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Abstract Pulmonary arterial hypertension (PAH) is a disease characterized by pulmonary vascular remodeling. Since dephosphorylated-uncarboxylated Matrix Gla-Protein (dp-ucMGP) is associated with cardiovascular mortality in systemic sclerosis, a disease associated with PAH, and immune-system involvement in PAH is increasingly recognized, we investigated the relationship between dp-ucMGP, vascular remodeling and soluble immune-checkpoint proteins in PAH. This prospective cohort study included patients with idiopathic (I)PAH, connective tissue disease (CTD)-PAH, chronic thrombo-embolic PH (CTEPH) and CTD patients without PAH. Patients with IPAH and CTD-PAH were stratified by clinical signs of immune-mediated inflammatory disease (IMID). We measured dp-ucMGP plasma levels, soluble immune-checkpoint proteins (sICPs), and vascular smooth muscle cell (iVSMC) calcification. We found elevated dp-ucMGP levels in all PAH subtypes and CTD patients compared to healthy controls. PAH patients showed increased iVSMC calcification, but no direct correlation was found with dp-ucMGP. IMID-PAH patients had higher dp-ucMGP levels than non-IMID PAH patients. dp-ucMGP correlated with several sICPs in both IPAH and CTD patients; multiple sICPs were elevated in IMID PAH patients. High dp-ucMGP levels in IPAH patients were associated with worse survival. Our findings suggest dp-ucMGP as a potential biomarker of immune-mediated vascular remodeling in PAH. Hence, dp-ucMGP, could help identify PAH patients who might benefit from immunosuppressive therapies.

Objective: Systemic sclerosis (SSc) related mortality and morbidity remains high. Immunosuppressive therapy is considered most effective when immune activity and inflammation but not fibrosis still dominates the disease process. This study evaluated long-term intensified immunosuppression combined with therapeutic plasma exchange (TPE) in early-onset progressive SSc-related interstitial lung disease (ILD). Methods: The study cohort consisted of 161 SSc patients, with a median follow-up time of 8.9 years. The standardized mortality rate (SMR) and overall survival was calculated in patients with and without cardiopulmonary involvement. We used a standardized, pragmatic, non-randomized approach to treat 24 consecutive early progressive SSc-ILD patients with intensified immunosuppressive therapy, including plasma exchange. Outcome measurements were event-free survival (EFS), pulmonary function and safety profile. The outcome was compared with the analyzed data from the other SSc-ILD patients, who did not fulfill the inclusion criteria, and instead were treated with estimated optimal care (EOc). Results: The age-adjusted SMR of all 161 SSc patients was 3.0 (CI95%; 0.32–5.68). EFS at 10 years was 49.9% in the intensified treatment group and 43.3% in the EOc group (p = 0.106). Improvement of the percentage of predicted forced vital capacity (%pFVC) and percentage of predicted diffusing capacity for carbon monoxide (%pDLco) in the intensified treatment group was +10.1% respectively +3.6%, compared to a decrease of respectively 10.8% and 7% in the EOc (p

An asymptomatic respiratory viral infection during cardiac surgery could lead to pulmonary complications and increased mortality. For elective surgery, testing for respiratory viral infection before surgery or vaccination could reduce the number of these pulmonary complications. The aim of this study was to investigate the association between influenzalike illness (ILI) seasons and prolonged mechanical ventilation and inhospital mortality in a Dutch cohort of adult elective cardiac surgery patients. Cardiac surgery patients who were admitted to the intensive care unit between January 1, 2014, and February 1, 2020, were included. The primary endpoint was the duration of invasive mechanical ventilation in the ILI season compared with baseline season. Secondary endpoints were the median Pa o 2 to fraction of inspired oxygen ratio on days 1, 3, and 7 and postoperative inhospital mortality. A total of 42,277 patients underwent cardiac surgery, 12,994 (30.7%) in the ILI season, 15,843 (37.5%) in the intermediate season, and 13,440 (31.8%) in the baseline season. No hazard rates indicative of a longer duration of invasive mechanical ventilation during the ILI season were found. No differences were found for the median Pa o 2 to fraction of inspired oxygen ratio between seasons. However, inhospital mortality was higher in the ILI season compared with baseline season (odds ratio 1.67; 95% CI, 1.14-2.46). Patients undergoing cardiac surgery during the ILI season were at increased risk of inhospital mortality compared with patients in the baseline season. No evidence was found that this difference is caused by direct postoperative pulmonary complications. [Display omitted] [ABSTRACT FROM AUTHOR]

Hypertensive emergency can cause thrombotic microangiopathy (TMA) in the kidneys with high rates of end-stage renal disease (ESRD) and vice versa. The conundrum of hypertension as the cause of TMA or consequence of TMA on the background of defects in complement regulation remains difficult. Patients with hypertensive emergency and TMA on kidney biopsy were tested for ex vivo C5b9 formation on the endothelium and rare variants in complement genes to identify complement-mediated TMA. We identified factors associated with defects in complement regulation and poor renal outcomes. Massive ex vivo C5b9 formation was found on resting endothelial cells in 18 (69%) out of 26 cases at the presentation, including the 9 patients who carried at least one rare genetic variant. Thirteen (72%, N=18) and 3 (38%, N=8) patients with massive and normal ex vivo complement activation, respectively, progressed to ESRD (P=0.03). In contrast to BP control, inhibition of C5 activation prevented ESRD to occur in 5 (83%, N=6) patients with massive ex vivo complement activation. TMA-related graft failure occurred in 7 (47%, N=15) donor kidneys and was linked to genetic variants. The assessment of both ex vivo C5b9 formation and screening for rare variants in complement genes may categorize patients with hypertensive emergency and TMA into different groups with potential therapeutic and prognostic implications. We propose an algorithm to recognize patients at the highest risk for defects in complement regulation. [ABSTRACT FROM AUTHOR]

Highlights • Both metis and techne are employed in tick control practices in Laikipia. • Ranchers mainly use techne, pastoralists construct additional metis for tick management. • Collapse of state tick control did not stop community tick control. • Acaricide use practices needs techne advise to make it safe for livestock and humans. • Knowledge is shared within groups, though not between groups. Abstract Prevention of tick borne diseases is often through tick control practices. This article diagnoses tick control practices, knowledge underlying these practices and how knowledge is shared at the wildlife-livestock interface in Laikipia County, Kenya. It identifies diverse land use and tick control practices by different land and livestock owners from a scientific knowledge-based (techne) and context driven experiential knowledge-based (metis) perspective. Interviews, focus group discussions, observations and documents yielded qualitative data to unravel i) the historical development of tick control in Kenya ii) techne and metis tick control practices within three ranches and among pastoralists in Laikipia County, and iii) status of tick knowledge sharing between stakeholders. Historical tick control measures date back to about 100 years ago, with increasingly strong veterinary measures over the decades under government control. However, the veterinary control system collapsed around 1991 and livestock owners took tick control into their own hands. All respondents indicated having relevant techne available about tick ecology and tick management practices. To adapt to the changing social, economic and institutional context, they further developed metis, integrating the known techne. Metis and techne complemented each other. Our study reveals that metis is developed within stakeholder groups. The data also suggest that metis practices sometimes develop risky effects to animal, human and environmental health. Knowledge on tick control is mainly shared within a social group, not between groups. We esteem, knowledge sharing between different stakeholder groups (ranchers, pastoralists, DVS) may provide opportunities for better informed decision-making based on fruitful combinations of techne and metis for effective and safe tick management. [ABSTRACT FROM AUTHOR]

Highlights • Mistrust, information gaps and weak control measures impede maize credit cooperation. • Digital platforms promise to decentralize data collection and information delivery to enhance trust building and cooperation. • Platforms enable new connectivity and cooperation particularly for coordinated responsiveness to agro-ecological farm conditions. • Appropriate intermediation, network governance and farmer digital inclusion needed for realizing digital platform potential. • Reflection, contextualization and learning necessary to adapt digital platforms for trust building in credit provision. Abstract Maize production is of critical importance to smallholder farmers in Ghana. Various factors limit the productivity of smallholder maize farming systems undergirded by the lack of capital for critical investments both at the farm and at national policy levels. Using a value chain approach, this diagnostic study explains how a complex configuration of actor interaction within an institutionally and agro-ecologically challenged value chain leads to the enduring absence of maize farming credit support. We find a cycle of credit rationing resulting from value chain challenges such as agro-ecological uncertainties, inadequate GAPs training, weak farmer groups and market insecurity. This condition is sustained by an interplay between mistrust, insufficient information across the value chain and inadequate control strategies in the maize credit system. We argue that Digital Platforms (DPs) show potential to help overcome some information and communication gaps and related uncertainties that impede traditional value chain credit arrangements. This is promising in terms of aiding awareness and coordinated responsiveness to agro-ecological farm conditions and the development of farming records databases. Thus, DPs could generate new networks and forms of cooperation in the maize value chain in this regard. As a tool for mediating trust in value chain credit cooperation, strategic use of these DP contributions could help initiate an entry point for recalibration of trust perceptions. Significant considerations and improvements are however needed to harness DPs effectively in mediating trust for maize credit provision, not least being farmer digital inclusion in DP implementation, effective intermediation and network governance arrangements and digital contributions towards cost-effective agro-ecological controls in the erratic maize farming context. This approach to trust building should therefore not be viewed as a quick fix but as a process of trial and error, and learning by doing. [ABSTRACT FROM AUTHOR]

Highlights • Public and private extension organisations use new-ICTs to augment service delivery and facilitate aspects of innovation-intermediation. • Efforts to support innovation-intermediation used decentralised data collection, monitoring and enhanced connectivity. • The potential of new-ICTs to support innovation-intermediation roles is far from realised. • Conventional communication media remain appropriate for extension service delivery and innovation-intermediation. • Self-organised social media platforms may enhance interaction in innovations systems to achieve collective goals. Abstract Agricultural extension in sub-Saharan Africa has often been criticised for its focus on linear knowledge transfer, and limited attention to systemic approaches to service delivery. Currently, the region is experiencing a new-ICT revolution and there are high expectations of new-ICTs to enhance interaction and information exchange in extension service delivery. Using an innovation systems perspective, we distinguish the roles demand-articulation, matching demand and supply, and innovation process management for innovation-intermediaries. The study explores literature on how new-ICT may support these roles, with specific interest in the possibilities of environmental monitoring and new forms of organisation enabled by enhanced connectivity. In order to contribute to the understanding of this area, the paper reports on a comparative study of two new-ICT platforms embedded in Ghanaian public and private extension organisations respectively. We assess the roles that these platforms (aim to) support, and document achievements and constraints based on interviews with extension staff and farmers. The findings indicate that while both platforms aim to support innovation-intermediation roles the focus areas and level of detail differ due to diverging organisational rationales to service delivery. In addition, we see that new-ICTs' potential to support innovation-intermediation roles is far from realised. This is not due to (new) ICTs lacking the capacity to link people in new ways and make information accessible, but due to the wider social, organisational and institutional factors that define the realisation of their potential. Therefore, more conventional modes of interaction around production advice and also credit provision continue to be dominant and better adapted to the situation. However, beyond the two platforms that were developed specifically by and for the extension organisations, there were indications that more informal and self-organised new-ICT initiatives can transform and enhance interaction patterns in innovations systems to achieve collective goals through standard virtual platforms such as WhatsApp and Telegram. [ABSTRACT FROM AUTHOR]

Trade globalisation and climate change pose new challenges for food security in Africa. To unlock smallholder productivity, more understanding is needed of the institutional context and the role of development interventions, such as partnerships, in the food sector. This article proposes institutional logics as a theory and methodology for institutional diagnosis to gain insight into context-embedded negotiation and change processes created by project-based partnership interventions. We analyse the institutional logics of organisations active in the development of two value chains in Ghana to subsequently show how, in partnerships, these logics are negotiated in light of the objectives and interests of the intervention. The main findings are that donors, with their market and professionalisation logics, are quite influential, but many other development actors still adhere to principles of grassroots empowerment and social security. In the evolving partnership process, market logic remains strong, but coupled with institutional logics endorsing farmer empowerment and solidarity with the resource-poor. This is done in a process of bricolage in which field level implementers go against the dominant logic of project initiators: showing that newly introduced development logics are mitigated by an existing local structure fostering other development logics. The broader implication is that new development paradigms may need a considerable transition period to become mainstream. The concepts of institutional logics and bricolage as a diagnostic tool allow researchers to characterise the adherence to and blending of institutional logics by actors. This tool helps to understand the mobilisation strategy of the initiator and to follow the negotiation of logics that takes place amongst partners in partnerships. Detailed insights into the blending of potential partners’ logics, pathways of negotiation processes and the plausible outcomes enable development practitioners to strategically prepare and manage their collaborative interventions. [ABSTRACT FROM AUTHOR]

BACKGROUND: Inflammatory cardiomyopathy (infl-CMP) is characterized by increased cardiac inflammation in the absence of viruses, ischemia, valvular disease, or other apparent causes. Studies addressing the efficacy of immunosuppressive therapy in patients with infl-CMP are sparse. This study retrospectively investigates whether immunosuppressive agents on top of heart failure therapy according to current guidelines improves cardiac function and long-term outcome in patients with infl-CMP. METHODS AND RESULTS: Within the Innsbruck and Maastricht Cardiomyopathy Registry, a total of 209 patients fulfilled the criteria for infl-CMP using endomyocardial biopsy (≥14 infiltrating inflammatory cells/mm2). A total of 110 (53%) patients received immunosuppressive therapy and 99 (47%) did not. To correct for potential selection bias, 1:1 propensity score matching was used on all significant baseline parameters, resulting in a total of 90 patients per group. Baseline characteristics did not significantly differ between both patient groups, reflecting optimal propensity score matching. After a median follow-up of 31 (15--47) months, immunosuppressive therapy resulted in an improved long-term outcome (eg, heart transplantation--free survival) as compared with standard heart failure therapy alone (Log-rank P=0.043; hazard ratio, 0.34 [95% CI, 0.17--0.92]) and in a significant larger increase of left ventricular ejection fraction after a mean of 12 months follow-up, as compared with patients receiving standard heart failure treatment only (12.2% versus 7.3%, respectively; P=0.036). CONCLUSIONS: To conclude, this study suggests that immunosuppressive therapy in infl-CMP patients results in an improved heart transplantation-- free survival as compared with standard heart failure therapy alone, underscoring the urgent need for a large prospective multicenter trial. [ABSTRACT FROM AUTHOR]