Implementation of the Convention on the Protection and Promotion of the Diversity of Cultural Expressions in the Digital Age: Challenges, Priority Actions and Recommendations

Report presented to the Intergovernmental Committee of the Convention on the Protection and Promotion of the Diversity of Cultural Expressions Seventh Ordinary Session, Paris, December 10-­‐13, 2013

Increased expression of putative cancer stem cell markers in the bone marrow of prostate cancer patients is associated with bone metastasis progression.

BACKGROUND The number of cells positive for the α-6 and α-2 integrin subunits and the c-Met receptor in primary tumors and bone biopsies from prostate cancer patients has been correlated with metastasis and disease progression. The objective of this study was to quantify disseminated tumour cells present in bone marrow in prostate cancer patients using specific markers and determine their correlation with metastasis and survival. METHODS Patients were included at different stage of prostate cancer disease, from localised to metastatic castration-resistant prostate cancer. Healthy men were used as a control group. Bone marrow samples were collected and nucleated cells separated. These were stained for CD45, α-2, α-6 integrin subunits and c-Met and samples were processed for analysis and quantification of CD45-/α2+/α6+/c-met + cells using flow cytometry. Clinical and pathological parameters were assessed and survival measured. Statistical analyses were made of associations between disease specific parameters, bone marrow flow cytometry data, prostate-specific antigen (PSA) progression free survival and bone metastases progression free survival. RESULTS For all markers, the presence of more than 0.1% positive cells in bone marrow aspirates was significantly associated with the risk of biochemical progression, the risk of developing metastasis and death from prostate cancer. CONCLUSIONS Quantification of cells carrying putative stem cell markers in bone marrow is a potential indicator of disease progression. Functional studies on isolated cells are needed to show more specifically their property for metastatic spread in prostate cancer.

Dynamics of red blood cells in microporous membranes

We have performed microfluidic experiments with erythrocytes passing through a network of microchannels of 20–25 μm width and 5 μm of height. Red blood cells (RBCs) were flowing in countercurrent directions through microchannels connected by μm pores. Thereby, we have observed interesting flow dynamics. All pores were blocked by erythrocytes. Some erythrocytes have passed through pores, depending on the channel size and cell elasticity. Many RBCs split into two or more smaller parts. Two types of splits were observed. In one type, the lipid bilayer and spectrin network were cut at the same time. In the second type, the lipid bilayer reconnected, but the part of spectrin network stayed outside the cell forming a rope like structure, which could eventually break. The microporous membrane results in multiple breakups of the cells, which can have various clinical implications, e.g., glomerulus hematuria and anemia of patients undergoing dialysis. The cell breakup procedure is similar to the one observed in the droplet breakage of viscoelastic liquids in confinement.

Initial orthodontic alignment effectiveness with self-ligating and conventional appliances: a network meta-analysis in practice.

Systematic reviews of well-designed trials constitute a high level of scientific evidence and are important for medical decision making. Meta-analysis facilitates integration of the evidence using a transparent and systematic approach, leading to a broader interpretation of treatment effectiveness and safety than can be attained from individual studies. Traditional meta-analyses are limited to comparing just 2 interventions concurrently and cannot combine evidence concerning multiple treatments. A relatively recent extension of the traditional meta-analytical approach is network meta-analysis, which allows, under certain assumptions, the quantitative synthesis of all evidence under a unified framework and across a network of all eligible trials. Network meta-analysis combines evidence from direct and indirect information via common comparators; interventions can therefore be ranked in terms of the analyzed outcome. In this article, the network meta-analysis approach is introduced in a nontechnical manner using a worked example on the treatment effectiveness of conventional and self-ligating appliances.

Geomorphology and evolution of the late Pleistocene to Holocene fluvial system in the south-eastern Llanos de Moxos, Bolivian Amazon

In the Bolivian Amazon several paleochannel generations are preserved. Their wide spectrum of morphologies clearly provides crucial information on the type and magnitude of geomorphic and hydrological changes within the drainage network of the Andean foreland. Therefore, in this study we mapped geomorphological characteristics of paleochannels, and applied radiocarbon and optically stimulated luminescence dating. Seven paleochannel generations are identified. Significant changes in sinuosity, channel widths and river pattern are observed for the successive paleochannel generations. Our results clearly reflect at least three different geomorphic and hydrological periods in the evolution of the fluvial system since the late Pleistocene. Changes in discharge and sediment load may be controlled by combinations of two interrelated mechanisms: (i) spatial changes and re-organizations of the drainage network in the upper catchment, and/or (ii) climate changes with their associated local to catchment-scale modifications in vegetation cover, and changes in discharge, inundation frequencies and magnitudes, which have likely affected the evolution of the fluvial system in the Llanos de Moxos. In summary, our study has revealed the enormous potential which geomorphic mapping and analysis combined with luminescence based chronologies hold for the reconstruction of the late Pleistocene to recent fluvial system in a large portion of Amazonia.

Evaluation of genome-wide loci of iron metabolism in hereditary hemochromatosis identifies PCSK7 as a host risk factor of liver cirrhosis

Genome-wide association studies (GWAS) have revealed genetic determinants of iron metabolism, but correlation of these with clinical phenotypes is pending. Homozygosity for HFE C282Y is the predominant genetic risk factor for hereditary hemochromatosis (HH) and may cause liver cirrhosis. However, this genotype has a low penetrance. Thus, detection of yet unknown genetic markers that identify patients at risk of developing severe liver disease is necessary for better prevention. Genetic loci associated with iron metabolism (TF, TMPRSS6, PCSK7, TFR2 and Chr2p14) in recent GWAS and liver fibrosis (PNPLA3) in recent meta-analysis were analyzed for association with either liver cirrhosis or advanced fibrosis in 148 German HFE C282Y homozygotes. Replication of associations was sought in additional 499 Austrian/Swiss and 112 HFE C282Y homozygotes from Sweden. Only variant rs236918 in the PCSK7 gene (proprotein convertase subtilisin/kexin type 7) was associated with cirrhosis or advanced fibrosis (P = 1.02 × 10(-5)) in the German cohort with genotypic odds ratios of 3.56 (95% CI 1.29-9.77) for CG heterozygotes and 5.38 (95% CI 2.39-12.10) for C allele carriers. Association between rs236918 and cirrhosis was confirmed in Austrian/Swiss HFE C282Y homozygotes (P = 0.014; ORallelic = 1.82 (95% CI 1.12-2.95) but not in Swedish patients. Post hoc combined analyses of German/Swiss/Austrian patients with available liver histology (N = 244, P = 0.00014, ORallelic = 2.84) and of males only (N = 431, P = 2.17 × 10(-5), ORallelic = 2.54) were consistent with the premier finding. Association between rs236918 and cirrhosis was not confirmed in alcoholic cirrhotics, suggesting specificity of this genetic risk factor for HH. PCSK7 variant rs236918 is a risk factor for cirrhosis in HH patients homozygous for the HFE C282Y mutation.

Neural representation and clinically relevant moderators of individualised self-criticism in healthy subjects

Many people routinely criticise themselves. While self-criticism is largely unproblematic for most individuals, depressed patients exhibit excessive self-critical thinking, which leads to strong negative affects. We used functional magnetic resonance imaging in healthy subjects (N = 20) to investigate neural correlates and possible psychological moderators of self-critical processing. Stimuli consisted of individually selected adjectives of personally negative content and were contrasted with neutral and negative non-self-referential adjectives. We found that confrontation with self-critical material yielded neural activity in regions involved in emotions (anterior insula/hippocampus-amygdala formation) and in anterior and posterior cortical midline structures, which are associated with self-referential and autobiographical memory processing. Furthermore, contrasts revealed an extended network of bilateral frontal brain areas. We suggest that the co-activation of superior and inferior lateral frontal brain regions reflects the recruitment of a frontal top-down pathway, representing cognitive reappraisal strategies for dealing with evoked negative affects. In addition, activation of right superior frontal areas was positively associated with neuroticism and negatively associated with cognitive reappraisal. Although these findings may not be specific to negative stimuli, they support a role for clinically relevant personality traits in successful regulation of emotion during confrontation with self-critical material.

Ischemia/reperfusion injury: effect of simultaneous inhibition of plasma cascade systems versus specific complement inhibition.

Ischemia/reperfusion injury (IRI) may occur from ischemia due to thrombotic occlusion, trauma or surgical interventions, including transplantation, with subsequent reestablishment of circulation. Time-dependent molecular and structural changes result from the deprivation of blood and oxygen in the affected tissue during ischemia. Upon restoration of blood flow a multifaceted network of plasma cascades is activated, including the complement-, coagulation-, kinin-, and fibrinolytic system, which plays a major role in the reperfusion-triggered inflammatory process. The plasma cascade systems are therefore promising therapeutic targets for attenuation of IRI. Earlier studies showed beneficial effects through inhibition of the complement system using specific complement inhibitors. However, pivotal roles in IRI are also attributed to other cascades. This raises the question, whether drugs, such as C1 esterase inhibitor, which regulate more than one cascade at a time, have a higher therapeutic potential. The present review discusses different therapeutic approaches ranging from specific complement inhibition to simultaneous inhibition of plasma cascade systems for reduction of IRI, gives an overview of the plasma cascade systems in IRI as well as highlights recent findings in this field.

Establishing the skill of climate field reconstruction techniques for precipitation with pseudoproxy experiments

This study aims at assessing the skill of several climate field reconstruction techniques (CFR) to reconstruct past precipitation over continental Europe and the Mediterranean at seasonal time scales over the last two millennia from proxy records. A number of pseudoproxy experiments are performed within the virtual reality ofa regional paleoclimate simulation at 45 km resolution to analyse different aspects of reconstruction skill. Canonical Correlation Analysis (CCA), two versions of an Analog Method (AM) and Bayesian hierarchical modeling (BHM) are applied to reconstruct precipitation from a synthetic network of pseudoproxies that are contaminated with various types of noise. The skill of the derived reconstructions is assessed through comparison with precipitation simulated by the regional climate model. Unlike BHM, CCA systematically underestimates the variance. The AM can be adjusted to overcome this shortcoming, presenting an intermediate behaviour between the two aforementioned techniques. However, a trade-off between reconstruction-target correlations and reconstructed variance is the drawback of all CFR techniques. CCA (BHM) presents the largest (lowest) skill in preserving the temporal evolution, whereas the AM can be tuned to reproduce better correlation at the expense of losing variance. While BHM has been shown to perform well for temperatures, it relies heavily on prescribed spatial correlation lengths. While this assumption is valid for temperature, it is hardly warranted for precipitation. In general, none of the methods outperforms the other. All experiments agree that a dense and regularly distributed proxy network is required to reconstruct precipitation accurately, reflecting its high spatial and temporal variability. This is especially true in summer, when a specifically short de-correlation distance from the proxy location is caused by localised summertime convective precipitation events.

Legal Aspects of Sino-­African Tied Aid: The Art of Playing with a Legal Grey Area

Sino-African trade has seen a fifty-fold increase in the years 1999 to 2008. In some African regions, particularly in sub-Saharan Africa, China has even replaced the US as the most important trading partner today. But China holds not a single FTA on the African continent, while other major trading partners of African economies rely on an extensive framework of different trade agreements. What is, thus, the legal basis of the recent increase of Sino-African trade? Interestingly, Sino-African trade has seen a particularly strong increase in countries that have entered into tied aid agreements with China. These agreements are commonly known under the term ‘Angola-Model’ and consist of a multifaceted network of barter-trading-systems, aspects of tied aid and concessions for oil and other commodities linked with a state loan. It is likely that these agreements have an impact on the trade-flows between African countries and China. This paper discusses the legal character of this new form of economic cooperation, or modern version of tied aid. Critical legal aspects related to this form of tied aid refer to violation of the principle of most-favoured nation (MFN), illegitimate export subsidies, market access, public procurement and transparency in the international trading system. However, despite the recent outcry of the foremost Western community against the strategy of the Chinese government on the African continent, the practice of the Angola-Model based tied aid is not entirely new, and neither is it against the law. The case of tied aid is situated in a legal grey area that should be examined thoroughly in order to strengthen the international trading system and to support developing countries in their attempt to gain from tied aid arrangements.

The European Network for Translational Research in Atrial Fibrillation (EUTRAF): objectives and initial results

Atrial fibrillation (AF) is the most common sustained arrhythmia in the general population. As an age-related arrhythmia AF is becoming a huge socio-economic burden for European healthcare systems. Despite significant progress in our understanding of the pathophysiology of AF, therapeutic strategies for AF have not changed substantially and the major challenges in the management of AF are still unmet. This lack of progress may be related to the multifactorial pathogenesis of atrial remodelling and AF that hampers the identification of causative pathophysiological alterations in individual patients. Also, again new mechanisms have been identified and the relative contribution of these mechanisms still has to be established. In November 2010, the European Union launched the large collaborative project EUTRAF (European Network of Translational Research in Atrial Fibrillation) to address these challenges. The main aims of EUTRAF are to study the main mechanisms of initiation and perpetuation of AF, to identify the molecular alterations underlying atrial remodelling, to develop markers allowing to monitor this processes, and suggest strategies to treat AF based on insights in newly defined disease mechanisms. This article reports on the objectives, the structure, and initial results of this network.

Assisted and unassisted suicide in men and women: longitudinal study of the Swiss population.

BackgroundIn Switzerland assisted suicide is legal if no self-interest is involved.AimsTo compare the strength and direction of associations with sociodemographic factors between assisted and unassisted suicides.MethodWe calculated rates and used Cox and logistic regression models in a longitudinal study of the Swiss population.ResultsAnalyses were based on 5 004 403 people, 1301 assisted and 5708 unassisted suicides from 2003 to 2008. The rate of unassisted suicides was higher in men than in women, rates of assisted suicides were similar in men and women. Higher education was positively associated with assisted suicide, but negatively with unassisted. Living alone, having no children and no religious affiliation were associated with higher rates of both.ConclusionsSome situations that indicate greater vulnerability such as living alone were associated with both assisted and unassisted suicide. Among the terminally ill, women were more likely to choose assisted suicide, whereas men died more often by unassisted suicide.

Sublimation of ice–tholins mixtures: A morphological and spectro-photometric study

Sublimation, the direct transition from solid to gas phase, is a process responsible for shaping and changing the reflectance properties of many Solar System surfaces. In this study, we have characterized the evolution of the structure/texture and of the visible and near-infrared (VIS–NIR) spectral reflectance of surfaces made of water ice mixed with analogues of complex extraterrestrial organic matter, named tholins, under low temperature (<-70° C) and pressure (10-⁵mbar) conditions. The experiments were carried out in the SCITEAS simulation setup recently built as part of the Laboratory for Outflow Studies of Sublimating Materials (LOSSy) at the University of Bern (Pommerol, A. et al. [2015a]. Planet. Space Sci. 109–110, 106–122). As the water ice sublimated, we observed in situ the formation of a sublimation lag deposit made of a water-free porous (>90% porosity) network of organic filaments on top of the ice. The temporal evolution of the tholins and water ice spectral features (reflectance at the absorption bands wavelengths, red slope, from 0.40 to 1.90lm) are analyzed throughout the sublimation of the samples. We studied how different mixtures of tholins with water (0.1 wt.% tholins as coating or inclusions within the water particles), and different ice particle sizes (4.5 ± 2.5 or 67 ± 31lm) influence the morphological and spectral evolutions of the samples. The sublimation of the ice below the mantle produces a gas flow responsible for the ejection of mm to cm-sized fragments of the deposit in outbursts-like events. The results show remarkable differences between these samples in term of mantle structure, speed of mantle building, rates and surface area of mantle ejections. These data provide useful references for interpreting remote-sensing observations of icy Solar System surfaces, in particular the activity of comet nuclei where sublimation of organic-rich ices and deposition of organic-dust particles likely play a major role. Consequently, the data presented here could be of high interest for the interpretation of Rosetta, and also New Horizons, observations.