Alternative Systems of Inquiry for a Sustainable Agriculture

Summary Scientific investigation has long been dominated by positivism, which holds that an independent reality driven by immutable laws exists. Consequently, it should be possible to define sustainability in absolute terms. Advances in alternative paradigms, however, suggest: that any attempt precisely to define sustainability is flawed; that problems are always open to interpretation; that the resolution of one problem inevitably leads to the production of another ‘problem?situation’, as problems are endemic; that the key feature now becomes the capacity of actors continually to learn about these changing conditions, so that they can act rapidly to transform existing activities; and that systems of learning and inquiry are needed to seek the multiple perspectives of the various stakeholders and encourage wider involvement and action. These systems of inquiry are participatory in nature, and the information and action arising from them is judged by a framework of trustworthiness criteria. Resumé Les systèmes de renseignement alternatifs pour l'agriculture durable Depuis longtemps, l'enquête scientifique se trouve dominée par le positivisme, qui maintient l'existence d'une réalité indépendante mue par des lois ellesmêmes immuables. Par conséquent, il devrait être possible de définir la durabilité dans des termes absolus. Toutefois, les progrès au niveau des paradigmes alternatifs auraient tendance à suggérer, d'abord, que toute tentative de définir la durabilité de manière précise est à priori fausse; ensuite, que tout problème est capable d'interprétations différentes; que la solution d'un problème mène inéluctablement à la production de situations problématiques, étant donné que les problèmes sont endémiques; que le facteur primordial est désormais, la capacité des acteurs à apprendre continûment quelles sont ces situations changeantes, de sorte qu'ils puissent agir rapidement pour transformer les activités existantes; et que la mise en place de systèmes d'enquête et d'acquisition des connaissances sont nécessaires afin que l'on puisse interroger les nombreuses perspectives des divers participants et par là, encourager une participation plus grande et plus active. Ces systèmes d'enquète sont intrinsèquement participatoires, aussi l'information et l'action qui en découlent doiventelles être jugées dans le cadre d'un ensemble de critères de fiabilité. Resumen Sistemas alternativos de investigación para una agricultura sostenible La investigación científica ha sido dominada durante mucho tiempo por el positivismo, que mantiene la existencia de una realidad independiente manejada por leyes inmutables. Consecuentemente, debe ser posible definir el mantenimiento en términos absolutos. Sin embargo, el avance de paradigmas alternativos sugiere: a) cualquier intento de definir la sostenibilidad con precisión es defectuoso; b) los problemas siempre están abiertos a la interpretación; c) la solución de un problema inevitablemente lleva a la producción de otra situación problemática, ya que los problemas son endémicos; d) el rasgo clave es la capacidad de los protagonistas para aprender continuamente de estas condiciónes cambiantes, y poder actuar rápidamente en la transformación de las actividades existentes; y e) se necesitan sistemas de averiguación y aprendizaje para registrar las múltiples perspectivas de las varias partes interesadas y estimular un compromiso y una acción mas emplios. Estos sistemas de averiguación son de por sí participatorios, y la información y acción que de ellos surgen son juzgadas por un conjunto de criterios de fiabilidad

Cardiac reserve and exercise capacity: insights from combined cardiopulmonary and exercise echocardiography stress testing

Abstract Funding Acknowledgements Type of funding sources: None. Aims. Combined cardiopulmonary exercise test (CPET) and exercise stress echocardiography (ESE) provides a non-invasive tool to study cardiopulmonary pathophysiology. We analyzed how cardiac functional reserve during exercise relates to peak oxygen consumption (VO2). Methods and Results. We performed a symptom-limited graded ramp bicycle CPET-ESE in 30 healthy controls and 357 patients: 113 at risk of developing heart failure (American College of Cardiology/American Heart Association HF Stages A-B) and 244 in HF Stage C with preserved (HFpEF, n = 101) or reduced ejection fraction (HFrEF, n = 143). Peak VO2 significantly decreased from controls to Stage A-B and Stage C (Table 1). A multivariable regression model to predict peak VO2 revealed peak left ventricular systolic annulus tissue velocity (S"), peak TAPSE/PAPs (tricuspid annular plane systolic excursion/systolic pulmonary artery pressure) and low-load left atrial reservoir strain/E/e' were independent predictors, in addition to peak heart rate, stroke volume and workload (adjusted R²=0.76, p < 0.0001). The model was successfully tested in subjects with atrial fibrillation (n = 49), and with (n = 224) and without (n = 163) beta-blockers (all p < 0.01). Peak S' showed the highest accuracy in predicting peak VO2 < 10 mL/kg/min (cut-point ≤ 7.5 cm/s; AUC = 0.92, p < 0.0001) and peak VO2 > 20 mL/kg/min (cut-point > 12.5 cm/s; AUC = 0.84, p < 0.0001) in comparison to the other cardiac variables of the model (p < 0.05). Conclusions. A model incorporating different measures of cardiac mechanics is strongly related to peak aerobic capacity and may help in identifying different causes of effort intolerance from HF Stage A to C. Table 1 Variable Overall population (n = 387) Controls (n = 30) Stage A-B (n = 113) Stage C-HFpEF (n = 101) Stage c-HFrEF (n = 143) p-value Age, years 68.9 ± 11.1 67.1 ± 10.6 67.7 ± 10.4 70.5 ± 10.1 68.5 ± 11 0.1 Male, n (%) 247 (64) 18 (60) 70 (62) 57 (56) 102 (71) 0.1 VO2 @peak, mL/min/kg 15.7 (12.1-19.6) 23 (21.7- 29.7) 18 (15.4- 20.7)* 13.6 (11.8- 16.8)*† 14.2 (10.7- 17.5)*† <0.0001 Workload @peak, W 90 (65-120) 130 (115-195) 110 (84-130)* 70 (55-100)*† 80 (60-110)*† <0.0001 Heart rate @peak, bpm 123 ± 22 142 ± 12 130 ± 20* 115 ± 17*† 119 ± 23*† <0.0001 Stroke volume @peak, mL 83 (71-99) 98 (85-114) 86 (76-107) 83 (74-97)* 75 (63-95)*† <0.0001 Average S" @peak, cm/s 11.2 ± 3.8 17.1 ± 3.9 13.3 ± 2.9* 10.6 ± 2.5*† 8.7 ± 2.7*†‡ <0.0001 TAPSE/PAPs @peak, mm/mmHg 0.75 (0.46-0.97) 1.05 (0.93- 1.16) 0.81 (0.52- 0.91)* 0.52 (0.38- 0.83)*† 0.58 (0.41- 0.89)*† <0.0001 Left atrial reservoir strain/E/e" @low-load, % 2.25 (1.17-5.04) 6.23 (4.45-6.77) 4.34 (3.89- 5.58)* 2.23 (1.31- 2.86)*† 1.91 (1.07-2.44)*†‡ <0.0001 * p < 0.01 vs Controls; † p < 0.01 vs Stage A-B; ‡ p < 0.01 vs Stage C-HFpEF. PAPs systolic pulmonary artery pressure; TAPSE: tricuspid annular plane systolic excursion; VO2: oxygen consumption.  Abstract Figure

Predicting heart failure transition and progression: a weighted risk score from bio-humoral, cardiopulmonary and echocardiographic stress testing

Abstract Funding Acknowledgements Type of funding sources: None. Aims. We tested the prognostic role of a risk score including bio-humoral evaluation, cardiopulmonary-echocardiographic stress (CPET-ESE) and lung ultrasound, in patients with heart failure (HF) with reduced and preserved ejection fraction (HFrEF and HFpEF), and subjects at risk of developing HF (American College of Cardiology/American Heart Association Stages A and B). Methods and results. We evaluated 318 subjects: 94 in Stages A-B, 194 in Stage C (85 HFpEF and 109 HFrEF), and 30 age and sex-matched controls (Stage 0). During a median follow-up of 18.5 months, we reported 40 urgent HF visits, 31 HF hospitalisations and 10 cardiovascular deaths. Cox proportional-hazards regression for predicting adverse events identified five independent predictors and each was assigned a number of points proportional to its regression coefficient: Δstress-rest B-lines >10 (3 points), peak oxygen consumption <16 mL/kg/min (2 points), minute ventilation/carbon dioxide production slope ≥36 (2 points), peak systolic pulmonary artery pressure ≥50 mmHg (1 point) and resting N-terminal pro-brain natriuretic peptide (NT-proBNP) >900 pg/mL (1 point). We defined three risk categories: low-risk (<3 points), intermediate-risk (3-6 points), and high-risk (>6 points). The event-free survival probability for these three groups were 93%, 52% and 20%, respectively. Hazard Ratio was 4.55 for each risk category upgrade (95% confidence interval [CI], 3.44-5.93). The area-under-curve for the scoring system to predict events was 0.92 (95% CI 0.88-0.96). Conclusion. A multiparametric risk score including indices of exercise-induced pulmonary congestion, markers of cardiopulmonary dysfunction and NT-proBNP identifies patients at increased risk for HF events across the HF spectrum. Table 1 Variable EPYC score EPYC score <3 (low risk) n = 217 EPYC score 3-6 (intermediate risk) n = 70 EPYC score >6 (high risk) n = 31 p-value (between risk categories) Event-free (n = 244) 0 (0 - 2) 210 (97) 32 (46) 2 (6) <0.0001 With events (n = 74) 6 (4 - 9) 7 (3) 38 (54) 29 (94) <0.0001 p-value (event-free vs with events) <0.0001 <0.0001 <0.0001 <0.0001 Stage 0-Controls (n = 30) 0 (0 - 1) 30 0 0 <0.0001 Stages A-B (n = 94) 1 (0 - 2) 85 (45) 6 (9) 3 (10) <0.0001 Stage C-HFpEF (n = 85) 3 (1 - 6)*† 46 (25) 29 (41) 10 (32) <0.0001 Stage C-HFrEF (n = 109) 4 (2 - 7)*† 56 (30) 35 (50) 18 (58) <0.0001 p-value (between HF Stages) <0.0001 <0.0001 <0.0001 <0.0001 Values are mean ± standard deviation, n (%), or median [25th quartile, 75th quartile]. * p < 0.01 vs Stage 0-Controls; † p < 0.01 vs Stages A-B. Abstract Figure

Social-ecological outcomes of agricultural intensification

Land-use intensification in agrarian landscapes is seen as a key strategy to simultaneously feed humanity and use ecosystems sustainably, but the conditions that support positive social-ecological outcomes remain poorly documented. We address this knowledge gap by synthesizing research that analyses how agricultural intensification affects both ecosystem services and human well-being in low- and middle-income countries. Overall, we find that agricultural intensification is rarely found to lead to simultaneous positive ecosystem service and well-being outcomes. This is particularly the case when ecosystem services other than food provisioning are taken into consideration

Semaglutide and NYHA functional class in obesity-related heart failure with preserved ejection fraction the STEP-HFpEF program

Background In the Semaglutide Treatment Effect in People with obesity and HFpEF (STEP-HFpEF) program, semaglutide improved heart failure (HF)-related symptoms, physical limitations, and exercise function, and reduced bodyweight in patients with obesity-related heart failure with preserved ejection fraction (HFpEF). Whether semaglutide improves functional status, as assessed by NYHA functional class, is unknown. Objectives The goal of this study was to examine the effects of semaglutide on change in NYHA functional class over time. We also investigated the effects of semaglutide on HF-related symptoms, physical limitations, and bodyweight and other trial endpoints across baseline NYHA functional class categories. Methods This was a prespecified analysis of pooled data from 2 international, double-blind, randomized trials (STEP-HFpEF and STEP-HFpEF type 2 diabetes [STEP-HFpEF DM], comprising the STEP-HFpEF program), which collectively randomized 1,145 participants with obesity-related HFpEF to once-weekly semaglutide 2.4 mg or placebo for 52 weeks. The outcome of interest for this analysis was the change in NYHA functional class (baseline to 52 weeks). We also investigated the effects of semaglutide on the dual primary, confirmatory secondary, and selected exploratory endpoints according to baseline NYHA functional class. Results More semaglutide-treated than placebo-treated patients had an improvement in NYHA functional class (32.6% vs 21.5%, respectively; OR: 2.20 [95% CI: 1.62-2.99; P < 0.001]) and fewer semaglutide-treated patients experienced deterioration in NYHA functional class (2.09% vs 5.24%, respectively; OR: 0.36 [95% CI: 0.19-0.70; P = 0.003]) at 52 weeks. Semaglutide (vs placebo) improved the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CCS) across NYHA functional class categories; this was especially pronounced in those in NYHA functional classes III/IV (10.5 points [95% CI: 6.6-14.4 points]) vs NYHA functional class II (6.0 points [95% CI: 3.4-8.6 points]) (P interaction = 0.06). By contrast, the degree of reduction in bodyweight was similar with semaglutide vs placebo regardless of baseline NYHA functional class category (NYHA functional class II, −8.4% [95% CI: −9.4% to −7.3%]; NYHA functional classes III/IV, −8.3% [95% CI: −9.9% to −6.8%]; P interaction = 0.96). Semaglutide consistently improved 6-minute walking distance (6MWD), the hierarchical composite endpoint (death, HF events, differences in KCCQ-CSS, and 6MWD changes), and reduced C-reactive protein and N-terminal prohormone of brain natriuretic peptide across NYHA functional class categories (all P interactions = NS). Conclusions In patients with obesity-related HFpEF, fewer semaglutide-treated than placebo-treated patients had a deterioration, and more had an improvement, in NYHA functional class at 52 weeks. Semaglutide consistently improved HF-related symptoms, physical limitations, and exercise function, and reduced bodyweight and biomarkers of inflammation and congestion in all NYHA functional class categories. Semaglutide-mediated improvements in health status were especially large in patients with NYHA functional classes III/IV

Effects of semaglutide on symptoms, function, and quality of life in patients with heart failure with preserved ejection fraction and obesity: a prespecified analysis of the STEP-HFpEF trial

BACKGROUND: Patients with heart failure (HF) with preserved ejection fraction (HFpEF) and obesity experience a high burden of symptoms and functional impairment, and a poor quality of life. In the STEP-HFpEF trial (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity), once-weekly semaglutide 2.4 mg improved symptoms, physical limitations, and exercise function, and reduced inflammation and body weight. This prespecified analysis investigated the effects of semaglutide on the primary and confirmatory secondary end points across the range of the Kansas City Cardiomyopathy Questionnaire (KCCQ) scores at baseline and on all key summary and individual KCCQ domains. METHODS: STEP-HFpEF randomly assigned 529 participants with symptomatic HF, an ejection fraction of ≥45%, and a body mass index of ≥30 kg/m2 to once-weekly semaglutide 2.4 mg or placebo for 52 weeks. Dual primary end points change in KCCQ-Clinical Summary Score (CSS) and body weight. Confirmatory secondary end points included change in 6-minute walk distance, a hierarchical composite end point (death, HF events, and change in KCCQ-CSS and 6-minute walk distance) and change in C-reactive protein. Patients were stratified by KCCQ-CSS tertiles at baseline. Semaglutide effects on the primary, confirmatory secondary, and select exploratory end points (N-terminal pro-brain natriuretic peptide) were examined across these subgroups. Semaglutide effects on additional KCCQ domains (Total Symptom Score [including symptom burden and frequency], Physical Limitations Score, Social Limitations Score, Quality of Life Score, and Overall Summary Score) were also evaluated. RESULTS: Baseline median KCCQ-CSS across tertiles was 37, 59, and 77 points, respectively. Semaglutide consistently improved primary end points across KCCQ tertiles 1 to 3 (estimated treatment differences [95% CI]: for KCCQ-CSS, 10.7 [5.4 to 16.1], 8.1 [2.7 to 13.4], and 4.6 [–0.6 to 9.9] points; for body weight, –11 [–13.2 to –8.8], –9.4 [–11.5 to –7.2], and –11.8 [–14.0 to –9.6], respectively; Pinteraction=0.28 and 0.29, respectively); the same was observed for confirmatory secondary and exploratory end points (Pinteraction>0.1 for all). Semaglutide-treated patients experienced improvements in all key KCCQ domains (estimated treatment differences, 6.7–9.6 points across domains; P≤0.001 for all). Greater proportion of semaglutide-treated versus placebo-treated patients experienced at least 5-, 10-, 15-, and 20-point improvements in all KCCQ domains (odds ratios, 1.6–2.9 across domains; P<0.05 for all). CONCLUSIONS: In patients with HFpEF and obesity, semaglutide produced large improvements in HF-related symptoms, physical limitations, exercise function, inflammation, body weight, and N-terminal pro-brain natriuretic peptide, regardless of baseline health status. The benefits of semaglutide extended to all key KCCQ domains

Erectile dysfunction and heart failure: the role of phosphodiesterase type 5 inhibitors

The phosphodiesterase type 5 (PDE-5) inhibitors are effective in treating erectile dysfunction (ED). ED and heart failure (HF) share similar risk factors, and commonly present together. This association has led to questions ranging from the safety and efficacy of PDE-5 inhibitors in HF patients to a possible role for this class of medication to treat HF patients with or without ED. In addition to endothelial dysfunction, there are causes of ED specific to patients with HF including low exercise tolerance, depression and HF medications. Before treating HF patients with PDE-5 inhibitors, patients should be assessed for their risk of a cardiac event during sexual activity. PDE-5 inhibitors are safe and effective in treating ED in HF patients. An improvement in erectile function by PDE-5 inhibitors was associated with an improvement in quality of life and reduction in depression. Several studies demonstrated the effect of PDE-5 inhibitors on HF per se. PDE-5 inhibitors improved endothelial dysfunction, increased exercise tolerance, decreased pulmonary vascular resistance and pulmonary artery pressure, and increased cardiac index. Several mechanisms whereby PDE-5 inhibitors improve HF have been proposed. PDE-5 inhibitors already have a role in treating primary pulmonary hypertension; however additional studies are needed to determine if they will become a standard therapy for HF patients

Impact of Diabetes on Postinfarction Heart Failure and Left Ventricular Remodeling

Diabetes mellitus, the metabolic syndrome, and the underlying insulin resistance are increasingly associated with diastolic dysfunction and reduced stress tolerance. The poor prognosis associated with heart failure in patients with diabetes after myocardial infarction is likely attributable to many factors, important among which is the metabolic impact from insulin resistance and hyperglycemia on the regulation of microvascular perfusion and energy generation in the cardiac myocyte. This review summarizes epidemiologic, pathophysiologic, diagnostic, and therapeutic data related to diabetes and heart failure in acute myocardial infarction and discusses novel perceptions and strategies that hold promise for the future and deserve further investigation