Scaling of innovations is a key requirement for addressing societal challenges in sectors such as health, agriculture, and the environment. Research for development (R4D) programs, projects and other ...interventions struggle to make particular innovations go to scale. Current conceptualizations of scaling are often too simplistic; more systemic and multidimensional perspectives, frameworks and measures are needed. There is a gap between new complexity-aware theories and perspectives on innovation, and tools and approaches that can improve strategic and operational decision-making in R4D interventions that aim to scale innovations. This paper aims to bridge that gap by developing the key concepts and measures of Scaling Readiness. Scaling Readiness is an approach that encourages critical reflection on how ready innovations are for scaling and what appropriate actions could accelerate or enhance scaling. Scaling Readiness provides action-oriented support for (1) characterizing the innovation and innovation system; (2) diagnosing the current readiness and use of innovations as a proxy for their readiness to scale; (3) developing strategy to overcome bottlenecks for scaling; (4) facilitating and negotiating multi-stakeholder innovation and scaling processes; and (5) navigating and monitoring the implementation process to allow for adaptive management. Scaling Readiness has the potential to support evidence-based scaling strategy design, implementation and monitoring, and – if applied across multiple interventions – can be used to manage a portfolio of innovation and scaling investments.
•Scaling of innovation to achieve impact requires systems approaches.•There is need to translate systems theory into action-oriented decision support.•Performance management of innovation and scaling processes is key in R4D.•Scaling Readiness offers a stepwise process to develop scaling strategies.•Scaling Readiness can monitor a portfolio of innovation and scaling investment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
IMPORTANCE: Cardiogenic shock affects between 40 000 and 50 000 people in the US per year and is the leading cause of in-hospital mortality following acute myocardial infarction. OBSERVATIONS: ...Thirty-day mortality for patients with cardiogenic shock due to myocardial infarction is approximately 40%, and 1-year mortality approaches 50%. Immediate revascularization of the infarct-related coronary artery remains the only treatment for cardiogenic shock associated with acute myocardial infarction supported by randomized clinical trials. The Percutaneous Coronary Intervention Strategies with Acute Myocardial Infarction and Cardiogenic Shock (CULPRIT-SHOCK) clinical trial demonstrated a reduction in the primary outcome of 30-day death or kidney replacement therapy; 158 of 344 patients (45.9%) in the culprit lesion revascularization–only group compared with 189 of 341 patients (55.4%) in the multivessel percutaneous coronary intervention group (relative risk, 0.83 95% CI, 0.71-0.96; P = .01). Despite a lack of randomized trials demonstrating benefit, percutaneous mechanical circulatory support devices are frequently used to manage cardiogenic shock following acute myocardial infarction. CONCLUSIONS AND RELEVANCE: Cardiogenic shock occurs in up to 10% of patients immediately following acute myocardial infarction and is associated with mortality rates of nearly 40% at 30 days and 50% at 1 year. Current evidence and clinical practice guidelines support immediate revascularization of the infarct-related coronary artery as the primary therapy for cardiogenic shock following acute myocardial infarction.
Feedlots are potential point sources for the flow of antibiotics into the environment due to common use of antibiotics such as sulfamethazine, chlortetracycline and tylosin. Hence soils and manures ...originating from a grassland control, an experimental and a commercial feedlot were analyzed and mass balances were calculated for these antibiotics. Up to 9990
μg
kg
−1 sulfamethazine and 401
μg
kg
−1 chlortetracycline on a dry matter basis were determined in feedlot manure. Soil concentrations were two orders of magnitude smaller. This corresponds to 7–40% of the calculated residual amount. In the commercial feedlot chlortetracycline was found down to soil depths of −40
cm; sulfamethazine was still detectable 1 year after medication. Sulfamethazine and chlortetracycline were additionally determined in manure of a control treatment in the experimental feedlot where cattle never received antibiotics. This was attributed to runoff from upslope pens. Consequently, antibiotics partially persist within feedlots and may be dislocated into the surrounding environment by vertical transport and runoff.
Veterinary antibiotics partially persist within feedlots and may be dislocated to the environment by transport processes following subtherapeutic application to cattle.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In aneurysmal subarachnoid hemorrhage (aSAH), accurate diagnosis of aneurysm is essential for subsequent treatment to prevent rebleeding. However, aneurysm detection proves to be challenging and ...time-consuming. The purpose of this study was to develop and evaluate a deep learning model (DLM) to automatically detect and segment aneurysms in patients with aSAH on computed tomography angiography. In this retrospective single-center study, three different DLMs were trained on 68 patients with 79 aneurysms treated for aSAH (2016-2017) using five-fold-cross-validation. Their outputs were combined to a single DLM via ensemble-learning. The DLM was evaluated on an independent test set consisting of 185 patients with 215 aneurysms (2010-2015). Independent manual segmentations of aneurysms in a 3D voxel-wise manner by two readers (neurosurgeon, radiologist) provided the reference standard. For aneurysms > 30 mm
(mean diameter of ~ 4 mm) on the test set, the DLM provided a detection sensitivity of 87% with false positives (FPs)/scan of 0.42. Automatic segmentations achieved a median dice similarity coefficient (DSC) of 0.80 compared to the reference standard. Aneurysm location (anterior vs. posterior circulation; P = .07) and bleeding severity (Fisher grade ≤ 3 vs. 4; P = .33) did not impede detection sensitivity or segmentation performance. For aneurysms > 100 mm
(mean diameter of ~ 6 mm), a sensitivity of 96% with DSC of 0.87 and FPs/scan of 0.14 were obtained. In the present study, we demonstrate that the proposed DLM detects and segments aneurysms > 30 mm
in patients with aSAH with high sensitivity independent of cerebral circulation and bleeding severity while producing FP findings of less than one per scan. Hence, the DLM can potentially assist treating physicians in aSAH by providing automated detection and segmentations of aneurysms.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Patients experiencing out-of-hospital cardiac arrest (OHCA) without ST-segment elevation are a heterogenic group with a variety of underlying causes. Up to one-third of patients display a significant ...coronary lesion compatible with myocardial infarction as OHCA trigger. There are no randomized data on patient selection and timing of invasive coronary angiography after admission.
The TOMAHAWK trial randomly assigns 558 patients with return of spontaneous circulation after OHCA with no obvious extracardiac origin of cardiac arrest and no ST-segment elevation/left bundle-branch block on postresuscitation electrocardiogram to either immediate coronary angiography or initial intensive care assessment with delayed/selective angiography in a 1:1 ratio. The primary end point is 30-day all-cause mortality. Secondary analyses will be performed with respect to initial rhythm, electrocardiographic patterns, myocardial infarction as underlying cause, neurological outcome, as well as clinical and laboratory markers. Clinical follow-up will be performed at 6 and 12 months. Safety end points include bleeding and stroke.
The TOMAHAWK trial will address the unresolved issue of timing and general indication of angiography after OHCA without ST-segment elevation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Intrinsic timescales characterize dynamics of endogenous fluctuations in neural activity. Variation of intrinsic timescales across the neocortex reflects functional specialization of cortical areas, ...but less is known about how intrinsic timescales change during cognitive tasks. We measured intrinsic timescales of local spiking activity within columns of area V4 in male monkeys performing spatial attention tasks. The ongoing spiking activity unfolded across at least two distinct timescales, fast and slow. The slow timescale increased when monkeys attended to the receptive fields location and correlated with reaction times. By evaluating predictions of several network models, we found that spatiotemporal correlations in V4 activity were best explained by the model in which multiple timescales arise from recurrent interactions shaped by spatially arranged connectivity, and attentional modulation of timescales results from an increase in the efficacy of recurrent interactions. Our results suggest that multiple timescales may arise from the spatial connectivity in the visual cortex and flexibly change with the cognitive state due to dynamic effective interactions between neurons.
Soil metabolism of sulfonamides is largely unknown. Hence the sulfonamides sulfanilamide (SAA), sulfadimethoxine (SDT) and sulfapyridine (SPY) were reacted in model experiments with a fungal laccase ...from
Trametes versicolor. Enzymatic transformation after a reaction time of 15
d ranged from 10.0% for SAA up to 95.6% for SPY and the difference was attributed to the different molecular substituents. Metabolites were first tentatively assigned after LC–ESI
+–MS full-scan analysis. Secondly, the proposed metabolites were further confirmed employing either multiple reaction monitoring in comparison with standard substances or precursor ion scan LC–ESI
+–MS/MS experiments striving for the precursor and two to three product ions. Aniline was confirmed as a breakdown product of SPY and further metabolites of SPY and of SDT were identified as rearranged SO
2 extrusion products. Thirdly, some of the metabolites matched those that were previously reported for sulfonamide photodegradation and degradation in soil. It was concluded that enzymatic metabolism as investigated here also occurs in soil.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Quality indicators (QIs) are tools to improve the delivery of evidence-base medicine. In 2017, the European Society of Cardiology (ESC) Association for Acute Cardiovascular Care (ACVC) developed a ...set of QIs for acute myocardial infarction (AMI), which have been evaluated at national and international levels and across different populations. However, an update of these QIs is needed in light of the accumulated experience and the changes in the supporting evidence.
The ESC methodology for the QI development was used to update the 2017 ACVC QIs. We identified key domains of AMI care, conducted a literature review, developed a list of candidate QIs, and used a modified Delphi method to select the final set of indicators. The same seven domains of AMI care identified by the 2017 Study Group were retained for this update. For each domain, main and secondary QIs were developed reflecting the essential and complementary aspects of care, respectively. Overall, 26 QIs are proposed in this document, compared to 20 in the 2017 set. New QIs are proposed in this document (e.g. the centre use of high-sensitivity troponin), some were retained or modified (e.g. the in-hospital risk assessment), and others were retired in accordance with the changes in evidence e.g. the proportion of patients with non-ST segment elevation myocardial infarction (NSTEMI) treated with fondaparinux and the feasibility assessments (e.g. the proportion of patients with NSTEMI whom risk assessment is performed using the GRACE and CRUSADE risk scores).
Updated QIs for the management of AMI were developed according to contemporary knowledge and accumulated experience. These QIs may be applied to evaluate and improve the quality of AMI care.
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