Making Free Trade Fair

Philosophers have done very little work on what makes trade fair. Perhaps the most extensive discussion is Malgorzata Kurjanska and Mathias Risse’s article, “Fairness in Trade II: export subsidies and the fair trade movement.”2 In their article, Kurjanska and Risse consider the case for trade subsidies and the Fair Trade movement. They suggest that it is not permissible for developed countries to give their producers subsidies because doing so does not strike an appropriate balance between meeting the needs of the global poor and protecting domestic workers (Kurjanska and Risse, 2008: 34). Kurjanska and Risse also argue that the case for Fair Trade hinges, primarily, on whether or not it is part of the best development strategy for poor countries. They do not think Fair Trade is part of the best development strategy and, so, they believe purchasing Fair Trade certified goods is only acceptable because doing so does not constitute a large share of the market in traded goods. This chapter argues that the case against subsidies and Fair Trade Kurjanska and Risse present is much weaker than they make out. To the contrary, it argues that giving some subsidies and purchasing some Fair Trade certified goods may even be necessary to make trade fair. Section 11.2 starts by saying a few words about the normative framework Kurjanska and Risse adopt

Two different charge-separation pathways in photosystem II

Charge separation is an essential step in the conversion of solar energy into chemical energy in photosynthesis. To investigate this process, we performed transient absorption experiments at 77 K with various excitation conditions on the isolated Photosystem II reaction center preparations from spinach. The results have been analyzed by global and target analysis and demonstrate that at least two different excited states, (Ch

Enabling global clinical collaborations on identifiable patient data: The Minerva Initiative

The clinical utility of computational phenotyping for both genetic and rare diseases is increasingly appreciated; however, its true potential is yet to be fully realized. Alongside the growing clinical and research availability of sequencing technologies, precise deep and scalable phenotyping is required to serve unmet need in genetic and rare diseases. To improve the lives of individuals affected with rare diseases through deep phenotyping, global big data interrogation is necessary to aid our understanding of disease biology, assist diagnosis, and develop targeted treatment strategies. This includes the application of cutting-edge machine learning methods to image data. As with most digital tools employed in health care, there are ethical and data governance challenges associated with using identifiable personal image data. There are also risks with failing to deliver on the patient benefits of these new technologies, the biggest of which is posed by data siloing. The Minerva Initiative has been designed to enable the public good of deep phenotyping while mitigating these ethical risks. Its open structure, enabling collaboration and data sharing between individuals, clinicians, researchers and private enterprise, is key for delivering precision public health

Cyclin D1 overexpression is an indicator of poor prognosis in resectable non-small cell lung cancer

Cyclin D1 is one of the G1 cyclins that control cell cycle progression by allowing G1 to S transition. Overexpression of cyclin D1 has been postulated to play an important role in the development of human cancers. We have investigated the correlation between cyclin D1 overexpression and known clinicopathological factors and also its prognostic implication on resected non-small-cell lung cancer (NSCLC) patients. Formalin-fixed and paraffin-embedded tumour tissues resected from 69 NSCLC patients between stages I and IIIa were immunohistochemically examined to detect altered cyclin D1 expression. Twenty-four cases (34.8%) revealed positive immunoreactivity for cyclin D1. Cyclin D1 overexpression is significantly higher in patients with lymph node metastasis (50.0% vs 14.4%, P = 0.002) and with advanced pathological stages (I, 10%; II, 53.8%; IIIa, 41.7%, P = 0.048; stage I vs II, IIIa, P = 0.006). Twenty-four patients with cyclin D1-positive immunoreactivity revealed a significantly shorter overall survival than the patients with negativity (24.0 ± 3.9 months vs 50.1 ± 6.4 months, P = 0.0299). Among 33 patients between stages I and II, nine patients with cyclin D1-positive immunoreactivity had a much shorter overall survival (29.7 ± 6.1 months vs 74.6 ± 8.6 months, P = 0.0066). These results suggest that cyclin D1 overexpression is involved in tumorigenesis of NSCLCs from early stage and could be a predictive molecular marker for poor prognosis in resectable NSCLC patients, which may help us to choose proper therapeutic modalities after resection of the tumor. © 1999 Cancer Research Campaig

IsoBED: a tool for automatic calculation of biologically equivalent fractionation schedules in radiotherapy using IMRT with a simultaneous integrated boost (SIB) technique

<p>Abstract</p> <p>Background</p> <p>An advantage of the Intensity Modulated Radiotherapy (IMRT) technique is the feasibility to deliver different therapeutic dose levels to PTVs in a single treatment session using the Simultaneous Integrated Boost (SIB) technique. The paper aims to describe an automated tool to calculate the dose to be delivered with the SIB-IMRT technique in different anatomical regions that have the same Biological Equivalent Dose (BED), i.e. IsoBED, compared to the standard fractionation.</p> <p>Methods</p> <p>Based on the Linear Quadratic Model (LQM), we developed software that allows treatment schedules, biologically equivalent to standard fractionations, to be calculated. The main radiobiological parameters from literature are included in a database inside the software, which can be updated according to the clinical experience of each Institute. In particular, the BED to each target volume will be computed based on the alpha/beta ratio, total dose and the dose per fraction (generally 2 Gy for a standard fractionation). Then, after selecting the reference target, i.e. the PTV that controls the fractionation, a new total dose and dose per fraction providing the same isoBED will be calculated for each target volume.</p> <p>Results</p> <p>The IsoBED Software developed allows: 1) the calculation of new IsoBED treatment schedules derived from standard prescriptions and based on LQM, 2) the conversion of the dose-volume histograms (DVHs) for each Target and OAR to a nominal standard dose at 2Gy per fraction in order to be shown together with the DV-constraints from literature, based on the LQM and radiobiological parameters, and 3) the calculation of Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) curve versus the prescribed dose to the reference target.</p

Brugia malayi microfilariae adhere to human vascular endothelial cells in a C3-dependent manner

Brugia malayi causes the human tropical disease, lymphatic filariasis. Microfilariae (Mf) of this nematode live in the bloodstream and are ingested by a feeding mosquito vector. Interestingly, in a remarkable co-evolutionary adaptation, Mf appearance in the peripheral blood follows a circadian periodicity and reaches a peak when the mosquito is most likely to feed. For the remaining hours, the majority of Mf sequester in the lung capillaries. This circadian phenomenon has been widely reported and is likely to maximise parasite fitness and optimise transmission potential. However, the mechanism of Mf sequestration in the lungs remains largely unresolved. In this study, we demonstrate that B. malayi Mf can, directly adhere to vascular endothelial cells under static conditions and under flow conditions, they can bind at high (but not low) flow rates. High flow rates are more likely to be experienced diurnally. Furthermore, a non-periodic nematode adheres less efficiently to endothelial cells. Strikingly C3, the central component of complement, plays a crucial role in the adherence interaction. These novel results show that microfilariae have the ability to bind to endothelial cells, which may explain their sequestration in the lungs, and this binding is increased in the presence of inflammatory mediators

ATG24 represses autophagy and differentiation and is essential for homeostasy of the flagellar pocket in trypanosoma brucei

We have previously identified homologs for nearly half of the approximately 30 known yeast Atg's in the genome database of the human sleeping sickness parasite Trypanosoma brucei. So far, only a few of these homologs have their role in autophagy experimentally confirmed. Among the candidates was the ortholog of Atg24 that is involved in pexophagy in yeast. In T. brucei, the peroxisome-like organelles named glycosomes harbor core metabolic processes, especially glycolysis. In the autotrophic yeast, autophagy is essential for adaptation to different nutritional environments by participating in the renewal of the peroxisome population. We hypothesized that autophagic turnover of the parasite's glycosomes plays a role in differentiation during its life cycle, which demands adaptation to different host environments and associated dramatic changes in nutritional conditions. We therefore characterized T. brucei ATG24, the T. brucei ortholog of yeast Atg24 and mammalian SNX4, and found it to have a regulatory role in autophagy and differentiation as well as endocytic trafficking. ATG24 partially localized on endocytic membranes where it was recruited via PI3-kinase III/VPS34. ATG24 silencing severely impaired receptor-mediated endocytosis of transferrin, but not adsorptive uptake of a lectin, and caused a major enlargement of the flagellar pocket. ATG24 silencing approximately doubled the number of autophagosomes, suggesting a role in repressing autophagy, and strongly accelerated differentiation, in accordance with a role of autophagy in parasite differentiation. Overexpression of the two isoforms of T. brucei ATG8 fused to GFP slowed down differentiation, possibly by a dominant-negative effect. This was overcome by ATG24 depletion, further supporting its regulatory role

Accurate Distinction of Pathogenic from Benign CNVs in Mental Retardation

Copy number variants (CNVs) have recently been recognized as a common form of genomic variation in humans. Hundreds of CNVs can be detected in any individual genome using genomic microarrays or whole genome sequencing technology, but their phenotypic consequences are still poorly understood. Rare CNVs have been reported as a frequent cause of neurological disorders such as mental retardation (MR), schizophrenia and autism, prompting widespread implementation of CNV screening in diagnostics. In previous studies we have shown that, in contrast to benign CNVs, MR-associated CNVs are significantly enriched in genes whose mouse orthologues, when disrupted, result in a nervous system phenotype. In this study we developed and validated a novel computational method for differentiating between benign and MR-associated CNVs using structural and functional genomic features to annotate each CNV. In total 13 genomic features were included in the final version of a Naïve Bayesian Tree classifier, with LINE density and mouse knock-out phenotypes contributing most to the classifier's accuracy. After demonstrating that our method (called GECCO) perfectly classifies CNVs causing known MR-associated syndromes, we show that it achieves high accuracy (94%) and negative predictive value (99%) on a blinded test set of more than 1,200 CNVs from a large cohort of individuals with MR. These results indicate that this classification method will be of value for objectively prioritizing CNVs in clinical research and diagnostics