Since the discovery of America, many domesticated animals and plants have been traded between the Old and the new World. They were often accompanied by damaging pests. Phylloxera invaded Europe in ...1863, and the gypsy moth became established in the USA in 1869. The most active pathways for forest pests are currently the trade in planting stock and wood packaging material. Under comparable circumstances (commercial flows etc.), the biological traits that favour an invader’s success are to some extent predictive. Scolytine beetles provide an excellent example. Analysis of establishment successes by alien species uncovers at least three non-exclusive features of an « efficient invader »: sib-mating, polyphagia and association with a virulent pathogen. These features allow the successfully establishment and spread of small inoculums; they give a low «Allee threshold » to these species.
Ravageurs animaux et maladies des plantes parcourent le monde. Le phylloxéra, venu d’Amérique, envahit l’Europe dès 1863 ; le bombyx disparate, eurasiatique, se répand aux États-Unis d’Amérique dès 1869. Plus récemment, le nématode du pin est découvert au Portugal en 1999 et Xylella fastidiosa en Italie en 2013. Les filières d’introduction les plus actives actuellement sont le commerce des plantes vivantes et le bois d’emballage. À contexte (flux commerciaux, etc.) égal, les caractéristiques biologiques qui favorisent le succès d’un envahisseur permettent certaines prédictions. Les scolytes sont exemplaires à cet égard. L’analyse des succès d’installation d’espèces exotiques nous indique au moins trois caractéristiques non exclusives d’un « envahisseur efficace » : mode de reproduction endogame, polyphagie et association avec un pathogène. Ces caractéristiques favorisent l’installation et la propagation de petits inoculums ; elles confèrent aux espèces qui en jouissent un « seuil Allee » bas.
High-density lipoproteins (HDLs) have several potentially protective vascular effects. Most clinical studies of therapies targeting HDL have failed to show benefits vs. placebo.
To investigate the ...effects of an HDL-mimetic agent on atherosclerosis by intravascular ultrasonography (IVUS) and quantitative coronary angiography (QCA).
A prospective, double-blinded, randomized trial was conducted at 51 centres in the USA, the Netherlands, Canada, and France. Intravascular ultrasonography and QCA were performed to assess coronary atherosclerosis at baseline and 3 (2-5) weeks after the last study infusion.
Five hundred and seven patients were randomized; 417 and 461 had paired IVUS and QCA measurements, respectively.
Patients were randomized to receive 6 weekly infusions of placebo, 3 mg/kg, 6 mg/kg, or 12 mg/kg CER-001.
The primary efficacy parameter was the nominal change in the total atheroma volume. Nominal changes in per cent atheroma volume on IVUS and coronary scores on QCA were also pre-specified endpoints.
The nominal change in the total atheroma volume (adjusted means) was -2.71, -3.13, -1.50, and -3.05 mm(3) with placebo, CER-001 3 mg/kg, 6 mg/kg, and 12 mg/kg, respectively (primary analysis of 12 mg/kg vs. placebo: P = 0.81). There was also no difference among groups for the nominal change in per cent atheroma volume (0.02, -0.02, 0.01, and 0.19%; nominal P = 0.53 for 12 mg/kg vs. placebo). Change in the coronary artery score was -0.022, -0.036, -0.022, and -0.015 mm (nominal P = 0.25, 0.99, 0.55), and change in the cumulative coronary stenosis score was -0.51, 2.65, 0.71, and -0.77% (compared with placebo, nominal P = 0.85 for 12 mg/kg and nominal P = 0.01 for 3 mg/kg). The number of patients with major cardiovascular events was 10 (8.3%), 16 (13.3%), 17 (13.7%), and 12 (9.8%) in the four groups.
CER-001 infusions did not reduce coronary atherosclerosis on IVUS and QCA when compared with placebo. Whether CER-001 administered in other regimens or to other populations could favourably affect atherosclerosis must await further study. Name of the trial registry: Clinicaltrials.gov; Registry's URL: http://clinicaltrials.gov/ct2/show/NCT01201837?term=cer-001&rank=2;
NCT01201837.
Examples of totally specific predators are rare, and the mechanisms underlying this specificity are often poorly understood. In Eurasia, the Monotomid beetle
Rhizophagus grandis
is found only in the ...galleries of its prey, the bark beetle
Dendroctonus micans
. The specificity of
R. grandis
relies on kairomones which female predators use to adjust their oviposition to the number of prey larvae available in a gallery. Yet these chemical signals are still largely unknown. The North American
D. punctatus
and
D. valens
, which are not sympatric with
R. grandis
but have a similar ecology as
D. micans
, could also elicit predator oviposition, which would suggest that specificity in this predator-prey system is constrained by geography. In order to further identify these determinants of specificity, we used artificial oviposition boxes to compare the oviposition level of
R. grandis
in the presence of larvae of each of the three prey species
.
We jointly used sequential dynamic headspace extractions and gas chromatography coupled with mass spectrometry to investigate oviposition stimuli associated with each prey species and potential oviposition inhibitors emitted by the predator. We further assessed potential stimuli with the analysis of emissions from
D. micans
larvae reared alone. Overall, we identified and quantified 67 compounds, mostly terpenes. Several robust candidate stimulants or inhibitors of
R. grandis
’ oviposition were identified. The three prey species elicited similar oviposition levels in
R. grandis
, which suggests that this predator could form new associations outside of its native range.
Machine Learning (ML) has been proposed for tissue fate prediction after acute ischemic stroke (AIS), with the aim to help treatment decision and patient management. We compared three different ML ...models to the clinical method based on diffusion-perfusion thresholding for the voxel-based prediction of final infarct, using a large MRI dataset obtained in a cohort of AIS patients prior to recanalization treatment. Baseline MRI (MRI0), including diffusion-weighted sequence (DWI) and Tmax maps from perfusion-weighted sequence, and 24-hr follow-up MRI (MRI24h) were retrospectively collected in consecutive 394 patients AIS patients (median age = 70 years; final infarct volume = 28mL). Manually segmented DWI24h lesion was considered the final infarct. Gradient Boosting, Random Forests and U-Net were trained using DWI, apparent diffusion coefficient (ADC) and Tmax maps on MRI0 as inputs to predict final infarct. Tissue outcome predictions were compared to final infarct using Dice score. Gradient Boosting had significantly better predictive performance (median IQR Dice Score as for median age, maybe you can replace the comma with an equal sign for consistency 0.53 0.29–0.68) than U-Net (0.48 0.18–0.68), Random Forests (0.51 0.27–0.66), and clinical thresholding method (0.45 0.25–0.62) (P < 0.001). In this benchmark of ML models for tissue outcome prediction in AIS, Gradient Boosting outperformed other ML models and clinical thresholding method and is thus promising for future decision-making.
The performance of three species of predatory ladybirds was compared in a flight mill and the effect of diet on their flight parameters was tested. The invasive ladybird Harmonia axyridis Pallas ...(Coleoptera: Coccinellidae) outperformed Cryptolaemus montrouzieri Mulsant (Coleoptera: Coccinellidae) and Adalia bipunctata (L.) (Coleoptera: Coccinellidae) in terms of flight distance, duration and velocity. Harmonia axyridis flew at least two times further, needed three times less breaks and flew two times faster than C. montrouzieri and A. bipunctata fed the same diet. Ladybirds reared on eggs of Ephestia kuehniella (Zeller) (Lepidoptera: Pyralidae) performed better than their counterparts reared on natural prey (aphids for H. axyridis and A. bipunctata, mealybugs for C. montrouzieri). The findings of this study indicate that comparative flight studies can be useful to identify candidate biocontrol agents with pronounced dispersal abilities and thus can yield significant evidence to be used in an environmental risk assessment. However, it also demonstrates that variability related to mass rearing conditions should not be ignored when standardizing a risk assessment procedure for candidate biocontrol agents.
Bark beetles (Curculionidae: Scolytinae) are one of the most species-rich herbivorous insect groups with many shifts in ecology and host-plant use, which may be mediated by their bacterial and fungal ...symbionts. While symbionts are well studied in economically important, tree-killing species, little is known about parasitic species whose broods develop in living trees. Here, using culture-dependent and independent methods, we provide a comprehensive overview of the associated bacteria, yeasts and filamentous fungi of the parasitic Dendroctonus micans, D. punctatus and D. valens, and compare them to those of other tree-inhabiting insects. Despite inhabiting different geographical regions and/or host trees, the three species showed similar microbial communities. Enterobacteria were the most prevalent bacteria, in particular Rahnella, Pantoea and Ewingella, in addition to Streptomyces. Likewise, the yeasts Candida/Cyberlindnera were the most prominent fungi. All these microorganisms are widespread among tree-inhabiting insects with various ecologies, but their high prevalence overall might indicate a beneficial role such as detoxification of tree defenses, diet supplementation or protection against pathogens. As such, our results enable comparisons of symbiont communities of parasitic bark beetles with those of other beetles, and will contribute to our understanding of how microbial symbioses facilitate dietary shifts in insects.
The parasitic bark beetles Dendroctonus micans, D. punctatus and D. valens house bacterial and fungal communities commonly associated with tree-inhabiting insects, and likely benefit from these symbionts in various ways.
Graphical Abstract Figure.
The parasitic bark beetles Dendroctonus micans, D. punctatus and D. valens house bacterial and fungal communities commonly associated with tree-inhabiting insects, and likely benefit from these symbionts in various ways.
CONTEXT High-density lipoprotein (HDL) cholesterol is an inverse predictor of coronary atherosclerotic disease. Preliminary data have suggested that HDL infusions can induce atherosclerosis ...regression. OBJECTIVE To investigate the effects of reconstituted HDL on plaque burden as assessed by intravascular ultrasound (IVUS). DESIGN AND SETTING A randomized placebo-controlled trial was conducted at 17 centers in Canada. Intravascular ultrasound was performed to assess coronary atheroma at baseline and 2 to 3 weeks after the last study infusion. PATIENTS Between July 2005 and October 2006, 183 patients had a baseline IVUS examination and of those, 145 had evaluable serial IVUS examinations after 6 weeks. INTERVENTION Sixty patients were randomly assigned to receive 4 weekly infusions of placebo (saline), 111 to receive 40 mg/kg of reconstituted HDL (CSL-111); and 12 to receive 80 mg/kg of CSL-111. MAIN OUTCOME MEASURES The primary efficacy parameter was the percentage change in atheroma volume. Nominal changes in plaque volume and plaque characterization index on IVUS and coronary score on quantitative coronary angiography were also prespecified end points. RESULTS The higher-dosage CSL-111 treatment group was discontinued early because of liver function test abnormalities. The percentage change in atheroma volume was −3.4% with CSL-111 and −1.6% for placebo (P = .48 between groups, P<.001 vs baseline for CSL-111). The nominal change in plaque volume was −5.3 mm3 with CSL-111 and −2.3 mm3 with placebo (P = .39 between groups, P<.001 vs baseline for CSL-111). The mean changes in plaque characterization index on IVUS (−0.0097 for CSL-111 and 0.0128 with placebo) and mean changes in coronary score (−0.039 mm for CSL-111 and −0.071 mm with placebo) on quantitative coronary angiography were significantly different between groups (P = .01 and P =.03, respectively). Administration of CSL-111 40 mg/kg was associated with mild, self-limiting transaminase elevation but was clinically well tolerated. CONCLUSIONS Short-term infusions of reconstituted HDL resulted in no significant reductions in percentage change in atheroma volume or nominal change in plaque volume compared with placebo but did result in statistically significant improvement in the plaque characterization index and coronary score on quantitative coronary angiography. Elevation of HDL remains a valid target in vascular disease and further studies of HDL infusions, including trials with clinical end points, appear warranted. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00225719Published online: March 26, 2007 (doi:10.1001/jama.297.15.jpc70004).
Females present a higher risk of adverse drug reactions. Sex‐related differences in drug concentrations may contribute to these observations but they remain understudied given the underrepresentation ...of females in clinical trials. The aim of this study was to investigate whether anthropometric and socioeconomic factors and comorbidities could explain sex‐related differences in concentrations and dosing for metoprolol and oxypurinol, the active metabolite of allopurinol. We conducted an analysis of two cross‐sectional studies. Participants were self‐described “White” adults taking metoprolol or allopurinol selected from the Montreal Heart Institute Hospital Cohort. A total of 1007 participants were included in the metoprolol subpopulation and 459 participants in the allopurinol subpopulation; 73% and 86% of the participants from the metoprolol and allopurinol subpopulations were males, respectively. Females presented higher age‐ and dose‐adjusted concentrations of both metoprolol and oxypurinol (both p < 0.03). Accordingly, females presented higher unadjusted and age‐adjusted concentration:dose ratio of both metoprolol and allopurinol/oxypurinol compared to males (all p < 3.0 × 10−4). Sex remained an independent predictor of metoprolol concentrations (p < 0.01), but not of oxypurinol concentrations, after adjusting for other predictors. In addition to sex, age, daily dose, use of moderate to strong CYP2D6 inhibitors, weight, and CYP2D6 genotype‐inferred phenotype were associated with concentrations of metoprolol (all p < 0.01). Daily dose, weight, estimated glomerular filtration rate (eGFR), and employment status were associated with oxypurinol concentrations (all p < 0.01). Females present higher dose‐adjusted concentrations of metoprolol and oxypurinol than males. This suggests the need for sex‐specific dosing requirements for these drugs, although this hypothesis should be validated in prospective studies.
Abstract
Aims
In a retrospective analysis of dal-Outcomes, the effect of dalcetrapib on cardiovascular events was influenced by an adenylate cyclase type 9 (ADCY9) gene polymorphism. The dal-GenE ...study was conducted to test this pharmacogenetic hypothesis.
Methods and results
dal-GenE was a double-blind trial in patients with an acute coronary syndrome within 1–3 months and the AA genotype at variant rs1967309 in the ADCY9 gene. A total of 6147 patients were randomly assigned to receive dalcetrapib 600 mg or placebo daily. The primary endpoint was the time from randomization to first occurrence of cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction, or non-fatal stroke. After a median follow-up of 39.9 months, the primary endpoint occurred in 292 (9.5%) of 3071 patients in the dalcetrapib group and 327 (10.6%) of 3076 patients in the placebo group hazard ratio 0.88; 95% confidence interval (CI) 0.75–1.03; P = 0.12. The hazard ratios for the components of the primary endpoint were 0.79 (95% CI 0.65–0.96) for myocardial infarction, 0.92 (95% CI 0.64–1.33) for stroke, 1.21 (95% CI 0.91–1.60) for death from cardiovascular causes, and 2.33 (95% CI 0.60–9.02) for resuscitated cardiac arrest. In a pre-specified on-treatment sensitivity analysis, the primary endpoint event rate was 7.8% (236/3015) in the dalcetrapib group and 9.3% (282/3031) in the placebo group (hazard ratio 0.83; 95% CI 0.70–0.98).
Conclusion
Dalcetrapib did not significantly reduce the risk of occurrence of the primary endpoint of ischaemic cardiovascular events at end of study. A new trial would be needed to test the pharmacogenetic hypothesis that dalcetrapib improves the prognosis of patients with the AA genotype.
Clinical Trial Registration
Trial registration dal-GenE ClinicalTrials.gov Identifier: NCT02525939
The EFSA Panel on Plant Health performed a pest categorisation of Dendrolimus superans Butler (Lepidoptera: Lasiocampidae), the larch caterpillar, for the EU territory. D. superans is a major pest of ...conifer forests in Japan, northeast China and non‐European Russia. However, reports of damage are to conifer species not grown in EU forestry. Larix gmelinii and Pinus pumila are regarded as major hosts. Eggs are laid on host needles and developing larvae feed on host foliage. Larvae overwinter in the soil. In its native range, D. superans usually takes one or two years to develop. In principle, host plants for planting and plant products, such as cut branches and wood with bark, could provide pathways into the EU. However, prohibitions on the import of Abies, Cedrus, Larix, Picea, Pinus and Tsuga from areas where D. superans occurs closes such pathways. Nevertheless, a derogation for specific dwarfed Pinus plants from Japan exists. Climates similar to those in some of its existing range occur in the EU. Norway spruce (Picea abies) is a known host in Japan although reports of any impact are lacking. Experiments on the related species D. sibiricus indicated that larvae were able to develop on forestry conifer species occurring in the EU, but which are found outside the native range of D. sibiricus. Were D. superans to be introduced into the EU, impacts on P. abies are possible and it is conceivable that D. superans could expand its host range, as seems possible with D. sibiricus. However, this remains uncertain. Other hosts are grown in the EU as ornamentals or amenity trees. D. superans satisfies all the criteria that are within the remit of EFSA to assess for it to be regarded as a potential Union quarantine pest. Some uncertainty exists over the magnitude of potential environmental and economic impacts.
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