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Background: A risk-stratified approach to colorectal cancer (CRC) screening could result in a more acceptable balance of benefits and harms, and be more cost-effective., Aim: To determine the effect of a consultation in general practice using a computerised risk assessment and decision support tool (Colorectal cancer RISk Prediction, CRISP) on risk-appropriate CRC screening., Design and Setting: Randomised controlled trial in 10 general practices in Melbourne, Australia, from May 2017 to May 2018., Method: Participants were recruited from a consecutive sample of patients aged 50-74 years attending their GP. Intervention consultations included CRC risk assessment using the CRISP tool and discussion of CRC screening recommendations. Control group consultations focused on lifestyle CRC risk factors. The primary outcome was risk-appropriate CRC screening at 12 months., Results: A total of 734 participants (65.1% of eligible patients) were randomised (369 intervention, 365 control); the primary outcome was determined for 722 (362 intervention, 360 control). There was a 6.5% absolute increase (95% confidence interval [CI] = -0.28 to 13.2) in risk-appropriate screening in the intervention compared with the control group (71.5% versus 65.0%; odds ratio [OR] 1.36, 95% CI = 0.99 to 1.86, P = 0.057). In those due CRC screening during follow-up, there was a 20.3% (95% CI = 10.3 to 30.4) increase (intervention 59.8% versus control 38.9%; OR 2.31, 95% CI = 1.51 to 3.53, P <0.001) principally by increasing faecal occult blood testing in those at average risk., Conclusion: A risk assessment and decision support tool increases risk-appropriate CRC screening in those due screening. The CRISP intervention could commence in people in their fifth decade to ensure people start CRC screening at the optimal age with the most cost-effective test., (© The Authors.)

This study aimed to test whether participation in colorectal cancer (CRC) screening can be increased by combining the standard invitation procedure with a pre-notification and/or an extra reminder. In a non-blinded randomised controlled trial nested in a population-based CRC screening programme employing the faecal immunochemical test, Group I received a three-staged invitation procedure (pre-notification, invitation and one reminder), Group II received a three-staged invitation procedure (invitation and two reminders) and Group III received a four-staged invitation procedure (pre-notification, invitation and two reminders). The control group received the invitation and one reminder (usual procedure). A total of 59,041 participants were included in the analyses. Overall participation rates increased from 66.9% in the control group to 69.8% in the four-staged invitation procedure corresponding to an increase in overall participation rate of 2.9% (95% CI: 1.8 to 4.0). In the age group 50-59 years, the four-staged invitation procedure increased the participation rate by 4.0% (95% CI: 2.4 to 5.6). An extra reminder increased participation with 2.7% (95% CI: 1.1; 4.2) for males compared to 1.1% (95% CI: -0.3; 2.5) for females. In conclusion, the four-staged invitation procedure was the most effective invitation procedure indicating that multiple invitation procedures are most effective, especially in the youngest age group. If a three-staged invitation procedure is applied, a second reminder should be preferred over a pre-notification. Trial registration The project was registered at ClinicalTrials.gov on 26 February 2020 and patient enrolment began in August 2020. ClinicalTrials.gov Identifier: NCT04292366., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. No external funding was provided for this study., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Colorectal cancer (CRC) is the second most diagnosed cancer in men and women and second most common cause of cancer death in Australia; Australia's CRC incidence and mortality are among the world's highest. The Australian National Bowel Cancer Screening Program began in 2006; however, only 33% of those approached for the first time by the Program between 2018 and 2019 returned the kit. Of the 5.7 million kits sent during this period, only 44% were returned. Our aim was to identify practices and features of national bowel cancer screening programs in countries with similar programs but higher screening participation, to identify potential interventions for optimising Australian CRC screening participation., Methods: We searched published and grey literature for CRC screening programs reporting at least 50% screening participation using postal invitation and free return of iFOBT home kits. Interviews were conducted with cancer registry staff and academic researchers, focused on participant and practitioner engagement in screening., Results: National programs in Netherlands, Scotland, Denmark, and Finland reported over 50% screening participation rates for all invitation rounds. Shared characteristics include small populations within small geographic areas relative to Australia; relatively high literacy; a one-sample iFOBT kit; national registration systems for population cancer screening research; and screening program research including randomised trials of program features., Conclusions: Apart from the one-sample kit, we identified no single solution to persistent Australian low uptake of screening. Research including randomised trials within the program promises to increase participation., Impact: This screening program comparison suggests that within-program intervention trials will lead to increased Australian screening participation.

Lactic acid fermentation could be used as a potential modification tool for faba bean flour to enable its incorporation in boosting the nutritional profile of gluten-free breads. Gluten-free breads made with fermented or unfermented faba bean flours were compared with commercial soy flour. The amounts of faba- and soy-bean flours were adjusted to obtain the same protein content in bread (16%). Both fermented and unfermented faba bean flour resulted in larger bread volume (2.1 mL/g and 2.4 mL/g, respectively) compared to bread made with soybean flour (1.5 mL/g). Breads made with unfermented and fermented faba flour had higher porosity (82% and 72%, respectively) than bread with soy flour (61%). The faba breads also were softer than the soy bread. Fermentation of faba flour prior to bread making significantly increased crumb hardness (584 vs. 817 g). Fermentation increased in vitro protein digestibility (72.3% vs. 64.8%). Essential Amino Acid and Biological Value indexes were significantly higher for breads containing fermented faba flour compared to breads made with unfermented faba and soy flour. The Protein Efficiency Ratio and Nutritional Index increased by fermentation from 33 to 36 and 1.6 to 2.7, respectively. Pre-fermentation of faba bean flour improved the nutritional properties of high-protein, gluten-free faba bread. A sensory panel indicated that fermentation did not affect the crumbliness, evenness of pore size and springiness of breadcrumb.

Unaffected relatives of individuals with Lynch syndrome can be offered predictive genetic testing to guide surveillance recommendations. The decision-making process of those who decline testing, particularly those who do not attend a clinical genetics service, is poorly understood. We have addressed this gap by interviewing 33 individuals from Lynch syndrome mutation-carrying families, unaffected by cancer, who declined predictive genetic testing. Here, we analyse the data provided by 20 participants who unequivocally declined testing. Those who indicated they did not have enough information to make a decision or intended to undergo testing in the future were excluded. Analysis revealed that few decliners discussed their decision with general practitioners or genetic counsellors. Family members were commonly involved to varying degrees, with participants either (1) making group decisions with family members, (2) feeling persuaded by family members to either accept or decline testing, (3) discussing the test but making their own decision. A minority did not discuss testing with family members while making their decision. This research reveals the health communication activities of an understudied group, those declining predictive testing, and indicates that for many, health professionals play a minor role in the decision compared to family.

Background: The Australian National Bowel Cancer Screening Programme (NBCSP) was introduced in 2006. When fully implemented, the programme will invite people aged 50 to 74 to complete an immunochemical faecal occult blood test (iFOBT) every 2 years., Methods and Findings: To investigate colorectal cancer (CRC) screening occurring outside of the NBCSP, we classified participants (n = 2,480) in the Australasian Colorectal Cancer Family Registry (ACCFR) into 3 risk categories (average, moderately increased, and potentially high) based on CRC family history and assessed their screening practices according to national guidelines. We developed a microsimulation to compare hypothetical screening scenarios (70% and 100% uptake) to current participation levels (baseline) and evaluated clinical outcomes and cost for each risk category. The 2 main limitations of this study are as follows: first, the fact that our cost-effectiveness analysis was performed from a third-party payer perspective, which does not include indirect costs and results in overestimated cost-effectiveness ratios, and second, that our natural history model of CRC does not include polyp sojourn time, which determines the rate of cancerous transformation. Screening uptake was low across all family history risk categories (64%-56% reported no screening). For participants at average risk, 18% reported overscreening, while 37% of those in the highest risk categories screened according to guidelines. Higher screening levels would substantially reduce CRC mortality across all risk categories (95 to 305 fewer deaths per 100,000 persons in the 70% scenario versus baseline). For those at average risk, a fully implemented NBCSP represented the most cost-effective approach to prevent CRC deaths (AUS$13,000-16,000 per quality-adjusted life year [QALY]). For those at moderately increased risk, higher adherence to recommended screening was also highly cost-effective (AUS$19,000-24,000 per QALY)., Conclusion: Investing in public health strategies to increase adherence to appropriate CRC screening will save lives and deliver high value for money., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: MAJ is a NHMRC Senior Research Fellow. JLH is a NHMRC Senior Principal Research Fellow. DDB is a University of Melbourne Research at Melbourne Accelerator Program (R@MAP) Senior Research Fellow and NHMRC R.D. Wright Career Development Fellow. JDE is a NHMRC Practitioner Fellow. The other authors have no conflict of interest to declare with respect to this manuscript.

Background: Australia and New Zealand have the highest incidence rates of colorectal cancer worldwide. In Australia there is significant unwarranted variation in colorectal cancer screening due to low uptake of the immunochemical faecal occult blood test, poor identification of individuals at increased risk of colorectal cancer, and over-referral of individuals at average risk for colonoscopy. Our pre-trial research has developed a novel Colorectal cancer RISk Prediction (CRISP) tool, which could be used to implement precision screening in primary care. This paper describes the protocol for a phase II multi-site individually randomised controlled trial of the CRISP tool in primary care., Methods: This trial aims to test whether a standardised consultation using the CRISP tool in general practice (the CRISP intervention) increases risk-appropriate colorectal cancer screening compared to control participants who receive standardised information on cancer prevention. Patients between 50 and 74 years old, attending an appointment with their general practitioner for any reason, will be invited into the trial. A total of 732 participants will be randomised to intervention or control arms using a computer-generated allocation sequence stratified by general practice. The primary outcome (risk-appropriate screening at 12 months) will be measured using baseline data for colorectal cancer risk and objective health service data to measure screening behaviour. Secondary outcomes will include participant cancer risk perception, anxiety, cancer worry, screening intentions and health service utilisation measured at 1, 6 and 12 months post randomisation., Discussion: This trial tests a systematic approach to implementing risk-stratified colorectal cancer screening in primary care, based on an individual's absolute risk, using a state-of-the-art risk assessment tool. Trial results will be reported in 2020., Trial Registration: Australian and New Zealand Clinical Trial Registry, ACTRN12616001573448p . Registered on 14 November 2016.

Background and Objectives: Many Australians at average risk of colorectal cancer (CRC) are undergoing unnecessary colonoscopic screening, while many at increased risk are getting inadequate screening. The aim of this study was to test different ways of communicating the risks and benefits of CRC screening, as part of the development of a CRC risk prediction (CRISP) tool., Method: General practice patients were shown five different risk presentations for hypothetical ‘average’ and ‘increased’ risk cases and were asked to choose the screening method they would undergo. Associations were explored between risk presentation type and ‘risk-appropriate screening’ choice., Results: All risk formats were associated with improved risk-appropriate screening by participants (n = 204); however, there was a statistical trend favouring absolute risk with a government recommendation and an ‘expected frequency tree’. The icon array was most weakly associated with appropriate screening., Discussion: This research will inform approaches to communicating risk in CRISP and may be of wider relevance to supporting informed decisions about cancer screening.

While medical research continues to investigate the genetic basis of cancer, and personalised prevention gains momentum, little research has been conducted with the individuals who decline predictive genetic testing for cancer. We recruited individuals who had been offered genetic testing for Lynch syndrome or bi-allelic MUTYH mutations due to their participation in a large, population-based, Australia-wide colorectal cancer study. Thirty-three individuals in mutation-carrying families, unaffected by cancer, who had actively or passively declined testing at one of four decision-making points, took part in a qualitative interview about their decision. Data analysis revealed a typology of 'decliners': (1) uninformed about genetic testing; (2) a weak intention to undergo genetic testing; (3) conditionally declining; and (4) unconditionally declining testing. In this population we found substantial barriers to achieving the benefits promised by predictive genetic testing; a lack of knowledge of the availability of genetic testing; a lack of trust in genetic test information; a desire to see a stronger benefit from genetic testing before proceeding; and a sense that there may be more negative than positive outcomes from genetic testing. These discourses must be addressed if medical research on the genetic basis of cancer continues to be funded, and personalised prevention of cancer continues to be recommended by experts.

Background and Aim: Tumor testing of colorectal cancers (CRC) for mismatch repair (MMR) deficiency is an effective approach to identify carriers of germline MMR gene mutation (Lynch syndrome). The aim of this study was to identify MMR gene mutation carriers in two cohorts of population-based CRC utilizing a combination of tumor and germline testing approaches., Methods: Colorectal cancers from 813 patients diagnosed with CRC < 60 years of age from the Australasian Colorectal Cancer Family Registry (ACCFR) and from 826 patients from the Melbourne Collaborative Cohort Study (MCCS) were tested for MMR protein expression using immunohistochemistry, microsatellite instability (MSI), BRAF V600E somatic mutation, and for MLH1 methylation. MMR gene mutation testing (Sanger sequencing and Multiplex Ligation Dependent Probe Amplification) was performed on germline DNA of patients with MMR-deficient tumors and a subset of MMR-proficient CRCs., Results: Of the 813 ACCFR probands, 90 probands demonstrated tumor MMR deficiency (11.1%), and 42 had a MMR gene germline mutation (5.2%). For the MCCS, MMR deficiency was identified in the tumors of 103 probands (12.5%) and seven had a germline mutation (0.8%). All the mutation carriers were diagnosed prior to 70 years of age. Probands with a MMR-deficient CRC without MLH1 methylation and a gene mutation were considered Lynch-like and comprised 41.1% and 25.2% of the MMR-deficient CRCs for the ACCFR and MCCS, respectively., Conclusions: Identification of MMR gene mutation carriers in Australian CRC-affected patients is optimized by immunohistochemistry screening of CRC diagnosed before 70 years of age. A significant proportion of MMR-deficient CRCs will have unknown etiology (Lynch-like) proving problematic for clinical management., (© 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: There is limited research on why some individuals who have undergone predictive genetic testing for Lynch syndrome do not adhere to screening recommendations. This study aimed to explore qualitatively how Lynch syndrome non-carriers and carriers translate genetic risk information and advice to decisions about risk managment behaviours in the Australian healthcare system., Methods: Participants of the Australasian Colorectal Cancer Family Registry who had undergone predictive genetic testing for Lynch syndrome were interviewed on their risk management behaviours. Transcripts were analysed thematically using a comparative coding analysis., Results: Thirty-three people were interviewed. Of the non-carriers ( n  = 16), 2 reported having apparently unnecessary colonoscopies, and 6 were unsure about what population-based colorectal cancer screening entails. Of the carriers ( n  = 17), 2 reported they had not had regular colonoscopies, and spoke about their discomfort with the screening process and a lack of faith in the procedure's ability to reduce their risk of developing colorectal cancer. Of the female carriers ( n  = 9), 2 could not recall being informed about the associated risk of gynaecological cancers., Conclusion: Non-carriers and female carriers of Lynch syndrome could benefit from further clarity and advice about appropriate risk management options. For those carriers who did not adhere to colonoscopy screening, a lack of faith in both genetic test results and screening were evident. It is essential that consistent advice is offered to both carriers and non-carriers of Lynch syndrome.

Protected area management agencies are increasingly using management effectiveness evaluation (MEE) to better understand, learn from and improve conservation efforts around the globe. Outcome assessment is the final stage of MEE, where conservation outcomes are measured to determine whether management objectives are being achieved. When quantitative monitoring data are available, best-practice examples of outcome assessments demonstrate that data should be assessed against quantitative condition categories. Such assessments enable more transparent and repeatable integration of monitoring data into MEE, which can promote evidence-based management and improve public accountability and reporting. We interviewed key informants from marine protected area (MPA) management agencies to investigate how scientific data sources, especially long-term biological monitoring data, are currently informing conservation management. Our study revealed that even when long-term monitoring results are available, management agencies are not using them for quantitative condition assessment in MEE. Instead, many agencies conduct qualitative condition assessments, where monitoring results are interpreted using expert judgment only. Whilst we found substantial evidence for the use of long-term monitoring data in the evidence-based management of MPAs, MEE is rarely the sole mechanism that facilitates the knowledge transfer of scientific evidence to management action. This suggests that the first goal of MEE (to enable environmental accountability and reporting) is being achieved, but the second and arguably more important goal of facilitating evidence-based management is not. Given that many MEE approaches are in their infancy, recommendations are made to assist management agencies realize the full potential of long-term quantitative monitoring data for protected area evaluation and evidence-based management., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Effects of fibre and β-glucan on satiety have been reported in many studies, but no consensus has been reached. The aim of this study was to examine the effects of breakfasts varying in the dose of oat bran (4g or 8g β-glucan). The approach was to study whether the food matrix (solid or liquid) into which the oat bran is incorporated influences postprandial satiety in otherwise similar meal settings. Thirty healthy females were offered four different breakfasts: biscuits+juice (0g β-glucan), enriched biscuits+juice (4g β-glucan), biscuits+enriched juice (4g β-glucan) and enriched biscuits+enriched juice (8g β-glucan) in a random order on separate test days. The sensations associated with hunger and satiety were evaluated using visual analogue scales (VAS) before and after ingesting the test breakfasts and every 30min until 210min. Oat bran addition in breakfasts increased postprandial satiety especially when both juice and biscuits were enriched (8g of β-glucan). Addition of oat bran to juice enhanced satiety and related feelings more effectively than the addition into biscuits., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

People carrying germline mutations in mismatch repair genes are at high risk of colorectal cancer (CRC), yet about half of people from mutation-carrying families decline genetic counselling and/or testing to identify mutation status. We studied the association of quantitative measures of risk perception, risk prediction and self-reported screening colonoscopy in this elusive yet high-risk group. The sample of 26 participants (mean age 43.1 years, 14 women) in the Australasian Colorectal Cancer Family Registry were relatives of mutation carriers; had not been diagnosed with any cancer at the time of recruitment and had declined an invitation to attend genetic counselling and/or testing. A structured elicitation protocol captured perceived CRC risk over the next 10 years. Self-reported colonoscopy screening was elicited during a 45-minute semi-structured interview. Predicted 10-year CRC risk based on age, gender, known mutation status and family history was calculated using "MMRpro." Mean perceived 10-year risk of CRC was 31 % [95 % CI 21, 40], compared with mean predicted risk of 4 % [2, 7] (p < 0.001); this was independent of age and sex (p = 0.9). Among those reporting any medical advice and any screening colonoscopy (n = 18), those with higher risk perception had less frequent colonoscopy (Pearson's r = 0.49 [0.02, 0.79]). People who decline genetic testing for CRC susceptibility mutations perceive themselves to be at substantially higher risk than they really are. Those with high perceived risk do not undertake screening colonoscopy more often than those who perceive themselves to be at average risk.

Effects of a Trichoderma reesei tyrosinase (TYR) and a Trametes hirsuta laccase (LAC) on breadmaking performance of gluten-free oat flour were investigated by SDS-PAGE analysis of oat protein fractions, large deformation rheology, and microscopy of the doughs, as well as on the basis of specific volume and firmness of the gluten-free breads. TYR induced the formation of higher molecular weight proteins in the SDS-PAGE assay. Microscopical analysis showed more intensive protein aggregation in the TYR-treated dough than in the dough without TYR. TYR also increased the firmness of the dough, which was assumed to be because of the cross-linking of oat globulins. LAC did not affect the oat globulins. TYR alone, or together with a commercial Thermomyces lanuginosus xylanase (XYL), increased significantly the specific volume of the gluten-free oat bread. A combination of TYR and XYL also increased the softness of the bread, whereas a combination of LAC and XYL improved the specific volume but did not affect the softness of oat bread. The results thus indicate that cross-linking of oat globulins by TYR, especially with the addition of XYL, was beneficial for improving the texture of gluten-free oat bread.

Expert judgements are essential when time and resources are stretched or we face novel dilemmas requiring fast solutions. Good advice can save lives and large sums of money. Typically, experts are defined by their qualifications, track record and experience. The social expectation hypothesis argues that more highly regarded and more experienced experts will give better advice. We asked experts to predict how they will perform, and how their peers will perform, on sets of questions. The results indicate that the way experts regard each other is consistent, but unfortunately, ranks are a poor guide to actual performance. Expert advice will be more accurate if technical decisions routinely use broadly-defined expert groups, structured question protocols and feedback.

Elicitation of expert opinion is important for risk analysis when only limited data are available. Expert opinion is often elicited in the form of subjective confidence intervals; however, these are prone to substantial overconfidence. We investigated the influence of elicitation question format, in particular the number of steps in the elicitation procedure. In a 3-point elicitation procedure, an expert is asked for a lower limit, upper limit, and best guess, the two limits creating an interval of some assigned confidence level (e.g., 80%). In our 4-step interval elicitation procedure, experts were also asked for a realistic lower limit, upper limit, and best guess, but no confidence level was assigned; the fourth step was to rate their anticipated confidence in the interval produced. In our three studies, experts made interval predictions of rates of infectious diseases (Study 1, n = 21 and Study 2, n = 24: epidemiologists and public health experts), or marine invertebrate populations (Study 3, n = 34: ecologists and biologists). We combined the results from our studies using meta-analysis, which found average overconfidence of 11.9%, 95% CI [3.5, 20.3] (a hit rate of 68.1% for 80% intervals)-a substantial decrease in overconfidence compared with previous studies. Studies 2 and 3 suggest that the 4-step procedure is more likely to reduce overconfidence than the 3-point procedure (Cohen's d = 0.61, [0.04, 1.18]).

Several lactic acid bacteria belonging to the genera Leuconostoc, Lactobacillus, and Weissella have been introduced to wheat sourdough baking for in situ production of exopolysaccharides. This is considered a novel method for improving the shelf-life, volume and nutritional value of bread without additives. However, in situ production of exopolysaccharides during sourdough fermentation is challenged by simultaneous acidification due to metabolic activities of the bacteria, which may significantly diminish the positive technological impact of exopolysaccharides. In this study, the growth, activity and in situ production of dextran by Weissella confusa VTT E-90392 in wheat sourdoughs were investigated. Furthermore, the influence of dextran-enriched sourdoughs, at the addition level of 43%, on the subsequent bread quality was established. W. confusa efficiently produced dextran from the added sucrose in wheat sourdough without strong acid production. A new specific enzyme-assisted method for in situ analysis of dextran in sourdoughs was developed. With this method, we could for the first time proof significant (11-16 g/kg DW) production of polymeric dextran in sourdoughs. Concomitant formation of shorter isomaltooligosaccharides by W. confusa was also detected. The produced dextran significantly increased the viscosity of the sourdoughs. Application of dextran-enriched sourdoughs in bread baking provided mildly acidic wheat bread with improved volume (up to 10%) and crumb softness (25-40%) during 6 days of storage. Hence, W. confusa is a promising new strain for efficient in situ production of dextrans and isomaltooligosaccharides in sourdoughs without strong acidification.