A 24-Week, Randomized, Treat-to-Target Trial Comparing Initiation of Insulin Glargine Once-Daily With Insulin Detemir Twice-Daily in Patients With Type 2 Diabetes Inadequately Controlled on Oral Glucose-Lowering Drugs

OBJECTIVE - To determine whether glargine is noninferior to detemir regarding the percentage of patients reaching A1C <7% without symptomatic hypoglycemia <= 3.1 mmol/l. RESEARCH DESIGN AND METHODS - In this 24-week trial, 973 insulin-naive type 2 diabetic patients on stable oral glucose-lowering drugs with A1CS. 7.0-10.5% were randomized to glargine once daily or detemir twice daily. Insulin doses were systematically titrated. RESULTS - 27.5 and 25.6% of patients reached the primary outcome with glargine and detemir, respectively, demonstrating the noninferiority of glargine. Improvements in A1C were -1.46 +/- 1.09% for glargine and -1.54 +/- 1.11% for detemir (P = 0.149), with similar proportions of patients achieving A1C <7% (P = 0.254) but more detemir-treated patients reaching A1C <6.5% (P = 0.017). Hypoglycemia risk was similar. Weight gain was higher for glargine (difference: 0.77 kg, P <0.001). Glargine doses were lower than detemir doses: 43.5 +/- 129.0 vs. 76.5 +/- 50.5 units/day (P <0.001). CONCLUSIONS - In insulin-naive type 2 diabetic patients, glargine reached similar control as detemir, with more weight gain, but required significantly lower dose

Coordination Dependence of Hyperfine Fields of 5sp Impurities on Ni Surfaces

We present first-principles calculations of the magnetic hyperfine fields H of 5sp impurities on the (001), (111), and (110) surfaces of Ni. We examine the dependence of H on the coordination number by placing the impurity in the surfaces, on top of them at the adatom positions, and in the bulk. We find a strong coordination dependence of H, different and characteristic for each impurity. The behavior is explained in terms of the on-site s-p hybridization as the symmetry is reduced at the surface. Our results are in agreement with recent experimental findings.Comment: 4 pages, 3 figure

Food Price Shocks and the Political Economy of Global Agricultural and Development Policy

The recent spikes of global food prices induced a rapid increase in mass media coverage, public policy attention, and donor funding for food security and for agriculture and rural poverty. This has occurred while the shift from low to high food prices has induced a shift in (demographic or social) location of the hunger and poverty effects, but the total number of undernourished and poor people has declined over the same period. We suggest that the observed pattern can be explained by the presence of a global urban bias on agriculture and food policy in developing countries, and we discuss whether this global urban bias may actually benefit poor farmers. We argue that the food price spikes have succeeded where others have failed in the past: to move the problems of poor and hungry farmers to the top of the policy agenda and to induce development and donor strategies to help them

Business process variant analysis based on mutual fingerprints of event logs

Comparing business process variants using event logs is a common use case in process mining. Existing techniques for process variant analysis detect statistically-significant differences between variants at the level of individual entities (such as process activities) and their relationships (e.g. directly-follows relations between activities). This may lead to a proliferation of differences due to the low level of granularity in which such differences are captured. This paper presents a novel approach to detect statistically-significant differences between variants at the level of entire process traces (i.e. sequences of directly-follows relations). The cornerstone of this approach is a technique to learn a directly-follows graph called mutual fingerprint from the event logs of the two variants. A mutual fingerprint is a lossless encoding of a set of traces and their duration using discrete wavelet transformation. This structure facilitates the understanding of statistical differences along the control-flow and performance dimensions. The approach has been evaluated using real-life event logs against two baselines. The results show that at a trace level, the baselines cannot always reveal the differences discovered by our approach, or can detect spurious differences.This research is partly funded by the Australian Research Council (DP180102839) and Spanish funds MINECO and FEDER (TIN2017-86727-C2-1-R).Peer ReviewedPostprint (author's final draft

Revisiting the 'Cotton Problem': A Comparative Analysis of Cotton Reforms in Sub-Saharan Africa

The cotton sector has been amongst the most regulated in Africa, and still is to a large extent in West and Central Africa (WCA), despite repeated refirm recommendations by international donors. On the other hand, orthodox refirms in East and Southern Africa (ESA) have not always yielded the expected results. This paper uses a stylised contracting model to investigate the link between market structure and equity and efficiency in sub-Saharan cotton sectors; explain the outcomes of refirms in ESA; and analyze the potential consequences of orthodox refirms in WCA. We argue that the level of the world price and of government intervention, the nature of pre-refirm institutional organisation, as well as the degree of parastatal inefficiency, all contribute to making refirms less attractive to firmers and governments in WCA today, as compared to ESA in the 1990s.We illustrate our arguments with empirical observations on the perfirmance of cotton sectors across sub-Saharan Africa

WiseEye: next generation expandable and programmable camera trap platform for wildlife research

Funding: The work was supported by the RCUK Digital Economy programme to the dot.rural Digital Economy Hub; award reference: EP/G066051/1. The work of S. Newey and RJI was part funded by the Scottish Government's Rural and Environment Science and Analytical Services (RESAS). Details published as an Open Source Toolkit, PLOS Journals at: http://dx.doi.org/10.1371/journal.pone.0169758Peer reviewedPublisher PD

ATP13A2 deficiency disrupts lysosomal polyamine export

ATP13A2 (PARK9) is a late endolysosomal transporter that is genetically implicated in a spectrum of neurodegenerative disorders, including Kufor-Rakeb syndrome—a parkinsonism with dementia1—and early-onset Parkinson’s disease2. ATP13A2 offers protection against genetic and environmental risk factors of Parkinson’s disease, whereas loss of ATP13A2 compromises lysosomes3. However, the transport function of ATP13A2 in lysosomes remains unclear. Here we establish ATP13A2 as a lysosomal polyamine exporter that shows the highest affinity for spermine among the polyamines examined. Polyamines stimulate the activity of purified ATP13A2, whereas ATP13A2 mutants that are implicated in disease are functionally impaired to a degree that correlates with the disease phenotype. ATP13A2 promotes the cellular uptake of polyamines by endocytosis and transports them into the cytosol, highlighting a role for endolysosomes in the uptake of polyamines into cells. At high concentrations polyamines induce cell toxicity, which is exacerbated by ATP13A2 loss due to lysosomal dysfunction, lysosomal rupture and cathepsin B activation. This phenotype is recapitulated in neurons and nematodes with impaired expression of ATP13A2 or its orthologues. We present defective lysosomal polyamine export as a mechanism for lysosome-dependent cell death that may be implicated in neurodegeneration, and shed light on the molecular identity of the mammalian polyamine transport system

Polar and hydrogen-bonding effects of alcohols on the emission spectrum of styrene-triethylamine system

The emission spectra of styrene (ST)-triethylamine (TEA) systems were measured under steady-state illumination conditions in some THF-protic solvent mixtures. The fluorescence spectrum of the ST-TEA system in THF consists of two bands (band A at 304 nm (fluorescence of ST) and band B at 460 nm (emission from an exciplex)). The intensity of band A increased and that of band B decreased with increasing amounts of protic solvents in THF-protic solvent mixtures. The increase in the intensity of band A was explained by the decrease in the concentration of free amine owing to the hydrogen-bonding interaction (or protonation) between TEA and protic solvents. The decrease in the intensity of band B was considered to be caused by the decrease in the concentration of free amine on the addition of protic solvents and the enhanced conversion of the exciplex to an ion pair with increasing solvent polarity. The polar effect was expressed as a function of the relative permittivity of the solution.</p

Excitability of the Motor Cortex Ipsilateral to the Moving Body Side Depends on Spatio-Temporal Task Complexity and Hemispheric Specialization

Unilateral movements are mainly controlled by the contralateral hemisphere, even though the primary motor cortex ipsilateral (M1ipsi) to the moving body side can undergo task-related changes of activity as well. Here we used transcranial magnetic stimulation (TMS) to investigate whether representations of the wrist flexor (FCR) and extensor (ECR) in M1ipsi would be modulated when unilateral rhythmical wrist movements were executed in isolation or in the context of a simple or difficult hand-foot coordination pattern, and whether this modulation would differ for the left versus right hemisphere. We found that M1ipsi facilitation of the resting ECR and FCR mirrored the activation of the moving wrist such that facilitation was higher when the homologous muscle was activated during the cyclical movement. We showed that this ipsilateral facilitation increased significantly when the wrist movements were performed in the context of demanding hand-foot coordination tasks whereas foot movements alone influenced the hand representation of M1ipsi only slightly. Our data revealed a clear hemispheric asymmetry such that MEP responses were significantly larger when elicited in the left M1ipsi than in the right. In experiment 2, we tested whether the modulations of M1ipsi facilitation, caused by performing different coordination tasks with the left versus right body sides, could be explained by changes in short intracortical inhibition (SICI). We found that SICI was increasingly reduced for a complex coordination pattern as compared to rest, but only in the right M1ipsi. We argue that our results might reflect the stronger involvement of the left versus right hemisphere in performing demanding motor tasks

Contact frequency determines outcome of basal insulin initiation trials in type 2 diabetes

Aims/hypothesis The aim of the present study was to investigate whether predetermined contact frequency with the study teamand endpoint insulin dose are associated with study outcomes in basal insulin initiation trials in type 2 diabetes. Methods A systematic Medline search was performed. Using data from the selected studies, contact frequency was plotted against HbA(1c) reduction and endpoint insulin dose. The importance of face-to-face vs telephone contact was also analysed. Insulin dose was plotted against HbA(1c) reduction, hypoglycaemia rate and weight gain. To investigate non-specific study effects, the relationship between contact frequency and HbA(1c) was also assessed in dipeptidyl peptidase-4 (DPP-4) inhibitor trials. Results The reduction in HbA(1c) was highly correlated with contact frequency and endpoint insulin dose (r(2)=0.751, p<0.001 and r(2)=0.433, p=0.008, respectively). However, after adjusting for contact frequency, the relationship between insulin dose and HbA(1c) reduction was no longer significant (p=0.270). The frequency of both clinical and telephone contacts were independent predictors of HbA(1c) improvement (p=0.010 and p<0.001, respectively). We found no dose response relationship between end-of-study insulin dose and hypoglycaemia or weight gain. In DPP-4 inhibitor studies, contact frequency was not positively associated with HbA(1c). Conclusions/interpretation The frequency of contact with the study team is highly correlated with the improvement in HbA(1c) achieved in basal insulin initiation trials in type 2 diabetic patients. This has important implications for trial design and interpretation, as well as for clinical car