An MLE method for finding LKB NTCP model parameters using Monte Carlo uncertainty estimates

The aims of this work were to establish a program to fit NTCP models to clinical data with multiple toxicity endpoints, to test the method using a realistic test dataset, to compare three methods for estimating confidence intervals for the fitted parameters and to characterise the speed and performance of the program

Implementation of a rapid learning platform: predicting 2-year survival in laryngeal carcinoma patients in a clinical setting

Background and Purpose To improve quality and personalization of oncology health care, decision aid tools are needed to advise physicians and patients. The aim of this work is to demonstrate the clinical relevance of a survival prediction model as a first step to multi institutional rapid learning and compare this to a clinical trial dataset. Materials and Methods Data extraction and mining tools were used to collect uncurated input parameters from Illawarra Cancer Care Centre\u27s (clinical cohort) oncology information system. Prognosis categories previously established from the Maastricht Radiation Oncology (training cohort) dataset, were applied to the clinical cohort and the radiotherapy only arm of the RTOG-9111 (trial cohort). Results Data mining identified 125 laryngeal carcinoma patients, ending up with 52 patients in the clinical cohort who were eligible to be evaluated by the model to predict 2-year survival and 177 for the trial cohort. The model was able to classify patients and predict survival in the clinical cohort, but for the trial cohort it failed to do so. Conclusions The technical infrastructure and model is able to support the prognosis prediction of laryngeal carcinoma patients in a clinical cohort. The model does not perform well for the highly selective patient population in the trial cohort

Opportunities and challenges in developing a whole-of-government national food and nutrition policy: lessons from Australia's National Food Plan

OBJECTIVE: The present article tracks the development of the Australian National Food Plan as a 'whole of government' food policy that aimed to integrate elements of nutrition and sustainability alongside economic objectives. DESIGN: The article uses policy analysis to explore the processes of consultation and stakeholder involvement in the development of the National Food Plan, focusing on actors from the sectors of industry, civil society and government. Existing documentation and submissions to the Plan were used as data sources. Models of health policy analysis and policy streams were employed to analyse policy development processes. SETTING: Australia. SUBJECTS: Australian food policy stakeholders. RESULTS: The development of the Plan was influenced by powerful industry groups and stakeholder engagement by the lead ministry favoured the involvement of actors representing the food and agriculture industries. Public health nutrition and civil society relied on traditional methods of policy influence, and the public health nutrition movement failed to develop a unified cross-sector alliance, while the private sector engaged in different ways and presented a united front. The National Food Plan failed to deliver an integrated food policy for Australia. Nutrition and sustainability were effectively sidelined due to the focus on global food production and positioning Australia as a food 'superpower' that could take advantage of the anticipated 'dining boom' as incomes rose in the Asia-Pacific region. CONCLUSIONS: New forms of industry influence are emerging in the food policy arena and public health nutrition will need to adopt new approaches to influencing public policy

Increasing engagement with an occupational digital stress management program through the use of an online facilitated discussion group: results of a pilot randomised controlled trial.

Introduction Rates of work-related stress, depression and anxiety are high, resulting in reduced work performance and absenteeism. There is evidence that digital mental health interventions delivered in the workplace are an effective way of treating these conditions, but intervention engagement and adherence remain a challenge. Providing guidance can lead to greater engagement and adherence; an online facilitated discussion group may be one way of providing that guidance in a time efficient way. This study compares engagement with a minimally guided digital mental health program (WorkGuru) delivered in the workplace with a discussion group (DG) and without a discussion group (MSG), and with a wait list control (WLC); it was conducted as a pilot phase of a definitive trial. Methods Eighty four individuals with elevated levels of stress from six organisations were recruited to the study and randomised to one of two active conditions (DG or MSG) or a WLC. The program WorkGuru is a CBT based, eight-week stress management intervention that is delivered with minimal guidance from a coach. Data was collected at baseline, post–intervention and at 16-week follow-up via online questionnaires. The primary outcome measure was number of logins. Secondary measures included further engagement measures, and measures of depression, anxiety, stress, comfort and enthusiasm. Quality measures including satisfaction and system usability were also collected. Results A greater number of logins was observed for the DG compared with the MSG; this was a medium between group effect size (d=0.51; 95% CI: -0.04, 1.05). Small to medium effect size differences were found at T2 in favour of the active conditions compared with the control on the DASS subscales depression, anxiety and stress, and the IWP subscales enthusiasm and comfort. This was largely maintained at T3. Satisfaction with the intervention was high with individuals in the MSG reporting greater satisfaction than individuals in the DG. Conclusions This study shows that access to an online facilitated discussion group increases engagement with a minimally supported occupational digital mental health intervention (as defined by the number of logins), but that this doesn’t necessarily result in improved psychological outcomes or increased satisfaction when compared to access to the intervention without the group. Access to the web-based program was associated with lower levels of depression, anxiety and stress and an increase in comfort and enthusiasm post intervention; these changes were largely maintained at follow-up. Trial registration This trial was registered with ClinicalTrials.gov on March the 18th 2016 NCT02729987 (website link https://clinicaltrials.gov/ct2/show/NCT02729987?term=NCT02729987&rank=1

Increasing engagement with an occupational digital stress management program through the use of an online facilitated discussion group: results of a pilot randomised controlled trial.

Introduction Rates of work-related stress, depression and anxiety are high, resulting in reduced work performance and absenteeism. There is evidence that digital mental health interventions delivered in the workplace are an effective way of treating these conditions, but intervention engagement and adherence remain a challenge. Providing guidance can lead to greater engagement and adherence; an online facilitated discussion group may be one way of providing that guidance in a time efficient way. This study compares engagement with a minimally guided digital mental health program (WorkGuru) delivered in the workplace with a discussion group (DG) and without a discussion group (MSG), and with a wait list control (WLC); it was conducted as a pilot phase of a definitive trial. Methods Eighty four individuals with elevated levels of stress from six organisations were recruited to the study and randomised to one of two active conditions (DG or MSG) or a WLC. The program WorkGuru is a CBT based, eight-week stress management intervention that is delivered with minimal guidance from a coach. Data was collected at baseline, post–intervention and at 16-week follow-up via online questionnaires. The primary outcome measure was number of logins. Secondary measures included further engagement measures, and measures of depression, anxiety, stress, comfort and enthusiasm. Quality measures including satisfaction and system usability were also collected. Results A greater number of logins was observed for the DG compared with the MSG; this was a medium between group effect size (d=0.51; 95% CI: -0.04, 1.05). Small to medium effect size differences were found at T2 in favour of the active conditions compared with the control on the DASS subscales depression, anxiety and stress, and the IWP subscales enthusiasm and comfort. This was largely maintained at T3. Satisfaction with the intervention was high with individuals in the MSG reporting greater satisfaction than individuals in the DG. Conclusions This study shows that access to an online facilitated discussion group increases engagement with a minimally supported occupational digital mental health intervention (as defined by the number of logins), but that this doesn’t necessarily result in improved psychological outcomes or increased satisfaction when compared to access to the intervention without the group. Access to the web-based program was associated with lower levels of depression, anxiety and stress and an increase in comfort and enthusiasm post intervention; these changes were largely maintained at follow-up. Trial registration This trial was registered with ClinicalTrials.gov on March the 18th 2016 NCT02729987 (website link https://clinicaltrials.gov/ct2/show/NCT02729987?term=NCT02729987&rank=1

Web-based patient-reported outcome measures for personalized treatment and care (PROMPT-Care) : multicenter pragmatic nonrandomized trial

Background: Despite the acceptability and efficacy of e–patient-reported outcome (ePRO) systems, implementation in routine clinical care remains challenging. Objective: This pragmatic trial implemented the PROMPT-Care (Patient Reported Outcome Measures for Personalized Treatment and Care) web-based system into existing clinical workflows and evaluated its effectiveness among a diverse population of patients with cancer. Methods: Adult patients with solid tumors receiving active treatment or follow-up care in four cancer centers were enrolled. The PROMPT-Care intervention supported patient management through (1) monthly off-site electronic PRO physical symptom and psychosocial well-being assessments, (2) automated electronic clinical alerts notifying the care team of unresolved clinical issues following two consecutive assessments, and (3) tailored online patient self-management resources. Propensity score matching was used to match controls with intervention patients in a 4:1 ratio for patient age, sex, and treatment status. The primary outcome was a reduction in emergency department presentations. Secondary outcomes were time spent on chemotherapy and the number of allied health service referrals. Results: From April 2016 to October 2018, 328 patients from four public hospitals received the intervention. Matched controls (n=1312) comprised the general population of patients with cancer, seen at the participating hospitals during the study period. Emergency department visits were significantly reduced by 33% (P=.02) among patients receiving the intervention compared with patients in the matched controls. No significant associations were found in allied health referrals or time to end of chemotherapy. At baseline, the most common patient reported outcomes (above-threshold) were fatigue (39%), tiredness (38.4%), worry (32.9%), general wellbeing (32.9%), and sleep (24.1%), aligning with the most frequently accessed self-management domain pages of physical well-being (36%) and emotional well-being (23%). The majority of clinical feedback reports were reviewed by nursing staff (729/893, 82%), largely in response to the automated clinical alerts (n=877). Conclusions: Algorithm-supported web-based systems utilizing patient reported outcomes in clinical practice reduced emergency department presentations among a diverse population of patients with cancer. This study also highlighted the importance of (1) automated triggers for reviewing above-threshold results in patient reports, rather than passive manual review of patient records; (2) the instrumental role nurses play in managing alerts; and (3) providing patients with resources to support guided self-management, where appropriate. Together, these factors will inform the integration of web-based PRO systems into future models of routine cancer care

Establishment of novel long-term cultures from EpCAM positive and negative circulating tumour cells from patients with metastatic gastroesophageal cancer

Circulating tumour cell (CTC) enumeration and profiling has been established as a valuable clinical tool in many solid malignancies. A key challenge in CTC research is the limited number of cells available for study. Ex vivo CTC culture permits expansion of these rare cell populations for detailed characterisation, functional assays including drug sensitivity testing, and investigation of the pathobiology of metastases. We report for the first time the establishment and characterisation of two continuous CTC lines from patients with gastroesophageal cancer. The two cell lines (designated UWG01CTC and UWG02CTC) demonstrated rapid tumorigenic growth in immunodeficient mice and exhibit distinct genotypic and phenotypic profiles which are consistent with the tumours of origin. UWG02CTC exhibits an EpCAM+, cytokeratin+, CD44+ phenotype, while UWG01CTC, which was derived from a patient with metastatic neuroendocrine cancer, displays an EpCAM−, weak cytokeratin phenotype, with strong expression of neuroendocrine markers. Further, the two cell lines show distinct differences in drug and radiation sensitivity which match differential cancer-associated gene expression pathways. This is strong evidence implicating EpCAM negative CTCs in metastasis. These novel, well characterised, long-term CTC cell lines from gastroesophageal cancer will facilitate ongoing research into metastasis and the discovery of therapeutic targets

Dynamical photon-photon interaction mediated by a quantum emitter

Single photons constitute a main platform in quantum science and technology: they carry quantum information over extended distances in the future quantum internet and can be manipulated in advanced photonic circuits enabling scalable photonic quantum computing. The main challenge in quantum photonics is how to generate advanced entangled resource states and efficient light-matter interfaces. Here we utilize the efficient and coherent coupling of a single quantum emitter to a nanophotonic waveguide for realizing quantum nonlinear interaction between single-photon wavepackets. This inherently multimode quantum system constitutes a new research frontier in quantum optics. We demonstrate control of a photon with another photon and experimentally unravel the dynamical response of two-photon interactions mediated by a quantum emitter, and show that the induced quantum correlations are controlled by the pulse duration. The work will open new avenues for tailoring complex photonic quantum resource states

Modelling cross-reactivity and memory in the cellular adaptive immune response to influenza infection in the host

The cellular adaptive immune response plays a key role in resolving influenza infection. Experiments where individuals are successively infected with different strains within a short timeframe provide insight into the underlying viral dynamics and the role of a cross-reactive immune response in resolving an acute infection. We construct a mathematical model of within-host influenza viral dynamics including three possible factors which determine the strength of the cross-reactive cellular adaptive immune response: the initial naive T cell number, the avidity of the interaction between T cells and the epitopes presented by infected cells, and the epitope abundance per infected cell. Our model explains the experimentally observed shortening of a second infection when cross-reactivity is present, and shows that memory in the cellular adaptive immune response is necessary to protect against a second infection.Comment: 35 pages, 12 figure

Proteomic Insights into the Hidden World of Phloem Sap Feeding

The physical interface between a phloem-feeding insect and its host plant is a single cell buried deep within the plant tissue. As such, the molecular interactions between these notorious agricultural pests and the crop plants upon which they feed are diffi cult to study. ‘Omic’ technologies have proved crucial in revealing some of the fascinating detail of the molecular interplay between these partners. Here we review the role of proteomics in identifying putative components of the secreted saliva of phloem-feeding insects, particularly aphids, and discuss the limited knowledge concerning the function of these proteins