We submit that the safe operating space of the planetary boundary of novel entities is exceeded since annual production and releases are increasing at a pace that outstrips the global capacity for ...assessment and monitoring. The novel entities boundary in the planetary boundaries framework refers to entities that are novel in a geological sense and that could have large-scale impacts that threaten the integrity of Earth system processes. We review the scientific literature relevant to quantifying the boundary for novel entities and highlight plastic pollution as a particular aspect of high concern. An impact pathway from production of novel entities to impacts on Earth system processes is presented. We define and apply three criteria for assessment of the suitability of control variables for the boundary: feasibility, relevance, and comprehensiveness. We propose several complementary control variables to capture the complexity of this boundary, while acknowledging major data limitations. We conclude that humanity is currently operating outside the planetary boundary based on the weight-of-evidence for several of these control variables. The increasing rate of production and releases of larger volumes and higher numbers of novel entities with diverse risk potentials exceed societies’ ability to conduct safety related assessments and monitoring. We recommend taking urgent action to reduce the harm associated with exceeding the boundary by reducing the production and releases of novel entities, noting that even so, the persistence of many novel entities and/or their associated effects will continue to pose a threat.
Abstract Background Current guidelines suggest that patients with left bundle branch block (LBBB) be treated with cardiac resynchronization therapy (CRT); however, one-third do not have a significant ...activation delay, which can result in nonresponse. By identifying characteristic opposing wall contraction, 2-dimensional strain echocardiography (2DSE) may detect true LBBB activation. Objectives This study sought to investigate whether the absence of a typical LBBB mechanical activation pattern by 2DSE was associated with unfavorable long-term outcome and if this is additive to electrocardiographic (ECG) morphology and duration. Methods From 2 centers, 208 CRT candidates (New York Heart Association classes II to IV, ejection fraction ≤35%, QRS duration ≥120 ms) with LBBB by ECG were prospectively included. Before CRT implantation, longitudinal strain in the apical 4-chamber view determined whether typical LBBB contraction was present. The pre-defined outcome was freedom from death, left ventricular assist device, or heart transplantation over 4 years. Results Two-thirds of patients (63%) had a typical LBBB contraction pattern. During 4 years, 48 patients (23%) reached the primary endpoint. Absence of a typical LBBB contraction was independently associated with increased risk of adverse outcome after adjustment for ischemic heart disease and QRS width (hazard ratio HR: 3.1; 95% CI: 1.64 to 5.88; p < 0.005). Adding pattern assessment to a risk prediction model including QRS duration and ischemic heart disease significantly improved the net reclassification index to 0.14 (p = 0.04) and improved the C-statistics (0.63 95% CI: 0.54 to 0.72 vs. 0.71 95% CI: 0.63 to 0.80; p = 0.02). Use of strict LBBB ECG criteria was not independently associated with outcome in the multivariate model (HR: 1.72; 95% CI: 0.89 to 3.33; p = 0.11. Assessment of LBBB contraction pattern was superior to time-to-peak indexes of dyssynchrony (p < 0.01 for all). Conclusions Contraction pattern assessment to identify true LBBB activation provided important prognostic information in CRT candidates.
Medication prescribed to patients suffering from chronic heart failure carries an increased risk of impaired potassium homeostasis. We examined the relation between different levels of serum ...potassium and mortality among patients with chronic heart failure.
From Danish National registries, we identified 19 549 patients with a chronic heart failure diagnosis who had a measurement of potassium within minimum 90 days after initiated medical treatment with loop diuretics and angiotensin converting enzyme inhibitors or angiotensin-II receptor blockers. All-cause mortality was examined according to eight predefined potassium levels: 2.8-3.4 mmol/L, 3.5-3.8 mmol/L, 3.9-4.1 mmol/L, 4.2-4.4 mmol/L, 4.5-4.7 mmol/L, 4.8-5.0 mmol/L, 5.1-5.5 mmol/L, and 5.6-7.4 mmol/L. Follow-up was 90 days from potassium measurement. We estimated the risk of all-cause mortality using multivariable adjusted Cox proportional hazard model, with normal serum potassium level at 4.2-4.4 mmol/L as reference. After 90 days, the mortality in the eight strata was 14.4, 8.0, 6.3, 5.0, 5.8, 7.9, 10.3, and 21.1% respectively. In multivariable adjusted analysis, patients with potassium levels of 2.8-3.4 mmol/L hazard ratio (HR): 3.16; confidence interval (CI): 2.43-4.11, 3.5-3.8 mmol/L (HR: 1.62; CI: 1.31-1.99), 3.9-4.1 mmol/L (HR: 1.29; CI: 1.08-1.55), 4.8-5.0 mmol/L (HR: 1.34; CI: 1.10-1.63), 5.1-5.5 mmol/L (HR: 1.60; CI: 1.29-1.97), and 5.6-7.4 mmol/L (HR: 3.31; CI: 2.61-4.20) had an increased risk of all-cause mortality.
Levels within the lower and upper levels of the normal serum potassium range (3.5-4.1 mmol/L and 4.8-5.0 mmol/L, respectively) were associated with a significant increased short-term risk of death in chronic heart failure patients. Likewise, potassium below 3.5 mmol/L and above 5.0 mmol/L was also associated with increased mortality.
Transgenic crops that produce insecticidal proteins from Bacillus thuringiensis (Bt) can suppress pests and reduce insecticide sprays, but their efficacy is reduced when pests evolve resistance. ...Although farmers plant refuges of non-Bt host plants to delay pest resistance, this tactic has not been sufficient against the western corn rootworm, Diabrotica virgifera virgifera. In the United States, some populations of this devastating pest have rapidly evolved practical resistance to Cry3 toxins and Cry34/35Ab, the only Bt toxins in commercially available corn that kill rootworms. Here, we analyzed data from 2011 to 2016 on Bt corn fields producing Cry3Bb alone that were severely damaged by this pest in 25 cropreporting districts of Illinois, Iowa, and Minnesota. The annual mean frequency of these problem fields was 29 fields (range 7 to 70) per million acres of Cry3Bb corn in 2011 to 2013, with a cost of $163 to $227 per damaged acre. The frequency of problem fields declined by 92% in 2014 to 2016 relative to 2011 to 2013 and was negatively associated with rotation of corn with soybean. The effectiveness of corn rotation for mitigating Bt resistance problems did not differ significantly between crop-reporting districts with versus without prevalent rotation-resistant rootworm populations. In some analyses, the frequency of problem fields was positively associated with planting of Cry3 corn and negatively associated with planting of Bt corn producing both a Cry3 toxin and Cry34/35Ab. The results highlight the central role of crop rotation for mitigating impacts of D. v. virgifera resistance to Bt corn.
Applying evolutionary biology to address global challenges Carroll, Scott P.; Jørgensen, Peter Søgaard; Kinnison, Michael T. ...
Science (American Association for the Advancement of Science),
10/2014, Volume:
346, Issue:
6207
Journal Article
Peer reviewed
Open access
Two categories of evolutionary challenges result from escalating human impacts on the planet. The first arises from cancers, pathogens, and pests that evolve too quickly and the second, from the ...inability of many valued species to adapt quickly enough. Applied evolutionary biology provides a suite of strategies to address these global challenges that threaten human health, food security, and biodiversity. This Review highlights both progress and gaps in genetic, developmental, and environmental manipulations across the life sciences that either target the rate and direction of evolution or reduce the mismatch between organisms and human-altered environments. Increased development and application of these underused tools will be vital in meeting current and future targets for sustainable development.
Abstract
Aims
The objective of the current study is to investigate the risk of heart failure (HF) after implantation of a pacemaker (PM) with a right ventricular pacing (RVP) lead in comparison to a ...matched cohort without a PM and factors associated with this risk.
Methods and results
All patients without a known history of HF who had a PM implanted with an RVP lead between 2000 and 2014 (n = 27 704) were identified using Danish nationwide registries. An age- and gender-matched control cohort (matched 1:5, n = 138 520) without PM and HF was identified to compare the risk. Outcome was the cumulative incidence of HF including fatal HF within the first 2 years of PM implantation, with all-cause mortality and myocardial infarction (MI) as competing risks. Due to violation of proportional hazards, the follow-up period was divided into three time-intervals: <30 days, 30–180 days, and >180 days–2 years. The cumulative incidence of HF including fatal HF was observed in 2937 (10.6%) PM patients. Risks for the three time-intervals were <30 days hazard ratio (HR) 5.98, 95% CI 5.19–6.90, 30–180 days (HR 1.84, 95% CI 1.71–1.98), and >180 days (HR 1.11, 95% CI 1.04–1.17). Among patients with a PM device, factors associated with increased risk of HF were male sex (HR 1.33, 95% CI 1.24–1.43), presence of chronic kidney disease (CKD) (HR 1.64, 95% CI 1.29–2.09), and prior MI (1.77, 95% 1.50–2.09).
Conclusions
Pacemaker with an RVP lead is strongly associated with risk of HF specifically within the first 6 months. Patients with antecedent history of MI and CKD had substantially increased risk.
It has been a challenge to verify the dose of exercise that will produce the maximum health benefits in hypertension. This study aimed to explore the association between level of daily physical ...activity, all-cause mortality and cardiovascular outcome at different blood pressure levels. A random sample of 18 974 white men and women aged 20 to 98 years were examined in a prospective cardiovascular population study. Self-reported activity level in leisure-time was drawn from the Physical Activity Questionnaire (level Iinactivity; IIlight activity; and IIImoderate/high-level activity). Blood pressure was defined as normal blood pressure<120/<80 mm Hg; Prehypertension120–139/80–89 mm Hg; Stage I hypertension140–159/90–99 mm Hg; Stage II hypertension ≥160/≥100 mm Hg. The mean follow-up time was 23.4±11.7 years. At all levels of blood pressure, higher levels of physical activity were associated with lower all-cause mortality in a dose-response pattern. The pattern remained unchanged after adjustment for following confounderssex, age, smoking status, education, diabetes mellitus, previous cardiovascular disease, body mass index, and calendar time. Compared with inactivity, following hazard ratios were found for stage I hypertensionlight activity, hazard ratio 0.78 (0.72–0.84; P<0.001), moderate/high-level activity, hazard ratio 0.69 (0.63–0.75; P<0.001). At all levels of blood pressure, the risk of cardiovascular events was significantly reduced independent of the level of physical activity. In conclusion, the association between physical activity and all-cause mortality was present in an inverse dose-response pattern at all levels of blood pressure. Physical activity was associated with reduction in cardiovascular events independent of the level of physical activity.
A total of 30% to 40% of patients with congestive heart failure eligible for cardiac resynchronization therapy (CRT) either do not respond to conventional CRT or remain untreated due to an inability ...or impediment to coronary sinus (CS) lead implantation. The WiSE-CRT system (EBR Systems, Sunnyvale, California) was developed to address this at-risk patient population by performing biventricular pacing via a wireless left ventricular (LV) endocardial pacing electrode.
The SELECT-LV (Safety and Performance of Electrodes implanted in the Left Ventricle) study is a prospective multicenter non-randomized trial assessing the safety and performance of the WiSE-CRT system.
A total of 35 patients indicated for CRT who had "failed" conventional CRT underwent implantation of an LV endocardial pacing electrode and a subcutaneous pulse generator. System performance, clinical efficacy, and safety events were assessed out to 6 months post-implant.
The procedure was successful in 97.1% (n = 34) of attempted implants. The most common indications for endocardial LV pacing were difficult CS anatomy (n =12), failure to respond to conventional CRT (n = 10), and a high CS pacing threshold or phrenic nerve capture (n = 5). The primary performance endpoint, biventricular pacing on the 12-lead electrocardiogram at 1 month, was achieved in 33 of 34 patients. A total of 28 patients (84.8%) had improvement in the clinical composite score at 6 months, and 21 (66%) demonstrated a positive echocardiographic CRT response (≥5% absolute increase in LV ejection fraction). There were no pericardial effusions, but serious procedure/device-related events occurred in 3 patients (8.6%) within 24 h, and 8 patients (22.9%) between 24 h and 1 month.
The SELECT-LV study demonstrates the clinical feasibility for the WiSE-CRT system, and provided clinical benefits to a majority of patients within an otherwise "failed" CRT population. (Safety and Performance of Electrodes Implanted in the Left Ventricle SELECT-LV; NCT01905670).
Antimicrobial resistance (AMR) is a global crisis that evolves from a complex system of factors. Understanding what factors interact is key to finding solutions. Our objective was to identify the ...factors influencing AMR in the European food system and places to intervene.
We conducted two workshops involving participants with diverse perspectives to identify the factors influencing AMR and leverage points (places) to target interventions. Transcripts were open coded for factors and connections, then transcribed into Vensim 8.0.4 to develop a causal loop diagram (CLD) and compute the number of feedback loops. Thematic analysis followed to describe AMR dynamics in Europe's food system and places for intervention. The CLD and themes were confirmed via participant feedback.
Seventeen participants representing human, animal and agricultural sectors identified 91 CLD factors and 331 connections. Seven themes (e.g., social and economic conditions) describing AMR dynamics in Europe's food system, five 'overarching factors' that impact the entire CLD system (e.g., leadership) and fourteen places for intervention (e.g., consumer demand) emerged from workshop discussions. Most leverage points fell on highly networked feedback loops suggesting that intervening at these places may create unpredictable consequences.
Our study produced a CLD of factors influencing AMR in Europe's food system that implicates sectors across the One Health spectrum. The high connectivity between the CLD factors described by participants and our finding that factors are connected with many feedback mechanisms underscores the complexity of the AMR problem and the challenge with finding long-term solutions. Identifying factors and feedbacks helped identify relevant leverage points in the system. Some actions, such as government's setting AMU standards may be easier to implement. These actions in turn can support multi-pronged actions that can help redefine the vision, values and goals of the system to sustainably tackle AMR.
Antimicrobial Resistance (AMR) is a global problem with large health and economic consequences. Current gaps in quantitative data are a major limitation for creating models intended to simulate the ...drivers of AMR. As an intermediate step, expert knowledge and opinion could be utilized to fill gaps in knowledge for areas of the system where quantitative data does not yet exist or are hard to quantify. Therefore, the objective of this study was to identify quantifiable data about the current state of the factors that drive AMR and the strengths and directions of relationships between the factors from statements made by a group of experts from the One Health system that drives AMR development and transmission in a European context. This study builds upon previous work that developed a causal loop diagram of AMR using input from two workshops conducted in 2019 in Sweden with experts within the European food system context. A secondary analysis of the workshop transcripts was conducted to identify semi-quantitative data to parameterize drivers in a model of AMR. Using transcripts of a workshop including participants with diverse expertise across the system that drives AMR, we gained invaluable insight into the past, current, and potential future states of the major drivers of AMR, particularly where quantitative data are lacking.
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