A. defectiva IE.

This study aimed to quantify the variability in the values of radiomic features extracted from a right parotid gland (RPG) delineated by a series of independent observers.This was a secondary analysis of anonymous data from a delineation workshop. Inter-observer variability of the RPG from 40 participants was quantified using DICE similarity coefficient (DSC) and Hausdorff distance (HD). An additional contour was generated using Varian SmartSegmentation. Radiomic features extracted include four shape features, six histogram features, and 32 texture features. The absolute mean paired percentage difference (PPD) in feature values from the expert and participants were ranked . Feature robustness was classified using pre- determined thresholds.63% of participants achieved a DSC 0.7, the auto- segmentation DSC was 0.76. The average HD for the participants was 16.16 mm ± 0.66 mm, and 15.16 mm for the auto-segmentation. 48% (n = 20) and 33% (n = 14) of features were deemed to be robust with a mean absolute PPD 5%, for the auto-segmentation and manual delineations respectively; the majority of which were from the grey-run length matrix family. 7% (n = 3) of features from the auto- segmentation and 10% (n = 4) from the manual contours were deemed to be unstable with a mean absolute PPD 50%. The value of the most robust feature was not related to DSC and HD.Inter-observer delineation variability affects the value of the radiomic features extracted from the RPG. This study identifies the radiomic features least sensitive to these uncertainties. Further investigation of the clinical relevance of these features in prediction of xerostomia is warranted.

Background PIK3CA-related overgrowth spectrum (PROS) refers to a group of rare disorders, caused by somatic activating mutations in PIK3CA, resulting in abnormal PI3K-AKT-mTOR pathway signalling. Significant associated morbidity is frequently observed, and approved treatments are lacking. Miransertib (ARQ 092) is a novel, orally available, selective pan-AKT inhibitor with proven in vitro efficacy. Following recent results of the use of AKT inhibitors in Proteus syndrome (PS) and AKT-mutant cancers, we investigated its therapeutic use in two patients with severe PROS who had exhausted conventional treatment methods. Results Two patients, one with CLOVES variant (P1) and one with facial infiltrating lipomatosis and hemimegalencephaly (P2), were commenced on miransertib treatment on a compassionate use basis. In patient one, intra-abdominal and paraspinal overgrowth had resulted in respiratory compromise, obstructive uropathy, dysfunctional seating and lying postures, and chronic pain. In patient two, hemifacial overgrowth and hemimegalencephaly had caused difficulties with articulation and oral function, and refractory epilepsy. Miransertib treatment was continued for a median duration of 22 months (range 22–28). In patient one, alleviation of respiratory compromise was observed and functionally, seating and lying postures improved. Serial volumetric MRI analysis revealed 15% reduction in calculated volumes of fatty overgrowth between treatment commencement and end. In patient two, reduction in seizure burden and improved parent-reported quality of life measures were reported. Treatment was discontinued in both patients due to lack of sustained response, and poor compliance in year two of treatment (P2). No significant toxicities were reported. Conclusion We report the first paediatric case series of the use of miransertib in two children with PROS. Objective clinical response was observed in patient one, and improvement in key qualitative outcomes was reported in patient two. Treatment was well tolerated with no significant toxicities reported. This case series highlights the potential therapeutic utility of miransertib in selected paediatric patients with severe PROS, and further demonstrates the potential for re-purposing targeted therapies for the treatment of rare diseases. An open label, Phase 1/2 study of miransertib in children with PROS and PS is underway to more accurately assess the efficacy of miransertib in the treatment of PROS disorder (NCT03094832).

Background: Both high energy density and fast eating rates contribute to excess energy intakes. The energy intake rate (EIR; kcal/min) combines both the energy density (kcal/g) and eating rate (g/min) of a food to quantify the typical rate at which calories of different foods are ingested. Objectives: We describe the EIRs of diets in a multi-ethnic Asian population, and examine relationships between the consumption of high-EIR foods and total energy intake, body composition, and cardio-metabolic risk factors. Methods: Diet and lifestyle data from the Singapore Multi-Ethnic Cohort 2 (n = 7011; 21-75 y), were collected through interviewer-administrated questionnaires. The EIR for each of the 269 foods was calculated as the product of its eating rate and energy density. Multivariable models were used to examine associations between the relative consumption of foods with higher and lower EIRs and energy intake, body composition, and cardio-metabolic risks, after adjusting for age, sex, ethnicity, education level, physical activity, smoking status, and alcohol drinking status. Results: Individuals with higher daily energy intakes and with obesity consumed a significantly larger percentage of their energy from high-EIR foods, with a smaller relative intake of lower-EIR foods. Individuals with raised serum cholesterol also consumed a significantly higher proportion of high-EIR foods, whereas those without hypertension consumed a larger percentage of energy intake from low-EIR foods. Individuals classified as having a "very high"dietary EIR had a significantly 1.3 kg higher body weight (95% CI, 0.2-1.5; P = 0.013), 0.4 kg/m2 higher BMI (95% CI, 0.03-0.8; P = 0.037), and 1.2 cm larger waist circumference (95% CI, 0.2-2.2; P = 0.010), and were more likely to have abdominal overweight (OR, 1.3; 95% CI, 1.1-1.5; P < 0.001) than those with a "low"dietary EIR. Conclusions: Comparing foods by their EIRs summarizes the combined impact of energy density and eating rate, and may identify foods and dietary patterns that are associated with obesogenic eating styles and higher diet-related cardiovascular disease risk in an Asian population.

Objectives: Tourette syndrome (TS) is characterized by the presence of sudden, rapid movements and vocalizations (tics). The nature of tics suggests impairments in inhibitory control. However, findings of impaired inhibitory control have so far been inconsistent, possibly due to small sample sizes, wide age ranges, or not taking medication use or attention-deficit/hyperactivity disorder (ADHD) comorbidity into account. Methods: We investigated group differences in response inhibition using an fMRI-based stop-signal task in 103 8-12-year-old children (n = 51 with TS, of whom n = 28 without comorbid ADHD [TS–ADHD] and n = 23 with comorbid ADHD [TS + ADHD]; and n = 52 healthy controls), and related these measures to tic and ADHD severity. Results: We observed an impaired response inhibition performance in children with TS + ADHD, but not in those with TS–ADHD, relative to healthy controls, as evidenced by a slower stop-signal reaction time, slower mean reaction times, and larger variability of reaction times. Dimensional analyses implicated ADHD severity as the driving force in these findings. Neural activation during failed inhibition was stronger in the inferior frontal gyrus and temporal and parietal areas in TS + ADHD compared to healthy controls. Conclusions: Impaired inhibitory performance and increased neural activity in TS appear to manifest predominantly in relation to ADHD symptomatology.

The carbohydrate–insulin model of obesity posits that high-carbohydrate diets lead to excess insulin secretion, thereby promoting fat accumulation and increasing energy intake. Thus, low-carbohydrate diets are predicted to reduce ad libitum energy intake as compared to low-fat, high-carbohydrate diets. To test this hypothesis, 20 adults aged 29.9 ± 1.4 (mean ± s.e.m.) years with body mass index of 27.8 ± 1.3 kg m−2 were admitted as inpatients to the National Institutes of Health Clinical Center and randomized to consume ad libitum either a minimally processed, plant-based, low-fat diet (10.3% fat, 75.2% carbohydrate) with high glycemic load (85 g 1,000 kcal−1) or a minimally processed, animal-based, ketogenic, low-carbohydrate diet (75.8% fat, 10.0% carbohydrate) with low glycemic load (6 g 1,000 kcal−1) for 2 weeks followed immediately by the alternate diet for 2 weeks. One participant withdrew due to hypoglycemia during the low-carbohydrate diet. The primary outcomes compared mean daily ad libitum energy intake between each 2-week diet period as well as between the final week of each diet. We found that the low-fat diet led to 689 ± 73 kcal d−1 less energy intake than the low-carbohydrate diet over 2 weeks (P

The ability to personalise radiotherapy to fit the individual patient and their diagnosis has been realised through technological advancements. There is now more opportunity to utilise these technologies and deliver precision radiotherapy for more patients. Image-guided radiotherapy (IGRT) has enabled users to safely and accurately plan, treat and verify complex cases; and deliver a high dose to the target volume, while minimising dose to normal tissue. Rapid changes in IGRT have required a multidisciplinary team (MDT) approach, carefully deciding optimum protocols to achieve clinical benefit. Therapeutic radiographer/radiation therapists (RTTs) play a pivotal role in this MDT. There is already a great deal of evidence that illustrates the contribution of RTTs in IGRT development; implementation; quality assurance; and maintaining training and competency programmes. Often this has required the RTT to undertake additional roles and responsibilities. These publications show how the profession has evolved, expanding the scope of practice. There are now more opportunities for RTT-led IGRT research. This is not only undertaken in the more traditional aspects of practice, but in recent times, more RTTs are becoming involved in imaging biomarkers research and radiomic analysis. The aim of this overview is to describe the RTT contribution to the ongoing development of IGRT and to showcase some of the profession's involvement in IGRT research.

Two unique aspects of antenatal care occur in the setting of fetal surgery and multiple gestations. As fetal interventions increase, so do the number of cases of iatrogenic preterm prelabor rupture of membranes (PPROM). Because of the amniotic sac's inability to heal, the risk of PPROM after surgery is directly correlated with the number of interventions, the size of the defect, and the surgery performed. Higher order gestations also carry an increased risk of PPROM. This paper reviews the risks and management of PPROM in the setting of the various prenatal interventions as well as in the setting of multiple gestations.

Aim: to describe diabetes nurses' perspectives on the impact of the COVID-19 pandemic on people with diabetes and diabetes services across Europe. Methods: an online survey developed using a rapid Delphi method. The survey was translated into 17 different languages and disseminated electronically in 27 countries via national diabetes nurse networks. Results: survey responses from 1829 diabetes nurses were included in the analysis. The responses indicated that 28% (n = 504) and 48% (n = 873) of diabetes nurses felt the COVID-19 pandemic had impacted 'a lot' on the physical and psychological risks of people with diabetes, respectively. The following clinical problems were identified as having increased 'a lot': anxiety 82% (n = 1486); diabetes distress 65% (n = 1189); depression 49% (n = 893); acute hyperglycaemia 39% (n = 710) and foot complications 18% (n = 323). Forty-seven percent (n = 771) of respondents identified that the level of care provided to people with diabetes had declined either extremely or quite severely. Self-management support, diabetes education and psychological support were rated by diabetes nurse respondents as having declined extremely or quite severely during the COVID-19 pandemic by 31% (n = 499), 63% (n = 1,027) and 34% (n = 551), respectively. Conclusion: the findings show that diabetes nurses across Europe have seen significant increases in both physical and psychological problems in their patient populations during COVID-19. The data also show that clinical diabetes services have been significantly disrupted. As the COVID-19 situation continues, we need to adapt care systems with some urgency to minimise the impact of the pandemic on the diabetes population., Foundation of European Nurses in Diabetes

The aim of this study is to systematically compare rates of erosion and chronic pain after mesh insertion for pelvic organ prolapse (POP) and stress urinary incontinence (SUI) surgery. A systematic electronic search was performed on studies that evaluated the incidence of erosion and chronic pain after mesh insertion for POP or SUI. The primary outcome measurement was to compare mesh erosion rates for POP and SUI surgery. Secondary outcome measurements were incidence of de novo pain and a comparison of patient demographics for both surgeries. Twenty-six studies on 292,606 patients (n = 9077 for POP surgery and n = 283,529 for SUI surgery) met the inclusion criteria. Median follow-up was 26.38 ± 22.17 months for POP surgery and 39.33 ± 27.68 months for SUI surgery. Overall, the POP group were older (p

BACKGROUND Patients with stage IV oligometastatic (≤ 3 sites) non-small-cell lung cancer have a progression-free survival (PFS) and overall survival benefit when all sites of metastatic disease and the primary tumor are treated radically with consolidative radiotherapy (cRT). However, the optimal selection of patients most likely from cRT is yet to be defined. PATIENTS AND METHODS Patients with metastatic non-small-cell lung cancer treated with definitive radiotherapy to all metastatic sites and primary tumor (2008-2019) were retrospectively identified. Univariable Cox proportional-hazards model was used to compare outcomes with demographic and clinical characteristics. A predictive nomogram model for selection of patients most likely to benefit from cRT was constructed. RESULTS There were 91 patients identified with a total of 114 metastases treated. Median PFS from the start of cRT was 10.9 months (95% confidence interval [CI], 8.1-16.6), while the median survival time was 37.0 months (95% CI, 31.3-NR). On univariable modeling, patients with squamous histology (hazard ratio, 4.16; 95% CI, 1.99-8.71; P < .001) and those treated with non-stereotactic body radiotherapy hypofractionated therapy (hazard ratio, 5.43; 95% CI, 2.10-14.01; P < .001) had worse overall survival, while patients with targetable mutations (hazard ratio, 0.49; 95% CI, 0.25-0.98; P = .04) had a longer survival. Using a predictive nomogram model, patients with a solitary site of metastasis, targetable mutations, intracranial disease, and metachronous timing of oligometastases had a larger PFS benefit from cRT. CONCLUSION cRT is associated with favorable outcomes in PFS and overall survival. These results may aid in patient counseling, selection for aggressive local therapy, and stratification in future prospective clinical trials.

Background Primary sclerosing cholangitis (PSC) is closely associated with inflammatory bowel disease, particularly ulcerative colitis (UC), with an increased risk of biliary and colorectal malignancy. We sought to clarify the prevalence, characteristics and long-term outcome of sub-clinical PSC diagnosed by magnetic resonance cholangiogram (MRC) in patients with UC and normal liver biochemistry, with or without colorectal dysplasia (CRD). Methods In this prospective case-control study, 70 patients with UC and normal liver function (51 extensive UC, 19 CRD), 28 healthy volunteers (negative controls) and 28 patients with PSC and cholestasis (positive controls) underwent MRC and blood evaluation. MRC scans were interpreted blindly by two radiologists who graded individually, the scans as definitive for PSC, possible for PSC or normal. Clinical outcome was assessed by blood monitoring, abdominal imaging and endoscopic surveillance. Results 7/51 (14%) with extensive UC and 4/19 (21%) with CRD had biliary abnormalities on MRC consistent with PSC. 7/11 (64%) with sub-clinical PSC had isolated intrahepatic duct involvement. Sub-clinical PSC was associated with advanced age (P = .04), non-smoking (P = .03), pANCA (P = .04), quiescent colitis (P = .02), absence of azathioprine (P = .04) and high-grade CRD (P = .03). Inter-observer (kappa = 0.88) and intra-observer (kappa = 0.96) agreement for MRC interpretation was high. No negative controls were assessed as definite PSC, 4/28 were considered on blinding as possible PSC. During follow-up of sub-clinical PSC (median 10.1(3.1-11.9) years), four patients developed abnormal liver biochemistry, two had radiological progression of PSC and seven developed malignancy, including two biliary and one colorectal carcinoma. Conclusions Prevalence of sub-clinical PSC appears high in patients with extensive UC and normal liver biochemistry, with or without CRD. Disease progression and malignancy were identified on long-term follow-up. MRC should be considered for all patients with extensive UC or CRD to stratify surveillance.

Lyme disease (LD) is the most common tick-borne illness in Europe. Population-based studies in European children are few. This study aimed to assess the incidence, clinical presentation, treatment and outcome of serologically confirmed paediatric LD in the Republic of Ireland over a 5-year period. A retrospective review of records from accredited laboratories performing Borrelia burgdorferi serological testing was undertaken. Proformas were distributed to clinicians of children and adolescents with positive Lyme serology. Data were requested regarding clinical presentation, treatment and outcome. Updated NICE guidelines were used to classify clinical cases. Serology testing for B. burgdorferi was performed on 2908 samples. Sixty-three (2.2%) children were two-tier positive, generating a crude annual incidence rate of 1.15/100,000. Proformas were returned for 55 (87%) and 47 met clinical and laboratory criteria for LD. Twenty-seven (57%) presented with non-focal symptoms (erythema migrans and/or influenza-like symptoms), and 20 (43%) with focal symptoms (cranial nerve involvement, 11; CNS involvement, 8; arthritis, 1). Median age at presentation was 8.2 (2.5-17.9) years. Seventeen (36%) acquired LD overseas. Twenty-five (83%) of the remaining 30 children acquired infection in the West/Northwest of Ireland. Full resolution of symptoms was reported in 97% of those with available data. Serologically confirmed LD in children is relatively rare in the Republic of Ireland. Ninety-eight percent of children tested were seronegative. Of the seropositive cases, 40% could have been diagnosed based on clinical findings alone. Neurological presentations (40%) were common. Full resolution of symptoms occurred in almost all (97%) where data were available.

Objective To investigate whether paternal age exerts an independent effect on the clinical outcomes of assisted reproductive technology (ART) cycles. Evidence Review Observational studies were identified through a systematic search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and National Health Service evidence. Data for women aged ≤39 years were extracted and analyzed. We included all studies, both autologous and donor oocyte, into separate analyses of the effect of paternal age on ART outcome. We excluded studies in azoospermic men, women aged ≥40 years, ART including preimplantation genetic testing, and involving donor sperm. The included studies scored well on the Newcastle-Ottawa Quality Assessment Scale for observational studies. The primary outcome was live birth rate and secondary outcome measures were clinical pregnancy rate and miscarriage rate. When pooling data, the random-effects model was used to counter the effect of heterogeneity in the studies. Result(s) Live birth rate was reported in three autologous oocyte studies (2,926 cycles) and five donor oocyte studies (7,648 cycles). Live birth rate was found to be increased significantly when male age was 40 years in autologous studies. In donor oocyte studies, the miscarriage rate was not increased when male age was >50 years. All of the autologous oocyte studies reported a statistically significant association between male age and female age. Conclusion(s) The findings of this review and meta-analysis, based on the donor oocyte model, suggest that advanced paternal age does not exert an independent effect on the outcome of ART cycles. Miscarriage rates do not appear to be increased even for men >50 years of age after treatment with donor oocytes. The meta-analysis of autologous oocyte studies suggests that increasing male age may have a deleterious effect on the outcome of ART, however, this may be confounded by the strong association with increasing maternal age.

Background and Aims: Portopulmonary hypertension (POPH) was previously associated with a single-nucleotide polymorphism (SNP) rs7175922 in aromatase (cytochrome P450 family 19 subfamily A member 1 [CYP19A1]). We sought to determine whether genetic variants and metabolites in the estrogen signaling pathway are associated with POPH. Approach and Results: We performed a multicenter case-control study. POPH patients had mean pulmonary artery pressure >25 mm Hg, pulmonary vascular resistance >240 dyn-sec/cm −5, and pulmonary artery wedge pressure ≤15 mm Hg without another cause of pulmonary hypertension. Controls had advanced liver disease, right ventricular (RV) systolic pressure

Burkitt lymphoma (BL) accounts for almost two-thirds of all B-cell non-Hodgkin lymphoma (B-NHL) in children and adolescents and is characterised by a MYC translocation and rapid cell turnover. Intensive chemotherapeutic regimens have been developed in recent decades, including the lymphomes malins B (LMB) protocol, which have resulted in a survival rate in excess of 90%. Recent clinical trials have focused on immunochemotherapy, with the addition of rituximab to chemotherapeutic backbones, showing encouraging results. Despite these advances, relapse and refractory disease occurs in up to 10% of patients and salvage options for these carry a dismal prognosis. Efforts to better understand the molecular and functional characteristics driving relapse and refractory disease may help improve this prognosis. This study has established a paediatric BL patient-derived xenograft (PDX) resource which captures and maintains tumour heterogeneity, may be used to better characterise tumours and identify cell populations responsible for therapy resistance.

Background Intussusception in adult patients is uncommon and appendiceal lead points are particularly rare. Case presentation We present the case of a 42-year-old male with a history of ulcerative colitis, presenting with sudden onset abdominal pain and bloody diarrhoea. Endoscopy revealed grossly normal mucosa in the descending colon with a congested polypoid mass in the proximal transverse colon. Computed tomography revealed ileocecal intussusception at the hepatic flexure. A right hemicolectomy was performed, where a grossly dilated appendix was noted, resected and sent for histopathological evaluation. Results revealed low-grade appendiceal mucinous neoplasm. Post-operatively, the patient remained symptom free, however required reintroduction of biologic therapy due to relapse of his ulcerative colitis 12 weeks later. Conclusion This case depicts a rare acute surgical presentation and reminds physicians and surgeons of the importance of ‘thinking outside the box’ in clinical practice.

Measurement of late night salivary cortisol (LNSF) is useful in the identification of cyclical Cushing’s syndrome (CS); the usefulness of its metabolite cortisone (late night salivary cortisone, LNSE) is less well described. The aim of this study was to determine the utility of measuring LNSE in patients with confirmed CS compared with other diagnostic tests and to analyse serial LNSF measurements for evidence of variable hormonogenesis. This was a retrospective observational study including patients with confirmed CS in whom LNSF and LNSE were measured. Twenty-three patients with confirmed CS were included, 21 with Cushing’s disease. LNSF had a sensitivity of 92%, LNSE 87% and combined LNSF/LNSE 94% per sample. Four patients had cyclical hormonogenesis, when the definition of one trough and two peaks was applied to LNSF measurements, and a fifth patient fell just outside the criteria. Six patients had evidence of variable hormonogenesis, defined as doubling of LNSF concentration on serial measurements. Sensitivity of 24-h urinary free cortisol (UFC) was 89% per collection. Sixteen patients had simultaneous measurements of LNSF and UFC; in three patients, they provided discordant results. LNSF appears more sensitive than LNSE and UFC in the diagnosis of CS, combining LNSF and LNSE results leads to superior sensitivity. Half of our cohort had evidence of cyclical or variable hormonogenesis. Fluctuations in LNSF did not always correlate with changes in UFC concentration, emphasising the importance of performing more than one screening test, particularly if pretest clinical suspicion is high.