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Contains fulltext : 252201.pdf (Publisher’s version ) (Open Access), Background In the GLOBAL LEADERS trial, ticagrelor monotherapy beyond 1 month compared with standard antiplatelet regimens after coronary stent implantation did not improve outcomes at intention-to-treat analysis. Considerable differences in treatment adherence between the experimental and control groups may have affected the intention-to-treat results. In this reanalysis of the GLOBAL LEADERS trial, we compared the experimental and control treatment strategies in a per-protocol analysis of patients who did not deviate from the study protocol. Methods and Results Baseline and postrandomization information were used to classify whether and when patients were deviating from the study protocol. With logistic regressions, we derived time-varying inverse probabilities of nondeviation from protocol to reconstruct the trial population without protocol deviation. The primary end point was a composite of all-cause mortality or nonfatal Q-wave myocardial infarction at 2 years. At 2-year follow-up, 1103 (13.8%) of 7980 patients in the experimental group and 785 (9.8%) of 7988 patients in the control group qualified as protocol deviators. At per-protocol analysis, the rate ratio for the primary end point was 0.88 (95% CI, 0.75-1.03; P=0.10) on the basis of 274 versus 325 events in the experimental versus control group. The rate ratio for the key safety end point of major bleeding was 1.00 (95% CI, 0.79-1.26; P=0.99). The per-protocol and intention-to-treat effect estimates were overall consistent. Conclusions Among patients who complied with the study protocol in the GLOBAL LEADERS trial, ticagrelor plus aspirin for 1 month followed by ticagrelor monotherapy was not superior to 1-year standard dual antiplatelet therapy followed by aspirin alone at 2 years after coronary stenting. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01813435.

Item does not contain fulltext, IMPORTANCE: Coronary plaques that are prone to rupture and cause adverse cardiac events are characterized by large plaque burden, large lipid content, and thin fibrous caps. Statins can halt the progression of coronary atherosclerosis; however, the effect of the proprotein convertase subtilisin kexin type 9 inhibitor alirocumab added to statin therapy on plaque burden and composition remains largely unknown. OBJECTIVE: To determine the effects of alirocumab on coronary atherosclerosis using serial multimodality intracoronary imaging in patients with acute myocardial infarction. DESIGN, SETTING, AND PARTICIPANTS: The PACMAN-AMI double-blind, placebo-controlled, randomized clinical trial (enrollment: May 9, 2017, through October 7, 2020; final follow-up: October 13, 2021) enrolled 300 patients undergoing percutaneous coronary intervention for acute myocardial infarction at 9 academic European hospitals. INTERVENTIONS: Patients were randomized to receive biweekly subcutaneous alirocumab (150 mg; n = 148) or placebo (n = 152), initiated less than 24 hours after urgent percutaneous coronary intervention of the culprit lesion, for 52 weeks in addition to high-intensity statin therapy (rosuvastatin, 20 mg). MAIN OUTCOMES AND MEASURES: Intravascular ultrasonography (IVUS), near-infrared spectroscopy, and optical coherence tomography were serially performed in the 2 non-infarct-related coronary arteries at baseline and after 52 weeks. The primary efficacy end point was the change in IVUS-derived percent atheroma volume from baseline to week 52. Two powered secondary end points were changes in near-infrared spectroscopy-derived maximum lipid core burden index within 4 mm (higher values indicating greater lipid content) and optical coherence tomography-derived minimal fibrous cap thickness (smaller values indicating thin-capped, vulnerable plaques) from baseline to week 52. RESULTS: Among 300 randomized patients (mean [SD] age, 58.5 [9.7] years; 56 [18.7%] women; mean [SD] low

Contains fulltext : 252150.pdf (Publisher’s version ) (Closed access), IMPORTANCE: Coronary plaques that are prone to rupture and cause adverse cardiac events are characterized by large plaque burden, large lipid content, and thin fibrous caps. Statins can halt the progression of coronary atherosclerosis; however, the effect of the proprotein convertase subtilisin kexin type 9 inhibitor alirocumab added to statin therapy on plaque burden and composition remains largely unknown. OBJECTIVE: To determine the effects of alirocumab on coronary atherosclerosis using serial multimodality intracoronary imaging in patients with acute myocardial infarction. DESIGN, SETTING, AND PARTICIPANTS: The PACMAN-AMI double-blind, placebo-controlled, randomized clinical trial (enrollment: May 9, 2017, through October 7, 2020; final follow-up: October 13, 2021) enrolled 300 patients undergoing percutaneous coronary intervention for acute myocardial infarction at 9 academic European hospitals. INTERVENTIONS: Patients were randomized to receive biweekly subcutaneous alirocumab (150 mg; n = 148) or placebo (n = 152), initiated less than 24 hours after urgent percutaneous coronary intervention of the culprit lesion, for 52 weeks in addition to high-intensity statin therapy (rosuvastatin, 20 mg). MAIN OUTCOMES AND MEASURES: Intravascular ultrasonography (IVUS), near-infrared spectroscopy, and optical coherence tomography were serially performed in the 2 non-infarct-related coronary arteries at baseline and after 52 weeks. The primary efficacy end point was the change in IVUS-derived percent atheroma volume from baseline to week 52. Two powered secondary end points were changes in near-infrared spectroscopy-derived maximum lipid core burden index within 4 mm (higher values indicating greater lipid content) and optical coherence tomography-derived minimal fibrous cap thickness (smaller values indicating thin-capped, vulnerable plaques) from baseline to week 52. RESULTS: Among 300 randomized patients (mean [SD] age, 58.5 [9.7] years; 56 [18.7%] women; mean [SD] low

Contains fulltext : 252201.pdf (Publisher’s version ) (Open Access), Background In the GLOBAL LEADERS trial, ticagrelor monotherapy beyond 1 month compared with standard antiplatelet regimens after coronary stent implantation did not improve outcomes at intention-to-treat analysis. Considerable differences in treatment adherence between the experimental and control groups may have affected the intention-to-treat results. In this reanalysis of the GLOBAL LEADERS trial, we compared the experimental and control treatment strategies in a per-protocol analysis of patients who did not deviate from the study protocol. Methods and Results Baseline and postrandomization information were used to classify whether and when patients were deviating from the study protocol. With logistic regressions, we derived time-varying inverse probabilities of nondeviation from protocol to reconstruct the trial population without protocol deviation. The primary end point was a composite of all-cause mortality or nonfatal Q-wave myocardial infarction at 2 years. At 2-year follow-up, 1103 (13.8%) of 7980 patients in the experimental group and 785 (9.8%) of 7988 patients in the control group qualified as protocol deviators. At per-protocol analysis, the rate ratio for the primary end point was 0.88 (95% CI, 0.75-1.03; P=0.10) on the basis of 274 versus 325 events in the experimental versus control group. The rate ratio for the key safety end point of major bleeding was 1.00 (95% CI, 0.79-1.26; P=0.99). The per-protocol and intention-to-treat effect estimates were overall consistent. Conclusions Among patients who complied with the study protocol in the GLOBAL LEADERS trial, ticagrelor plus aspirin for 1 month followed by ticagrelor monotherapy was not superior to 1-year standard dual antiplatelet therapy followed by aspirin alone at 2 years after coronary stenting. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01813435.

Contains fulltext : 235282.pdf (Publisher’s version ) (Closed access), BACKGROUND: The risk for cardiovascular adverse events after acute myocardial infarction (AMI) remains high despite potent medical treatment including low-density lipoprotein cholesterol (LDL-C) lowering with statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies substantially reduce LDL-C when added to statin. Alirocumab, a monoclonal antibody to PCSK9, reduces major adverse cardiovascular events after AMI. The effects of alirocumab on coronary atherosclerosis including plaque burden, plaque composition and fibrous cap thickness in patients presenting with AMI remains unknown. AIMS: To determine the effect of LDL-C lowering with alirocumab on top of high-intensity statin therapy on intravascular ultrasound (IVUS)-derived percent atheroma volume (PAV), near-infrared spectroscopy (NIRS)-derived maximum lipid core burden index within 4 mm (maxLCBI(4 mm)) and optical coherence tomography (OCT)-derived fibrous cap thickness (FCT) in patients with AMI. METHODS: In this multicenter, double-blind, placebo-controlled trial, 300 patients with AMI (ST-elevation or non-ST-elevation myocardial infarction) were randomly assigned to receive either biweekly subcutaneous alirocumab (150 mg) or placebo beginning <24 hours after the acute event as add-on therapy to rosuvastatin 20 mg. Patients undergo serial IVUS, NIRS and OCT in the two non-infarct related arteries at baseline (at the time of treatment of the culprit lesion) and at 52 weeks. The primary endpoint, change in IVUS-derived PAV, and the powered secondary endpoints, change in NIRS-derived maxLCBI(4 mm), and OCT-derived minimal FCT, will be assessed 52 weeks post randomization. SUMMARY: The PACMAN-AMI trial will determine the effect of alirocumab on top of high-intensity statin therapy on high-risk coronary plaque characteristics as assessed by serial, multimodality intracoronary imaging in patients presenting with AMI. CLINICAL TRIAL REGISTRATION: NCT03067844.

Contains fulltext : 235282.pdf (Publisher’s version ) (Closed access), BACKGROUND: The risk for cardiovascular adverse events after acute myocardial infarction (AMI) remains high despite potent medical treatment including low-density lipoprotein cholesterol (LDL-C) lowering with statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies substantially reduce LDL-C when added to statin. Alirocumab, a monoclonal antibody to PCSK9, reduces major adverse cardiovascular events after AMI. The effects of alirocumab on coronary atherosclerosis including plaque burden, plaque composition and fibrous cap thickness in patients presenting with AMI remains unknown. AIMS: To determine the effect of LDL-C lowering with alirocumab on top of high-intensity statin therapy on intravascular ultrasound (IVUS)-derived percent atheroma volume (PAV), near-infrared spectroscopy (NIRS)-derived maximum lipid core burden index within 4 mm (maxLCBI(4 mm)) and optical coherence tomography (OCT)-derived fibrous cap thickness (FCT) in patients with AMI. METHODS: In this multicenter, double-blind, placebo-controlled trial, 300 patients with AMI (ST-elevation or non-ST-elevation myocardial infarction) were randomly assigned to receive either biweekly subcutaneous alirocumab (150 mg) or placebo beginning <24 hours after the acute event as add-on therapy to rosuvastatin 20 mg. Patients undergo serial IVUS, NIRS and OCT in the two non-infarct related arteries at baseline (at the time of treatment of the culprit lesion) and at 52 weeks. The primary endpoint, change in IVUS-derived PAV, and the powered secondary endpoints, change in NIRS-derived maxLCBI(4 mm), and OCT-derived minimal FCT, will be assessed 52 weeks post randomization. SUMMARY: The PACMAN-AMI trial will determine the effect of alirocumab on top of high-intensity statin therapy on high-risk coronary plaque characteristics as assessed by serial, multimodality intracoronary imaging in patients presenting with AMI. CLINICAL TRIAL REGISTRATION: NCT03067844.

Contains fulltext : 235282.pdf (Publisher’s version ) (Closed access), BACKGROUND: The risk for cardiovascular adverse events after acute myocardial infarction (AMI) remains high despite potent medical treatment including low-density lipoprotein cholesterol (LDL-C) lowering with statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies substantially reduce LDL-C when added to statin. Alirocumab, a monoclonal antibody to PCSK9, reduces major adverse cardiovascular events after AMI. The effects of alirocumab on coronary atherosclerosis including plaque burden, plaque composition and fibrous cap thickness in patients presenting with AMI remains unknown. AIMS: To determine the effect of LDL-C lowering with alirocumab on top of high-intensity statin therapy on intravascular ultrasound (IVUS)-derived percent atheroma volume (PAV), near-infrared spectroscopy (NIRS)-derived maximum lipid core burden index within 4 mm (maxLCBI(4 mm)) and optical coherence tomography (OCT)-derived fibrous cap thickness (FCT) in patients with AMI. METHODS: In this multicenter, double-blind, placebo-controlled trial, 300 patients with AMI (ST-elevation or non-ST-elevation myocardial infarction) were randomly assigned to receive either biweekly subcutaneous alirocumab (150 mg) or placebo beginning <24 hours after the acute event as add-on therapy to rosuvastatin 20 mg. Patients undergo serial IVUS, NIRS and OCT in the two non-infarct related arteries at baseline (at the time of treatment of the culprit lesion) and at 52 weeks. The primary endpoint, change in IVUS-derived PAV, and the powered secondary endpoints, change in NIRS-derived maxLCBI(4 mm), and OCT-derived minimal FCT, will be assessed 52 weeks post randomization. SUMMARY: The PACMAN-AMI trial will determine the effect of alirocumab on top of high-intensity statin therapy on high-risk coronary plaque characteristics as assessed by serial, multimodality intracoronary imaging in patients presenting with AMI. CLINICAL TRIAL REGISTRATION: NCT03067844.

Changes in the frequency of extreme climatic events (ECEs) can have profound impacts on individual fitness by degrading habitat quality. Organisms may respond to such changes through habitat selection, favouring those areas less affected by ECEs; however, documenting habitat selection in response to ECEs is difficult in the wild due to the rarity of such events and the long‐term biological data required. Sea level rise and changing weather patterns over the past decades have led to an increase in the frequency of coastal flooding events, with serious consequences for ground nesting shorebirds. Shorebirds therefore present a useful natural study system to understand habitat selection as a response to ECEs. We used a 32‐year study of the Eurasian oystercatcher (Haematopus ostralegus) to investigate whether habitat selection can lead to an increase in nest elevation and minimize the impacts of coastal flooding. The mean nest elevation of H. ostralegus has increased during the last three decades. We hypothesized that this change has been driven by changes in H. ostralegus territory settlement patterns over time. We compared various possible habitat selection cues to understand what information H. ostralegus might use to inform territory settlement. There was a clear relationship between elevation and territory settlement in H. ostralegus. In early years, settlements were more likely at low elevations but in more recent years the likelihood of settlement was similar between high and low elevation areas. Territory settlement was associated with conspecific fledgling output and conspecific density. Settlement was more likely in areas of high density and areas with high fledgling output. This study shows that habitat selection can minimize the effects of increasingly frequent ECEs. However, it seems unlikely that the changes we observe will fully alleviate the consequences of anthropogenic climate change. Rates of nest elevation increase were insufficient to

pragmatic and superiority randomised controlled trial designed to challenge the current treatment paradigm of dual antiplatelet therapy (DAPT) for 12 months followed by aspirin monotherapy among patients undergoing percutaneous coronary intervention. By design, all study endpoints are investigator reported (IR) and not subject to formal adjudication by an independent Clinical Event Committee (CEC), which may introduce detection, reporting or ascertainment bias. Methods and analysis We designed the GLOBAL LEADERS Adjudication Sub-StudY (GLASSY) to prospectively implement, in a large sample of patients enrolled within the GLOBAL LEADERS trial (7585 of 15 991, 47.5%), an independent adjudication process of reported and unreported potential endpoints, using standardised CEC procedures, in order to assess whether 23-month ticagrelor monotherapy (90mg twice daily) after 1-month DAPT is non-inferior to a standard regimen of DAPT for 12 months followed by aspirin monotherapy for the primary efficacy endpoint of death, nonfatal myocardial infarction, non-fatal stroke or urgent target vessel revascularisation and superior for the primary safety endpoint of type 3 or 5 bleeding according to the Bleeding Academic Research Consortium criteria. This study will comprehensively assess the comparative safety and efficacy of the two tested antithrombotic strategies on CEC-adjudicated ischaemic and bleeding endpoints and will provide insights into the role of a standardised CEC adjudication process on the interpretation of study findings by quantifying the level of concordance between IR-reported and CEC-adjudicated events. Ethics and dissemination GLASSY has been approved by local ethics committee of all study sites and/or by the central ethics committee for the country depending on country-specific regulations. In all cases, they deemed that it was not necess

Changes in the frequency of extreme climatic events (ECEs) can have profound impacts on individual fitness by degrading habitat quality. Organisms may respond to such changes through habitat selection, favouring those areas less affected by ECEs; however, documenting habitat selection in response to ECEs is difficult in the wild due to the rarity of such events and the long‐term biological data required. Sea level rise and changing weather patterns over the past decades have led to an increase in the frequency of coastal flooding events, with serious consequences for ground nesting shorebirds. Shorebirds therefore present a useful natural study system to understand habitat selection as a response to ECEs. We used a 32‐year study of the Eurasian oystercatcher (Haematopus ostralegus) to investigate whether habitat selection can lead to an increase in nest elevation and minimize the impacts of coastal flooding. The mean nest elevation of H. ostralegus has increased during the last three decades. We hypothesized that this change has been driven by changes in H. ostralegus territory settlement patterns over time. We compared various possible habitat selection cues to understand what information H. ostralegus might use to inform territory settlement. There was a clear relationship between elevation and territory settlement in H. ostralegus. In early years, settlements were more likely at low elevations but in more recent years the likelihood of settlement was similar between high and low elevation areas. Territory settlement was associated with conspecific fledgling output and conspecific density. Settlement was more likely in areas of high density and areas with high fledgling output. This study shows that habitat selection can minimize the effects of increasingly frequent ECEs. However, it seems unlikely that the changes we observe will fully alleviate the consequences of anthropogenic climate change. Rates of nest elevation increase were insufficient to

Changes in the frequency of extreme climatic events (ECEs) can have profound impacts on individual fitness by degrading habitat quality. Organisms may respond to such changes through habitat selection, favouring those areas less affected by ECEs; however, documenting habitat selection in response to ECEs is difficult in the wild due to the rarity of such events and the long‐term biological data required. Sea level rise and changing weather patterns over the past decades have led to an increase in the frequency of coastal flooding events, with serious consequences for ground nesting shorebirds. Shorebirds therefore present a useful natural study system to understand habitat selection as a response to ECEs. We used a 32‐year study of the Eurasian oystercatcher (Haematopus ostralegus) to investigate whether habitat selection can lead to an increase in nest elevation and minimize the impacts of coastal flooding. The mean nest elevation of H. ostralegus has increased during the last three decades. We hypothesized that this change has been driven by changes in H. ostralegus territory settlement patterns over time. We compared various possible habitat selection cues to understand what information H. ostralegus might use to inform territory settlement. There was a clear relationship between elevation and territory settlement in H. ostralegus. In early years, settlements were more likely at low elevations but in more recent years the likelihood of settlement was similar between high and low elevation areas. Territory settlement was associated with conspecific fledgling output and conspecific density. Settlement was more likely in areas of high density and areas with high fledgling output. This study shows that habitat selection can minimize the effects of increasingly frequent ECEs. However, it seems unlikely that the changes we observe will fully alleviate the consequences of anthropogenic climate change. Rates of nest elevation increase were insufficient to

Item does not contain fulltext, BACKGROUND: We hypothesised that ticagrelor, in combination with aspirin for 1 month, followed by ticagrelor alone, improves outcomes after percutaneous coronary intervention compared with standard antiplatelet regimens. METHODS: GLOBAL LEADERS was a randomised, open-label superiority trial at 130 sites in 18 countries. Patients undergoing percutaneous coronary intervention with a biolimus A9-eluting stent for stable coronary artery disease or acute coronary syndromes were randomly assigned (1:1) to 75-100 mg aspirin daily plus 90 mg ticagrelor twice daily for 1 month, followed by 23 months of ticagrelor monotherapy, or standard dual antiplatelet therapy with 75-100 mg aspirin daily plus either 75 mg clopidogrel daily (for patients with stable coronary artery disease) or 90 mg ticagrelor twice daily (for patients with acute coronary syndromes) for 12 months, followed by aspirin monotherapy for 12 months. Randomisation was concealed, stratified by centre and clinical presentation (stable coronary artery disease vs acute coronary syndrome), and blocked, with randomly varied block sizes of two and four. The primary endpoint at 2 years was a composite of all-cause mortality or non-fatal centrally adjudicated new Q-wave myocardial infarction as assessed by a core lab in a blinded manner. The key secondary safety endpoint was site-reported bleeding assessed according to the Bleeding Academic Research Consortium criteria (grade 3 or 5). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01813435, and is closed to new participants, with follow-up completed. FINDINGS: Between July 1, 2013, and Nov 9, 2015, 15 968 participants were randomly assigned, 7980 to the experimental group and 7988 to the control group. At 2 years, 304 (3.81%) participants in the experimental group had died or had a non-fatal centrally adjudicated new Q-wave myocardial infarction, compared with 349 (4.37%) participants in the control group (rate ratio 0.87

Item does not contain fulltext, BACKGROUND: We hypothesised that ticagrelor, in combination with aspirin for 1 month, followed by ticagrelor alone, improves outcomes after percutaneous coronary intervention compared with standard antiplatelet regimens. METHODS: GLOBAL LEADERS was a randomised, open-label superiority trial at 130 sites in 18 countries. Patients undergoing percutaneous coronary intervention with a biolimus A9-eluting stent for stable coronary artery disease or acute coronary syndromes were randomly assigned (1:1) to 75-100 mg aspirin daily plus 90 mg ticagrelor twice daily for 1 month, followed by 23 months of ticagrelor monotherapy, or standard dual antiplatelet therapy with 75-100 mg aspirin daily plus either 75 mg clopidogrel daily (for patients with stable coronary artery disease) or 90 mg ticagrelor twice daily (for patients with acute coronary syndromes) for 12 months, followed by aspirin monotherapy for 12 months. Randomisation was concealed, stratified by centre and clinical presentation (stable coronary artery disease vs acute coronary syndrome), and blocked, with randomly varied block sizes of two and four. The primary endpoint at 2 years was a composite of all-cause mortality or non-fatal centrally adjudicated new Q-wave myocardial infarction as assessed by a core lab in a blinded manner. The key secondary safety endpoint was site-reported bleeding assessed according to the Bleeding Academic Research Consortium criteria (grade 3 or 5). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01813435, and is closed to new participants, with follow-up completed. FINDINGS: Between July 1, 2013, and Nov 9, 2015, 15 968 participants were randomly assigned, 7980 to the experimental group and 7988 to the control group. At 2 years, 304 (3.81%) participants in the experimental group had died or had a non-fatal centrally adjudicated new Q-wave myocardial infarction, compared with 349 (4.37%) participants in the control group (rate ratio 0.87

Item does not contain fulltext, BACKGROUND: We hypothesised that ticagrelor, in combination with aspirin for 1 month, followed by ticagrelor alone, improves outcomes after percutaneous coronary intervention compared with standard antiplatelet regimens. METHODS: GLOBAL LEADERS was a randomised, open-label superiority trial at 130 sites in 18 countries. Patients undergoing percutaneous coronary intervention with a biolimus A9-eluting stent for stable coronary artery disease or acute coronary syndromes were randomly assigned (1:1) to 75-100 mg aspirin daily plus 90 mg ticagrelor twice daily for 1 month, followed by 23 months of ticagrelor monotherapy, or standard dual antiplatelet therapy with 75-100 mg aspirin daily plus either 75 mg clopidogrel daily (for patients with stable coronary artery disease) or 90 mg ticagrelor twice daily (for patients with acute coronary syndromes) for 12 months, followed by aspirin monotherapy for 12 months. Randomisation was concealed, stratified by centre and clinical presentation (stable coronary artery disease vs acute coronary syndrome), and blocked, with randomly varied block sizes of two and four. The primary endpoint at 2 years was a composite of all-cause mortality or non-fatal centrally adjudicated new Q-wave myocardial infarction as assessed by a core lab in a blinded manner. The key secondary safety endpoint was site-reported bleeding assessed according to the Bleeding Academic Research Consortium criteria (grade 3 or 5). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01813435, and is closed to new participants, with follow-up completed. FINDINGS: Between July 1, 2013, and Nov 9, 2015, 15 968 participants were randomly assigned, 7980 to the experimental group and 7988 to the control group. At 2 years, 304 (3.81%) participants in the experimental group had died or had a non-fatal centrally adjudicated new Q-wave myocardial infarction, compared with 349 (4.37%) participants in the control group (rate ratio 0.87

The ‘benefits of philopatry' hypothesis states that helpers in cooperatively breeding species derive higher benefits from remaining home, instead of dispersing and attempting to breed independently. We tested experimentally whether dispersal options influence dispersal propensity in the cooperatively breeding Lake Tanganyika cichlids Neolamprologus pulcher and N. savoryi. Cooperative groups of these fishes breed in densely packed colonies, surrounded by unoccupied, but apparently suitable breeding habitat. Breeding inside colonies and living in groups seems to benefit individuals, for example by early detection and deterrence of predators. We show that despite a slight preference of both species for habitat with a higher stone cover, 40% of the preferred habitat remained unoccupied. On average, the colonies contained a higher number of (1) predators of adults, juveniles and eggs, (2) shelter competitors, and (3) other species including potential food competitors, compared to the outside colony habitat. Apparently, habitat differences cannot explain why these cichlids breed in colonies. Accordingly, dispersal may not be limited by a lack of suitable breeding shelters, but by the relatively higher risk of establishing an outside- compared to a within-colony breeding territory. To test whether cichlids prefer within- to outside-colony breeding territories, we provided breeding shelters inside the colony and at the colony edge and studied helper dispersal. As expected, significantly more shelters were occupied within the colony compared to the edge. New breeding pairs with several helpers occupied these shelters. We conclude that although breeding habitat is plentiful outside the colonies, helpers delay dispersal to obtain a higher quality breeding position within the group or colony eventually, or they disperse in groups. Our results suggest that (1) group augmentation and Allee effects are generally important for dispersal decisions in cooperatively breeding cichlids

Background Among the 3 approved oral P2Y12 inhibitors for the treatment for patients with acute coronary syndrome (ACS), ticagrelor, but not prasugrel or clopidogrel, has been associated with off-target properties, such as improved endothelial-dependent vasomotion and increased adenosine plasma levels. Methods The HI-TECH study (NCT02587260) is a multinational, randomized, open-label, crossover study with a Latin squares design, conducted at 5 European sites, in which patients free from recurrent ischemic or bleeding events ≥30 days after a qualifying ACS were allocated to sequentially receive a 30 ± 5-day treatment with prasugrel, clopidogrel, and ticagrelor in random order. The primary objective was to evaluate whether ticagrelor, at treatment steady state (ie, after 30 ± 5 days of drug administration), as compared with both clopidogrel and prasugrel, is associated with an improved endothelial function, assessed with peripheral arterial tonometry. Thirty-six patients undergoing evaluable endothelial function assessment for each of the assigned P2Y12 inhibitor were needed to provide 90% power to detect a 10% relative change of the reactive hyperemia index in the ticagrelor group. Conclusion The HI-TECH study is the first randomized, crossover study aiming to ascertain whether ticagrelor, when administered at approved regimen in post-ACS patients, improves endothelial function as compared with both clopidogrel and prasugrel.

Background--Rehospitalizations (RHs) after ST-elevation myocardial infarction carry a high economic burden and may deteriorate quality of life. Characterizing patients at higher risk may allow the design of preventive measures. We studied the frequency, reasons, and predictors for unplanned cardiac and noncardiac RHs in ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention. Methods and Results--In this post-hoc analysis of the COMFORTABLE AMI (Comparison of Biolimus Eluted F

Phenotypic plasticity is a crucial mechanism for responding to changes in climatic means, yet we know little about its role in responding to extreme climatic events (ECEs). ECEs may lack the reliable cues necessary for phenotypic plasticity to evolve; however, this has not been empirically tested. We investigated whether behavioural plasticity in nest-site selection allows a long-lived shorebird (Haematopus ostralegus) to respond to flooding. We collected longitudinal nest elevation data on individuals over two decades, during which time flooding events have become increasingly frequent. We found no evidence that individuals learn from flooding experiences, showing nest elevation change consistent with random nest-site selection. There was also no evidence of phenotypic plasticity in response to potential environmental cues (lunar nodal cycle and water height). A small number of individuals, those nesting near an artificial sea wall, did show an increase in nest elevation over time; however, there is no conclusive evidence this occurred in response to ECEs. Our study population showed no behavioural plasticity in response to changing ECE patterns. More research is needed to determine whether this pattern is consistent across species and types of ECEs. If so, ECEs may pose a major challenge to the resilience of wild populations

Phenotypic plasticity is a crucial mechanism for responding to changes in climatic means, yet we know little about its role in responding to extreme climatic events (ECEs). ECEs may lack the reliable cues necessary for phenotypic plasticity to evolve; however, this has not been empirically tested. We investigated whether behavioural plasticity in nest-site selection allows a long-lived shorebird (Haematopus ostralegus) to respond to flooding. We collected longitudinal nest elevation data on individuals over two decades, during which time flooding events have become increasingly frequent. We found no evidence that individuals learn from flooding experiences, showing nest elevation change consistent with random nest-site selection. There was also no evidence of phenotypic plasticity in response to potential environmental cues (lunar nodal cycle and water height). A small number of individuals, those nesting near an artificial sea wall, did show an increase in nest elevation over time; however, there is no conclusive evidence this occurred in response to ECEs. Our study population showed no behavioural plasticity in response to changing ECE patterns. More research is needed to determine whether this pattern is consistent across species and types of ECEs. If so, ECEs may pose a major challenge to the resilience of wild populations

We assessed the feasibility and the procedural and long-term safety of intracoronary (i.c) imaging for documentary purposes with optical coherence tomography (OCT) and intravascular ultrasound (IVUS) in patients with acute ST-elevation myocardial infarction (STEMI) undergoing primary PCI in the setting of IBIS-4 study. IBIS4 (NCT00962416) is a prospective cohort study conducted at five European centers including 103 STEMI patients who underwent serial three-vessel coronary imaging during primary PCI and at 13 months. The feasibility parameter was successful imaging, defined as the number of pullbacks suitable for analysis. Safety parameters included the frequency of peri-procedural complications, and major adverse cardiac events (MACE), a composite of cardiac death, myocardial infarction (MI) and any clinically-indicated revascularization at 2 years. Clinical outcomes were compared with the results

We assessed the feasibility and the procedural and long-term safety of intracoronary (i.c) imaging for documentary purposes with optical coherence tomography (OCT) and intravascular ultrasound (IVUS) in patients with acute ST-elevation myocardial infarction (STEMI) undergoing primary PCI in the setting of IBIS-4 study. IBIS4 (NCT00962416) is a prospective cohort study conducted at five European centers including 103 STEMI patients who underwent serial three-vessel coronary imaging during primary PCI and at 13 months. The feasibility parameter was successful imaging, defined as the number of pullbacks suitable for analysis. Safety parameters included the frequency of peri-procedural complications, and major adverse cardiac events (MACE), a composite of cardiac death, myocardial infarction (MI) and any clinically-indicated revascularization at 2 years. Clinical outcomes were compared with the results from a cohort of 485 STEMI patients undergoing primary PCI without additional imaging. Imaging of the infarct-related artery at baseline (and follow-up) was successful in 92.2 % (96.6 %) of patients using OCT and in 93.2 % (95.5 %) using IVUS. Imaging of the non-infarct-related vessels was successful in 88.7 % (95.6 %) using OCT and in 90.5 % (93.3 %) using IVUS. Periprocedural complications occurred < 2.0 % of OCT and none during IVUS. There were no differences throughout 2 years between the imaging and control group in terms of MACE (16.7 vs. 13.3 %, adjusted HR1.40, 95 % CI 0.77-2.52, p = 0.27). Multi-modality three-vessel i.c. imaging in STEMI patients undergoing primary PCI is consistent a high degree of success and can be performed safely without impact on cardiovascular events at long-term follow-up.

In most species, some individuals delay reproduction or occupy inferior breeding positions. The queue hypothesis tries to explain both patterns by proposing that individuals strategically delay breeding (queue) to acquire better breeding or social positions. In 1995, Ens, Weissing, and Drent addressed evolutionarily stable queuing strategies in situations with habitat heterogeneity. However, their model did not consider the non - mutually exclusive individual quality hypothesis, which suggests that some individuals delay breeding or occupy inferior breeding positions because they are poor competitors. Here we extend their model with individual differences in competitive abilities, which are probably plentiful in nature. We show that including even the smallest competitive asymmetries will result in individuals using queuing strategies completely different from those in models that assume equal competitors. Subsequently, we investigate how well our models can explain settleme! nt patterns in the wild, using a long-term study on oystercatchers. This long-lived shorebird exhibits strong variation in age of first reproduction and territory quality. We show that only models that include competitive asymmetries can explain why oystercatchers' settlement patterns depend on natal origin. We conclude that predictions from queuing models are very sensitive to assumptions about competitive asymmetries, while detecting such differences in the wild is often problematic., In most species, some individuals delay reproduction or occupy inferior breeding positions. The queue hypothesis tries to explain both patterns by proposing that individuals strategically delay breeding (queue) to acquire better breeding or social positions. In 1995, Ens, Weissing, and Drent addressed evolutionarily stable queuing strategies in situations with habitat heterogeneity. However, their model did not consider the non - mutually exclusive individual quality hypothesis, which suggests that some individuals delay breeding or occupy inferior breeding positions because they are poor competitors. Here we extend their model with individual differences in competitive abilities, which are probably plentiful in nature. We show that including even the smallest competitive asymmetries will result in individuals using queuing strategies completely different from those in models that assume equal competitors. Subsequently, we investigate how well our models can explain settleme! nt patterns in the wild, using a long-term study on oystercatchers. This long-lived shorebird exhibits strong variation in age of first reproduction and territory quality. We show that only models that include competitive asymmetries can explain why oystercatchers' settlement patterns depend on natal origin. We conclude that predictions from queuing models are very sensitive to assumptions about competitive asymmetries, while detecting such differences in the wild is often problematic.

In most species, some individuals delay reproduction or occupy inferior breeding positions. The queue hypothesis tries to explain both patterns by proposing that individuals strategically delay breeding (queue) to acquire better breeding or social positions. In 1995, Ens, Weissing, and Drent addressed evolutionarily stable queuing strategies in situations with habitat heterogeneity. However, their model did not consider the non - mutually exclusive individual quality hypothesis, which suggests that some individuals delay breeding or occupy inferior breeding positions because they are poor competitors. Here we extend their model with individual differences in competitive abilities, which are probably plentiful in nature. We show that including even the smallest competitive asymmetries will result in individuals using queuing strategies completely different from those in models that assume equal competitors. Subsequently, we investigate how well our models can explain settleme! nt patterns in the wild, using a long-term study on oystercatchers. This long-lived shorebird exhibits strong variation in age of first reproduction and territory quality. We show that only models that include competitive asymmetries can explain why oystercatchers' settlement patterns depend on natal origin. We conclude that predictions from queuing models are very sensitive to assumptions about competitive asymmetries, while detecting such differences in the wild is often problematic., In most species, some individuals delay reproduction or occupy inferior breeding positions. The queue hypothesis tries to explain both patterns by proposing that individuals strategically delay breeding (queue) to acquire better breeding or social positions. In 1995, Ens, Weissing, and Drent addressed evolutionarily stable queuing strategies in situations with habitat heterogeneity. However, their model did not consider the non - mutually exclusive individual quality hypothesis, which suggests that some individuals delay breeding or occupy inferior breeding positions because they are poor competitors. Here we extend their model with individual differences in competitive abilities, which are probably plentiful in nature. We show that including even the smallest competitive asymmetries will result in individuals using queuing strategies completely different from those in models that assume equal competitors. Subsequently, we investigate how well our models can explain settleme! nt patterns in the wild, using a long-term study on oystercatchers. This long-lived shorebird exhibits strong variation in age of first reproduction and territory quality. We show that only models that include competitive asymmetries can explain why oystercatchers' settlement patterns depend on natal origin. We conclude that predictions from queuing models are very sensitive to assumptions about competitive asymmetries, while detecting such differences in the wild is often problematic.

Comparative analyses of avian population fluctuations have shown large interspecific differences in population variability that have been difficult to relate to variation in general ecological characteristics. Here we show that interspecific variation in demographic stochasticity, caused by random variation among individuals in their fitness contributions, can be predicted from a knowledge of the species' position along a "slow-fast" gradient of life-history variation, ranging from high reproductive species with short life expectancy at one end to species that often produce a single offspring but survive well at the other end of the continuum. The demographic stochasticity decreased with adult survival rate, age at maturity, and generation time or the position of the species toward the slow end of the slow-fast life-history gradient. This relationship between life-history characteristics and demographic stochasticity was related to interspecific differences in the variation among females in recruitment as well as to differences in the individual variation in survival. Because reproductive decisions in birds are often subject to strong natural selection, our results provide strong evidence for adaptive modifications of reproductive investment through life-history evolution of the influence of stochastic variation on avian population dynamics. [KEYWORDS: demographic stochasticity ; environmental stochasticity ; life-history variation ; stochastic population dynamics ; birds], Comparative analyses of avian population fluctuations have shown large interspecific differences in population variability that have been difficult to relate to variation in general ecological characteristics. Here we show that interspecific variation in demographic stochasticity, caused by random variation among individuals in their fitness contributions, can be predicted from a knowledge of the species' position along a "slow-fast" gradient of life-history variation, ranging from high reproductive species with short life expectancy at one end to species that often produce a single offspring but survive well at the other end of the continuum. The demographic stochasticity decreased with adult survival rate, age at maturity, and generation time or the position of the species toward the slow end of the slow-fast life-history gradient. This relationship between life-history characteristics and demographic stochasticity was related to interspecific differences in the variation among females in recruitment as well as to differences in the individual variation in survival. Because reproductive decisions in birds are often subject to strong natural selection, our results provide strong evidence for adaptive modifications of reproductive investment through life-history evolution of the influence of stochastic variation on avian population dynamics. [KEYWORDS: demographic stochasticity ; environmental stochasticity ; life-history variation ; stochastic population dynamics ; birds]

Comparative analyses of avian population fluctuations have shown large interspecific differences in population variability that have been difficult to relate to variation in general ecological characteristics. Here we show that interspecific variation in demographic stochasticity, caused by random variation among individuals in their fitness contributions, can be predicted from a knowledge of the species' position along a "slow-fast" gradient of life-history variation, ranging from high reproductive species with short life expectancy at one end to species that often produce a single offspring but survive well at the other end of the continuum. The demographic stochasticity decreased with adult survival rate, age at maturity, and generation time or the position of the species toward the slow end of the slow-fast life-history gradient. This relationship between life-history characteristics and demographic stochasticity was related to interspecific differences in the variation among females in recruitment as well as to differences in the individual variation in survival. Because reproductive decisions in birds are often subject to strong natural selection, our results provide strong evidence for adaptive modifications of reproductive investment through life-history evolution of the influence of stochastic variation on avian population dynamics. [KEYWORDS: demographic stochasticity ; environmental stochasticity ; life-history variation ; stochastic population dynamics ; birds], Comparative analyses of avian population fluctuations have shown large interspecific differences in population variability that have been difficult to relate to variation in general ecological characteristics. Here we show that interspecific variation in demographic stochasticity, caused by random variation among individuals in their fitness contributions, can be predicted from a knowledge of the species' position along a "slow-fast" gradient of life-history variation, ranging from high reproductive species with short life expectancy at one end to species that often produce a single offspring but survive well at the other end of the continuum. The demographic stochasticity decreased with adult survival rate, age at maturity, and generation time or the position of the species toward the slow end of the slow-fast life-history gradient. This relationship between life-history characteristics and demographic stochasticity was related to interspecific differences in the variation among females in recruitment as well as to differences in the individual variation in survival. Because reproductive decisions in birds are often subject to strong natural selection, our results provide strong evidence for adaptive modifications of reproductive investment through life-history evolution of the influence of stochastic variation on avian population dynamics. [KEYWORDS: demographic stochasticity ; environmental stochasticity ; life-history variation ; stochastic population dynamics ; birds]

Eurasian Oystercatchers Haematopus ostralegus are infested with a wide range of gut parasites, but experimental evidence of their effects on host fitness is scant. We investigated prevalence of parasites, and experimentally tested the effects of gut parasites on chick survival and growth. One hundred and fifty-nine hatchlings from 66 nests were treated with a single dose anthelminthic medicine (0.5 mL Spectril + 0.0025 mL Ivomec) and compared with a sham-treated control group of 163 hatchlings from 66 nests. Unexpectedly, chicks treated with the anthelminthic drug survived less well than control chicks. Fledglings from the treated group were significantly less infected with gut parasites than untreated fledglings, although they were of similar body mass. One possible explanation for these findings is that the treatment interferes with the development of the immune system in the hatchlings. This might have caused mass mortality of treated hatchlings after the drug ceased to work and the treated chicks became susceptible to infections for the first time. Furthermore, all chicks and adults from both saltmarsh and adjacent freshwater habitat appeared free from blood parasites. Thus, in the Eurasian Oystercatcher, we found no support for the hypothesis, based on between-species comparisons, that the presence of blood parasites is related to the saltiness of the environment., Eurasian Oystercatchers Haematopus ostralegus are infested with a wide range of gut parasites, but experimental evidence of their effects on host fitness is scant. We investigated prevalence of parasites, and experimentally tested the effects of gut parasites on chick survival and growth. One hundred and fifty-nine hatchlings from 66 nests were treated with a single dose anthelminthic medicine (0.5 mL Spectril + 0.0025 mL Ivomec) and compared with a sham-treated control group of 163 hatchlings from 66 nests. Unexpectedly, chicks treated with the anthelminthic drug survived less well than control chicks. Fledglings from the treated group were significantly less infected with gut parasites than untreated fledglings, although they were of similar body mass. One possible explanation for these findings is that the treatment interferes with the development of the immune system in the hatchlings. This might have caused mass mortality of treated hatchlings after the drug ceased to work and the treated chicks became susceptible to infections for the first time. Furthermore, all chicks and adults from both saltmarsh and adjacent freshwater habitat appeared free from blood parasites. Thus, in the Eurasian Oystercatcher, we found no support for the hypothesis, based on between-species comparisons, that the presence of blood parasites is related to the saltiness of the environment.

Eurasian Oystercatchers Haematopus ostralegus are infested with a wide range of gut parasites, but experimental evidence of their effects on host fitness is scant. We investigated prevalence of parasites, and experimentally tested the effects of gut parasites on chick survival and growth. One hundred and fifty-nine hatchlings from 66 nests were treated with a single dose anthelminthic medicine (0.5 mL Spectril + 0.0025 mL Ivomec) and compared with a sham-treated control group of 163 hatchlings from 66 nests. Unexpectedly, chicks treated with the anthelminthic drug survived less well than control chicks. Fledglings from the treated group were significantly less infected with gut parasites than untreated fledglings, although they were of similar body mass. One possible explanation for these findings is that the treatment interferes with the development of the immune system in the hatchlings. This might have caused mass mortality of treated hatchlings after the drug ceased to work and the treated chicks became susceptible to infections for the first time. Furthermore, all chicks and adults from both saltmarsh and adjacent freshwater habitat appeared free from blood parasites. Thus, in the Eurasian Oystercatcher, we found no support for the hypothesis, based on between-species comparisons, that the presence of blood parasites is related to the saltiness of the environment., Eurasian Oystercatchers Haematopus ostralegus are infested with a wide range of gut parasites, but experimental evidence of their effects on host fitness is scant. We investigated prevalence of parasites, and experimentally tested the effects of gut parasites on chick survival and growth. One hundred and fifty-nine hatchlings from 66 nests were treated with a single dose anthelminthic medicine (0.5 mL Spectril + 0.0025 mL Ivomec) and compared with a sham-treated control group of 163 hatchlings from 66 nests. Unexpectedly, chicks treated with the anthelminthic drug survived less well than control chicks. Fledglings from the treated group were significantly less infected with gut parasites than untreated fledglings, although they were of similar body mass. One possible explanation for these findings is that the treatment interferes with the development of the immune system in the hatchlings. This might have caused mass mortality of treated hatchlings after the drug ceased to work and the treated chicks became susceptible to infections for the first time. Furthermore, all chicks and adults from both saltmarsh and adjacent freshwater habitat appeared free from blood parasites. Thus, in the Eurasian Oystercatcher, we found no support for the hypothesis, based on between-species comparisons, that the presence of blood parasites is related to the saltiness of the environment.

1. We studied the mechanisms of territory acquisition in an oystercatcher (Haematopus ostralegus) breeding population on Schiermonnikoog (1983-1997), competing for low quality (leapfrog) and high quality (resident) territories. 2. Numbers of nonbreeders o, Addresses: Heg D, Univ Bonn, Abt Ethol, Inst Zool, Kirschallee 1, D-53115 Bonn, Germany. Univ Groningen, Zool Lab, NL-9750 AA Haren, Netherlands. DLO, IBN, NL-1790 AD Den Burg, Netherlands. Uppsala Univ, Evolut Biol Ctr, Dept Anim Ecol, S-75236 Uppsala, S

We investigated hatchling and fledgling sex ratios in Eurasian Oystercatchers (Haematopus ostralegus) using random amplified polymorphic DNA markers. The overall hatchling (53% males, n = 374 hatchlings from 177 broods) and fledgling (49% males, n = 51) sex ratio did not differ significantly from unity. Hatchling and fledgling sex ratios were not correlated with laying date, clutch size, brood size, egg-laying sequence, territory quality male age, or male breeding experience, but hatchling sex ratio was positively correlated with age and breeding experience of females (0.05

We investigated hatchling and fledgling sex ratios in Eurasian Oystercatchers (Haematopus ostralegus) using random amplified polymorphic DNA markers. The overall hatchling (53% males, n = 374 hatchlings from 177 broods) and fledgling (49% males, n = 51) sex ratio did not differ significantly from unity. Hatchling and fledgling sex ratios were not correlated with laying date, clutch size, brood size, egg-laying sequence, territory quality male age, or male breeding experience, but hatchling sex ratio was positively correlated with age and breeding experience of females (0.05

The ‘benefits of philopatry' hypothesis states that helpers in cooperatively breeding species derive higher benefits from remaining home, instead of dispersing and attempting to breed independently. We tested experimentally whether dispersal options influence dispersal propensity in the cooperatively breeding Lake Tanganyika cichlids Neolamprologus pulcher and N. savoryi. Cooperative groups of these fishes breed in densely packed colonies, surrounded by unoccupied, but apparently suitable breeding habitat. Breeding inside colonies and living in groups seems to benefit individuals, for example by early detection and deterrence of predators. We show that despite a slight preference of both species for habitat with a higher stone cover, 40% of the preferred habitat remained unoccupied. On average, the colonies contained a higher number of (1) predators of adults, juveniles and eggs, (2) shelter competitors, and (3) other species including potential food competitors, compared to the outside colony habitat. Apparently, habitat differences cannot explain why these cichlids breed in colonies. Accordingly, dispersal may not be limited by a lack of suitable breeding shelters, but by the relatively higher risk of establishing an outside- compared to a within-colony breeding territory. To test whether cichlids prefer within- to outside-colony breeding territories, we provided breeding shelters inside the colony and at the colony edge and studied helper dispersal. As expected, significantly more shelters were occupied within the colony compared to the edge. New breeding pairs with several helpers occupied these shelters. We conclude that although breeding habitat is plentiful outside the colonies, helpers delay dispersal to obtain a higher quality breeding position within the group or colony eventually, or they disperse in groups. Our results suggest that (1) group augmentation and Allee effects are generally important for dispersal decisions in cooperatively breeding cichlids