Academic literature on the topic 'Fr 13 risk modelling'

145 Background: In men with intermediate-risk prostate cancer (IR-PC) treated with low dose EBRT, the addition of androgen deprivation therapy (ADT) prolongs overall survival. Zumsteg proposes a subdivision for de IR-PC group: favorable or unfavorable. Purpose: retrospective evaluation of EBRT efficacy according to IR-PC subgroups (favorable or unfavorable). Methods: From the institutional radiotherapy department database, from 2000 to 2011, 95 men with IR-PC were identified and subdivided as follows: Favorable Risk (FR) – Gleason 3+4 or less and positive prostate biopsies (ppb) not exceeding 50% and only one intermediate-risk factor excluding 4+3; Unfavorable risk (UR) – Gleason 4+3 or at least 2 intermediate-risk factors or at least one intermediate risk factor and ppb >50%. Results: 95 patients were included in the analysis, mean FUP 6.2 years. 32.6% (31) had >50% ppb, 14.7% (14) had Gleason 4+3, 38.9% (37) had 2 intermediate-risk factors. 42.1% (40) were FR and 57.9% (55) were UR. Median EBRT dose: 79.8Gy. Only 25% of FR patients received some hormonal therapy treatment. There were no differences in time to Prostatic Specific Androgen (PSA) nadir (FR 12 vs UR 13 months; p= .50), biochemical relapse free survival (RFS) (FR 60 vs US 58 months; p= .80), or doubling time PSA (FR 12 vs UR 11 months; p= .19). Biochemical relapse (BR) and local relapse (LR) rates were lower for FR (BR: FR 27.5 vs UR 38.2%, p= .17; LR: FR 5 vs UR 14.5%, p= .40). Local RFS (FR 13.6 vs UR 9.6 years; p= .11) and distant RFS (FR 13.1 vs UR 12.4 years; p= .65) were longer for FR patients. Conclusions: Short course ADT is the standard treatment in IR-PC patients when EBRT is indicated, especially if they have UR features. In our study IR-PC group had heterogeneous outcomes and, in spite the study limitations, FR patients had a trend for better prognosis even with a very low use of ADT. If Favorable IR-PC patients may avoid ADT morbidity should be answered by a randomized trial.

Abstract Abstract 761 Conventional cytogenetics and morphologic response to induction chemotherapy have historically provided the tools for predicting outcome in patients with acute myeloid leukemia (AML). Several mutations are predictive of clinical outcome and have provided additional tools to help predict outcome in patients with AML without other risk features. Despite these recent advances, our ability to identify specific risk groups has been limited to a subset of patients, and nearly half of the patients with AML are regarded as having standard-risk (SR) disease. We inquired whether adding response by multidimensional flow cytometry (MDF) to data from conventional cytogenetics analysis and presence/absence of genomic alterations of FLT3 (FLT3-ITD), CEBPA, and NPM would provide a more robust risk-stratification system for risk-based therapy allocation. COG AML protocol AAML03P1 collected comprehensive cytogenetics characteristics, mutation profile (FLT3/ITD, CEBPA, and NPM mutation status), and MDF data on most of the 340 eligible patients enrolled on the study. Molecular and cytogenetic data were available for 275 of the 293 (94%) patients with responsive disease at the end of induction I. Disease-free survival (DFS) from the end of induction I was determined based on a combined molecular and cytogenetic risk profile. Risk status was defined based on the presence of t(8;21), inv(16), NPMc, and CEBPA mutations (favorable risk, FR) or the presence of monosomy 7, monosomy 5/del5q, and high allelic ratio FLT3-ITD (high risk, HR). On the basis of this allocation, 88 (32%) patients had FR AML, and 26 (10%) had HR AML. The remaining 161 (59%) patients without specific risk features were considered to have SR AML. DFS at 2 years from the end of induction I was 70%±12% for the FR cohort, 55% ±9% for the SR cohort, and 17%±20% for the HR cohort (p<0.001). The prevalence and prognostic significance of minimal residual disease (MRD) were assessed in the 103 patients with SR disease; 31 (30%) had evidence of MRD by MDF. DFS at 3 years from the end of induction I was significantly worse for those with MRD than for those without it (26%±21% vs. 67%±13%, p=0.01). Corresponding relapse risk in patients with or without MRD was 69%±21% and 30%±13%, respectively (p=0.011). We assessed the clinical impact of MRD in patients with HR or FR disease. Of the 18 patients with HR AML who had MRD data, 8 (44%) had MRD. DFS at 2 years for patients with HR disease with or without MRD was not significantly different (13%±23% vs. 36%±40%; p=0.127). Of the 73 patients with FR AML, MRD was detected in 12 (16%); MRD did not significantly influence DFS at 3 years from the end of induction I in those patients (45%±33% vs. 72%±17%, p=0.138). Thus, although the presence of MRD was significantly associated with worse outcome in patients with SR AML, similar significance could not be demonstrated in the FR or HR cohorts. Clinical outcomes of risk groups were reassessed after combining the MRD data with specific cytogenetic and molecular risk groups, i.e., patients with SR AML and MRD were added to the HR cohort, and those without MRD were added to the FR cohort. In the new risk-stratification system, 57 of 217 (26%) patients were in the HR cohort, and the remaining 160 (74%) patients were in the FR cohort. DFS at 3 years from induction I was 68%±9% for the FR cohort and 20%±16% (p<0.001) for the HR cohort. Cumulative incidence of relapse at 3 years from the end of induction I for those with FR or HR disease was 27%±9% and 71%±17%, respectively (p<0.001). Cytogenetics, molecular genotyping, and post-induction MDF analysis provide a robust means of stratifying all pediatric patients with AML into 2 risk groups with significantly different outcomes. This novel risk-allocation schema will be implemented in the upcoming COG Phase III AML trial. Disclosures: No relevant conflicts of interest to declare.

Background:Low bone mineral density (BMD) is common in ankylosing spondylitis (AS). The fracture risk (FR) is increased and its reduction with pharmacologic therapy is not clearly defined in this population. However, early screening and bisphosphonates as first-line treatment are recommended.Objectives:To investigate the influence of dual-energy X-ray absorptiometry (DXA) in the ten-year risk of fracture assessed by FR Assessment Tool (FRAX) and to determine possible demographic or clinical factors associated with an increased FR in a spondyloarthritis (SpA) population.Methods:Retrospective study including all the over 40 years-old SpA patients (ASAS classification criteria) followed at our Rheumatology Department and registered in the national database. Demographic, clinical and laboratorial data were collected at the time of the last follow-up visit. Data from the last DXA (until 3 years prior to the last visit) were collected. Indication for pharmacological treatment by FRAX was assessed according to the national recommendations.Results:A total of 231 SpA patients were included: 126 males (54.5%), 53 (22.9%) smokers; 171 (74%) had AS, 23 (10%) had Inflammatory Bowel Disease Associated SpA and 37 (16%) had Undifferentiated SpA. At the last follow-up visit, the mean age was 52.9 years (±9.6) and the median disease duration was 21.9 years [1.0-55.5]. The mean ASDAS-CRP was 2.5 (±0.9) and the majority of patients had moderate (25.5%) or high (48.5%) disease activity (according to ASDAS). One hundred and thirty patients (56.3%) were taking NSAIDs, 45 (19.5%) were taking glucocorticoids, 85 (36.8%) were under csDMARDs and 170 (73.6%) under bDMARDs [157 (68%) under TNFi, 11 (4.8%) under secukinumab and 2 (0.9%) under ustekinumab].Eleven patients (4.8%) had previous fragility fractures, 118 (51.1%) had DXA in the last 3 years and 167 (72.3%) were taking calcium and/or vitamin D supplements.Sixteen patients (6.9%) had indication for treatment by FRAX without DXA and 9 of these (56.3%) were already under treatment. Similarly, 16 (6.9%) had indication for treatment by FRAX with DXA and 13 of these (81.3%) were already under treatment. Ten patients (4.3%) were reclassified in FRAX with DXA: 7 (3%) had no indication for treatment by FRAX without DXA but obtained it by FRAX with DXA and 3 (1.3%) had indication for treatment by FRAX without DXA but they lost it by FRAX with DXA. We found a moderate level of agreement in the indication for treatment between FRAX with and without DXA (kappa=0.595; p<0.001). The use of DXA in FRAX estimated a significant higher median FR, both for major osteoporotic fracture (2.4% [0.8-31.0] vs 1.8% [0.6-20.0]; p<0.001) and for hip fracture (0.5% [0.0-23.0] vs 0.2% [0.0-14.0]; p<0.001).We found significant correlations between FR and some disease-related variables (table 1).Table 1.Correlations between the risk of fracture estimated by FRAX and disease-related variables.Disease durationBASDAIASDAS-CRPBASMIBASFIEstimated fracture risk by FRAX:without DXAmajor osteoporotic fracturer=0.352p<0.001r=0.204p=0.002r=0.214p=0.001r=0.301p<0.001r=0.317p<0.001hip fracturer=0.389p<0.001r=0.142p=0.034r=0.170p=0.011r=0.305p<0.001r=0.275p<0.001with DXAmajor osteoporotic fracturer=0.227p=0.014r=0.314p=0.001r=0.356p<0.001r=0.293p=0.002r=0.379p<0.001hip fracturen.s.r=0.197p=0.036r=0.269p=0.004r=0.271p=0.004r=0.258p=0.006Conclusion:Our results showed that a similar number of patients had indication for pharmacological treatment by FRAX both with and without DXA. Although the inclusion of DXA resulted in a higher estimated FR by FRAX, the observed moderate level of agreement between FRAX with and without DXA suggests that the FR estimation by FRAX, even without DXA, may be a reasonable approach in SpA patients. In line with literature, we found significant associations between the estimated risk fracture by FRAX and some disease activity and function measures.Disclosure of Interests:Bruno Miguel Fernandes: None declared, Salomé Garcia: None declared, Sara Ganhão: None declared, Maria Rato: None declared, Filipe Pinheiro: None declared, Miguel Bernardes Speakers bureau: Abbvie, Amgen, Biogen, Eli-Lilly, Glaxo-Smith-Kline, Pfizer, Janssen, Novartis, Lúcia Costa: None declared

This study aimed to assess the safety and feasibility of the ULtrasound-guided uSe Of exoSEAL technique (ULSOSEAL technique) in patients at a high risk of complications following the use of ExoSeal. ExoSeal is a novel, completely extravascular hemostatic device that can treat punctures of the common femoral artery; however, it is not preferable for use in cases that require hemostasis of complex puncture sites. From November 2019 to August 2020, the ULSOSEAL technique was performed in 35 patients with implanted stents (6 patients, 17%), severe calcification (32 patients, 91%), and plaque (7 patients, 20%) around the puncture site; the presence of these conditions is usually undesirable when using ExoSeal. The antegrade approach was used in 22 patients (71%). The size of the ExoSeal used was 5 Fr (13 patients, 37%), 6 Fr (21 patients, 60%), and 7 Fr (1 patient, 2%). Technical success was achieved in 34 patients (97%), while ExoSeal malfunction occurred in 1 patient. There was no incidence of vessel occlusion, pseudoaneurysm, arteriovenous fistula, infection, and secondary bleeding. One patient developed a hematoma (>5 cm in size); however, it occurred before the use of ExoSeal due to side leakage from the inserted sheath. The ULSOSEAL technique was safe and feasible for hemostasis in patients who were considered unsuitable for the ExoSeal device.

Impermeable base layers that are made of materials with low permeability, such as clay soil, are necessary to prevent leachate in landfills from harming the environment. However, over time, the permeability of the clay soil changes. Therefore, to reduce and minimize the risk, the permeability-related characteristics of the base layers must be improved. Thus, this study aims to serve this purpose by experimentally investigating the effects of nanomaterial addition (aluminum oxide, iron oxide) into kaolin samples. The obtained samples are prepared by applying standard compaction, and the permeability of the soil sample is experimentally investigated by passing leachate from the reactors, in which these samples are placed. Therefore, Flow Resistance (FR) analysis is conducted and the obtained results show that the Al additives are more successful than the Fe additive in reducing leachate permeability. Besides, the concentration values of some polluting parameters (Chemical Oxygen Demand (COD), Total Kjeldahl Nitrogen (TKN), and Total Phosphorus (TP)) at the inlet and outlet of the reactors are analyzed. Three different models (Artificial Neural Networks (ANN), Multiple Linear Regression (MLR), Support Vector Machine (SVM)) are applied to the data obtained from the experimental study. The results have shown that polluting parameters produce high FR regression similarity rates (>75%), TKN, TP, and COD features are highly correlated with the FR value (>60%) and the most successful method is found to be the SVM model.

Abstract CVC-related complications were retrospectively analysed for 373 CVCs inserted in 261 hematologic pts consecutively admitted to our Hematology Department between January 2002 and March 2004. Pts diagnosis comprised AML (96 pts, 36.8%), ALL (19 pts, 7.3%), lymphoproliferative disorders (74 pts, 28.3%), MM (51 pts, 19.5%), CML (13 pts, 5%), others (8 pts, 3.1%). The CVCs were polyurethane Plastimed three lumen 7 Fr (193 cases) for chemotherapy and polyurethane Arrow three lumen 12 Fr (173 cases) for chemotherapy and peripheral blood stem cell (PBSC) apheresis. CVCs were inserted, according to physician’s judgement, either at bedside (369 cases) or in the operating room (4 cases) and were used for drug infusion in 309 cases (82.8%), for total parenteral nutrition in 19 cases (5.1%), for blood transfusions in 226 cases (60.6%), for PBSC apheresis in 152 cases (40.7%). Fifty five CVCs were inserted in neutropenic pts ( N < 1 x 109/L); severe thrombocytopenia (Plts < 30 x 109/L) was present in 33/373 cases. Antithrombotic prophylaxis with low molecular weight heparin because of previous thrombosis was instituted in 33 cases (8.8%). At univariate and multivariate analysis the following risk factors for catheter-related bloodstream infections were considered: pt age, number of days/catheter, haematological disease, catheter lumen, administration of chemotherapy (standard- vs high-dose), presence of neutropenia. The median duration of CVCs after placement was 22.7 days (range 2–70) for the 7 Fr lumen, and 9 (range 1–39) for the 12 Fr. Major hemorrhagic complications related to the insertion procedure were observed in 4 cases of whom 2 were severely thrombocytopenic. CVC occlusion were observed in 24 cases (6.4%). Thrombotic complications developed in 7 cases (1.87% of inserted CVCs) and in 2/7 were complicated by pulmonary embolism; thrombophilia tests were negative in all 7 pts who developed thrombosis. Among febrile pts the frequency of bacteriemias was 19.6% (73/373 cases) of which 52/373 were CVC-related (13.9%). Approximately 6% of cases (23/373 CVCs) had CVC exit point infection with or without associated bacteriemia. Gram positive bacteria were isolated in 49 cases (67.1%), 38 of which were CVC-related (19 S. epidermidis, 4 S. pneumoniae, 3 S. aureus, 3 Enterococci species, 9 others). Gram negative bacteria were isolated in 23 cases, of which 13 were CVC-related (5 E.coli, 4 E. cloacae, 2 P. aeruginosa, 2 K pneumoniae). Candida was isolated in one case. Overall mortality in our patient population was 4.2% (11/261 pts); one patient only died of infection (P. aeruginosa sepsis) not CVC-related. At univariate and multivariate analysis significant risk factors for infection (p<0.0001) were only the number of days/catheters and duration of neutropenia. Among severely thrombocytopenic pts, haemorrhagic complications at CVC insertion were infrequent (6%). Although pts in our study population frequently displayed prolonged and severe neutropenia, frequency of CVC-related bacteremias was low (13.9%) compared to a general population reported frequency of 5–25%. Moreover, none of the pts died of CVC-related infection.

Abstract Rationale: Hyponatremia occurs in approximately 20% of patients after transsphenoidal pituitary surgery (TSS). Symptomatic delayed hyponatremia from SIADH is a major cause of morbidity and hospital readmission. Prophylactic fluid restriction (FR) protocols starting 2-5 days after surgery may potentially reduce rates of symptomatic hyponatremia and readmissions. Methods Patients who underwent TSS for sellar and parasellar masses at a tertiary referral center were discharged with a one-liter fluid restriction protocol. Serum sodium levels were measured on post-operative day (POD) 7 with telephone follow-up care. Rates of hyponatremia and readmissions were compared to a cohort of 316 post-operative patients treated prior to the protocol. Numerical variables were summarized as mean ± SD and significance testing calculated by Chi-square and t-test. Results 105 patients were enrolled on the FR protocol upon discharge. Twelve patients were excluded as they had diabetes insipidus or prolonged hospitalization beyond POD 7. Ninety-three patients were included in the analysis, of whom 74.3% had pituitary adenomas, 5.4% Rathke's Cleft cysts, 8.6% meningiomas, 5.4% apoplexy, 2.2% craniopharyngiomas, and 4.3% other masses. Hyponatremia occurred in 13/93 (14%) patients. Mean POD 7 sodium was 137.9 mmol/L across the entire cohort. Two patients (2.1%) were readmitted for hyponatremia, while 3 were re-admitted for other causes. 88/93 (94.6%) of patients complied with the FR protocol. Of the 5 non-compliant patients, 2 developed hyponatremias (40%) compared to 3/88 (3.4%) in those who complied (p=0.008). Mean POD7 sodium was 138 (+/-4.5) mmol/L in those that complied and 135 (+/- 4.7) mmol/L in those who did not. Overall readmission rate for those with postoperative hyponatremia was 23% compared to 2.5% for those with normal sodium levels (p=0.0023). 15.4% of patients with hyponatremia were re-admitted for hyponatremia treatment, compared to 0/80 (0%) of those who did not develop post-operative hyponatremia (p=0.0004). Age and BMI did not impact hyponatremia rates. In 316 patients treated in 2012-2018 prior to the FR protocol, 78 (24.7%) developed delayed hyponatremia with 6% readmitted for hyponatremia. Thirty nine percent of patients with delayed hyponatremia were re-admitted, compared to 7.6% for those without hyponatremia. Compared to patients not on FR, patients on the FR protocol had 50% reduced risk of hyponatremia (OR=0.49 (95% CI 0.26-0.94, p=0.03), and a 3-fold reduced risk of overall readmissions (OR=0.31; 95% CI 0.12-0.81, p=0.0157) and readmission for hyponatremia (OR= 0.34;95% CI 0.08-1.5, p=0.16). A post-operative CSF leak or use of a lumbar drain were associated with an increased readmission rate in the historical cohort. Conclusion Instituting a one-liter daily FR protocol in patients after TSS results in significantly reduced rates of hyponatremia, overall readmissions, and readmission for symptomatic hyponatremia. A FR protocol should become routine practice in the post-operative care of patients undergoing pituitary surgery. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Abstract Aims It is not known whether transaortic flow rate (FR) in aortic stenosis (AS) differs between men and women, and whether the commonly used cut-off of 200 mL/s is prognostic in females. We aimed to explore sex differences in the determinants of FR, and determine the best sex-specific cut-offs for prediction of all-cause mortality. Methods and results Between 2010 and 2017, a total of 1564 symptomatic patients (mean age 76 ± 13 years, 51% men) with severe AS were prospectively included. Mean follow-up was 35 ± 22 months. The prevalence of cardiovascular disease was significantly higher in men than women (63% vs. 42%, P &lt; 0.001). Men had higher left ventricular mass and lower left ventricular ejection fraction compared to women (both P &lt; 0.001). Men were more likely to undergo an aortic valve intervention (AVI) (54% vs. 45%, P = 0.001), while the death rates were similar (42.0% in men and 40.6% in women, P = 0.580). A total of 779 (49.8%) patients underwent an AVI in which 145 (18.6%) died. In a multivariate Cox regression analysis, each 10 mL/s decrease in FR was associated with a 7% increase in hazard ratio (HR) for all-cause mortality (HR 1.07; 95% CI 1.03–1.11, P &lt; 0.001). The best cut-off value of FR for prediction of all-cause mortality was 179 mL/s in women and 209 mL/s in men. Conclusion Transaortic FR was lower in women than men. In the group undergoing AVI, lower FR was associated with increased risk of all-cause mortality, and the optimal cut-off for prediction of all-cause mortality was lower in women than men.

La prima parte dell’elaborato presenta le origini e lo sviluppo delle politiche di valutazione del rischio per le sostanze chimiche. Dopo un primo inquadramento storico, l’attenzione è stata dedicata a temi emergenti come la valutazione delle incertezze, la necessità di integrazione delle valutazioni del rischio per l’uomo e per l'ambiente. La seconda parte presenta l’evoluzione delle politiche di valutazione del rischio dei prodotti fitosanitari, soprattutto a livello europeo (dall’applicazione della direttiva 91/414 all’attuale regolamento 1107/2009), con particolare attenzione all’applicazione del principio di precauzione. Il terzo capitolo approfondisce le fasi e gli approcci delle attuali procedure di valutazione ambientale del rischio dei pesticidi usati a livello europeo e americano; è stato in particolar modo esplorato il tema dell’individuazione degli obiettivi specifici di protezione in fase preliminare di valutazione del rischio. Il quarto capitolo tratta di un tema attualmente molto dibattuto, ovvero la valutazione dei potenziali effetti combinati sugli organismi non bersaglio esposti a più sostanze attive simultaneamente. Infine, l’obiettivo del quinto capitolo è quello di valutare la contaminazione ambientale dovuta all’applicazione di fungicidi a base rame su melo. A tale scopo è stato testato un nuovo modello per il calcolo integrato dell’esposizioni umana e ambientale MERLIN – Expo, sviluppato grazie al progetto europeo 4FUN. I risultati ottenuti per le acque superficiali e il sedimento sono stati confrontati con i risultati degli attuali modelli usati in Unione Europea, i modelli FOCUS. Le simulazioni probabilistiche hanno anche permesso di effettuare valutazioni di incertezza e sensitività sui parametri utilizzati nelle simulazioni.
This PhD thesis is a multidisciplinary work on the risk assessment of plant protection products including both legislative and scientific aspects. The first part of the thesis introduces the origin of risk assessment procedures with a wide glance on the whole process of risk analysis to protect the humans and the environment. The accent is put on emerging issues and trends, such as the uncertainties appraisal, the necessity of integration between human and environmental impacts without ignoring socio- economic and behavioural factors. The second chapter deals with the origin and development of global risk assessment policies on pesticides. It focuses in particular on European policies, from the original Directive 91/414 to the current Regulation 1107/2009 and the application of the precautionary principle. A brief comparison with US approaches for risk assessment is also presented. The third chapter gives an overview on the risk assessment procedures that nowadays provide the highest achievable protection for the environment, starting with the definition of clear and specific protection goals. The fourth chapter addresses the issue of combined risk assessment of pesticides: current approaches for the evaluation of effects on non-target organisms are analysed. The last chapter is dedicated to the estimation of the environmental contamination following the application of copper –based fungicides sprayed on orchards by using MERLIN - Expo, which is a multimedia model developed in the frame of the FP7 EU project 4FUN. The performance of the MERLIN- Expo software in estimating the contamination of the metal is also analysed through a comparison with the currently used FOCUS standard models for the calculation of pesticides concentrations in surface water and sediment. Both deterministic and probabilistic simulations have been run; the latter has allowed to perform uncertainty and sensitivity assessment.

Steady-state operations are used globally in chemical engineering. Advantages include ease of control and a more uniform product quality (Ghasem and Henda, 2008; McCabe et al, 2001). Importantly however, there will be naturally occurring, random (stochastic) fluctuations in parameter values about the ‘set’ mean when process control is inadequate. These are not addressed explicitly in traditional chemical engineering because they are not sufficient on their own to be considered transient (unsteady) and because, generally, fluctuations in one parameter are off-set by changes in others with plant output behaviour seeming to remain steady (Amundson et al., 1980; Sinnott, 2005; Zou and Davey, 2016). Davey and co-workers, however, have demonstrated these fluctuations can unexpectedly accumulate in one direction and leverage significant (sudden and surprise) change in output behaviour with failure in product or plant (e.g. Abdul-Halim and Davey, 2016; Zou and Davey, 2016; Chandrakash and Davey, 2017). To underscore the unexpected element of the failure event they titled their risk framework Fr 13 2 (Friday 13th Syndrome). Case studies of their probabilistic risk framework to 1-step operations include loss of thermal efficiency in a coal-fired boiler (Davey, 2015 a) and failure to remove whey deposits in Clean-In-Place (CIP) milk processing (Davey et al., 2015). More recently, to advance their risk framework for progressively, multi-step and complex (in the sense of ‘integrated’, not ‘complicated’) processes they demonstrated its usefulness to 2-step membrane fouling with combined ultrafiltration-osmotic distillation (UF-OD) (Zou and Davey, 2016), and; a 3-step microbiological raw milk pasteurization (Chandrakash and Davey, 2017). Findings overall revealed no methodological complications in application - and it was concluded the risk framework was generalizable (Zou and Davey, 2016; Chandrakash and Davey, 2017). A significant advantage of the framework is it can be used in ‘second-tier studies’ to reduce risk through simulations of intervention strategies and re-design of physical plant or operating practice. It can be applied at both synthesis and analysis stages. 2 see Appendix A for a definition of some important terms used in this research. Although the risk framework has been successfully applied to corrosive pitting of AISI 316L metal widely used in off-shore oil and gas structures (Davey et al., 2016) 3 it was not known if it could provide new insight into corrosion of metal, more specifically microbiologically influenced corrosion (MIC), a major problem globally that accounts for ~ 20 % of overall corrosion (Flemming, 1996). It is estimated to cost AUD$7 billion to Australia annually (Javaherdashti and Raman-Singh, 2001). A review of the literature showed that a thorough understanding of MIC has been slow to emerge, both because of the role of micro-organisms in corrosion and because of a lack of methodology to determine any impact of natural fluctuations in the internal pipe environment. Importantly, the insidious nature of MIC was known to pose a practical risk of failure of pipes used to transport wet-fluids. However, because modelling of direct MIC would be uniquely complex it was planned that a general model for corrosion should be synthesized and understood that could be extended. A limited research program was therefore undertaken with the aim to advance the Fr 13 framework and to gain unique insight into how naturally occurring fluctuations in fluid temperature (T) and pH of the internal pipe environment can be transmitted and impact corrosion. A logical and stepwise approach was implemented as a research strategy. The initial model of Smith et al. (2011) was modified to simulate MIC causing micro-organisms such as sulphate-reducing bacteria (SRB) on widely used ASTM A105 carbon-steel pipe that is corroded under steady-state, abiotic and synthetic conditions. This was solved using traditional, deterministic simulations to give a predicted, underlying corrosion rate (CR) of 0.5 mm yr-1 as impacted by internal pipe-fluid T and pH. Importantly, findings underscored the controlling importance of low pH on CR. This initial model was then simulated, for the first time, using the probabilistic Fr 13 framework (Collins et al., 2016) 4 in which distributions to mimic fluctuations in T (K) and 3 This research was a Finalist, IChemE Global Awards 2016, Innovative Product, Manchester, UK, Nov. 4 Collins, S.D., Davey, K.R., Chu, J.Y.G., O’Neill, B.K., 2016. A new quantitative risk assessment of Microbiologically Influenced Corrosion (MIC) of carbon steel pipes used in chemical engineering. In: pH in the pipe were (reasonably) assumed as truncated Normal, and; a new corrosion risk factor (p) was synthesized such that all p > 0 characterized a CR failure i.e. a corrosion rate greater than 0.5 mm yr-1. Normal distributions that were truncated were used because these permitted T and pH to fluctuate randomly during process operations but limited these to values that could occur only practically. Predictions showed that 28.1 % of all corrosion of ASTM A105 pipe, averaged over the long term for a range of fluctuations 290.15 ≤ T ≤ 298.15 K, and 4.64 ≤ pH ≤ 5.67, would in fact be greater than the underlying value despite a design margin of safety (tolerance) of 50 % CR, and were therefore process failures (p > 0). Findings highlighted that corrosion was a combination of ‘successful’ and ‘failed’ operations. This insight is not available from traditional risk approaches, with or without sensitivity analyses. It was concluded that the Fr 13 framework was an advance over the traditional, deterministic methods because all corrosion scenarios that can practically exist are simulated. It was concluded also that if each simulation was (reasonably) thought of as one operational day, there would be (28.1/100 days × 365.25 days / year) ~103 corrosion failures in ASTM A105 pipe per year. However it was acknowledged that to enhance corrosion simulation, the free corrosion potential (Ecorr, V vs SCE), a key parameter in this initial model formulation, should more realistically be considered a combined function of the internal pipe-fluid T and pH, and; that this assumption should be tested, and, that this would necessitate a trial-and-error simulation for corrosion rate (CR). It was also determined that the truncations that were used for T and pH were too restrictive for off-shore oil processing (Arnold and Stewart, 1999; J. Y. G. Chu, Upstream Production Services Pty Ltd., Australia, pers. comm.). To address this, the initial model was extended mathematically for the first time, and; Fr 13 risk simulations carried out using spread-sheeting techniques utilizing the Solver CHEMECA 2016: Chemical Engineering – Regeneration, Recovery and Reinvention, Sept. 25-28, Adelaide, Australia, paper 3386601. ISBN: 9781922107831 function (Microsoft Excel™). A significant advantage was that the distributions defining the naturally occurring fluctuations in T and pH could be entered, viewed, copied, pasted and manipulated as Excel formulae. Predictions showed (Collins and Davey, 2018) 5 an underlying corrosion rate CR = 0.45 mm yr-1 – a change of approximately 10 % when the design margin of safety (tolerance) was reduced from 50 % to a more realistic 20 % for the improved model. This is significant because the tolerance of a model should be as low as can be accepted, as higher tolerances can infer that the process is safer than it actually is. Fr 13 simulations showed that 43.6 % of all corrosion of internal ASTM A105 pipe, averaged over the long term for a range of realistic fluctuations 282.55 ≤ T ≤ 423.75 K, and 4.12 ≤ pH ≤ 6.18 would be deemed to be process pipe-failures (p > 0). This translates to a corrosion failure in ASTM A105 pipe every 160 days, averaged over the long term. It is not expected that these would be equally spaced however. Findings were used in investigative ‘second-tier’ studies to explore possible intervention strategies to reduce vulnerability to corrosion and to improve plant design and safety. For example, repeat Fr 13 simulations revealed that, for a fixed mean-value of T = 353.15 K a decrease in pH from 5.15 to 4.5 resulted in an increase in carbon-steel pipe corrosion of ~1.55 mm yr-1 i.e. ~347 % increase. This implied that the pipe vulnerability to Fr 13 corrosion failure could be practically minimised by adding bases, such as potassium hydroxide or sodium carbonate (Kemmer, 1988). However, if the pH is too high, anions in the pipe-fluid could precipitate and form insoluble mineral scales, leading to fouling (Pichtel, 2016). It is acknowledged that the present research is limited to an abiotic system i.e. one without micro-organism kinetics. A justification is that the models presented in this research should be seen as a ‘starting point’, which could be expanded in later iterations to include: biotic model components such as the simple bacterial kinetics in the predictive MIC model of Maxwell and Campbell (2006); other species that are involved in MIC such 5 Collins, S.D., Davey, K.R., 2018. A novel Fr 13 risk assessment of corrosion of carbon-steel pipe in de-aerated water. Chemical Engineering Science – submitted CES-D-18-00449, Feb. as sulphates, chlorides and hydrogen sulphide (H2S); different metals/alloys that are used in pipe equipment where MIC can be found e.g. copper or zinc (Roberge, 2000), or; a ‘global’ model i.e. two or more connected unit-operations (Chandrakash and Davey, 2017). (A global model however, might not be applicable because MIC can be initiated in localized sites (Roberge, 2000)). It is concluded that these thesis findings nevertheless significantly enhance understanding of factors that lead to excessive corrosion rates in ASTM A105 pipes. It is concluded also that the Fr 13 risk framework appears generalizable to a range of micro-organism-metal systems and is an advancement over current existing risk and hazard assessments. If properly developed, it is thought that this risk technique could be adopted as a new design tool for steady-state unit-operations in both the design and synthesis stages and to increase understanding of MIC behaviour and outcomes. This research is original and not incremental work. Results and findings will be of immediate benefit and interest to a range of risk analysts, and to a broad range of practical operations involving carbon-steel pipe flows
Thesis (MPhil) -- University of Adelaide, School of Chemical Engineering & Advanced Materials, 2018

Steady-state ultraviolet (UV) irradiation for potable water production is becoming an important global alternative to traditional disinfection by chlorination. Failure of UV to reduce the number of viable contaminant pathogens however can lead to enduring health legacies (with or without fatalities). To better understand vulnerability of UV operations to failure, the probabilistic Fr 13 risk framework of Davey and co-workers1 is applied for the first time in this thesis. Fr 13 is predicated on underlying chemical engineering unit-operations. It is based on the hypothesis that naturally occurring, chance (stochastic) fluctuations about the value of ‘set’ process parameters can unexpectedly combine and accumulate in one direction and leverage significant change across a binary ‘failure– not failure’ boundary. Process failures can result from the accumulation of these fluctuations within an apparent steady-state process itself. That is to say, even with good design and operation of plant, there can be unexpected (surprise and sudden) occasional failures without ‘human error’ or ‘faulty fittings’. Importantly, the impact of these naturally occurring random fluctuations is not accounted for explicitly in traditional chemical engineering. Here, the Fr 13 risk framework is applied for the first time to quantitatively assess operations of logically increasing complexity, namely, a laminar flow-through UV reactor, with turbulent flow in a concentric annular-reactor, both with and without suspended solids present (Davey, Abdul-Halim and Lewis, 2012; Davey and Abdul-Halim, 2013; Abdul-Halim and Davey, 2015; 2016), and; a two-step ‘global’ risk model of combined rapid-sand-filtration and UV irradiation (SF-UV) (Abdul-Halim and Davey, 2017). The work is illustrated with extensive independent data for the survival of viable Escherichia coli - a pathogenic species of faecal bacteria widely used as an indicator for health risk. A logical and step-wise approach was implemented as a research strategy. UV reactor unit-operations models are first synthesized and developed. A failure factor is defined in terms of the design reduction and actual reduction in viable E. coli contaminants. UV reactor operation is simulated using a refined Monte Carlo (with Latin Hypercube) sampling of UV lamp intensity (I), suspended solids concentrations [conc] and water flow (Q). A preliminary Fr 13 failure simulation of a single UV reactor unit-operation (one-step), developed for both simplified laminar flow and turbulent flow models, showed vulnerability to failure with unwanted survival of E. coli of, respectively, 0.4 % and 16 %, averaged over the long term, of all apparently successful steady-state continuous operations. A practical tolerance, as a design margin of safety, of 10 % was assumed. Results from applied ‘second-tier’ studies to assess re-design to improve UV operation reliability and safety and to reduce vulnerability to Fr 13 failure showed that any increased costs to improve control and reduce fluctuations in raw feed-water flow, together with reductions in UV lamp fluence, would be readily justified. The Fr 13 analysis was shown to be an advance on alternate risk assessments because it produced all possible practical UV outcomes, including failures. A more developed and practically realistic model for UV irradiation for potable water production was then synthesized to investigate the impact of the presence of suspended solids (SS) (median particle size 23 μm) as UV shielding and UV absorbing agents, on overall UV efficacy. This resulted in, respectively, some 32.1 % and 43.7 %, of apparent successful operations could unexpectedly fail over the long term due, respectively, to combined impact of random fluctuations in feed-water flow (Q), lamp intensity (I0) and shielding and absorption of UV by SS [conc]. This translated to four (4) failures each calendar month (the comparison rate without suspended solids was two (2) failures per month). Results highlighted that the efficacy of UV irradiation decreased with the presence of SS to 1-log10 reduction, compared with a 4.35-log10 reduction without solids present in the raw feed-water. An unexpected outcome was that UV failure is highly significantly dependent on naturally occurring fluctuations in the raw feed-water flow, and not on fluctuations in the concentration of solids in the feed-water. It was found that the initial presence of solids significantly reduced the practically achievable reductions in viable bacterial contaminants in the annular reactor, but that fluctuations in concentration of solids in the feed-water did not meaningfully impact overall vulnerability of UV efficacy. This finding pointed to a pre-treatment that would be necessary to remove suspended solids prior to the UV reactor, and; the necessity to improve control in feed-water flow to reduce fluctuations. The original synthesis was extended therefore for the first time to include a rapid sand-filter (SF) for pre-treatment of the raw feed-water flow to the UV reactor, and; a Fr 13 risk assessment on both the SF, and sequential, integrated rapid sand-filtration and UV reactor (SF-UV). For the global two-step SF-UV results showed vulnerability to failure of some 40.4 % in overall operations over the long term with a safety margin (tolerance) of 10 %. Pre-treatment with SF removed SS with a mean of 1-log10 reduction (90 %). Subsequently, an overall removal of viable E. coli from the integrated SF-UV reactor was a 3-log10 reduction (99.9 %). This is because the efficacy of UV light to penetrate and inactivate viable E. coli, and other pathogens, is not inhibited by SS in the UV reactor. This showed that the physical removal of E. coli was accomplished by a properly functioning SF and subsequently disinfection was done by UV irradiation to inactivate viable E. coli in the water. Because the Regulatory standard for potable water is a 4-log10 reduction, it was concluded that flocculation and sedimentation prior to SF was needed to exploit these findings. Flocculation is a mixing process to increase particle size from submicroscopic microfloc to visible suspended particles prior to sedimentation and SF. This research will aid understanding of factors that contribute to UV failure and increase confidence in UV operations. It is original, and not incremental, work. Findings will be of immediate interest to risk analysts, water processors and designers of UV reactors for potable water production.
Thesis (Ph.D.) -- University of Adelaide, School of Chemical Engineering & Advanced Materials, 2017

Steady-state unit-operations are globally used in chemical engineering. Advantages include ease of control and a uniform product quality. Nonetheless there will be naturally occurring, random (stochastic) fluctuations about any steady-state ‘set’ value of a process parameter. Traditional chemical engineering does not explicitly take account of these. This is because, generally, fluctuation in one parameter appears to be off-set by change in another – with the process outcome remaining apparently steady. However Davey and co-workers (e.g. Davey et al., 2015; Davey, 2015 a; Zou and Davey, 2016; Abdul-Halim and Davey, 2016; Chandrakash and Davey, 2017 a) have shown these naturally occurring fluctuations can accumulate and combine unexpectedly to leverage significant impact and thereby make apparently well-running processes vulnerable to sudden and surprise failure. They developed a probabilistic and quantitative risk framework they titled Fr 13 (Friday 13th) to underscore the nature of these events. Significantly, the framework can be used in ‘second-tier’ studies for re-design to reduce vulnerability to failure. Here, this framework is applied for the first time to show how naturally occurring fluctuations in peak ambient temperature (T₀) and occupancy (room traffic flows) (Lᴛ) can impact heat transfers for conditioning of room air. The conditioning of air in large buildings, including hotels and hospitals, is globally important (Anon., 2012 a). The overarching aim is to quantitatively ‘use’ these fluctuations to develop a strategy for minimum energy. A justification is that methods that permit quantitative determination of reliable strategies for conditioning of air can lead to better energy use, with potential savings, together with reductions in greenhouse gases (GHG). Oddly many buildings do not appear to have a quantitative strategy to minimize conditioning heat transfers. Wide-spread default practice is to simply use an on-off strategy i.e. conditioning-on when the room is occupied and conditioning-off, when un-occupied. One alternative is an on-only strategy i.e. leave the conditioner run continuously. A logical and stepwise combined theoretical-and-experimental, approach was used as a research strategy. A search of the literature showed that work had generally focused on discrete, deterministic aspects and not on mathematically rigorous developments to minimise overall whole-of-building conditioning heat transfers. A preliminary steady-state convective model was therefore synthesized for conditioning air in a (hotel) room (4.5 x 5.0 x 2.5, m) in dry, S-E Australia during summer (20 ≤ T₀ ≤ 40, °C) to an auto-set room bulk temperature of 22 °C for the first time. This was solved using traditional, deterministic methods to show the alternative on-only strategy would use less electrical energy than that of the default on-off for Lᴛ > 36 % (Chu et al., 2016). Findings underscored the importance of the thermal capacitance of a building. The model was again solved using the probabilistic Fr 13 framework in which distributions to mimic fluctuations in T₀ and Lᴛ were (reasonably) assumed and a new energy risk factor (p) was synthesized such that all p > 0 characterized a failure in applied energy strategy (Chu and Davey, 2015). Predictions showed on-only would use less energy on 86.6 % of summer days. Practically, this meant that a continuous on-only strategy would be expected to fail in only 12 of the 90 days of summer, averaged over the long term. It was concluded the Fr 13 framework was an advance over the traditional, deterministic method because all conditioning scenarios that can practically exist are simulated. It was acknowledged however that: 1) a more realistic model was needed to account for radiative heat transfers, and; 2) to improve predictive accuracy, local distributions for T₀ and Lᴛ were needed. To address these: 1) the model was extended mathematically to account for radiative transfers from ambient to the room-interior, and; 2) distributions were carefully-defined based on extensive historical data for S-E Australia from, respectively, Bureau of Meteorology (BoM) (Essendon Airport) and Clarion Suites Gateway Hotel (CSGH) (Melbourne) – a large (85 x 2-room suites) commercial hotel (latitude -37.819708, longitude 144.959936) – for T₀ and Lᴛ for 541 summer days (Dec. 2009 to Feb. 2015) (Chu and Davey, 2017 a). Predictions showed that radiative heat transfers were significant and highlighted that for Lᴛ ≥ 70 %, that is, all commercially viable occupancies, the on-only conditioning strategy would be expected to use less energy. Because findings predicted meaningful savings with the on-only strategy, ‘proof-of-concept’ experiments were carried out for the first time in a controlled-trial in-situ in CSGH over 10 (2 x 5 contiguous) days of summer with 24.2 ≤ T₀ ≤ 40.5, °C and 13.3 ≤ Lᴛ ≤ 100, %. Independent invoices (Origin Energy Ltd, or Simply Energy Ltd, Australia) (at 30 min intervals from nationally registered ‘smart’ power meters) for geometrically identical control and treated suites showed a mean saving of 18.9 % (AUD $2.23 per suite per day) with the on-only strategy, with a concomitant 20.7 % reduction (12.2 kg CO₂-e) in GHG. It was concluded that because findings supported model predictions, and because robust experimental SOPs had been established and agreed by CSGH, a large-scale validation test of energy strategies should be undertaken in the hotel. Commercial-scale testing over 77 contiguous days of summer (Jan. to Mar., 2016) was carried out in two, dimensionally-identical 2-room suites, with the same fit-out and (S-E) aspect, together with identical air-conditioner (8.1 kW) and nationally registered meters to automatically transmit contiguous (24-7) electrical use (at 30 min intervals) (n = 3,696) for the first time. Each suite (10.164 x 9.675, m floor plan) was auto-set to a bulk air temperature of 22 °C (Chu and Davey, 2017 b). In the treated suite the air-conditioner was operated on-only, whilst in the control it was left to wide-spread industry practice of on-off. The suites had (standard) single-glazed pane windows with heat-attenuating (fabric) internal curtains. Peak ambient ranged from 17.8 ≤ T₀ ≤ 39.1, °C. There were 32 days with recorded rainfall. The overall occupancy Lᴛ of both suites was almost identical at 69.7 and 71.2, % respectively for the treated and control suite. Importantly, this coincided with a typical business period for the CSGH hotel. Based on independent electrical invoices, results showed the treated suite used less energy on 47 days (61 %) of the experimental period, and significantly, GHG was reduced by 12 %. An actual reduction in electrical energy costs of AUD $0.75 per day (9 %) averaged over the period was demonstrated for the treated suite. It was concluded therefore that experimental findings directly confirmed the strategy hypothesis that continuous on-only conditioning will use less energy. Although the hypothesis appeared generalizable, and adaptable to a range of room geometries, it was acknowledged that a drawback was that extrapolation of results could not be reliably done because actual energy used would be impacted by seasons. The in-situ commercial-scale experimental study was therefore extended to encompass four consecutive seasons. The research aim was to provide sufficient experimental evidence (n = 13,008) to reliably test the generalizability of the on-only hypothesis (Chu and Davey, 2017 c). Ambient peak ranged from 9.8 ≤ T₀ ≤ 40.5, °C, with rainfall on 169 days (62 %). Overall, Lᴛ was almost identical at 71.9 and 71.7, % respectively, for the treated and control suite. Results based on independent electrical energy invoices showed the on-only strategy used less energy on 147 days (54 %) than the on-off. An overall mean energy saving of 2.68 kWh per suite per day (9.2 %) (i.e. AUD $0.58 or 8.0 %) with a concomitant reduction in indirect GHG of 3.16 kg CO₂-e was demonstrated. Extrapolated for the 85 x 2-room suites of the hotel, this amounted to a real saving of AUD $18,006 per annum - plus credit certificates that could be used to increase savings. Overall, it was concluded therefore the on-only conditioning hypothesis is generalizable to all seasons, and that there appears no barrier to adaption to a range of room geometries. Highly significantly, the methodology could be readily applied to existing buildings without capital outlays or increases in maintenance. A total of five (5) summative research presentations of results and findings were made to the General Manager and support staff of CSGH over the period to July 2017 inclusive (see Appendix I) that maintained active industry-engagement for the study. To apply these new findings, the synthesis of a computational algorithm in the form of a novel App (Anon., 2012 b; Davey, 2015 b) was carried out for the first time (Chu and Davey, 2017 d). The aim was to demonstrate an App that could be used practically to minimize energy in conditioning of dry air in buildings that must maintain an auto-set temperature despite the impact of fluctuations in T₀ and Lᴛ . The App was synthesized from the extensive experimental commercial-scale data and was applied to compute energy for both strategies from independently forecast T₀ and Lᴛ . Practical performance of the App was shown to be dependent on the accuracy of locally forecast T₀ and Lᴛ . Overall results predicted a saving of 2.62 kWh per 2-room suite per day ($47,870 per annum for CSGH) where accuracy of forecast T₀ is 77 % and Lᴛ is 99 %, averaged over the long term. A concomitant benefit was a predicted reduction greenhouse emissions of 3.1 kg CO₂-e per day. The App appears generalizable – and importantly it is not limited by any underlying heat-model. Its predictive accuracy can be refined with accumulation of experimental data for a range of geo-locations and building-types to make it globally applicable. It was concluded that the App is a useful new tool to minimize energy transfers in conditioning of room dry air in large buildings – and could be readily developed commercially 6. Importantly, it can be applied without capital outlays or additional maintenance cost and at both design and analysis stages. This research is original and not incremental work. Results of this research will be of immediate benefit to risk analysts, heat-design engineers, and owners and operators of large buildings.
Thesis (Ph.D.) -- University of Adelaide, School of Chemical Engineering, 2018

Steady-state unit-operations are used globally in chemical engineering processing. Importantly however, there are naturally occurring (random) fluctuations in parameter values about a ‘set’ mean. These are not sufficient to be considered transient and a random change in one is often off-set by a change in another - with the result that the output remains seemingly steady. Significantly, traditional chemical engineering does not address these random fluctuations explicitly. Davey and co-workers (e.g. Abdul Halim and Davey, 2015; Zou and Davey, 2016) have shown that these natural fluctuations can combine and accumulate in one direction and leverage unexpected and surprise behaviour across a ‘failure - not failure’ boundary. Their hypothesis they titled Fr 13 (Friday 13th) to underscore the surprise element of the failure event. Their probabilistic Fr 13 framework has been usefully applied to a number of 1-step unit-operations including failure in: UV irradiation for potable water (Abdul-Halim and Davey, 2015; 2016); thermal efficiency of a commercial coal-fired boiler (Davey, 2015), metals pitting (Davey et al., 2016), and; failure to remove whey protein deposits in Clean-In-Place milk processing (Davey et al., 2015). A significant advantage is that the framework can be used in quantitative ‘second-tier’ studies (Abdul-Halim and Davey, 2016) to improve design and safety of unit-operations. A limitation however is that the framework had been applied to only 1-step (single) unit-operations until very recently when Zou and Davey (2016) demonstrated its applicability to integrated 2-step membranes processing. Generally however, it is not known if there is any benefit in developing the framework as a useful tool for integrated, greater multi-step unit-operations and its possible combination (Davey et al., 2013) with existing software to enhance design capability. Davey (2011) had suggested these integrated multi-step analyses be termed ‘global’ models. A research program is therefore undertaken with the aim to advance the Fr 13 framework to gain unique insight into how naturally occurring fluctuations in apparent steady-state plant parameters can be transmitted and impact in progressively complex (in the context of ‘integrated’ not ‘complicated’) multi-step processes, and to assess the framework as a new design tool. A logical and stepwise approach is implemented as a research strategy. Because foods processing is globally the largest manufacturing sector, and within it, pasteurization is the most widely used unit-operation, a typical 3-step pasteurization unit operation, consisting of individual 1) heat-up, 2) holding and 3) cool-down, unit-operations is selected as a prudent and stringent test of the Fr 13 risk thesis to multi-step unit-operations. An initial assessment, based on typical commercial pasteurization equipment for raw milk (plate heat exchangers and an external-coil holding tube) is synthesized for the first time (Chandrakash et al., 2015; 2014; Davey et al., 2014) and a generalized method of notation for the Fr 13 risk framework is developed to unambiguously identify particular unit-operations in integrated multi-step processes. Failure is defined in terms of not meeting a globally used Regulatory combination of temperature (T) - time (t) (72 °C, 15 s). Results revealed that pasteurization of raw milk is vulnerable to failure in 12.5 % of all cases over the long-term as a result of with-in system fluctuations in flows, and thermal conditions. If each simulation is (reasonably) considered a daily process this translated to some 46 failures each year with a 2 % design tolerance 2 to meet the required T - t pasteurization criteria. Results highlighted that apparent steady-state pasteurization is actually a combination of successful and (potential) failed operations. This insight could not be obtained from existing traditional risk and hazard approaches, with or without sensitivity analyses. A drawback soon acknowledged however, is that this equipment model did not explicitly address the reduction in unwanted levels of survival of potential contaminant microorganisms in the treated milk. To overcome this, a microbiological global risk model is developed for the first time for the 3-step pasteurization. The logarithmic reduction of viable Mycobacterium avium subsp. paratuberculosis (MAP), a common bacterial contaminant and pathogen, is selected as an indicator of efficacy of process, and an inactivation model is then synthesized (Chandrakash and Davey, 2017 a). Results showed that for a design Regulatory reduction of log₁₀ = 5.5 in viable MAP the 3-step pasteurization is vulnerable to failure in 5.75 % of cases with a 2 % design tolerance averaged over the long term. This equated to ~ 21 failures with viable MAP each year based on a daily operation. To further test applicability of the risk framework to multi-step processing, a fourth integrated step, the storage of the pasteurized milk, is added for the first time (Chandrakash and Davey, 2017 b). A justification is that this simulated commercial practice more closely. Results of simulation of this 4-step model showed that with a design tolerance of 2 % for a Regulatory design reduction of log₁₀ = 5.5 in viable MAP on heat-up to 72 °C with 15 s holding in commercial plate equipment, there would be no further failures i.e. the rate of vulnerability to failure in a 4-step microbiological model for pasteurizing and storing milk remained 5.75 %, averaged over the long term. Results from investigative second-tier studies with the new 4-step Fr 13 model to improve design and safety, revealed vulnerability to microbiological failure can be readily mitigated by installing precise safety-integrity-level (SIL) mass flow control on the raw milk in existing plant to ensure a holding time of ≥ 15 s. It is concluded the Fr 13 framework appears generalizable to integrated multi-step steady-state processes without methodological problems and an advance over current existing risk/hazard methodologies. If properly developed, it is believed that this novel framework could be adopted as a new design tool for steady-state processing at both design and synthesis stages. Research findings will aid a detailed understanding of factors that contribute to failures, and to increased confidence in steady-state unit-operations processing. This research work is original and not incremental work. Findings will be of direct interest to risk analysts, milk processors and manufacturers of pasteurizer equipment.
Thesis (Ph.D.) -- University of Adelaide, School of Chemical Engineering, 2017.

AbstractThe innovative transformation in geospatial information technology (GIT) and Earth observation (EO) data provides a significant opportunity to study the Earth’s environment and enables an advanced understanding of natural and anthropogenic impacts on ecosystems at the local, regional, and global levels (Thapa et al. in Carbon Balance Manag 10(23):1–13, 2015; Flores et al. in SAR handbook: comprehensive methodologies for forest monitoring and biomass estimation. NASA Publication, 2019; Leibrand et al. in Front Environ Sci 7:123, 2019; Chap. 10.1007/978-3-030-73569-2_1). The major advantages of these technologies can be briefly categorized into five broad areas: multidisciplinary; innovative and emerging; providing platforms for analysis, modelling, and visualization; capability to support decision-making; and impact on policies.

The purpose of this chapter is to finalize requirements to undertake non-linear Monte Carlo modelling. Besides mathematical aspects (Chapter 13), additional requirements to identification and addressing of risk interactions should be put forward. All relevant instances of risk interactions should be identified. Identification of ‘chronic’ project system issues that serve as additional causes of risks is required to pin down internal risk amplifications. Identification of cross-risk interactions can be undertaken by visualization of dynamic risk patterns (cross-risk interaction mapping). Principles of risk interaction calibration are introduced keeping in mind two challenges. First, a calibration of aggregated risk interactions at the project level. Second, evaluation of individual instances of risk interactions based on the overall calibration. Methods to address identified risk interactions are discussed. In the case of intra-risk interactions, the ‘chronic’ issues should be addressed. In the case of cross-risk interactions, the dynamic risk patterns should be disrupted.

The Reserve Bank of India suspected a cartel among 15 banks in fixing interest rates on deposits of the savings bank accounts over a period from 2011-12 to 2012-13 and lodged a complaint with the Competition Commission of India. The latter could not find any motive of the banks to collude and hence ruled out the complaint. The authors collected data on the banks' activities and performances on the said periods and examined in this chapter whether the commission was right in ruling out the complaint. The results of the analyses in this work lead to the conclusion that the commission was right in ruling out the complaint, but there are certain limitations and policy prescriptions that cropped out of this work, which should be conveyed to policy makers and researchers.

Forest fuel moisture content is an important parameter that determines fire risk and fire behaviour. An accurate prediction of moisture content is therefore of great importance in fire management. In the fire risk period, dead forest fuel moisture content changes mainly by water vapour sorption processes so its knowledge enables the development of predictive fire risk models. In the present work, the adsorption and desorption processes and equilibrium moisture content of 10-hour dead Pinus pinaster branches (diameter between 0.6 cm and 2.5 cm) were described in order to develop a moisture content prediction model for this type of fuels. Laboratorial tests were used to determine sorption curves, timelag and equilibrium moisture content for different sets of air temperature (range between 20°C and 40°C) and relative humidity (range between 10% and 90%). The sorption curves and equilibrium moisture were also modelled with forest fuels and agricultural and food products existing models. Field tests were used to evaluate the sorption and equilibrium moisture content models performance. Dead Pinus pinaster branches were collected in central Portugal through the year 2020 and 2021 on the Portuguese fire risk period (15th May to 15th October) between 12:00h and 13:00h LST. Samples with 0.6 cm to 2.5 cm diameter were collected and transported to laboratory to determine moisture content. The laboratorial drying and wetting curves of dead Pinus pinaster branches (0.6 cm to 2.5 cm diameter) show that they are not pure exponential functions, but with different timelag values until equilibrium is reached. Additionally, the results suggest no significant relationship of the timelag periods with air relative humidity but a dependence with air temperature, showing an increase in the sorption rates with temperature. In terms of sorption curves, Modified Henderson and Pabis model provide the best fitting. For this type of fuels, the representation of EMC values as a function of air relative humidity at constant temperature allowed to obtain a typical sigmoid curve. The EMC values obtained were higher for desorption process than for adsorption process, indicated the typical hysteresis effect in these processes. It was found that, besides the models used in forest fires, other EMC models are also suitable to predict fuel moisture content of dead Pinus pinaster branches, as the ones used in agricultural and food analysis.

ABSTRACT Background: Most of the neonatal deaths that occur after 6-48 hours postpartum can be prevented with appropriate newborn care and initiated immediately after delivery through adequate and standardized first neonatal visit. In Indonesia, it is still not in accordance with the expected target. This study aimed to analyze the factors that influence the first neonatal visit from various levels through a multilevel analysis approach. Subjects and Method: This was a cross sectional study with samples of individual level (level 1) was 1014 mother babies, village Level (level 2) as many as 95 village managers, public health center (level 3) was 51 manager of child health programs, and district level (level 4) was 13 managers of health programs in eight provinces Indonesia. The dependent variable was first neonatal visits. The independent variables were birth attendant and pregnancy counselling (level 1), number of village midwives and community control in development (level 2), partnership and resources (level 3), and policy strategy (level 4). Data analysis was performed through univariate, bivariate, multivariate analysis with logistic regression and multilevel modeling using multilevel regression logistic random intercept analysis run on Stata 14.0. Results: At level 1, birth attendants increased first neonatal visits (OR = 3.21; 95% CI 95% = 1,984 to 5,182; p <0.001), pregnancy counselling (OR = 1,705; 95% CI 95% = 1,162 to 2,503; p = 0.007) significantly. At level 2 modelling, the number of village midwives increased the risk of the first neonatal visit (OR = 1,815; 95% CI = 0.950 to 3,467; p = 0.049), community control (OR = 2,659; 95% CI = 1.396 to 5.066; p = 0.009) significantly. At level 3 modelling, partnerships and resources significantly increased the first neonatal visit (OR = 2,131; 95% CI = 1,114 to 4,078; p = 0.012) significantly. At level 4 modelling, birth attendants significantly increased the first neonatal visits (OR = 3.056; 95% CI = 1.901 to 4,914; p = 0.029) significantly. Conclusion: Birth attendants, pregnancy counselling, the number of village midwives, community control, partnerships and resources, birth attendants increase the risk of first neonatal visit. Contextual village areas, public health center, and district health offices have contextual effects on the first neonatal visit. Keywords: first neonatal visit, multilevel analysis Correspondence: Triseu Setianingsih. Drg. Suherman Medical Institut. Jl. Industri Pasirgombong Jababeka Cikarang, Bekasi, West Java. Email: triseu.pantyarso@imds.ac.id. Mobile: +6281299192199. DOI: https://doi.org/10.26911/the7thicph.03.85

As part of a major pipeline expansion, two deactivated 24″ diameter pipeline segments with a combined length of 192 kilometres will be assessed and upgraded to operational status. These line segments include a 42 kilometre section within the North Thompson valley of British Columbia, and a 150 kilometre segment through the Rocky Mountains of Alberta and British Columbia. Reactivating the lines to operational condition is a multi-staged process, which will be partially guided by a National Energy Board Condition requiring the issuance of a certificate from an independent certifying body that the system is fit for service and meets all applicable requirements of CSA Z662, Oil and Gas Pipeline Systems. This certificate must be unconditional and remain in effect for a period of 5 years. The need for unconditional certification of fitness for service drives the need for a comprehensive assessment of the pipeline condition using a broad slate of inline inspection technologies. Tools were selected for the assessment of deformations, metal loss, manufacturing anomalies and cracking. The lines were maintained with a low pressure nitrogen blanket for between 9 and 13 years prior to the start of the reactivation work and it was therefore not possible to run the tools using service fluid. Several options were considered for propelling the inline inspection tools including nitrogen, compressed air and water slugs in compressed nitrogen or air. Each method has advantages and disadvantages and modelling was carried out to simulate the transport of the tools through each segment. The modelling needed to account for pipe elevation changes, wall thickness changes, valves, tool drive friction, acceptable tool velocity, and the pressure of the drive medium in the pipeline. The modelling focused on the following constraints: i. Ensure ILI data quality ii. Ensure safety considering the potential presence of defects in the lines iii. Minimize risk iv. Minimize overall cost These constraints guided a flow modelling/feasibility study for inspecting the lines with the 4 tools. The objective of the study was to determine the optimum configuration of propellant, inspection tools, and line segmentation while ensuring a safe, economical operation resulting in optimal data collection. The paper will provide some background on the line segments being reactivated and pressure limitations that were adopted for ILI runs. The majority of the content will focus on the determination of tool drive technique, how simulation occurred and how the actual execution of the runs compared. Details regarding the challenges and troubleshooting required to successfully complete the integrity surveys will also be discussed in depth.

Abstract Sand production is a common issue, especially in a depleting field as water production commences, and sand strength weakens. Conventional sand management focuses on downhole sand exclusion from the wellbore either through completion design or production reduction by choke optimisation as passive sand control. The objective of the paper is to share the company's journey in sand management in collaboration of various supporting units. The Holistic Sand Management methodological process adopts a 5 keys action plan, namely: Establishment of dedicated focus sand team with multidisciplinary support covering surface and subsurface activities Situational Assessment to develop baseline in sand management preparedness in each field, identifying gaps and developing an intervention plan Development and utilisation of an in-house erosion prediction tool, Continuous upskilling in sand management best practices, and Technology review and active pilot testing utilising digital enhancement to assist in sand management activities. Establishment of a dedicated and collaborative focus group, Integrated Sand Management (ISM) team in the centre which is replicated at the region as Regional Sand Team (RST), has allowed for continuous communication on sand management matters. Situational Assessment consists of 13 integrated subsurface and surface elements to evaluate a field capability to manage sand production. These 13 elements include sand management philosophy and organisation setup, sand prediction, sand control design, sand sampling and monitoring as well as surface sand handling and disposal. Findings from the assessment are used to gauge the field's readiness and ability to manage sand operation and develop gaps closure plan to achieve the optimum holistic sand management. The Sand Erosional and Transportation (SET) tool, an in-house developed tool, is used to evaluate sand erosion and deposition risk in the production system. The tool is used extensively to generate a safe operating envelope for sand producing well during open-up and continuous production. This has allowed the company to shift from limiting production up to a specific sand concentration to erosion risk-based approach, which in turn creates production optimization opportunities. Regular and continuous upskilling sessions ensure the frontline operations are updated and abreast with best practices in sand management. In addition, the ISM team reviews and leverages on latest technology, actively organises pilot test at a selected site supported with digital enhancement to assist in sand management activities. The application of a Holistic Sand Management methodology is seen to reduce erosion related Loss of Primary Containment (LOPC), sustain production, and minimise unplanned deferment. However, this is just the beginning and the battle in sand operation will continue to be very challenging in balancing between production while ensuring asset integrity. The methodology is a novel approach for the company with the formation of a dedicated and collaborative team spearheading sand management initiatives which include situation assessment for gaps identification supported by in-house erosion modelling tool.

Self-loosening of fastened systems is known as a severe damage mechanism besides the loss of preload due to relaxation and as a result of this the failure of the joint. Main problem is, that self-loosening mostly leads to a rapid preload loss when occurs. In the 1970s first systematic investigations due to this are reported from Junker et al. using a transverse-vibrational test stand [13]. Nowadays numeric calculation approaches are available (e.g. [12]). All approaches show that very small displacements from loading before complete sliding are sufficient to induce self-loosening — which is a screw rotation against its tightening direction without material rupture of the screw. Today the mechanism of self-loosening under uni-axial transverse load of single-screwed joints with plain bearing surface is understood and predictable. Also combined loads of vibration and rotation became the focus of university-based research. The challenge is to transfer the knowledge about the mechanism to component fastened systems with multi-screw joints. The fundamental mechanism is not sufficient for component design. This is the reason why up to now no prediction in advance is established in guidelines. First, this paper shows the time-sequence of self-loosening in general with its different stages. The second step is to work out important influences on self-loosening which will be shown by existing calculations. Then a stress-based calculation and a better criterion for self-loosening will be developed. Next step, if analytics come to their limits, is the numeric simulation of system behavior. With this the critical preload for self-loosening must be determined to ensure safety of the connection. Following from this screw joints can be dimensioned without risk of self-loosening. The simulation procedure includes right modelling with boundary conditions as well as defining evaluation procedure for a ‘self-loosening-safety-margin’. With simulation of a single-screw joint it gets clear that either analytical or numerical approach can be used. But already for two screws in a fastened system the limits of known equations become obvious. Finally, results of a vibrational test are shown before conclusions and outlook.

Abstract The objective of this work was to quantify the in-situ stress contrast between the reservoir and the surrounding dense carbonate layers above and below for accurate hydraulic fracturing propagation modelling and precise fracture containment prediction. The goal was to design an optimum reservoir stimulation treatment in a Lower Cretaceous tight oil reservoir without fracturing the lower dense zone and communicating the high-permeability reservoir below. This case study came from Abu Dhabi onshore where a vertical pilot hole was drilled to perform in-situ stress testing to design a horizontal multi-stage hydraulic fractured well in a 35-ft thick reservoir. The in-situ stress tests were obtained using a wireline straddle packer microfrac tool able to measure formation breakdown and fracture closure pressures in multiple zones across the dense and reservoir layers. Standard dual-packer micro-injection tests were conducted to measure stresses in reservoir layers while single-packer sleeve-frac tests were done to breakdown high-stress dense layers. The pressure versus time was monitored in real-time to make prompt geoscience decisions during the acquisition of the data. The formation breakdown and fracture closure pressures were utilized to calibrated minimum and maximum lateral tectonic strains for accurate in-situ stress profile. Then, the calibrated stress profile was used to simulate fracture propagation and containment for the subsequent reservoir stimulation design. A total 17 microfrac stress tests were completed in 13 testing points across the vertical pilot, 12 with dual-packer injection and 5 with single-packer sleeve fracturing inflation. The fracture closure results showed stronger stress contrast towards the lower dense zone (900 psi) in comparison with the upper dense zone (600 psi). These measurements enabled the oilfield operating company to place the lateral well in a lower section of the tight reservoir without the risk of fracturing out-of-zone. The novelty of this in-situ stress testing consisted of single packer inflations (sleeve frac) in an 8½-in hole in order to achieve higher differential pressures (7,000 psi) to breakdown the dense zones. The single packer breakdown permitted fracture propagation and reliable closure measurements with dual-packer injection at a lower differential reopening pressure (4,500 psi). Microfracturing the tight formation prior to fluid sampling produced clean oil samples with 80% reduction of pump out time in comparison to conventional straddle packer sampling operations. This was a breakthrough operational outcome in sampling this reservoir.

Abstract Originally, an infill well from project H was approved in 2013 to be completed as a single zone Open Hole Gravel Pack (OHGP) to produce gas commingled from three sands located at the shallowest reservoir in that field. Interpretation of recent logs from a nearby producing well indicated that there was significant water threat at two of the sands which would lead to water influx from the beginning of production if the well was to be completed as a single zone OHGP. The well was then redesigned to be completed as a Cased Hole Gravel Pack (CHGP) in order to have mechanical isolation from the water zones with an inner string and internal isolation packers to allow feasibility of zonal isolation to shut off the water producing zone in the future. This feature however resulted in higher well cost as compared to the approved design. Due to recent hostile low oil price, a more cost-effective sand control design was evaluated to reduce the well cost while maintaining similar performances as a CHGP design in terms of the capability to delay water breakthrough. Design feasibility study was performed on multizone OHGP with open hole mechanical packer and an inner string design to evaluate its performance and magnitude of cost reduction relative to a CHGP design. Skin analysis was performed for both OHGP and CHGP completion designs to evaluate any additional pressure loss for each sand. Prior to compartment optimization, an OHGP completion without packer placement was simulated in a dynamic simulation to generate the production profile as a base case. This was followed by a compartment optimization that was performed with OH mechanical packer placement at various standoff distances from the Gas-Water Contact (GWC) such as 5ft, 10ft, 15ft, 20ft and 30ft respectively. Subsequently, similar analysis was then performed on the CHGP completion design with a higher skin value estimated for the CHGP completion to reflect a higher degree of damage resulting from the cementing and perforation operations. Several production sensitivities were simulated by varying the perforation length and standoff from the GWC to replicate the same scenario of the open hole mechanical packer placement in the OHGP design analysis. Finally, analysis on the effectiveness of the base case (OHGP with no packer) against the cases of OHGP with optimum packer placement and CHGP with optimum perforation depth were compared and ranked over cumulative gas production, cumulative water production, operational complexity, and risk as well as total well cost. Based on the dynamic modelling, the base case (OHGP without packer) showed water breakthrough occurring right at the start of production as expected. Once breakthrough occured, water production would rapidly dominate production. On the other hand, packer placement sensitivity analysis for the OHGP design showed that the optimum depth for packer placement was 20ft or 30ft above the GWC depth where it provided highest gas cumulative and lowest water cumulative production throughout the well life. With offset distance of at least 20ft away from the GWC, the cumulative gas production for the OHGP and the CHGP cases were found to be similar and the cumulative water production for the OHGP case was slightly lower than the CHGP case. Mechanical open hole packer was recommended instead of swell packer after considering the risk of inadequate isolation by swellable packer that would lead to early water breakthrough which would subsequently reduce the cumulative gas production. As a result, an OHGP with open hole mechanical packer and inner string was selected to be the most optimum design for this well with estimated cost reduction of nearly 13% from a CHGP design. In general, an OHGP with OH mechanical packer at 20ft or 30ft standoff from the GWC brought benefit to the infill well in terms of cumulative gas production gain and low water production while eliminating sand production.

Background Lung cancer is the number one cause of cancer death worldwide.(1) It is the fifth most commonly diagnosed cancer in Australia (12,741 cases diagnosed in 2018) and the leading cause of cancer death.(2) The number of years of potential life lost to lung cancer in Australia is estimated to be 58,450, similar to that of colorectal and breast cancer combined.(3) While tobacco control strategies are most effective for disease prevention in the general population, early detection via low dose computed tomography (LDCT) screening in high-risk populations is a viable option for detecting asymptomatic disease in current (13%) and former (24%) Australian smokers.(4) The purpose of this Evidence Check review is to identify and analyse existing and emerging evidence for LDCT lung cancer screening in high-risk individuals to guide future program and policy planning. Evidence Check questions This review aimed to address the following questions: 1. What is the evidence for the effectiveness of lung cancer screening for higher-risk individuals? 2. What is the evidence of potential harms from lung cancer screening for higher-risk individuals? 3. What are the main components of recent major lung cancer screening programs or trials? 4. What is the cost-effectiveness of lung cancer screening programs (include studies of cost–utility)? Summary of methods The authors searched the peer-reviewed literature across three databases (MEDLINE, PsycINFO and Embase) for existing systematic reviews and original studies published between 1 January 2009 and 8 August 2019. Fifteen systematic reviews (of which 8 were contemporary) and 64 original publications met the inclusion criteria set across the four questions. Key findings Question 1: What is the evidence for the effectiveness of lung cancer screening for higher-risk individuals? There is sufficient evidence from systematic reviews and meta-analyses of combined (pooled) data from screening trials (of high-risk individuals) to indicate that LDCT examination is clinically effective in reducing lung cancer mortality. In 2011, the landmark National Lung Cancer Screening Trial (NLST, a large-scale randomised controlled trial [RCT] conducted in the US) reported a 20% (95% CI 6.8% – 26.7%; P=0.004) relative reduction in mortality among long-term heavy smokers over three rounds of annual screening. High-risk eligibility criteria was defined as people aged 55–74 years with a smoking history of ≥30 pack-years (years in which a smoker has consumed 20-plus cigarettes each day) and, for former smokers, ≥30 pack-years and have quit within the past 15 years.(5) All-cause mortality was reduced by 6.7% (95% CI, 1.2% – 13.6%; P=0.02). Initial data from the second landmark RCT, the NEderlands-Leuvens Longkanker Screenings ONderzoek (known as the NELSON trial), have found an even greater reduction of 26% (95% CI, 9% – 41%) in lung cancer mortality, with full trial results yet to be published.(6, 7) Pooled analyses, including several smaller-scale European LDCT screening trials insufficiently powered in their own right, collectively demonstrate a statistically significant reduction in lung cancer mortality (RR 0.82, 95% CI 0.73–0.91).(8) Despite the reduction in all-cause mortality found in the NLST, pooled analyses of seven trials found no statistically significant difference in all-cause mortality (RR 0.95, 95% CI 0.90–1.00).(8) However, cancer-specific mortality is currently the most relevant outcome in cancer screening trials. These seven trials demonstrated a significantly greater proportion of early stage cancers in LDCT groups compared with controls (RR 2.08, 95% CI 1.43–3.03). Thus, when considering results across mortality outcomes and early stage cancers diagnosed, LDCT screening is considered to be clinically effective. Question 2: What is the evidence of potential harms from lung cancer screening for higher-risk individuals? The harms of LDCT lung cancer screening include false positive tests and the consequences of unnecessary invasive follow-up procedures for conditions that are eventually diagnosed as benign. While LDCT screening leads to an increased frequency of invasive procedures, it does not result in greater mortality soon after an invasive procedure (in trial settings when compared with the control arm).(8) Overdiagnosis, exposure to radiation, psychological distress and an impact on quality of life are other known harms. Systematic review evidence indicates the benefits of LDCT screening are likely to outweigh the harms. The potential harms are likely to be reduced as refinements are made to LDCT screening protocols through: i) the application of risk predication models (e.g. the PLCOm2012), which enable a more accurate selection of the high-risk population through the use of specific criteria (beyond age and smoking history); ii) the use of nodule management algorithms (e.g. Lung-RADS, PanCan), which assist in the diagnostic evaluation of screen-detected nodules and cancers (e.g. more precise volumetric assessment of nodules); and, iii) more judicious selection of patients for invasive procedures. Recent evidence suggests a positive LDCT result may transiently increase psychological distress but does not have long-term adverse effects on psychological distress or health-related quality of life (HRQoL). With regards to smoking cessation, there is no evidence to suggest screening participation invokes a false sense of assurance in smokers, nor a reduction in motivation to quit. The NELSON and Danish trials found no difference in smoking cessation rates between LDCT screening and control groups. Higher net cessation rates, compared with general population, suggest those who participate in screening trials may already be motivated to quit. Question 3: What are the main components of recent major lung cancer screening programs or trials? There are no systematic reviews that capture the main components of recent major lung cancer screening trials and programs. We extracted evidence from original studies and clinical guidance documents and organised this into key groups to form a concise set of components for potential implementation of a national lung cancer screening program in Australia: 1. Identifying the high-risk population: recruitment, eligibility, selection and referral 2. Educating the public, people at high risk and healthcare providers; this includes creating awareness of lung cancer, the benefits and harms of LDCT screening, and shared decision-making 3. Components necessary for health services to deliver a screening program: a. Planning phase: e.g. human resources to coordinate the program, electronic data systems that integrate medical records information and link to an established national registry b. Implementation phase: e.g. human and technological resources required to conduct LDCT examinations, interpretation of reports and communication of results to participants c. Monitoring and evaluation phase: e.g. monitoring outcomes across patients, radiological reporting, compliance with established standards and a quality assurance program 4. Data reporting and research, e.g. audit and feedback to multidisciplinary teams, reporting outcomes to enhance international research into LDCT screening 5. Incorporation of smoking cessation interventions, e.g. specific programs designed for LDCT screening or referral to existing community or hospital-based services that deliver cessation interventions. Most original studies are single-institution evaluations that contain descriptive data about the processes required to establish and implement a high-risk population-based screening program. Across all studies there is a consistent message as to the challenges and complexities of establishing LDCT screening programs to attract people at high risk who will receive the greatest benefits from participation. With regards to smoking cessation, evidence from one systematic review indicates the optimal strategy for incorporating smoking cessation interventions into a LDCT screening program is unclear. There is widespread agreement that LDCT screening attendance presents a ‘teachable moment’ for cessation advice, especially among those people who receive a positive scan result. Smoking cessation is an area of significant research investment; for instance, eight US-based clinical trials are now underway that aim to address how best to design and deliver cessation programs within large-scale LDCT screening programs.(9) Question 4: What is the cost-effectiveness of lung cancer screening programs (include studies of cost–utility)? Assessing the value or cost-effectiveness of LDCT screening involves a complex interplay of factors including data on effectiveness and costs, and institutional context. A key input is data about the effectiveness of potential and current screening programs with respect to case detection, and the likely outcomes of treating those cases sooner (in the presence of LDCT screening) as opposed to later (in the absence of LDCT screening). Evidence about the cost-effectiveness of LDCT screening programs has been summarised in two systematic reviews. We identified a further 13 studies—five modelling studies, one discrete choice experiment and seven articles—that used a variety of methods to assess cost-effectiveness. Three modelling studies indicated LDCT screening was cost-effective in the settings of the US and Europe. Two studies—one from Australia and one from New Zealand—reported LDCT screening would not be cost-effective using NLST-like protocols. We anticipate that, following the full publication of the NELSON trial, cost-effectiveness studies will likely be updated with new data that reduce uncertainty about factors that influence modelling outcomes, including the findings of indeterminate nodules. Gaps in the evidence There is a large and accessible body of evidence as to the effectiveness (Q1) and harms (Q2) of LDCT screening for lung cancer. Nevertheless, there are significant gaps in the evidence about the program components that are required to implement an effective LDCT screening program (Q3). Questions about LDCT screening acceptability and feasibility were not explicitly included in the scope. However, as the evidence is based primarily on US programs and UK pilot studies, the relevance to the local setting requires careful consideration. The Queensland Lung Cancer Screening Study provides feasibility data about clinical aspects of LDCT screening but little about program design. The International Lung Screening Trial is still in the recruitment phase and findings are not yet available for inclusion in this Evidence Check. The Australian Population Based Screening Framework was developed to “inform decision-makers on the key issues to be considered when assessing potential screening programs in Australia”.(10) As the Framework is specific to population-based, rather than high-risk, screening programs, there is a lack of clarity about transferability of criteria. However, the Framework criteria do stipulate that a screening program must be acceptable to “important subgroups such as target participants who are from culturally and linguistically diverse backgrounds, Aboriginal and Torres Strait Islander people, people from disadvantaged groups and people with a disability”.(10) An extensive search of the literature highlighted that there is very little information about the acceptability of LDCT screening to these population groups in Australia. Yet they are part of the high-risk population.(10) There are also considerable gaps in the evidence about the cost-effectiveness of LDCT screening in different settings, including Australia. The evidence base in this area is rapidly evolving and is likely to include new data from the NELSON trial and incorporate data about the costs of targeted- and immuno-therapies as these treatments become more widely available in Australia.