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Abstract Exotic Eucalyptus spp. are the most planted trees species in forest cultivation in Brazil. The red gum lerp psyllid Glycaspis brimblecombei Moore (Hemiptera: Aphalaridae), an invasive exotic pest, reduces the development and wood production of Eucalyptus spp. plantations. The search for natural enemies targeting the egg life stage is beneficial for the integrated pest management of G. brimblecombei. The objective of this work was to test a range of Coccinellidae species that potentially prey on G. brimblecombei eggs. Cycloneda sanguinea Linnaeus, Eriopsis conexa Germar, Harmonia axyridis Pallas, Hippodamia convergens Guerin-Meneville, Jaguarita conjugata Mulsant and Olla v-nigrum Mulsant (Coleoptera: Coccinellidae), reported to be associated with G. brimblecombei infestations, were evaluated. Newly emerged adults of O. v-nigrum and J. conjugata preyed on G. brimblecombei eggs, unlike C. sanguinea, E. conexa, H. axyridis and H. convergens. Predation of eggs by O. v-nigrum was highest, with a mean of 1,016 in 24 hours. These results, evaluating a range of Coccinellidae as predators of G. brimblecombei eggs, confirm the high predation rate of G. brimblecombei eggs by O. v-nigrum and that this ladybug may be important in the integrated management of this pest. Resumo O gênero Eucalyptus ocupa a maior área plantada no setor florestal brasileiro com alta produtividade. O psilídeo de concha Glycaspis brimblecombei Moore (Hemiptera: Aphalaridae), praga exótica, reduz o desenvolvimento e produção de madeira nesses plantios. A busca de inimigos naturais para a fase de ovos de G. brimblecombei é essencial para complementar o manejo integrado e quebrar o ciclo da praga. O objetivo deste trabalho foi avaliar a predação de ovos de G. brimblecombei por seis espécies de Coccinelidae. A predação de ovos de G. brimblecombei por Cycloneda sanguinea Linnaeus, Eriopsis conexa Germar, Harmonia axyridis Pallas, Hippodamia convergens Guerin-Meneville, Jaguarita conjugata Mulsant e Olla v-nigrum Mulsant (Coleoptera: Coccinellidae), comumente associadas com infestações por essa praga, foi avaliada. Adultos recém emergidos de O. v-nigrum e J. conjugata predaram ovos de G. brimblecombei, mas isto não foi observado para C. sanguinea, E. conexa, H. axyridis e H. convergens. A predação de ovos, dessa praga, por O. v-nigrum foi maior em todas as avaliações, com 1.016 após 24 horas. Estes resultados são pioneiros na utilização de coccinelídeos no manejo de pragas do eucalipto. A maior predação de ovos de G. brimblecombei por O. v-nigrum indica que este predador pode ser importante para complementar o manejo integrado dessa praga.

Abstract The Brazilian forestry sector stands out for its technology, forestry management practices, social and environmental responsibility and, mainly, for its high productivity and exotic pests can reduce it. The red gum lerp psyllid Glycaspis brimblecombei (Moore, 1964) (Hemiptera: Aphalaridae) is an important pest in Eucalyptus plantations. The parasitoid Psyllaephagus bliteus (Riek, 1962) (Hymenoptera: Encyrtidae), predatory bugs and entomopathogenic fungi such as Beauveria bassiana and Metarhizium anisopliae are the natural enemies and used in the biological control of the red gum lerp psyllid. The use of entomopathogenic fungi against exotic pests is increasing in the forestry sector and the prospecting and identification of fungus isolates is important for integrated pest management. The objective of this work was the isolation and molecular identification of Cordyceps spp. And to evaluate the pathogenicity of isolates, obtained from Bemisia tabaci (Gennadius, 1889) (Hemiptera: Aleyrodidae) adults, against to the red gum lerp psyllid G. brimblecombei. The fungi were isolated from B. tabaci adults found in soybean and tomato crops and molecularly identified. The conidia obtained were suspended in solution with Tween 80 (0.1%) at a concentration of 1.0 × 108 conidia/mL and sprayed on ten G. brimblecombei nymphs per Eucalyptus leaf cut and placed on a hydroretentive gel inside per Petri dishes as a replication. The number of dead insects was quantified, daily, for seven days, and transferred to humid chambers. Cordyceps javanica (LCBPF 11) and C. fumosorosea (LCBPF 12 and LCBPF 63) were identified with a molecular analysis and all isolates were pathogenic to the insects and indicates that they could be used to manage G. brimblecombei and adds to reports that, normally, fungi cause greater mortality on insects of the same order as that from which they were isolated. Resumo O setor florestal brasileiro se destaca pela tecnologia, práticas de manejo florestal, responsabilidade social e ambiental e, principalmente, alta produtividade, mas pragas exóticas podem reduzir isto. O parasitoide Psyllaephagus bliteus (Riek, 1962) (Hymenoptera: Encyrtidae), percevejos predadores e fungos entomopatogênicos como Beauveria bassiana e Metarhizium anisopliae são inimigos naturais usados no controle biológico do psilídeo-de-concha do eucalipto Glycaspis brimblecombei (Moore, 1964) (Hemiptera: Aphalaridae), praga em plantios de eucalipto. A utilização de fungos entomopatogênicos contra pragas exóticas vem aumentando no setor florestal e a prospecção e identificação de isolados fúngicos é importante para o manejo integrado de pragas. O objetivo deste estudo foi o isolamento e identificação molecular de Cordyceps spp. e avaliar a patogenicidade dos isolados de Cordyceps javanica (LCBPF 11) e Cordyceps fumosorosea (LCBPF 12 e LCBPF 63), obtidos de adultos de Bemisia tabaci Gennadius (Hemiptera: Aleyrodidae), ao psilídeo-de-concha G. brimblecombei. Os fungos foram isolados de adultos de B. tabaci encontrados em culturas de soja e tomate e identificados molecularmente. Os conídios foram suspensos em solução com Tween 80 (0,1%) na concentração de 1,0 x 108 conídios/mL e pulverizados sobre dez ninfas de G. brimblecombei por folha de Eucalyptus cortada e colocada sobre gel hidrorretentor no interior de placas de Petri por repetição. O número de insetos mortos foi quantificado, diariamente, por sete dias e transferidos para câmaras úmidas. Cordyceps javanica (LCBPF 11) e C. fumosorosea (LCBPF 12 e LCBPF 63) foram identificados por análise molecular e todos os isolados foram patogênicos para os insetos. Isto indica serem importantes para o manejo de G. brimblecombei e confirma relatos de que, normalmente, fungos causam maiores mortalidades em insetos da mesma ordem daquela da qual foram isolados.

The eucalyptus snout beetle (ESB), Gonipterus platensis , is endemic to Australia but has become a major invasive, destructive pest of Brazilian eucalyptus plantations. Efforts to develop insecticides based on entomopathogenic fungi against ESB are limited by the lack of known virulent strains. We therefore explored the virulence of indigenous Brazilian strains of major entomopathogenic fungi— Beauveria spp. and Metarhizium anisopliae —against ESB adults. We found widely varying virulence and later capacities for conidial production on infected adult cadavers. Two strains stood out, B. bassiana IBCB-240 and M. anisopliae IBCB-364, as especially lethal for ESB adults under laboratory conditions, sporulated abundantly on infected insects, and also outperformed comparable strains used in commercial mycoinsecticides. Notably, B. bassiana IBCB-240 exhibited lower LT 50 values at low inoculum levels (≤ 10 7 conidia mL −1 ) and smaller LC 50 values than M. anisopliae IBCB-364. Taken together, this study emphasizes natural variation in virulence among indigenous Beauveria and Metarhizium strains against ESB adults and identifies fungal strains with superior lethality to existing commercialized strains for managing this eucalyptus pest in Brazil.

Severe droughts have the potential to reduce forest productivity and trigger tree mortality. Most trees face several drought events during their life and therefore resilience to dry conditions may be crucial to long-term survival. We assessed how growth resilience to severe droughts, including its components resistance and recovery, is related to the ability to survive future droughts by using a tree-ring database of surviving and now-dead trees from 118 sites (22 species, >3,500 trees). We found that, across the variety of regions and species sampled, trees that died during water shortages were less resilient to previous non-lethal droughts, relative to coexisting surviving trees of the same species. In angiosperms, drought-related mortality risk is associated with lower resistance (low capacity to reduce impact of the initial drought), while it is related to reduced recovery (low capacity to attain pre-drought growth rates) in gymnosperms. The different resilience strategies in these two taxonomic groups open new avenues to improve our understanding and prediction of drought-induced mortality. Resilience to drought is crucial for tree survival under climate change. Here, DeSoto et al. show that trees that died during drought were less resilient to previous dry events compared to surviving conspecifics, but the resilience strategies differ between angiosperms and gymnosperms.

Aim Invasive alien species are a growing problem worldwide due to their ecological, economic and human health impacts. The “killer shrimp” Dikerogammarus villosus is a notorious invasive alien amphipod from the Ponto‐Caspian region that has invaded many fresh and brackish waters across Europe. Understandings of large‐scale population dynamics of highly impactful invaders such as D. villosus are lacking, inhibiting predictions of impact and efficient timing of management strategies. Hence, our aim was to assess trends and dynamics of D. villosus as well as its impacts in freshwater rivers and streams. Location Europe. Methods We analysed 96 European time series between 1994 and 2019 and identified trends in the relative abundance (i.e. dominance %) of D. villosus in invaded time series, as well as a set of site‐specific characteristics to identify drivers and determinants of population changes and invasion dynamics using meta‐regression modelling. We also looked at the spread over space and time to estimate the invasion speed (km/year) of D. villosus in Europe. We investigated the impact of D. villosus abundance on recipient community metrics (i.e. abundance, taxa richness, temporal turnover, Shannon diversity and Pielou evenness) using generalized linear models. Results Population trends varied across the time series. Nevertheless, community dominance of D. villosus increased over time across all time series. The frequency of occurrences (used as a proxy for invader spread) was well described by a Pareto distribution, whereby we estimated a lag phase (i.e. the time between introduction and spatial expansion) of approximately 28 years, followed by a gradual increase before new occurrences declined rapidly in the long term. D. villosus population change was associated with decreased taxa richness, community turnover and Shannon diversity. Main Conclusion Our results show that D. villosus is well‐established in European waters and its abundance significantly alters ecological communities. However, the multidecadal lag phase prior to observed spatial expansion suggests that initial introductions by D. villosus are cryptic, thus signalling the need for more effective early detection methods.

There are no effective therapies for achondroplasia. An open-label study suggested that vosoritide administration might increase growth velocity in children with achondroplasia. This phase 3 trial was designed to further assess these preliminary findings. This randomised, double-blind, phase 3, placebo-controlled, multicentre trial compared once-daily subcutaneous administration of vosoritide with placebo in children with achondroplasia. The trial was done in hospitals at 24 sites in seven countries (Australia, Germany, Japan, Spain, Turkey, the USA, and the UK). Eligible patients had a clinical diagnosis of achondroplasia, were ambulatory, had participated for 6 months in a baseline growth study and were aged 5 to less than 18 years at enrolment. Randomisation was done by means of a voice or web-response system, stratified according to sex and Tanner stage. Participants, investigators, and trial sponsor were masked to group assignment. Participants received either vosoritide 15·0 μg/kg or placebo, as allocated, for the duration of the 52-week treatment period administered by daily subcutaneous injections in their homes by trained caregivers. The primary endpoint was change from baseline in mean annualised growth velocity at 52 weeks in treated patients as compared with controls. All randomly assigned patients were included in the efficacy analyses (n=121). All patients who received one dose of vosoritide or placebo (n=121) were included in the safety analyses. The trial is complete and is registered, with EudraCT, number, 2015-003836-11. All participants were recruited from Dec 12, 2016, to Nov 7, 2018, with 60 assigned to receive vosoritide and 61 to receive placebo. Of 124 patients screened for eligibility, 121 patients were randomly assigned, and 119 patients completed the 52-week trial. The adjusted mean difference in annualised growth velocity between patients in the vosoritide group and placebo group was 1·57 cm/year in favour of vosoritide (95% CI [1·22–1·93]; two-sided p<0·0001). A total of 119 patients had at least one adverse event; vosoritide group, 59 (98%), and placebo group, 60 (98%). None of the serious adverse events were considered to be treatment related and no deaths occurred. Vosoritide is an effective treatment to increase growth in children with achondroplasia. It is not known whether final adult height will be increased, or what the harms of long-term therapy might be. BioMarin Pharmaceutical.

BackgroundChronic obstructive pulmonary disease (COPD) is increasingly considered a heterogeneous condition. It was hypothesised that COPD, as currently defined, includes different clinically relevant subtypes.MethodsTo identify and validate COPD subtypes, 342 subjects hospitalised for the first time because of a COPD exacerbation were recruited. Three months after discharge, when clinically stable, symptoms and quality of life, lung function, exercise capacity, nutritional status, biomarkers of systemic and bronchial inflammation, sputum microbiology, CT of the thorax and echocardiography were assessed. COPD groups were identified by partitioning cluster analysis and validated prospectively against cause-specific hospitalisations and all-cause mortality during a 4 year follow-up.ResultsThree COPD groups were identified: group 1 (n=126, 67 years) was characterised by severe airflow limitation (postbronchodilator forced expiratory volume in 1 s (FEV1) 38% predicted) and worse performance in most of the respiratory domains of the disease; group 2 (n=125, 69 years) showed milder airflow limitation (FEV1 63% predicted); and group 3 (n=91, 67 years) combined a similarly milder airflow limitation (FEV1 58% predicted) with a high proportion of obesity, cardiovascular disorders, diabetes and systemic inflammation. During follow-up, group 1 had more frequent hospitalisations due to COPD (HR 3.28, p<0.001) and higher all-cause mortality (HR 2.36, p=0.018) than the other two groups, whereas group 3 had more admissions due to cardiovascular disease (HR 2.87, p=0.014).ConclusionsIn patients with COPD recruited at their first hospitalisation, three different COPD subtypes were identified and prospectively validated: ‘severe respiratory COPD’, ‘moderate respiratory COPD’, and ‘systemic COPD’.

In children with symptoms suggestive of inflammatory bowel disease (IBD) who present in primary care, the optimal test strategy for identifying those who require specialist care is unclear. We evaluated the following three test strategies to determine which was optimal for referring children with suspected IBD to specialist care: 1) alarm symptoms alone, 2) alarm symptoms plus c-reactive protein, and 3) alarm symptoms plus fecal calprotectin. A prospective cohort study was conducted, including children with chronic gastrointestinal symptoms referred to pediatric gastroenterology. Outcome was defined as IBD confirmed by endoscopy, or IBD ruled out by either endoscopy or unremarkable clinical 12 month follow-up with no indication for endoscopy. Test strategy probabilities were generated by logistic regression analyses and compared by area under the receiver operating characteristic curves (AUC) and decision curves. We included 90 children, of whom 17 (19%) had IBD (n = 65 from primary care physicians, n = 25 from general pediatricians). Adding fecal calprotectin to alarm symptoms increased the AUC significantly from 0.80 (0.67-0.92) to 0.97 (0.93-1.00), but adding c-reactive protein to alarm symptoms did not increase the AUC significantly (p > 0.05). Decision curves confirmed these patterns, showing that alarm symptoms combined with fecal calprotectin produced the diagnostic test strategy with the highest net benefit at reasonable threshold probabilities. In primary care, when children are identified as being at high risk for IBD, adding fecal calprotectin testing to alarm symptoms was the optimal strategy for improving risk stratification.

Clinical decompensation of cirrhosis is associated with poor prognosis. Clinically significant portal hypertension (CSPH), defined by a hepatic venous pressure gradient (HVPG) ≥10 mm Hg, is the strongest predictor of decompensation. This study aimed at assessing whether lowering HVPG with β blockers could decrease the risk of decompensation or death in compensated cirrhosis with CSPH. This study on β blockers to prevent decompensation of cirrhosis with portal hypertension (PREDESCI) was an investigator-initiated, double-blind, randomised controlled trial done in eight hospitals in Spain. We enrolled patients with compensated cirrhosis and CSPH without high-risk varices. All participants had HVPG measurements with assessment of acute HVPG-response to intravenous propranolol. Responders (HVPG-decrease ≥10%) were randomly assigned to propranolol (up to 160 mg twice a day) versus placebo and non-responders to carvedilol (≤25 mg/day) versus placebo. Doses were individually determined during an open-label titration period after which randomisation was done with 1:1 allocation by a centralised web-based system. The primary endpoint was incidence of cirrhosis decompensation (defined as development of ascites, bleeding, or overt encephalopathy) or death. Since death in compensated cirrhosis is usually unrelated to the liver, an intention-to-treat analysis considering deaths unrelated to the liver as competing events was done. This study is registered with ClinicalTrials.gov, number NCT01059396. The trial is now completed. Between Jan 18, 2010, and July 31, 2013, 631 patients were evaluated and 201 were randomly assigned. 101 patients received placebo and 100 received active treatment (67 propranolol and 33 carvedilol). The primary endpoint occurred in 16 (16%) of 100 patients in the β blockers group versus 27 (27%) of 101 in the placebo group (hazard ratio [HR] 0·51, 95% CI 0·26–0·97, p=0·041). The difference was due to a reduced incidence of ascites (HR 0·42, 95% CI 0·19–0·92, p=0·03). The overall incidence of adverse events was similar in both groups. Six patients (four in the β blockers group) had severe adverse events. Long-term treatment with β blockers could increase decompensation-free survival in patients with compensated cirrhosis and CSPH, mainly by reducing the incidence of ascites. Spanish Ministries of Health and Economy.

Purpose Achondroplasia is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene that lead to impaired endochondral ossification. Vosoritide, an analog of C-type natriuretic peptide, stimulates endochondral bone growth and is in development for the treatment of achondroplasia. This phase 3 extension study was conducted to document the efficacy and safety of continuous, daily vosoritide treatment in children with achondroplasia, and the two-year results are reported. Methods After completing at least six months of a baseline observational growth study, and 52 weeks in a double-blind, placebo-controlled study, participants were eligible to continue treatment in an open-label extension study, where all participants received vosoritide at a dose of 15.0 μg/kg/day. Results In children randomized to vosoritide, annualized growth velocity increased from 4.26 cm/year at baseline to 5.39 cm/year at 52 weeks and 5.52 cm/year at week 104. In children who crossed over from placebo to vosoritide in the extension study, annualized growth velocity increased from 3.81 cm/year at week 52 to 5.43 cm/year at week 104. No new adverse effects of vosoritide were detected. Conclusion Vosoritide treatment has safe and persistent growth-promoting effects in children with achondroplasia treated daily for two years.