Developing a temperature-dependent simulation model for Sitobion avenae: Impacts of climate change for spring barley in Ireland

The last two decades have facilitated considerable progress in understanding the impacts of climate change on crop sensitivity and production, however very few of these studies have incorporated the activity of herbivorous insect pests into their assessments of potential yield losses. In Ireland, the grain aphid (Sitobion avenae) is the most commonly encountered aphid pest in cereal crops. This pest confers significant decreases in crop yields owing to its mechanical feeding damage, as well as its ability to vector plant viruses. Despite the damage potential, climate-induced changes to aphid populations have not been considered in the context of Irish agricultural production. The work presented here integrates biological data from various studies to inform the development of a simulation model to describe the population dynamics of S. avenae for multiple locations in Ireland in response to climate change. The simulation model (SAV4) describes the compartmentalised life cycle history of S. avenae in response to temperature, incorporating immigration, reproduction, survival, development and morph determination, facilitating the calculation of annual phenological and quantitative aphid metrics. The model was evaluated using observations describing aphid immigration, timing and size of populations in order to ensure that it was fit for purpose. Projected temperature data derived from three Global Climate Models (GCMs) and two green house gas projection pathways, were used to drive the aphid simulation model for eleven locations in Ireland. Reported findings include increases in both aphid abundance and voltinism, as well as advanced phenology across all sites for Ireland. The extent of modelled change was found to differ spatially, with current areas of spring barley cultivation experiencing some of the most significant alterations to S. avenae’s dynamics over time. These findings highlight potential increases in pest risk under climate change in Ireland, emphasising the need for monitoring programmes in conjunction with an Integrated Pest Management (IPM) approach in order to ensure crop resilience in the future. This work constitutes the first explicit incorporation of pest dynamics into climate change projections for the Republic of Ireland, as well as providing a novel pest model for use in pest risk analysis. More broadly, the findings presented here contribute to a growing body of work concerning the mediating effects of climate-induced pest activities in food security

Application of hierarchical clustering to identify high risk pests to Sitka spruce: Ireland as a case study

Invertebrate forest pests and pathogens can cause considerable economic losses and modern patterns of trade have facilitated the international movement of pest species on an unprecedented level. This upsurge in trade has increased the pathways available to high risk species, facilitating entry and potential establishment in nations where they were previously absent. To support policy and pest prioritization, pest risk analyses are conducted to decide ‘if’ and ‘how’ pests should be regulated in order to prevent entry or establishment; however, they cannot be carried out for every potential pest. This paper utilizes a hierarchical clustering (HC) approach to analyse distribution data for pests of Sitka spruce (Picea sitchensis (Bong.) Carr.) in order to identify species of high risk to Ireland, as well as potential source regions of these pests. The presence and absence of almost a 1000 pests across 386 regions globally are clustered based on their similarity of pest assemblages, to provide an objective examination of the highest risk pests to Irish forestry. Regional clusters were produced for each taxon analysed including the Coleoptera, Diptera, Hemiptera, Hymenoptera, Nematoda, Lepidoptera and the Fungi. The results produced by the HC analysis were interpreted with regard to biological realism and climate. Biologically meaningful clusters were produced for each of the groups, except for the Diptera and Nematoda, and each of the species analysed were ranked within their group by a quantitative risk index specific to the island of Ireland. The impact of uncertainty in the distribution data is also examined, in order to assess its influence over the final groupings produced. The outputs from this analysis suggest that the highest risk pests for Ireland’s Sitka spruce plantations will originate from within Europe. Ultimately, Ireland could benefit from seeking regulation for some of the higher ranking pests identified in this analysis. This analysis provides the first of its type for Sitka spruce, as well as its application in Ireland. It also serves to highlight the potential utility of HC as a ‘first approach’ to assessing the risk posed by alien species to hitherto novel regions

Irish droughts in newspaper archives: rediscovering forgotten hazards?

Irish newspaper collections are a rich source of information on historical droughts. Following a search of 250 years of such archives, this paper brings to light four newspaper articles describing three drought events that convey the cultural impacts and unusual societal responses to nineteenth century drought in Ireland. Amongst the archives we find two poems from 1806 and 1893, a call to pray for rain in 1887, and a suggestion for weather modification in 1893. These records demonstrate that, contrary to recent experience, Ireland is surprisingly prone to drought

Azithromycin Failure in Mycoplasma genitalium Urethritis

We report significant failure rates (28%, 95% confidence interval 15%–45%) after administering 1 g azithromycin to men with Mycoplasma genitalium–positive nongonococcal urethritis. In vitro evidence supported reduced susceptibility of M. genitalium to macrolides. Moxifloxacin administration resulted in rapid symptom resolution and eradication of infection in all cases. These findings have implications for management of urethritis

phenModel: A temperature-dependent phenology/voltinism model for a herbivorous insect incorporating facultative diapause and budburst

A comprehensive phenology/voltinism model was developed for Phratora vulgatissima, an important pest of bioenergy crops. The model, phenModel, was developed based on development times of different life cycle stages (eggs, larvae, pupae, pre-oviposition, oviposition, sexual maturation) obtained from constant temperature laboratory experiments. As part of this study, a number of linear and non-linear models which describe the temperature-dependent development rate (inverse of development time) for each of the different life cycle stages were fitted. Based on the criteria of model parsimony and model fit, the non-linear Lactin-2 model was chosen as the optimum model to describe temperature-driven development in P. vulgatissima. To account for the variation in development times between individuals, an important but often ignored aspect in phenology models, a number of stochastic models (2- and 3- parameter Weibull and logistic models) were evaluated, based on the assumption that normalised development times conform to a similar shaped ('same shape') distribution. Novel aspects of the phenology model include the incorporation of a biologically relevant biofix, based on a budburst model for Salix viminalis, and a photoperiod threshold to induce facultative diapause. The model, which is written in R for accessibility, requires inputs of daily minimum and maximum temperature and site latitude and produces outputs describing the timing of completion of developmental stages for specified proportions of the population. It was evaluated against available field data and found to largely reproduce the observations providing a measure of its potential utility. A key component of the model allows for a sensitivity analysis of the model parameters. The model is structured so that it can easily be adapted for other leaf-feeding beetles which display a facultative reproductive diapause cued by photoperiod, and where the onset of oviposition is dependent on budburst, assuming relevant life cycle stage parameters are available

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society