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Background In Scotland a new, easier to complete bowel screening test, the Faecal Immunochemical Test (FIT), has been introduced. This test gives more accurate information about an individual’s risk of having colorectal cancer (CRC), based on their age and gender, and could lead to fewer missed cancers compared to the current screening test. However, there is no evidence of the effect on colonoscopy uptake of providing individuals with personalised risk information following a positive FIT test. The objectives of the study are:1)To develop novel methods of presenting personalised risk information in an easy-to-understand format using infographics with involvement of members of the public2)To assess the impact of different presentations of risk information on informed choice and intention to take up an offer of colonoscopy after FIT3)To assess participants’ responses to receiving personal risk information (knowledge, attitudes to screening/risk, emotional responses including anxiety). Methods Adults (age range 50–74) registered on the Scottish Bowel Screening database will be invited by letter to take part. Consenting participants will be randomised to one of three groups to receive hypothetical information about their risk of cancer, based on age, gender and faecal haemoglobin concentration: 1) personalised risk information in numeric form (e.g. 1 in 100) with use of infographics, 2) personalised information described as ‘highest’, ‘moderate’ or ‘lowest’ risk with use of infographics, and 3) as a ‘positive’ test result, as is current practice. Groups will be compared on informed choice, intention to have a colonoscopy, and satisfaction with their decision. Follow-up semi-structured qualitative interviews will be conducted, by telephone, with a small number of consenting participants (n = 10 per group) to explore the acceptability/readability and any potential negative impact of the risk information, participants’ understanding of risk factors, attitudes to the different scenarios, and reasons for reported intentions. Discussion Proving personalised risk information and allowing patient choice could lead to improved detection of CRC and increase patient satisfaction by facilitating informed choice over when/whether to undergo further invasive screening. However, we need to determine whether/how informed choice can be achieved and assess the potential impact on the colonoscopy service. Trial registration The trial is registered on www.isrctn.com on 08/12/2017. Registration no: ISRCTN14254582.

Emergency admissions involve unplanned admissions for which admission must occur at the earliest possible point of time. Being able to predict in-hospital mortality at the point of admission has significant clinical importance. In this work we have drawn from a large state-wide dataset to train predictive models for in-hospital mortality of emergency admissions, that can be applicable at time of admission. A number of models demonstrate high predictive performance, with AUC scores of up to 0.861. The approach taken represents an alternative to models based upon rich clinical data and may offer a number of comparative advantages in terms of very early point-in-time applicability and broad generalizability.

In the current qualitative research study, we focused on understanding the ecological systems, contexts, behaviors, and strategies of parents (N = 435) advocating for their children with an intellectual and developmental disability diagnosis, specifically Down syndrome (DS). Based on the data analysis, parents of children with DS advocate for their children frequently, in a variety of settings, with different actions, attitudes, motivations, and outcomes. The most common settings where advocacy occurred were primarily school and healthcare systems. The goals of parents often included inclusiveness, equality, and acceptance, whereas a few parents reported advocating due to discrimination and judgment. Implications for further research and professional practice also are described.

Purpose\ud \ud There are no internationally agreed upon clinical guidelines as to which women with gynecological cancer would benefit from Lynch syndrome screening or how best to manage the risk of gynecological cancer in women with Lynch syndrome. The Manchester International Consensus Group was convened in April 2017 to address this unmet need. The aim of the Group was to develop clear and comprehensive clinical guidance regarding the management of the gynecological sequelae of Lynch syndrome based on existing evidence and expert opinion from medical professionals and patients.\ud \ud Methods\ud \ud Stakeholders from Europe and North America worked together over a two-day workshop to achieve consensus on best practice.\ud \ud Results\ud \ud Guidance was developed in four key areas: (1) whether women with gynecological cancer should be screened for Lynch syndrome and (2) how this should be done, (3) whether there was a role for gynecological surveillance in women at risk of Lynch syndrome, and (4) what preventive measures should be recommended for women with Lynch syndrome to reduce their risk of gynecological cancer.\ud \ud Conclusion\ud \ud This document provides comprehensive clinical guidance that can be referenced by both patients and clinicians so that women with Lynch syndrome can expect and receive appropriate standards of care.

The all-condition prediction of patient mortality at the time of hospital admission has significant clinical value and broader implications for patient care and clinical decision support capabilities. In this study we have applied machine learning models to predict inpatient mortality, that is whether a patient will die during the hospital stay, as predicted from a time near to admission. We have utilized an Agency for Healthcare Research and Quality-provided large dataset of hospital discharges, to develop and evaluate a number of machine learning models. We report on the performance of the best performing of these models, with the best performing model having an AUC score of 0.802. We also evaluate the generalizability of the models via evaluating these on a separate large dataset corresponding to a different time period. We describe the results and provide an analysis and discussion of their significance.

Background Many patients present in primary care with lower bowel symptoms, but significant bowel disease (SBD), comprising colorectal cancer (CRC), advanced adenoma (AA), or inflammatory bowel disease (IBD), is uncommon. Quantitative faecal immunochemical tests for haemoglobin (FIT), which examine faecal haemoglobin concentrations (f-Hb), assist in deciding who would benefit from colonoscopy. Incorporation of additional variables in an individual risk-score might improve this approach. We investigated if the published f-Hb, age and sex test score (FAST score) added value. Methods Data from the first year of routine use of FIT in primary care in one NHS Board in Scotland were examined: f-Hb was estimated using one HM-JACKarc FIT system (Kyowa Medex Co., Ltd., Tokyo, Japan) with a cut-off for positivity ≥10 μg Hb/g faeces. 5660 specimens were received for analysis in the first year. 4072 patients were referred to secondary care: 2881 (70.6%) of these had returned a FIT specimen. Of those referred, 1447 had colonoscopy data as well as the f-Hb result (group A): 2521 patients, also with f-Hb, were not immediately referred (group B). The FAST score was assessed in both groups. Results 1196 (41.7%) of patients who returned a specimen for FIT analysis had f-Hb ≥10 μg Hb/g faeces. In group A, 252 of 296 (85.1%) with SBD had f-Hb > 10 μg Hb/g faeces, as did 528 of 1151 (45.8%) without SBD. Using a FAST score > 2.12, which gives high clinical sensitivity for CRC, only 1143 would have been referred for colonoscopy (21.0% reduction in demand): 286 of 296 (96.6%) with SBD had a positive FAST score, as did 857 of 1151 (74.5%) without SBD. However, one CRC, five AA and four IBD would have been missed. In group B, although 95.2% had f-Hb > 2.12 was found in 13 of 15 (86.7%) with SBD. Conclusions The performance characteristics of the FAST score did not seem to enhance the utility of f-Hb alone. Locally-derived formulae might confer desired benefits.

Simple Summary The incidence of head and neck cancer (HNC), one of the most aggressive cancers, is increasing rapidly globally. Conventional and targeted therapies show limited success with several undesirable side effects. Thus, there is a critical clinical need to identify additional alternative therapeutic strategies for successfully managing the disease. Preclinical and clinical studies indicate the crucial roles of dietary phytochemicals to manage different cancers. We and others previously showed the potential anticancer effect of bitter melon extract (BME) to prevent various cancers, including HNC. In this study, we identified momordicine-I (M-I) as a bioactive component in the BME. Subsequent mechanistic study showed that M-I inhibited HNC cell (JHU022, JHU029, Cal27) proliferation involving c-Met and downstream signaling. In pre-clinical mouse models, M-I showed similar effectiveness to prevent HNC tumor growth in mice with no apparent toxic side effect, suggesting an additional option for HNC therapy. Abstract Head and neck cancer (HNC) is one of the most aggressive cancers, and treatments are quite challenging due to the difficulty in early diagnosis, lack of effective chemotherapeutic drugs, adverse side effects and therapy resistance. We identified momordicine-I (M-I), a bioactive secondary metabolite in bitter melon (Momordica charantia), by performing liquid chromatography-high resolution electrospray ionization mass spectrometry (LC-HRESIMS) analysis. M-I inhibited human HNC cell (JHU022, JHU029, Cal27) viability in a dose-dependent manner without an apparent toxic effect on normal oral keratinocytes. Mechanistic studies showed that M-I inhibited c-Met and its downstream signaling molecules c-Myc, survivin, and cyclin D1 through the inactivation of STAT3 in HNC cells. We further observed that M-I was non-toxic and stable in mouse (male C57Bl/6) blood, and a favorable pharmacokinetics profile was observed after IP administration. M-I treatment reduced HNC xenograft tumor growth in nude mice and inhibited c-Met and downstream signaling. Thus, M-I has potential therapeutic implications against HNC.

Objectives Quantitative faecal immunochemical tests (FIT) for faecal haemoglobin (f-Hb) in colorectal cancer (CRC) screening pose challenges when colonoscopy is limited. For low positivity rates, high f-Hb concentration cut-offs are required, but little is known about interval cancer (IC) proportions using FIT. We assessed IC proportions using an 80 µg Hb/g cut-off. Methods In two NHS Boards in the Scottish Bowel Screening Programme, f-Hb was estimated for 30,893 participants aged 50–75, of whom 753 participants with f-Hb ≥ 80 µg Hb/g were referred for colonoscopy. ICs, defined as CRC within two years of a negative result, were identified from the Scottish Cancer Registry. Results There were 31 ICs and 30 screen-detected (SD) CRCs, an IC proportion of 50.8% (48.4% for men, 53.3% for women). CRC site distribution was similar between ICs and SD, but ICs were later stage (46.7% and 33.3%, Dukes’ stages C and D, respectively). Of 31 ICs, 23 had f-Hb Conclusions The IC proportion was similar to that seen with guaiac-based FOBT. The later stage distribution of ICs highlights the benefits of lower f-Hb cut-offs, but with 19.4% of ICs having undetectable f-Hb, some cancers would have been missed, even with drastic reduction in the f-Hb cut-off.

Objective To examine associations between faecal haemoglobin concentrations below the cut-off used in colorectal cancer screening and outcomes in the next screening round. Methods In the Scottish Bowel Screening Programme, faecal haemoglobin concentrations and diagnostic outcomes were investigated for participants with a negative result (faecal haemoglobin concentrations Results Of 37,780 participants with negative results, at the next screening round, 556 (1.5%) screened positive and 30,293 (80.2%) negative. Initial median faecal haemoglobin concentrations (2.1 µg Hb/g faeces, IQR: 0.0–13.2) were higher in those with subsequent positive results than those with subsequent negative results (0.0 µg Hb/g faeces, IQR: 0.0–1.4; p Conclusions A higher proportion of participants with faecal haemoglobin concentrations of ≥ 20 µg Hb/g faeces had advanced neoplasia detected at the next round than participants with lower faecal haemoglobin concentrations. Although most relevant when using high faecal haemoglobin concentrations cut-offs, studies of faecal haemoglobin concentrations and outcomes over screening rounds may provide strategies to direct available colonoscopy towards those at highest risk.

On 7 December 2015, the British Society of Gastroenterology and the Royal College of Physicians held a joint conference: GI cancer in the UK: can we do better? The meeting was timely as, although outcomes for patients with most gastrointestinal cancers in the UK have steadily improved in the past 10 years, survival figures remain substantially worse than in many other comparable nations. After defining the scale of the problem, the issues around early diagnosis were discussed. Screening as prevention has huge potential where there are defined premalignant conditions. Uptake into the Bowel Cancer Screening Programme (BCSP) is variable but in some areas remains low. It is hoped that with the National Screening Committee recommendation to replace the guaiac faecal occult blood test (gFOBT) with the faecal immunochemical test (FIT), the planned age extension and the continued roll-out of bowel scope screening by the National Health Service (NHS) will extend the value of the programme further. The view from primary care suggested that many factors affect the decision to make a referral for suspected cancer. Lack of direct access to testing was highlighted as a concern, as was the compounding issue of the many patients who delay seeking care. The Independent Cancer Force is the latest of several bodies calling for general practitioners (GPs) to be able to refer ‘direct to test’. However, a particular concern from secondary care relates to further stretching of diagnostic resources already under pressure—and how that can be addressed in times of austerity. Waiting times for endoscopy have begun to rise, yet capacity to expand is limited. Training, recruitment and retention of clinical staff were all highlighted as key issues limiting the availability of these procedures. Various practical ways to improve detection with endoscopy were proposed, as were possible ways to support and retain staff. While …

// Sourav Bhattacharya 1 , Naoshad Muhammad 1 , Robert Steele 1 , Guangyong Peng 2 , Ratna B. Ray 1, 2 1 Department of Pathology, Saint Louis University, Saint Louis, Missouri, USA 2 Department of Internal Medicine, Saint Louis University, Saint Louis, Missouri, USA Correspondence to: Ratna B. Ray email: rayrb@slu.edu Keywords: bitter melon, TME, HNSCC Abbreviation: BME, bitter melon extract; HNSCC, head and neck squamous cell carcinoma; TIL, tumor infiltrating lymphocytes Received: February 20, 2016 Accepted: April 10, 2016 Published: April 21, 2016 ABSTRACT Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer and leading cause of cancer related mortality worldwide. Despite the advancement in treatment procedures the overall survival rate of patients has not considerably enhanced in the past few decades. Therefore, new strategies to achieve a favorable response for the improvement in the prognosis of HNSCC are urgently needed. In this study, we examined the role of bitter melon extract (BME) in HNSCC tumor microenvironment. Mouse head and neck cancer (SCCVII) cells were subcutaneously injected into the flanks of syngeneic mice. We observed that oral gavage of BME significantly inhibits the tumor growth in mice as compared to control group. Further study suggested that BME inhibits cell proliferation as evident from low expression of proliferating cell nuclear antigen (PCNA) and c-Myc in the tumors of BME fed mice as compared to that of control group. We next investigated the role of BME as an immunomodulator in HNSCC model. Forkhead box protein P3 + (FoxP3 + ) T cells suppress tumor immunity. Our data suggested that BME treatment decreases the infiltrating regulatory T (Treg) cells by inhibiting FoxP3 + populations in the tumors and in spleens. Additionally, BME treatment reduces Th17 cell population in the tumor. However, BME treatment did not alter Th1 and Th2 cell populations. Together, our findings offer a new insight into how bitter melon extract inhibits head and neck tumor growth by modulating cell proliferation and Treg populations, with implications for how to control tumor-infiltrating lymphocytes and tumor progression.

Hydra, a simple freshwater animal famous for its regenerative capabilities, must tear a hole through its epithelial tissue each time it opens its mouth. The feeding response of Hydra has been well-characterized physiologically and is regarded as a classical model system for environmental chemical biology. However, due to a lack of in vivo labeling and imaging tools, the biomechanics of mouth opening have remained completely unexplored. We take advantage of the availability of transgenic Hydra lines to perform the first dynamical analysis, to our knowledge, of Hydra mouth opening and test existing hypotheses regarding the underlying cellular mechanisms. Through cell position and shape tracking, we show that mouth opening is accompanied by changes in cell shape, but not cellular rearrangements as previously suggested. Treatment with a muscle relaxant impairs mouth opening, supporting the hypothesis that mouth opening is an active process driven by radial contractile processes (myonemes) in the ectoderm. Furthermore, we find that all events exhibit the same relative rate of opening. Because one individual can open consecutively to different amounts, this suggests that the degree of mouth opening is controlled through neuronal signaling. Finally, from the opening dynamics and independent measurements of the elastic properties of the tissues, we estimate the forces exerted by the myonemes to be on the order of a few nanoNewtons. Our study provides the first dynamical framework, to our knowledge, for understanding the remarkable plasticity of the Hydra mouth and illustrates that Hydra is a powerful system for quantitative biomechanical studies of cell and tissue behaviors in vivo.

Objective: This study aimed to examine the effect of perceived diagnostic delay on cancer-related distress, and determine whether fear of cancer-recurrence and quality of life mediate this relationship. Methods: Cross-sectional study in which 311 colorectal cancer (CRC) survivors in Scotland completed a survey which included questions on cancer-related distress (IES-R), perceived diagnostic delay, quality of life (trial outcome index of the FACT-C: FACT-C TOI) and fear of cancer recurrence. 15 patients withheld consent to data matching with medical records, leaving a sample size of 296. Participants were an average of 69 years old (range 56 to 81) and between 3.5 to 12 years post-diagnosis. Multiple regressions were used to test predictors of distress, and regression and bootstrapping to test for mediation. Results: Perceived diagnostic delay was correlated with higher cancer-related distress, while objective markers of diagnostic delay (disease stage at diagnosis and treatment received) were not. Some of the relationship between perceived diagnostic delay and cancer-related distress was mediated by quality of life, but not by fear of cancer recurrence. Conclusions: Perceived diagnostic delay was associated with higher cancer-related distress among CRC survivors. While poorer quality of life partly explained such associations, fear of cancer recurrence, stage at diagnosis and treatment did not. The exact features of diagnostic delay that are associated with cancer-related distress remain unclear. Future research should examine the experiences patients go through prior to diagnosis that may increase distress, in an effort to improve our understanding of the factors affecting emotional wellbeing among CRC survivors.

Hepatocellular carcinoma (HCC) is one of the most aggressive cancers and is the third leading cause of all cancer-related death. Limited noninvasive biomarkers are available for HCC detection. Early detection is the key in improving the survival of HCC patients. In this study, we tested the hypothesis that serum miRNAs can be used as a potential biomarker for HCC. Quantitative RT-PCR for miRNA analysis was performed using 70 serum samples. Receiver operating characteristic analysis was performed to measure the prognostic power of the miRNAs. The miRNA expression level was also measured from liver biopsy samples. Our study revealed that two miRNAs, miR-30e and miR-223, were expressed at significantly lower levels (P

More precise risk stratification is required to enable timely diagnosis of bowel cancer while avoiding unnecessary investigation, argue Michael Thompson and colleagues

Background: In their landmark report on the “Principles and Practice of Screening for Disease” (1968), Wilson and Jungner noted that the practice of screening is just as important for securing beneficial outcomes and avoiding harms as the formulation of principles. Many jurisdictions have since established various kinds of “screening governance organizations” to provide oversight of screening practice. Yet to date there has been relatively little reflection on the nature and organization of screening governance itself, or on how different governance arrangements affect the way screening is implemented and perceived and the balance of benefits and harms it delivers. Methods: An international expert policy workshop convened by Sturdy, Miller and Hogarth. Results: While effective governance is essential to promote beneficial screening practices and avoid attendant harms, screening governance organizations face enduring challenges. These challenges are social and ethical as much as technical. Evidence-based adjudication of the benefits and harms of population screening must take account of factors that inform the production and interpretation of evidence, including the divergent professional, financial and personal commitments of stakeholders. Similarly, when planning and overseeing organized screening programs, screening governance organizations must persuade or compel multiple stakeholders to work together to a common end. Screening governance organizations in different jurisdictions vary widely in how they are constituted, how they relate to other interested organizations and actors, and what powers and authority they wield. Yet we know little about how these differences affect the way screening is implemented, and with what consequences. Conclusions: Systematic research into how screening governance is organized in different jurisdictions would facilitate policy learning to address enduring challenges. Even without such research, informal exchange and sharing of experiences between screening governance organizations can deliver invaluable insights into the social as well as the technical aspects of governance.

Social media technologies represent an emerging means by which older adults can access health and community information, engage in peer-to-peer information sharing, and also potentially decrease social isolation. Privacy concerns, however, have been consistently identified as a barrier for older adults' use of the Web and social media technologies. The authors conduct a preliminary study involving 150 older adult participants, investigating their use and perceptions of social media technologies. The trial involved first providing the participants with brief training in three common social media technologies: Facebook, Twitter, and Skype. The authors carried out a quantitative and qualitative analysis of the participant's use and privacy perceptions of these technologies. Overall, the results are promising as to the potential to address privacy concerns to enable older adults to further utilize these technologies for improved mental, physical, and social health. Implications for future research and usage within the older adult community are also discussed.

We present the genome of the moon jellyfish Aurelia, a genome from a cnidarian with a medusa life stage. Our analyses suggest that gene gain and loss in Aurelia is comparable to what has been found in its morphologically simpler relatives—the anthozoan corals and sea anemones. RNA sequencing analysis does not support the hypothesis that taxonomically restricted (orphan) genes play an oversized role in the development of the medusa stage. Instead, genes broadly conserved across animals and eukaryotes play comparable roles throughout the life cycle. All life stages of Aurelia are significantly enriched in the expression of genes that are hypothesized to interact in protein networks found in bilaterian animals. Collectively, our results suggest that increased life cycle complexity in Aurelia does not correlate with an increased number of genes. This leads to two possible evolutionary scenarios: either medusozoans evolved their complex medusa life stage (with concomitant shifts into new ecological niches) primarily by re-working genetic pathways already present in the last common ancestor of cnidarians, or the earliest cnidarians had a medusa life stage, which was subsequently lost in the anthozoans. While we favour the earlier hypothesis, the latter is consistent with growing evidence that many of the earliest animals were more physically complex than previously hypothesized.

Capsule endoscopy (CE) has proved to be a powerful tool in the diagnosis and management of small bowel disorders since its introduction in 2001. However, white light imaging (WLI) is the principal technology used in clinical CE at present, and therefore, CE is limited to mucosal inspection, with diagnosis remaining reliant on visible manifestations of disease. The introduction of WLI CE has motivated a wide range of research to improve its diagnostic capabilities through integration with other sensing modalities. These developments have the potential to overcome the limitations of WLI through enhanced detection of subtle mucosal microlesions and submucosal and/or transmural pathology, providing novel diagnostic avenues. Other research aims to utilize a range of sensors to measure physiological parameters or to discover new biomarkers to improve the sensitivity, specificity and thus the clinical utility of CE. This multidisciplinary Review summarizes research into non-WLI CE devices by organizing them into a taxonomic structure on the basis of their sensing modality. The potential of these capsules to realize clinically useful virtual biopsy and computer-aided diagnosis (CADx) is also reported. The introduction of white light imaging capsule endoscopy has motivated research to improve its diagnostic capabilities through integration with other sensing modalities. In this Review, the authors summarize studies on non-white light imaging devices, such as those using optical coherence tomography, ultrasonography or biophysical measurements

An elective admission involves an hospital admission for which a doctor schedules the day and time of the visit in advance. That is, it is not an emergency or urgent admission. Factors in the scheduling of such admissions and also resource impacts include bed availability and utilization, and as such it is of benefit to be able to predict in advance the length of stay of patients. In this work we report on the use of data mining on a large, cross-provider dataset to develop potentially generalizable machine learning models to predict all- condition, high length of stay for elective admissions, prior to the time of admission based upon patient, admitting condition, hospital and locale attributes. The best of these models achieves an AUC score of 0.900. We also carry out evaluations to consider the generalizability of such models via measuring their predictive performance on a dataset from a different time period, and the models demonstrate that they maintain equivalent predictive levels on data from a different period.

Background: Quantitative faecal immunochemical tests (FIT) measure faecal haemoglobin concentration (f-Hb), which increases in the presence of colorectal neoplasia and is related to the severity of disease. We examined the diagnostic accuracy of FIT in patients at moderate to high risk of colorectal cancer (CRC) attending for surveillance colonoscopy as per national guidelines. Methods: We undertook a prospective study in two University hospitals, one in Scotland and one in England. Between June 2014 and September 2016, 1103 consecutive patients were invited to complete a FIT before their scheduled colonoscopy: f-Hb was analysed on an OC-Sensor io automated analyser (Eiken Chemical Co., Ltd, Tokyo, Japan)) with a limit of detection (LoD) of 2 µg Hb/g faeces. The diagnostic accuracy of f-Hb for CRC and higher-risk adenoma (HRA) was examined. Findings: 643 patients returned a FIT. Four patients with known IBD were excluded, leaving 639 (57·9%) in the study: age range: 25-90 years (median: 64 years, IQR: 55-71): 54·6% male. Of 593 patients who returned a FIT and completed colonoscopy, 41 (6·9%) had advanced neoplasia (4 CRC, 37 HRA): 238/593 patients (40·1%) had detectable f-Hb of whom 31 (13·0%) had advanced neoplasia (2 CRC, 29 HRA) compared to 10 (2·8%) in those with undetectable f-Hb (2 CRC, 8 HRA).Detectable f-Hb gave negative predictive values of 99·4% for CRC and 97·2% for CRC plus HRA. Interpretation: In patients at moderate to high risk of CRC who are under colonoscopy surveillance, a FIT at the LoD can provide an objective estimate of the risk of advanced neoplasia and could enable tailored scheduling of colonoscopy. Funding Statement: Chief Scientist Office; grant reference number CZH/4/1032. Declaration of Interests: CGF has undertaken consultancy with Kyowa-Medex Co., Ltd, Tokyo, Japan, and has received travel support from Alpha Labs Ltd, Eastleigh, UK. Other authors - none. Ethics Approval Statement: This study had ethical approval from NRES North of Scotland Ethics Committee: reference: 14/NS/0059.

The ability to predict prolonged length of hospital stay for newborn children has clinical value as an indicator of newborn health status but also can assist in such health system resource considerations as improved utilization of hospital wards and beds. In this paper, we describe the application of machine learning-based prediction to a Healthcare Cost and Utilization Project dataset and report on the performance of various developed predictive models. Via only utilizing administrative data and minimal clinical data available near to the time of admission/birth, we are able to demonstrate high performing models. The use of HCUP data for building newborn prolonged length of stay models potentially applicable across health care providers is an important contribution, and additionally the models represent high-performing models in the field of published predictive models of newborn length of stay in general.

Background In 2006, the Bowel Cancer Screening Programme (BCSP) in England began offering biennial faecal occult blood testing (FOBt) at ages 60–69 years. Although FOBt is aimed at detecting colorectal neoplasms, other conditions can affect the result. In a large UK prospective study, we examined associations, both before and after screening, between FOBt positivity and 10 conditions that are often associated with gastrointestinal bleeding. Methods By electronically linking BCSP and Million Women Study records, we identified 604 495 women without previous colorectal cancer who participated in their first routine FOBt screening between 2006 and 2012. Regression models, using linked national hospital admission records, yielded adjusted relative risks (RRs) in FOBt-positive versus FOBt-negative women for colorectal cancer, adenoma, diverticular disease, inflammatory bowel disease, haemorrhoids, upper gastrointestinal cancer, oesophagitis, peptic ulcer, anaemia and other haematological disorders. Results RRs in FOBt-positive versus FOBt-negative women were 201.3 (95% CI 173.8–233.2) for colorectal cancer and 197.9 (95% CI 180.6–216.8) for adenoma within 12 months after screening and 3.49 (95% CI 2.31–5.26) and 4.88 (95% CI 3.80–6.26), respectively, 12–24 months after screening; P

ObjectiveAn association between detectable faecal haemoglobin (f-Hb) and both the risk of death from colorectal cancer (CRC) and all-cause mortality has been reported. We set out to confirm or refute this observation in a UK population and to explore the association between f-Hb, as indicated by a positive guaiac faecal occult blood test (gFOBT) result, and different causes of death.DesignAll individuals (134 192) who participated in gFOBT screening in Tayside, Scotland between 29/03/2000 and 29/03/2016 were studied by linking their test result (positive or negative) with mortality data from the National Records of Scotland database and following to 30/03/2016.ResultsThose with a positive test result (n=2714) had a higher risk of dying than those with a negative result, from CRC: HR 7.79 (95% CI 6.13 to 9.89), pConclusionThe presence of detectable f-Hb is associated with increased risk of death from a wide range of causes.

Chronic hepatitis C virus (HCV) infection may lead to end-stage liver disease, including hepatocellular carcinoma (HCC). We have shown previously that microRNA-373 (miR-373) is upregulated in HCV-infected human liver biopsy specimens. To gain insight into the role of miR-373 in HCV-mediated pathogenesis, we investigated its interacting partner for hepatocyte growth regulation. Transcriptome sequencing (RNA-seq) data revealed that Wee1 is associated with miR-373 and is a direct target. Interestingly, higher expression of Wee1 was noted in HCV-infected hepatocytes than in uninfected hepatocytes, suggesting that other factors may block miR-373-mediated Wee1 inhibition. We subsequently found an association between the long noncoding RNA NORAD (LINC00657) and miR-373, and we demonstrated that NORAD binds to miR-373 and Wee1 independently. However, the high level of Wee1 expression in HCV-infected hepatocytes suggested that miR-373 forms a complex with NORAD. Depletion of miR-373 or the inhibitor Wee1 reduces the growth of Huh7.5 cells harboring the HCV genome as well as reducing Wee1 expression. Taken together, our data demonstrate a novel mechanism of hepatocyte growth promotion during HCV infection involving a miR-373–NORAD–Wee1 axis, which may be a target for future therapy against HCV-associated HCC. IMPORTANCE The mechanism of HCV-mediated liver pathogenesis is poorly understood. In this study, we observed that HCV infection upregulates miR-373 and Wee1, a pivotal player in the G(2) checkpoint in the cell cycle, although Wee1 is a direct target for miR-373. Subsequent investigation demonstrated that miR-373 forms a complex with the long noncoding RNA NORAD, resulting in the release of their common target, Wee1, in HCV-infected cells, which, in turn, favors uncontrolled cell growth. Our study suggested a previously unknown mechanism for hepatocyte growth promotion following HCV infection, and this pathway can be targeted for future therapy against HCV-mediated liver pathogenesis.

IntroductionPopulation-based screening has been shown to reduce cancer specific mortality. Within Scotland, three national screening programmes exist: breast, cervical and bowel. Despite being a common and preventable form of cancer, the uptake for bowel cancer screening among women lags behind that for breast and cervical cancer. Objectives and ApproachSince the benefits of screening accrue with participation, it is important to understand why differences in screening uptake exist. In this study, data on women aged 24-74 in the Greater Glasgow and Clyde Health Board, invited to take part in one or more screening programme during the period 2009-2013, were linked to demographic and medical data. Uptake was determined based on the presence of a screening attendance or result; the impact of age, deprivation and co-morbidity on uptake was determined using logistic regression for each individual programme, and for the cohort of women invited to participate in all three programmes. ResultsOverall, 430,591 women were invited to take part in one or more screening programme during the study period. The uptake for bowel screening was, at 61.7%, lower than that seen in either the breast (72.6%) or cervical (80.7%) programme. Despite these differences, the same demographic factors were associated with uptake of each individual screening programme: older women and those living in affluent areas were most likely to attend. Medical factors did differentially influence uptake, those with multi-morbid illness being less likely to participate in breast and bowel, but not the cervical programme. For the 68,324 women invited to participate in all programmes, 52.1% took part in all three while 7.2% participated in none. Conclusion/ImplicationsUptake of bowel screening was confirmed as lower than uptake of other programmes, although all were similarly impacted by demographic, clinical and socioeconomic factors. Individuals were more likely to complete bowel screening if they participate in another programme, suggesting these may serve as a vehicle for improving bowel screening uptake.

In this paper, we describe the application of data mining techniques in relation to an important clinical care quality indicator: the prediction of hospital readmission within 30 days of discharge. We retrieved six months of encounter data between dates April through September, 2017, from five inpatient hospitals in a large US metropolitan area. Each encounter includes both administrative and clinical data. We utilized a feature reduction technique to replace thousands of clinical features with a much smaller number of proxy features. The dimensionally reduced dataset was then used in the development, training and evaluation of numerous readmission predictive models. Using standard implementation techniques, our model can function within the hospital EHR from where the data was sourced, in real- time, for all patients, prior to discharge. Model performance of the best performing model compares favorably to existing comparable pre-discharge, all-patient predictive model studies.

Objectives To assess the feasibility of delivering and evaluating a lifestyle programme for patients with colorectal cancer undergoing potentially curative treatments. Study design Non-randomised feasibility trial. Setting National Health Service (NHS) Tayside. Participants Adults with stage I–III colorectal cancer. Intervention The programme targeted smoking, alcohol, physical activity, diet and weight management. It was delivered in three face-to-face counselling sessions (plus nine phone calls) by lifestyle coaches over three phases (1: presurgery, 2: surgical recovery and 3: post-treatment recovery). Primary outcome Feasibility measures (recruitment, retention, programme implementation, achieved measures, fidelity, factors affecting protocol adherence and acceptability). Secondary outcomes Measured changes in body weight, waist circumference, walking and self-reported physical activity, diet, smoking, alcohol intake, fatigue, bowel function and quality of life. Results Of 84 patients diagnosed, 22 (26%) were recruited and 15 (18%) completed the study. Median time for intervention delivery was 5.5 hours. Coaches reported covering most (>70%) of the intervention components but had difficulties during phase 2. Evaluation measures (except walk test) were achieved by all participants at baseline, and most (25 kg/m2 and none was underweight. Physical activity data showed a positive trend towards increased activity overall, but no other changes in secondary outcomes were detected. Conclusions To make this intervention feasible for testing as a full trial, further research is required on (a) recruitment optimisation, (b) appropriate assessment tools, (c) protocols for phase 2 and 3, which can build in flexibility and (d) ways for NHS staff to facilitate the programme. Trial registration number ISRCTN52345929; Post-results.

In this article, we describe and evaluate a crowdsensing approach that entails local cooperation between crowdsensing participants in smart environments, utilizing an underlying fog computing-enabled Internet of Things. A fog computing-based Internet-of-Things architecture involves a layer of computing nodes residing closer to the sensing devices, with this layer of fog nodes lying in between mobile and sensing devices at the network edge and the cloud. This motivates us to propose a model for crowdsensing in smart environments that involves both competition and cooperation between nearby crowdsensing participants at the edge network. Comprehensive simulations are presented to evaluate the performance of the proposed approach. The work shows desirable characteristics in terms of number of active participants, number of samples collected within a given budget and coverage, resulting from localized cooperation by crowdsensing participants at the edge layer that can support various smart environment applications.

Objectives Population-based colorectal (bowel) cancer screening using faecal occult blood tests leads to a reduction in cause-specific mortality. However, in people where the colon is defunctioned, the use of standard faecal occult blood test is not appropriate. The aim of this study was to examine the current trends of clinical practice for colorectal cancer screening in people with defunctioned colons. Methods An online survey was performed using SurveyMonkey. All members of the Association of Coloproctology of Great Britain and Ireland were invited by email to participate. Reminders were sent to non-responders and partial responders till six weeks. All responses were included in our analysis. Results Of the 206 (34.59%) questionnaires completed, all questions were answered in 110 (55.8%). Among responders, 94 (85.4%) were colorectal consultant surgeons, 72% had worked in their current capacity for more than five years, and 105 (50.9%) had encountered colorectal cancer in defunctioned colons during their career. Some 72.2% of responders stated that a screening test for colorectal cancer in patients with defunctioned colons was currently not offered, or that they did not know whether or not it was offered in their area. Conclusions Bowel screening in the United Kingdom is currently not offered to 72.2% of the age appropriate population with defunctioned colons. Among responding colorectal surgeons, 50% had encountered colorectal cancer in such patients. There is considerable variability in clinical practice regarding the optimal age for onset of screening, time interval, and the optimal modality to offer for screening in such cases.

Health screening can only be applied to populations, not individuals. For it to be effective, the initial screening test must be acceptable and reasonably accurate, the disease must be treatable with better outcomes when treated early and the harm and cost associated with screening must not outweigh its benefits. Robust evidence is therefore required before systematic screening is implemented. Surveillance implies the testing of people at high risk of disease and is therefore distinct from screening in both scale (smaller) and intensity (greater). In both cases, however, clear information must be provided to potential participants so that they can weigh up the balance of benefit and harm before deciding on whether or not to engage in the process.

Triple negative breast cancer (TNBC) is aggressive with a worse prognosis. We have recently shown that bitter melon extract (BME) treatment was more effective in inhibition of TNBC tumor growth in mouse models as compared to ER positive breast tumor growth. Aberrant dysregulation of lipid metabolism is associated with breast cancer progression, however, anti-cancer mechanism of BME linking lipid metabolism in breast cancer growth remains unexplored. Here, we observed that accumulation of esterified cholesterol was reduced in BME treated TNBC cell lines as compared to control cells. We next evaluated expression levels of acyl-CoA: cholesterol acyltransferase 1 (ACAT-1) in TNBC cells treated with BME. Our results demonstrated that BME treatment inhibited ACAT-1 expression in TNBC cells. Subsequently, we found that sterol regulatory element-binding proteins-1 and -2, and FASN was significantly reduced in BME treated TNBC cell lines. Low-density lipoprotein receptor was also downregulated in BME treated TNBC cells as compared to control cells. We further demonstrated that BME feeding reduced tumor growth in TNBC mammospheres implanted into NSG mice, and inhibits ACAT-1 expression. To our knowledge, this is the first report demonstrating BME suppresses TNBC cell growth through ACAT-1 inhibition, and have potential for additional therapeutic regimen against human breast cancer.

ObjectivesTo assess the feasibility of delivering and evaluating a weight management (WM) programme for overweight patients with a family history (FH) of breast cancer (BC) or colorectal cancer (CRC).Study designA two-arm (intervention vs usual care) randomised controlled trial.SettingNational Health Service (NHS) Tayside and NHS Grampian.ParticipantsPeople with a FH of BC or CRC aged≥18 years and body mass index of ≥25 kg/m2referred to NHS genetic services.InterventionParticipants were randomised to a control (lifestyle booklet) or 12-week intervention arm where they were given one face-to-face counselling session, four telephone consultations and web-based support. A goal of 5% reduction in body weight was set, and a personalised diet and physical activity (PA) programme was provided. Behavioural change techniques (motivational interviewing, action and coping plans and implementation intentions) were used.Primary outcomeFeasibility measures: recruitment, programme implementation, fidelity measures, achieved measurements and retention, participant satisfaction assessed by questionnaire and qualitative interviews.Secondary outcomesMeasured changes in weight and PA and reported diet and psychosocial measures between baseline and 12-week follow-up.ResultsOf 480 patients approached, 196 (41%) expressed interest in the study, and of those, 78 (40%) patients were randomised. Implementation of the programme was challenging within the time allotted and fidelity to the intervention modest (62%). Qualitative findings indicated the programme was well received. Questionnaires and anthropometric data were completed by >98%. Accelerometer data were attained by 84% and 54% at baseline and follow-up, respectively. Retention at 12 weeks was 76%. Overall, 36% of the intervention group (vs 0% in control) achieved 5% weight loss. Favourable increases in PA and reduction in dietary fat were also reported.ConclusionsA lifestyle programme for people with a family history of cancer is feasible to conduct and acceptable to participants, and indicative results suggest favourable outcomes.Trial registration numberISRCTN13123470; Pre-results.

BACKGROUND New screening tests for colorectal cancer continue to emerge, but the evidence needed to justify their adoption in screening programs remains uncertain. METHODS A review of the literature and a consensus approach by experts was undertaken to provide practical guidance on how to compare new screening tests with proven screening tests. RESULTS Findings and recommendations from the review included the following: Adoption of a new screening test requires evidence of effectiveness relative to a proven comparator test. Clinical accuracy supported by programmatic population evaluation in the screening context on an intention‐to‐screen basis, including acceptability, is essential. Cancer‐specific mortality is not essential as an endpoint provided that the mortality benefit of the comparator has been demonstrated and that the biologic basis of detection is similar. Effectiveness of the guaiac‐based fecal occult blood test provides the minimum standard to be achieved by a new test. A 4‐phase evaluation is recommended. An initial retrospective evaluation in cancer cases and controls (Phase 1) is followed by a prospective evaluation of performance across the continuum of neoplastic lesions (Phase 2). Phase 3 follows the demonstration of adequate accuracy in these 2 prescreening phases and addresses programmatic outcomes at 1 screening round on an intention‐to‐screen basis. Phase 4 involves more comprehensive evaluation of ongoing screening over multiple rounds. Key information is provided from the following parameters: the test positivity rate in a screening population, the true‐positive and false‐positive rates, and the number needed to colonoscope to detect a target lesion. CONCLUSIONS New screening tests can be evaluated efficiently by this stepwise comparative approach. Cancer 2016;122:826–39. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society., To provide practical guidance on how to compare new screening tests with proven screening tests for colorectal cancer, a panel of experts reviewed the literature and proposes a 4‐phase evaluation process that includes comparison with existing, proven tests but does not necessarily require randomized controlled trials with mortality as the endpoint. New screening tests can be evaluated efficiently using this stepwise comparative approach.

Human colon tissue explant culture provides a physiologically relevant model system to study human gut biology. However, the small (20–30 mg) and complex tissue samples used present challenges for monitoring tissue stability, viability, and provision of sufficient tissue for analyses. Combining molecular profiling with explant culture has potential to overcome such limitations, permitting interrogation of complex gene regulation required to maintain gut mucosa in culture, monitor responses to culture environments and interventions. Human ex vivo colon explant gene expression profiles were assayed using an in-house custom-designed hCellMarkerPlex assay at culture time points 0, 1, 2, 4, and 14 h. Characteristic profiles of epithelial cell markers linked to differentiation, cellular polarization, and apoptosis were correlated with visible histochemical changes in explant epithelium during culture and tissue donors. The GenomeLab System provides effective assay of multiple targets not possible from small tissue samples with conventional gene expression technology platforms. This is advantageous to increase the utility of the ex vivo human colon model in applications to interrogate this complex and dynamic tissue environment for use in analytical testing.

We have previously reported that hepatitis C virus (HCV) infection of primary human hepatocytes (PHH) induces the epithelial mesenchymal transition (EMT) state and extends hepatocyte life span (S. K. Bose, K. Meyer, A. M. Di Bisceglie, R. B. Ray, and R. Ray, J Virol 86:13621–13628, 2012, http://dx.doi.org/10.1128/JVI.02016-12 ). These hepatocytes displayed sphere formation on ultralow binding plates and survived for more than 12 weeks. The sphere-forming hepatocytes expressed a number of cancer stem-like cell (CSC) markers, including high levels of the stem cell factor receptor c-Kit. The c-Kit receptor is regarded as one of the CSC markers in hepatocellular carcinoma (HCC). Analysis of c-Kit mRNA displayed a significant increase in the liver biopsy specimens of chronically HCV-infected patients. We also found c-Kit is highly expressed in transformed human hepatocytes (THH) infected in vitro with cell culture-grown HCV genotype 2a. Further studies suggested that HCV core protein significantly upregulates c-Kit expression at the transcriptional level. HCV infection of THH led to a significant increase in the number of spheres displayed on ultralow binding plates and in enhanced EMT and CSC markers and tumor growth in immunodeficient mice. The use of imatinib or dasatinib as a c-Kit inhibitor reduced the level of sphere-forming cells in culture. The sphere-forming cells were sensitive to treatment with sorafenib, a multikinase inhibitor, that is used for HCC treatment. Further, stattic, an inhibitor of the Stat3 molecule, induced sphere-forming cell death. A combination of sorafenib and stattic had a significantly stronger effect, leading to cell death. These results suggested that HCV infection potentiates CSC generation, and selected drugs can be targeted to efficiently inhibit cell growth. IMPORTANCE HCV infection may develop into HCC as an end-stage liver disease. We focused on understanding the mechanism for the risk of HCC from chronic HCV infection and identified targets for treatment. HCV-infected primary and transformed human hepatocytes (PHH or THH) generated CSC. HCV-induced spheres were highly sensitive to cell death from sorafenib and stattic treatment. Thus, our study is highly significant for HCV-associated HCC, with the potential for developing a target-specific strategy for improved therapies.

Aim This study assessed the baseline type II diabetes mellitus (T2DM) risk status among overweight patients with screen-detected colorectal adenomas and explored the implications of the findings for preventative practice. Method Participants aged between 50 and 74 years (73% of whom were men) were recruited from four Scottish health boards and assessed for diabetes risk. Participants were categorized as at ‘high’ diabetes risk if glycated haemoglobin (HbA1c) was between 6.0 and 6.4% or fasting plasma glucose (FPG) was between 5.5 and 6.9 mmol/l and as potentially undiagnosed T2DM when HbA1c ≥ 6.5% or FPG ≥ 7 mmol/l. Secondary outcome measures included anthropometric measurements, blood pressure and the plasma lipid profile. The tests were repeated at 12 months and diabetes risk categories were reassessed following intervention procedures. Results Forty-seven (14.3%) of the 329 participants had a preexisting diagnosis of T2DM. Of the remainder with complete biochemistry results (n = 250), 19 (7.6%) were classified as having potentially undiagnosed T2DM and 125 (50.0%) as being at high risk of developing diabetes. More than a quarter of participants in all categories had raised waist circumference, hypertension and plasma lipids, indicative of raised cardiovascular risk. At 12 months' follow-up, the diabetes risk category diminished in 20% of the intervention group vs 11% in the controls [OR 2.26 (95% CI 1.03–4.96)]. Conclusion Our results suggest that a diagnosis of adenoma in overweight patients provides a health service opportunity for diabetes assessment, prevention and management in a high-risk population at a potentially teachable moment.

Background: Screening using fecal occult blood testing (FOBt) reduces colorectal cancer mortality, but the test has low sensitivity. A “missed” cancer may cause psychologic harms in the screened population that partially counteract the benefits of early detection. Methods: Three hundred and eleven people diagnosed with colorectal cancer (i) after a negative FOBt result (interval cancer), (ii) a positive result (screen-detected cancer), or (iii) in regions where screening was not offered, completed questions on quality of life (FACT-C), depression (CES-D), perceived diagnostic delay, and trust in the results of FOBt screening. Fifteen withheld consent to data matching with medical records, leaving a sample size of 296. Results: Controlling for demographic and clinical variables, patients with an interval cancer reported poorer quality of life (difference in means = 6.16, P = 0.03) and more diagnostic delay (OR, 0.37; P = 0.02) than patients with screen-detected disease, with no differences in depression. No differences were observed between the interval cancer group and the group not offered screening on these measures. Patients with an interval cancer reported the lowest levels of trust in FOBt. Conclusions: An interval cancer has adverse effects on trust in FOBt, but does not result in worse psychologic outcomes compared with people diagnosed in areas with no screening program. People with an interval cancer report poorer quality of life than people with screen-detected disease. Impact: Improvements in test sensitivity could improve quality of life among people who complete an FOB test over and above any benefits already conferred by earlier detection. Cancer Epidemiol Biomarkers Prev; 24(7); 1–7. ©2015 AACR .

Background: Colorectal cancers arise from benign adenomas, although not all adenomas progress to cancer and there are marked interpatient differences in disease progression. We have previously associated KRAS mutations with disease progression and reduced survival in colorectal cancer patients. Methods: We used TaqMan low-density array (TLDA) qRT–PCR analysis to identify miRNAs differentially expressed in normal colorectal mucosa, adenomas and cancers and in isogeneic KRAS WT and mutant HCT116 cells, and used a variety of phenotypic assays to assess the influence of miRNA expression on KRAS activity, chemosensitivity, proliferation and invasion. Results: MicroRNA-224 was differentially expressed in dysplastic colorectal disease and in isogeneic KRAS WT and mutant HCT116 cells. Antagomir-mediated miR-224 silencing in HCT116 KRAS WT cells phenocopied KRAS mutation, increased KRAS activity and ERK and AKT phosphorylation. 5-FU chemosensitivity was significantly increased in miR-224 knockdown cells, and in NIH3T3 cells expressing KRAS and BRAF mutant proteins. Bioinformatics analysis of predicted miR-224 target genes predicted altered cell proliferation, invasion and epithelial–mesenchymal transition (EMT) phenotypes that were experimentally confirmed in miR-224 knockdown cells. Conclusions: We describe a novel mechanism of KRAS regulation, and highlight the clinical utility of colorectal cancer-specific miRNAs as disease progression or clinical response biomarkers.