Public involvement in the governance of population-level biomedical research: unresolved questions and future directions.

Population-level biomedical research offers new opportunities to improve population health, but also raises new challenges to traditional systems of research governance and ethical oversight. Partly in response to these challenges, various models of public involvement in research are being introduced. Yet, the ways in which public involvement should meet governance challenges are not well understood. We conducted a qualitative study with 36 experts and stakeholders using the World Café method to identify key governance challenges and explore how public involvement can meet these challenges. This brief report discusses four cross-cutting themes from the study: the need to move beyond individual consent; issues in benefit and data sharing; the challenge of delineating and understanding publics; and the goal of clarifying justifications for public involvement. The report aims to provide a starting point for making sense of the relationship between public involvement and the governance of population-level biomedical research, showing connections, potential solutions and issues arising at their intersection. We suggest that, in population-level biomedical research, there is a pressing need for a shift away from conventional governance frameworks focused on the individual and towards a focus on collectives, as well as to foreground ethical issues around social justice and develop ways to address cultural diversity, value pluralism and competing stakeholder interests. There are many unresolved questions around how this shift could be realised, but these unresolved questions should form the basis for developing justificatory accounts and frameworks for suitable collective models of public involvement in population-level biomedical research governance

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial

Background Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. Methods In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in both groups continued to receive other therapies required to manage their condition. Participants, study staff, and investigators were masked to the study assignment. The primary outcome was the 7-point WHO ordinal scale for clinical status at day 29 after random assignment. The intention-to-treat population included all patients who were randomly assigned and met the enrolment criteria. The safety population included all participants who received at least one dose of study medication. This study was registered with the ISRCTN registry, ISRCTN30564012. Findings Between June 5, 2020, and Jan 25, 2021, 406 patients were randomly assigned to brensocatib or placebo; 192 (47·3%) to the brensocatib group and 214 (52·7%) to the placebo group. Two participants were excluded after being randomly assigned in the brensocatib group (214 patients included in the placebo group and 190 included in the brensocatib group in the intention-to-treat population). Primary outcome data was unavailable for six patients (three in the brensocatib group and three in the placebo group). Patients in the brensocatib group had worse clinical status at day 29 after being randomly assigned than those in the placebo group (adjusted odds ratio 0·72 [95% CI 0·57–0·92]). Prespecified subgroup analyses of the primary outcome supported the primary results. 185 participants reported at least one adverse event; 99 (46%) in the placebo group and 86 (45%) in the brensocatib group. The most common adverse events were gastrointestinal disorders and infections. One death in the placebo group was judged as possibly related to study drug. Interpretation Brensocatib treatment did not improve clinical status at day 29 in patients hospitalised with COVID-19

Winter and spring phenology of Australian pome fruit in historical and future climates

© 2013 Dr. Rebecca Olive DarbyshireSuccessful agricultural production relies on favourable environmental conditions in combination with sound management strategies and practices. The advent of anthropogenically induced climate change is likely to modify climate variables, potentially influencing the productivity of these systems. Pome fruit trees are vulnerable to future climate changes due to their perennial nature, extended juvenile phase and long productive lifespan (decades). Australian growers are further susceptible as Australia has been identified as particularly exposed to future climate change. To explore this potential exposure, interpretation of expected changes to the climate as applicable to Australian pome fruit trees was considered in this thesis. Specifically, two key phases in the growth cycle were evaluated, winter chilling and spring flowering phenology. These phases are both temperature dependent and therefore implications of changes to temperature conditions were the focus of the research. Prior to consideration of climate future impacts, assessment of plant responses under current conditions is required. For the two phenophases considered, substantial knowledge gaps persist in relation to physiological mechanisms as driven by environmental conditions. As a result, many methods have been developed to estimate these processes based on observed responses to temperature. In this study, several methods were applied in all the analyses to consider the implication of methodological selection on the results obtained. Winter chill was analysed at 13 locations across southern Australia representing the major pome fruit growing regions. Four different models were used to calculate chill historically and into the future (0-7.2°C, Positive Utah, Modified Utah and Dynamic models). Historically, many locations recorded notable declines in accumulated chill regardless of chill model selection (Orange, Lenswood, Tatura, Yarra Valley and Bacchus Marsh). Other locations have remained stable with no location exhibiting a consensus increase in chill across the tested models. Large season-to-season variability was observed at all locations and for all chill models. Comparison of output between the chill models indicated that the 0-7.2°C model frequently behaved differently to the other models. Projected changes in winter chill were assessed according to +1, 2 and 3°C increases to mean global temperatures. Reduced chill accumulation in the future was found for all locations with notable regional differences. The sites in Western Australia were found to bear the greatest impact with a substantial reduction in chill expected. The chill models tended to interpret changes differently with the 0-7.2°C model generally being most sensitive to changes in temperature followed by the Utah models and then the Dynamic model. The impact of climate on spring flowering was also considered. Collation of historical flowering phenological records of pome fruit in Australia was an important contribution of this research. No such information has been analysed for Australia and only one other study exists for the Southern Hemisphere. Observed relationships indicated flowering advancement of between 4.1 to 7.7 days per degree Celsius increase in mean spring temperature. Compared with similar phenological research in the Northern Hemisphere, the changes in timing in relation to temperature were often shallower in Australia, although the significance of observed hemispheric differences was not clear. To determine relationships to temperature, a sequential chill-growth model as well as correlation to mean springtime temperatures were used. The sequential chill-growth approach proved superior, with coefficients of determination between 0.49 and 0.85, indicating the inclusion of chill conditions are important for spring phenology modelling. Projections of future flowering timing were created using the relationships determined in the historical analysis combined with +1, 2 and 3°C increases to mean global temperatures. Both of the previous sequential chill-growth and the springtime temperature modelling approaches were used. The springtime temperature model predicted advancement in flowering timing for all datasets. With 1°C warming the sequential chill-growth model recorded similar flowering timing to current conditions for many of the species. Greater warming, however often tended towards later emergence. The timing of projected flowering was related the relative dominance of the protraction of the chill period versus the contraction of the growth phase. Finally, the implication of changes to flowering timing was considered in relation to frost risk. Results from projections of both phenology modelling approaches were used in combination with two assumptions about future frost conditions; current conditions or frost is modified with climate change. Depending on the combination of phenology method, frost assumption and level of warming, frost risk was predicted to notably increase, remain similar or decrease. Overall, chill accumulation in Australia is likely to decline. The changes reported are sensitive to chill model selection for Australian conditions, consistent with previous assessment made for other regions. Further research using the 0-7.2°C model is not recommended whilst greater uptake of the Dynamic model is encouraged. Modelling of flowering phenology, especially under climate perturbed conditions, illustrated flowering phenology model selection is important. Although the sequential chill-model model performed better than the springtime temperature approach, reservations still remain in employing this method for climate impact statements. Future research directed at greater understanding of physiological processes is required to better characterise current physiological responses and produce robust climate impact assessments

A crop and cultivar-specific approach to assess future winter chill risk for fruit and nut trees

Anthropogenic climate change will influence winter chill accumulation, with future declines likely in temperate locations. However, these declines only translate as impacts when cultivar winter chilling requirements are not satisfied. This study presents a methodology to evaluate future impacts of declining winter chill through a cultivarspecific approach which is useful for growers, industry and policy-makers to develop adaptation strategies. A risk based system was applied to represent the likelihood of meeting cultivar chilling requirements using low, medium, medium-high and high risk ratings based on percentiles. This was combined with climate projection uncertainty graphically at 16 Australian growing districts historically (1981–2010) and for 2030, 2050 and 2090. The results demonstrated that impacts and likely adaptation options differed between cultivars, some recording limited risk at all sites out to 2090 ('Nonpareil' almond) whilst others recorded greater risk both historically and into the future ('Chandler' walnut). Notably, risk differed across sites and with the future time period. These results highlight which cultivars are susceptible to low winter chill conditions, where this risk does and does not manifest and the different time horizons at which the risk will materialise across Australia's main growing districts. Using this approach, changes in winter chill conditions are presented in a useable form which allows for appropriate climate adaptation strategies to be developed, securing the industries into the future

Techniques for Workload Scheduling in Modern Cloud Computing Environments

64 σ.Σκοπός αυτής της διπλωματικής εργασίας είναι η διερεύνηση και μελέτη διαφόρων τεχνικών με τις οποίες μπορούμε να αναγνωρίσουμε τις απαιτήσεις μιας υπολογιστικής εργασίας, ώστε να την εντάξουμε κατά τρόπο βέλτιστο σε ένα υπάρχον υπολογιστικό νέφος. Το νέφος αυτό θεωρούμε ότι διαθέτει ετερογενή συστήματα, στα οποία ήδη λειτουργούν άλλες εργασίες, που καταναλώνουν μέρος των διαθέσιμων πόρων. Οι τεχνικές που μελετούμε προσπαθούν να εξασφαλίσουν για την εργασία ότι θα δρομολογηθεί σε ένα τμήμα του υπολογιστικού νέφους που θα είναι επαρκές να καλύψει τις απαιτήσεις της εργασίας, χωρίς δυσμενή επίπτωση στη λειτουργία της, ενώ ταυτόχρονα να εξασφαλίσουν για το υπολογιστικό νέφος ότι η εργασία θα ανατεθεί με τρόπο που θα μεγιστοποιεί την εξοικονόμηση πόρων. Η λεπτή αυτή ισορροπία απαιτεί, όχι μόνον να εξεταστούν οι απαιτήσεις της εργασίας σε σχέση με τους υπολογιστικούς πόρους που είναι διαθέσιμοι, αλλά να ληφθεί υπόψη και η συμπεριφορά της εργασίας σε σχέση με άλλες εργασίες που ήδη εκτελούνται στο ίδιο υπολογιστικό νέφος και μπορεί να της προκαλέσουν παρεμβολές. Επομένως, πριν την αναζήτηση και δέσμευση υπολογιστικών πόρων, πρέπει να προηγηθεί ένα βήμα αξιολόγησης της εργασίας και των απαιτήσεών της κάτω από διάφορες συνθήκες λειτουργίας. Η αξιολόγηση αυτή μπορεί να γίνει από το ίδιο το σύστημα που διαχειρίζεται τους εικονικούς πόρους, ή από άλλο σύστημα που διενεργεί ανεξάρτητους ελέγχους, πριν τροφοδοτήσει το σύστημα διαχείρισης του νέφους. Για αυτό ακριβώς το βήμα αξιολόγησης, εξετάζουμε διάφορες τεχνικές που έχουν προταθεί, αξιολογούμε την επάρκεια και αποτελεσματικότητά τους, μελετούμε το κόστος λειτουργίας τους και τις συγκρίνουμε ως προς το πραγματικό τους όφελος, τόσο για την απαίτηση (υπολογιστική εργασία) όσο και για το σύστημα εξυπηρέτησης της απαίτησης (υπολογιστικό νέφος).The purpose of this thesis is to investigate and study various techniques by which we can recognize the demands of a computational workload, in order to integrate it optimally into an existing cloud computing infrastructure. We assume that the cloud consists of heterogeneous systems, in which other workloads are already operating and consuming part of the available resources. The techniques under study are intended to ensure that the workload will be assigned to an appropriate section of the cloud computing infrastructure, capable of meeting its requirements, in a manner that will optimize the use of resources and maximize cost savings for the cloud infrastructure. This delicate balance requires us to examine the demands of a workload against all available resources, while also considering the interference of other workloads already being executed within the same cloud infrastructure. Therefore, before we commit any resources, we need to perform an initial step of classifying the workload. This classification can be performed by the system responsible for managing the cloud’s resources, or by a separate system, committed to profiling and scheduling the incoming workloads. For this step we consider various proposed techniques, we evaluate their adequacy and effectiveness, we study their cost and finally we compare them, in order to understand the benefits they offer to the workload itself and to the cloud environment.Αντώνιος Ε. Γιαννόπουλο

Predicting panicle initiation timing in rice grown using water efficient systems

Management strategies that improve water efficiency in water-limited rice systems are needed for sustainable production. In southeast Australia growers are increasing implementing drill seeding and also delayed permanent water (DPW) irrigation practice to improve water productivity. This change in timing of permanent water application has a large influence on crop phenology which impacts the timing of crop management practices. Two types of phenological models were assessed to predict panicle initiation (PI) timing in fields managed using drill sowing and DPW. A single-stage model was contrasted with a two-stage efficiency model. The single-stage model assumed temperature across the planting to PI period equally contributes to PI timing. The two-stage efficiency model allowed for differential temperature efficiencies between the pre (aerobic) and post (anaerobic) permanent water periods. Four temperature indices, one growing degree day and three parameterisations of degree day (DD) were tested. Observations of PI from seven seasons and seven locations were used to parameterise (n = 55) and validate (n = 7) the models. The best model was for the two-stage efficiency approach using the original DD parameters with RMSE of 3.8 and 4.4 days for the parameterising and validating data, respectively. The methodology outlined can be used for other varieties, physiological stages and water management strategies to develop models to better predict phenology in rice systems managed with DPW.Funding for the research was provided by AgriFutures Australia and NSW Department of Primary Industries, Australia

Complexity in chill calculations: A case study in cherries

This study seeks to highlight the range of chilling requirement values that can be obtained for one cherry cultivar (‘Lapins’) across different Australian locations by using the same data but different approaches in calculating chilling requirement (CR). We seek to test the assumption that chill thresholds are fixed. The physiological and in-field implications for management are explored. All sites and years showed a steady increase in chill accumulation during the year. Bud burst in relation to accumulated chill portions (CP) was not consistent between sites or years, but all sites exhibited a sharp increase in bud burst after 40 chill portions (CP). Using a 50% bud burst threshold performed statistically better than a 30% bud burst threshold, and observed CR values performed slightly better than modelled CR values. The spatial analyses of safe winter chill for the range of CR determined in this study confirm the variability in values between the 30% and 50% bud burst approach. Imposing a fixed start date for chill accumulation excluded varying amounts of chill compared with using the self-regulating start time and increased the variation of CR values. The implications of using different methods to estimate CR, using projected estimates of chill accumulation under climate change, are provided. This study has e xposed the complexity in not only comparing CR values from previous studies, but the inherent confusion in the communication of such knowledge, especially with the additional consideration of a warming climate

A global evaluation of apple flowering phenology models for climate adaptation

UMR AGAP - équipe AFEF - Architecture et fonctionnement des espèces fruitièresThis study presents the first evaluation of apple flowering phenology models using data from 14 sites across the globe. The dataset includes large variability in growing climates, a prerequisite to investigate phenology models for use in climate change applications. Two flowering stages, early and full, were investigated allowing for unique model evaluation based on both statistical performance and biological assumptions. Two overarching phenology models (Sequential and Chill Overlap) and two sub-models of chill (Dynamic and Triangular) and heat (GDH and Sigmoidal) were tested. Flowering times from the different sites illustrated the differing effects of contrasting winter and spring temperatures. Sites with similar springtime temperatures, but different winter temperatures, had different flowering patterns (warmer winter sites flowered later). Across all analyses, results from the Chill Overlap model were better than those from the Sequential model. Of the Chill Overlap models, those fitted with the Triangular or Dynamic chill model and the GDH heat sub-model performed well statistically and met the assumptions of the model across both flowering stages. The mild sites in the analysis were least well represented, regardless of model selection. This global evaluation demonstrated that flowering modelling in temperate fruit trees would progress through appropriate choices of overarching model, sub-models and parameters