Towards a developmental state? Provincial economic policy in South Africa

This paper explores the meaning of the developmental state for spatial economic policy in South Africa. Two main questions are addressed: do provincial governments have a role to play in promoting economic prosperity, and to what extent do current provincial policies possess the attributes of a developmental state? These attributes are defined as the ability to plan longer term, to focus key partners on a common agenda, and to mobilise state resources to build productive capabilities. The paper argues that the developmental state must harness the power of government at every level to ensure that each part of the country develops to its potential. However, current provincial capacity is uneven, and weakest where support is needed most. Many provinces seem to have partial strategies and lack the wherewithal for sustained implementation. Coordination across government appears to be poor. The paper concludes by suggesting ways provincial policies could be strengthened

Acquired resistance of human T cells to sulfasalazine: stability of the resistant phenotype and sensitivity to non-related DMARDs.

2.5 weeks) resumption of SSZ resistance and ABCG2 expression as in the original CEM/SSZ cells. CEM/SSZ cells displayed diminished sensitivity to the DMARDs leflunomide (5.1-fold) and methotrexate (1.8-fold), were moderately more sensitive (1.6-2.0 fold) to cyclosporin A and chloroquine, and markedly more sensitive (13-fold) to the glucocorticoid dexamethasone as compared with parental CEM cells. CONCLUSION: The drug efflux pump ABCG2 has a major role in conferring resistance to SSZ. The collateral sensitivity of SSZ resistant cells for some other (non-related) DMARDs may provide a further rationale for sequential mono- or combination therapies with distinct DMARDs upon decreased efficacy of SSZ

Magnetic Gaps related to Spin Glass Order in Fermionic Systems

We provide evidence for spin glass related magnetic gaps in the fermionic density of states below the freezing temperature. Model calculations are presented and proposed to be relevant for explaining resistivity measurements which observe a crossover from variable-range- to activated behavior. The magnetic field dependence of a hardgap and the low temperature decay of the density of states are given. In models with fermion transport a new metal-insulator transition is predicted to occur due to the spin-glass gap, anteceding the spin glass to quantum paramagnet transition at smaller spin density. Important fluctuation effects due to finite range frustrated interactions are estimated and discussed.Comment: 4 pages, 1 Postscript figure, revised version accepted for publication in Physical Review Letter

Endogenous orienting modulates the Simon effect: critical factors in experimental design

Responses are faster when the side of stimulus and response correspond than when they do not correspond, even if stimulus location is irrelevant to the task at hand: the correspondence, spatial compatibility effect, or Simon effect. Generally, it is assumed that an automatically generated spatial code is responsible for this effect, but the precise mechanism underlying the formation of this code is still under dispute. Two major alternatives have been proposed: the referential-coding account, which can be subdivided into a static version and an attention-centered version, and the attention-shift account. These accounts hold clear-cut predictions for attentional cuing experiments. The former would assume a Simon effect irrespective of attentional cuing in its static version, whereas the attention-centered version of the referential-coding account and the attention-shift account would predict a decreased Simon effect on validly as opposed to invalidly cued trials. However, results from previous studies are equivocal to the effects of attentional cuing on the Simon effect. We argue here that attentional cueing reliably modulates the Simon effect if some crucial experimental conditions, mostly relevant for optimizing attentional allocation, are met. Furthermore, we propose that the Simon effect may be better understood within the perspective of supra-modal spatial attention, thereby providing an explanation for observed discrepancies in the literature

Single electron magneto-conductivity of a nondegenerate 2D electron system in a quantizing magnetic field

We study transport properties of a non-degenerate two-dimensional system of non-interacting electrons in the presence of a quantizing magnetic field and a short-range disorder potential. We show that the low-frequency magnetoconductivity displays a strongly asymmetric peak at a nonzero frequency. The shape of the peak is restored from the calculated 14 spectral moments, the asymptotic form of its high-frequency tail, and the scaling behavior of the conductivity for omega -> 0. We also calculate 10 spectral moments of the cyclotron resonance absorption peak and restore the corresponding (non-singular) frequency dependence using the continuous fraction expansion. Both expansions converge rapidly with increasing number of included moments, and give numerically accurate results throughout the region of interest. We discuss the possibility of experimental observation of the predicted effects for electrons on helium.Comment: RevTeX 3.0, 14 pages, 8 eps figures included with eps

Opposing Effects of the Angiopoietins on the Thrombin-Induced Permeability of Human Pulmonary Microvascular Endothelial Cells

BACKGROUND: Angiopoietin-2 (Ang-2) is associated with lung injury in ALI/ARDS. As endothelial activation by thrombin plays a role in the permeability of acute lung injury and Ang-2 may modulate the kinetics of thrombin-induced permeability by impairing the organization of vascular endothelial (VE-)cadherin, and affecting small Rho GTPases in human pulmonary microvascular endothelial cells (HPMVECs), we hypothesized that Ang-2 acts as a sensitizer of thrombin-induced hyperpermeability of HPMVECs, opposed by Ang-1. METHODOLOGY/PRINCIPAL FINDINGS: Permeability was assessed by measuring macromolecule passage and transendothelial electrical resistance (TEER). Angiopoietins did not affect basal permeability. Nevertheless, they had opposing effects on the thrombin-induced permeability, in particular in the initial phase. Ang-2 enhanced the initial permeability increase (passage, P = 0.010; TEER, P = 0.021) in parallel with impairment of VE-cadherin organization without affecting VE-cadherin Tyr685 phosphorylation or increasing RhoA activity. Ang-2 also increased intercellular gap formation. Ang-1 preincubation increased Rac1 activity, enforced the VE-cadherin organization, reduced the initial thrombin-induced permeability (TEER, P = 0.027), while Rac1 activity simultaneously normalized, and reduced RhoA activity at 15 min thrombin exposure (P = 0.039), but not at earlier time points. The simultaneous presence of Ang-2 largely prevented the effect of Ang-1 on TEER and macromolecule passage. CONCLUSIONS/SIGNIFICANCE: Ang-1 attenuated thrombin-induced permeability, which involved initial Rac1 activation-enforced cell-cell junctions, and later RhoA inhibition. In addition to antagonizing Ang-1, Ang-2 had also a direct effect itself. Ang-2 sensitized the initial thrombin-induced permeability accompanied by destabilization of VE-cadherin junctions and increased gap formation, in the absence of increased RhoA activity

Rationale and design of the PHOspholamban RElated CArdiomyopathy intervention STudy (i-PHORECAST)

Background: The p.Arg14del (c.40_42delAGA) phospholamban (PLN) pathogenic variant is a founder mutation that causes dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM). Carriers are at increased risk of malignant ventricular arrhythmias and heart failure, which has been ascribed to cardiac fibrosis. Importantly, cardiac fibrosis appears to be an early feature of the disease, occurring in many presymptomatic carriers before the onset of overt disease. As with most monogenic cardiomyopathies, no evidence-based treatment is available for presymptomatic carriers. Aims: The PHOspholamban RElated CArdiomyopathy intervention STudy (iPHORECAST) is designed to demonstrate that pre-emptive treatment of presymptomatic PLN p.Arg14del carriers using eplerenone, a mineralocorticoid receptor antagonist with established antifibrotic effects, can reduce disease progression and postpone the onset of overt disease. Methods: iPHORECAST has a multicentre, prospective, randomised, open-label, blinded endpoint (PROBE) design. Presymptomatic PLN p.Arg14del carriers are randomised to receive either 50 mg eplerenone once daily or no treatment. The primary endpoint of the study is a multiparametric assessment of disease progression including cardiac magnetic resonance parameters (left and right ventricular volumes, systolic function and fibrosis), electrocardiographic parameters (QRS voltage, ventricular ectopy), signs and/or symptoms related to DCM and ACM, and cardiovascular death. The follow-up duration is set at 3 years. Baseline results: A total of 84 presymptomatic PLN p.Arg14del carriers (n = 42 per group) were included. By design, at baseline, all participants were in New York Heart Association (NHYA) class I and had a left ventricular ejection fraction > 45% and < 2500 ventricular premature contractions during 24-hour Holter monitoring. There were no statistically significant differences between the two groups in any of the baseline characteristics. The study is currently well underway, with the last participants expected to finish in 2021. Conclusion: iPHORECAST is a multicentre, prospective randomised controlled trial designed to address whether pre-emptive treatment of PLN p.Arg14del carriers with eplerenone can prevent or delay the onset of cardiomyopathy. iPHORECAST has been registered in the clinicaltrials.gov-register (number: NCT01857856)

Optimising primary molecular profiling in non-small cell lung cancer

Introduction Molecular profiling of NSCLC is essential for optimising treatment decisions, but often incomplete. We assessed the efficacy of protocolised molecular profiling in the current standard-of-care (SoC) in a prospective observational study in the Netherlands and measured the effect of providing standardised diagnostic procedures. We also explored the potential of plasma-based molecular profiling in the primary diagnostic setting. Methods This multi-centre prospective study was designed to explore the performance of current clinical practice during the run-in phase using local SoC tissue profiling procedures. The subsequent phase was designed to investigate the extent to which comprehensive molecular profiling (CMP) can be maximized by protocolising tumour profiling. Successful molecular profiling was defined as completion of at least EGFR and ALK testing. Additionally, PD-L1 tumour proportions scores were explored. Lastly, the additional value of centralised plasma-based testing for EGFR and KRAS mutations using droplet digital PCR was evaluated. Results Total accrual was 878 patients, 22.0% had squamous cell carcinoma and 78.0% had non-squamous NSCLC. Stage I-III was seen in 54.0%, stage IV in 46.0%. Profiling of EGFR and ALK was performed in 69.9% of 136 patients included in the run-in phase, significantly more than real-world data estimates of 55% (p<0.001). Protocolised molecular profiling increased the rate to 77.0% (p = 0.049). EGFR and ALK profiling rates increased from 77.9% to 82.1% in non-squamous NSCLC and from 43.8% to 57.5% in squamous NSCLC. Plasma-based testing was feasible in 98.4% and identified oncogenic driver mutations in 7.1% of patients for whom tissue profiling was unfeasible. Conclusion This study shows a high success rate of tissue-based molecular profiling that was significantly improved by a protocolised approach. Tissue-based profiling remains unfeasible for a substantial proportion of patients. Combined analysis of tumour tissue and circulating tumour DNA is a promising approach to allow adequate molecular profiling of more patients