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Malawi has been a trend-setter for agricultural policies in Africa for decades. The country��s focus on maximizing staple production through input subsidies, mainly for fertilizer, has been adopted by numerous other African governments. However, this study uncovers disturbing trends that indicate intensification and sustainability are at risk in Malawi. Two time-series of satellite data and combined results of several farmer survey-based analyses that span decades suggest declining land productivity and yield response rates to fertilizer. ��� These indications that narrowly focused policies may be harmful in the long run for Malawi are a warning to policy makers in the country and around the continent that a more holistic strategy that considers soil health will be necessary for sustainable intensification in agriculture.

We study planning problems for dynamical systems with uncertainty caused by measurement and process noise. Measurement noise causes limited observability of system states, and process noise causes uncertainty in the outcome of a given control. The problem is to find a controller that guarantees that the system reaches a desired goal state in finite time while avoiding obstacles, with at least some required probability. Due to the noise, this problem does not admit exact algorithmic or closed-form solutions in general. Our key contribution is a novel planning scheme that employs Kalman filtering as a state estimator to obtain a finite-state abstraction of the dynamical system, which we formalize as a Markov decision process (MDP). By extending this MDP with intervals of probabilities, we enhance the robustness of the model against numerical imprecision in approximating the transition probabilities. For this so-called interval MDP (iMDP), we employ state-of-the-art verification techniques to efficiently compute plans that maximize the probability of reaching goal states. We show the correctness of the abstraction and provide several optimizations that aim to balance the quality of the plan and the scalability of the approach. We demonstrate that our method is able to handle systems with a 6-dimensional state that result in iMDPs with tens of thousands of states and millions of transitions.

In upstream oil and gas production, flow measurement errors are common at multiple locations in the production system. These measurement errors lead to imbalances, which are reconciled by using allocation methods. The allocation method should redistribute the imbalance in a fair manner to all involved stakeholders. In this paper, data validation and reconciliation (DVR) is proposed as an alternative allocation method in multiphase production systems. DVR is a model-based optimization method that exploits redundancies in process data to minimize random measurement errors, and simultaneously provides a basis for the detection of gross errors. To study the applicability of DVR compared to conventional allocation methods, a model for generic multiphase production systems is developed, and the corresponding DVR problem is formulated. In order to deal with nonlinear flow effects (e.g. interphase mass transfer) the model is linearized around the operating conditions and the DVR problem is solved iteratively. From the simulation studies, it is concluded that DVR reduces measurement errors by up to 56% for gas allocation systems and 33% for multiphase systems. Gross errors in interior locations of the network can be located precisely, while allocating gross errors to exterior locations is generally not possible, due to limited network redundancy. Compared to conventional methods, DVR provides a better means for the detection of gross errors, and results in more accurate attribution of oil/gas ownership and more fair division of revenues between stakeholders.

Importance:Fixed-dose combination (FDC) therapies are being increasingly recommended for initial or early management of patients with hypertension, as they reduce treatment complexity and potentially reduce therapeutic inertia. Objective:To investigate the association of antihypertensive triple drug FDC therapy with therapeutic inertia and prescribing patterns compared with usual care. Design, Setting, and Participants:A post hoc analysis of the Triple Pill vs Usual Care Management for Patients With Mild-to-Moderate Hypertension (TRIUMPH) study, a randomized clinical trial of 700 patients with hypertension, was conducted. Patients were enrolled from 11 urban hospital clinics in Sri Lanka from February 2016 to May 2017; follow-up ended in October 2017. Data were analyzed from September to November 2019. Interventions:Once-daily FDC antihypertensive pill (telmisartan, 20 mg; amlodipine, 2.5 mg; and chlorthalidone, 12.5 mg) or usual care. Main Outcomes and Measures:Therapeutic inertia, defined as not intensifying therapy in those with blood pressure (BP) above target, was assessed at baseline and during follow-up visits. Prescribing patterns were characterized by BP-lowering drug class and treatment regimen potency. Predictors of therapeutic inertia were assessed with binomial logistic regression. Results:Of the 700 included patients, 403 (57.6%) were female, and the mean (SD) age was 56 (11) years. Among patients who did not reach the BP target, therapeutic inertia was more common in the triple pill group compared with the usual care group at the week 6 visit (92 of 106 [86.8%] vs 124 of 194 [63.9%]; P

In this work, we prove a refinement of the Gallai-Edmonds structure theorem for weighted matching polynomials by Ku and Wong. Our proof uses a connection between matching polynomials and branched continued fractions. We also show how this is related to a modification by Sylvester of the classical Sturm's theorem on the number of zeros of a real polynomial in an interval. In addition, we obtain some other results about zeros of matching polynomials.

This paper presents a dynamical Building-to-Grid (BtG) framework with explicit hierarchical interactions between Transmission System Operator (TSO), Distribution System Operator (DSO), and Building energy storage units (BLD). Such a proposed hierarchical multi-level framework, yields a realistic model of the future power system, which can be used to present the interaction between different stakeholders in the power system. Using a centralized model predictive control (MPC) to optimize BLD, DSO, and TSO control variables simultaneously over a common time horizon, we demonstrate the potential role of individual buildings in frequency control of the power system, by introducing electrical energy storage units in the BtG framework. We present the power grid regulative capacity of building storage flexibility by coupling BLD, DSO, and TSO decisions and solving the corresponding finite-horizon optimal control problem in a receding horizon fashion. An extended IEEE five bus power system case study coupled with two DSOs, each contains seven buildings, is presented to illustrate functionality of the developed integrated hierarchical BtG model and the flexibility obtained via building energy storage units for the frequency control service in power system.

• We highlight the need for and a path towards policies Malawi could adopt to achieve economic development and transformation. • Overarching challenges include policy unpredictability, incomplete implementation, and poor coordination among stakeholders. • FISP spending crowds out other investments that could address low productivity and environmental degradation. • Leadership requires political will, evidence-based analysis, and a coalition of public, private, donor and NGO interests. • MwAPATAʼs Agriculture Policy Reform Mechanism (MAReM) will facilitate this coalition to improve Malawian agriculture.

Purpose of Review Circadian rhythms, including 24-h activity rhythms, change with age. Disturbances in these 24-h activity rhythms at older age have also been implied in various diseases. This review evaluates recent findings on 24-h activity rhythms and disease in older adults. Recent Findings Growing evidence supports that 24-h activity rhythm disturbances at older age are related to the presence and/or progression of disease. Longitudinal and genetic work even suggests a potential causal contribution of disturbed 24-h activity rhythms to disease development. Interventional studies targeting circadian and 24-h activity rhythms demonstrate that 24-h rhythmicity can be improved, but the effect of improving 24-h rhythmicity on disease risk or progression remains to be shown. Summary Increasing evidence suggests that 24-h activity rhythms are involved in age-related diseases. Further studies are needed to assess causality, underlying mechanisms, and the effects of treating disturbed 24-h activity rhythms on age-related disease.

Sleep problems increase with ageing. Increasing evidence suggests that sleep problems are not only a consequence of age-related processes, but may independently contribute to developing vascular or neurodegenerative brain disease. Yet, it remains unclear what mechanisms underlie the impact sleep problems may have on brain health in the general middle-aged and elderly population. Here, we studied sleep's relation to brain functioning in 621 participants (median age 62 years, 55% women) from the population-based Rotterdam Study. We investigated cross-sectional associations of polysomnographic and subjectively measured aspects of sleep with intrinsic neural activity measured with resting-state functional magnetic resonance imaging on a different day. We investigated both functional connectivity between regions and brain activity (blood-oxygen-level-dependent signal amplitude) within regions, hierarchically towards smaller topographical levels. We found that longer polysomnographic total sleep time is associated with lower blood-oxygen-level-dependent signal amplitude in (pre)frontal regions. No objective or subjective sleep parameters were associated with functional connectivity between or within resting-state networks. The findings may indicate a pathway through which sleep, in a 'real-life' population setting, impacts brain activity or regional brain activity determines total sleep time.

Creutzfeldt–Jakob disease is a rare, fatal, neurodegenerative disease caused by the accumulation of abnormally folded prion proteins. The common polymorphism at codon 129 (methionine/valine) in the prion protein (PRNP) gene is the most important determinant of genetic susceptibility. Homozygotes of either allele have a higher risk of sporadic Creutzfeldt–Jakob disease. Various studies suggest that this polymorphism is also involved in other forms of dementia. We studied the association between the codon 129 polymorphism of the PRNP gene and mild cognitive impairment in 3605 participants from the Rotterdam Study using logistic regression analyses. Subsequently, we studied the association between this polymorphism and incident dementia, including Alzheimer’s disease, in 11 070 participants using Cox proportional hazard models. Analyses were adjusted for age and sex. We found the prevalence of mild cognitive impairment to be higher for carriers of the methionine/methionine genotype (odds ratio, 1.40; 95% confidence interval, 1.11–1.78; P = 0.005) as well as for carriers of the valine/valine genotype (odds ratio, 1.37; 95% confidence interval, 0.96–1.97; P = 0.08). The codon 129 polymorphism was not associated with the risk of incident dementia or Alzheimer’s disease. In conclusion, we found a statistically significant higher prevalence of mild cognitive impairment in carriers of the methionine/methionine genotype in the codon 129 polymorphism of the PRNP gene within this population-based study. No associations were found between the codon 129 polymorphism and dementia or Alzheimer’s disease in the general population., There is increasing interest in the role of the common polymorphism at codon 129 in the prion protein gene in neurodegenerative traits. We report a role of this polymorphism in mild cognitive impairment in the general population. However, no association was found with dementia., Graphical Abstract Graphical Abstract

• Closely monitoring food prices could be an early warning system for economic impacts. • Food price spikes could have several causes related to COVID-19, so the drivers will need to be investigated to find the best way to minimize negative impacts on welfare. • Social safety nets for those suffering from spread mitigation measures could improve compliance. • All facets of agricultural value chains are affected. However, the impacts on transportation, especially for inputs, could be the most detrimental to the economy if the pandemic persists. • The most effective economic strategy will likely be containing the spread of the disease. • Current monitoring may not be capturing the true scope of the spread and impact of COVID-19.

Study ObjectivesPoor sleep may destabilize axonal integrity and deteriorate cerebral white matter. In middle-aged and older adults sleep problems increase alongside structural brain changes, but the temporal relation between these processes is poorly understood. We studied longitudinal associations between sleep and cerebral white matter microstructure.MethodsOne thousand one persons (59.3 ± 7.9 years, 55% women) were followed across 5.8 years (3.9–10.8). Total sleep time (TST, hours), sleep efficiency (SE, percentage), sleep onset latency (SOL, minutes), and wake after sleep onset (WASO, minutes) were measured at baseline using a wrist-worn actigraph. White matter microstructure (global and tract-specific fractional anisotropy [FA] and mean diffusivity [MD]) was measured twice with diffusion tensor imaging (DTI).ResultsPoor sleep was associated with worse white matter microstructure up to 7 years later but did not predict trajectories of DTI over time. Longer TST was associated with higher global FA (β = 0.06, 95% CI: 0.01 to 0.12), but not with MD. Persons with higher SE had higher global FA (β = 0.01, 95% CI: 0.002 to 0.01) and lower MD (β = −0.01, 95% CI: −0.01 to −0.0004). Consistently, those with more WASO had lower global FA (β = −0.003, 95% CI: −0.005 to −0.001) and higher MD (β = 0.002, 95% CI: 0.0004 to 0.004). Global findings seemed to be driven by microstructural alterations in the cingulum, anterior forceps of corpus callosum, projection and association tracts.ConclusionsMiddle-aged and older persons with more WASO, lower SE and shorter TST have worse microstructure of cerebral white matter. Microstructural alterations are most pronounced projection and association tracts, in the cingulum, and in the anterior forceps of corpus callosum.

Thrombolytic therapy is one of the medical procedures in the treatment of acute ischaemic stroke (AIS), whereby the tissue plasminogen activator (tPA) is intravenously administered to dissolve the obstructive blood clot. The treatment of AIS by thrombolysis can sometimes be ineffective and it can cause serious complications, such as intracranial haemorrhage (ICH). In this study, we propose an efficient mathematical modelling approach that can be used to evaluate the therapeutic efficacy and safety of thrombolysis in various clinically relevant scenarios. Our model combines the pharmacokinetics and pharmacodynamics of tPA with local clot lysis dynamics. By varying the drug dose, bolus-infusion delay time, and bolus-infusion ratio, with the FDA approved dosing protocol serving as a reference, we have used the model to simulate 13 dose regimens. Simulation results are compared for temporal concentrations of fibrinolytic proteins in plasma and the time that is taken to achieve recanalisation. Our results show that high infusion rates can cause the rapid degradation of plasma fibrinogen, indicative of increased risk for ICH, but they do not necessarily lead to fast recanalisation. In addition, a bolus-infusion delay results in an immediate drop in plasma tPA concentration, which prolongs the time to achieve recanalisation. Therefore, an optimal administration regimen should be sought by keeping the tPA level sufficiently high throughout the treatment and maximising the lysis rate while also limiting the degradation of fibrinogen in systemic plasma. This can be achieved through model-based optimisation in the future.