Transition from initiation to promoter proximal pausing requires the CTD of RNA polymerase II

The C-terminal domain (CTD) of mammalian RNA polymerase II consists of 52 repeats of the consensus hepta-peptide YSPTSPS, and links transcription to the processing of pre-mRNA. Although Pol II with a CTD shortened to five repeats (Pol II Δ5) is transcriptionally inactive on chromatin templates, it is not clear whether CTD is required for promoter recognition in vivo. Here, we demonstrate that in the context of chromatin, Pol II Δ5 can bind to the c-myc promoter with the same efficiency as wild type Pol II. However, Pol II Δ5 does not form a stable initiation complex, and does not transcribe promoter proximal sequences. Fluorescence recovery after photobleaching (FRAP) experiments with cells expressing enhanced green fluorescent protein (EGFP)-tagged Δ5 or wildtype Pol II revealed a single, highly mobile Pol II Δ5 fraction whereas wildtype Pol II yielded less mobile fractions. These data suggest that CTD is not required for promoter recognition, but rather for subsequent formation of a stable initiation complex and isomerization to an elongation competent complex

A worldwide survey on incidence, management, and prognosis of oesophageal fistula formation following atrial fibrillation catheter ablation: the POTTER-AF study

AIMS Oesophageal fistula represents a rare but dreadful complication of atrial fibrillation catheter ablation. Data on its incidence, management, and outcome are sparse. METHODS AND RESULTS This international multicentre registry investigates the characteristics of oesophageal fistulae after treatment of atrial fibrillation by catheter ablation. A total of 553 729 catheter ablation procedures (radiofrequency: 62.9%, cryoballoon: 36.2%, other modalities: 0.9%) were performed, at 214 centres in 35 countries. In 78 centres 138 patients [0.025%, radiofrequency: 0.038%, cryoballoon: 0.0015% (P < 0.0001)] were diagnosed with an oesophageal fistula. Peri-procedural data were available for 118 patients (85.5%). Following catheter ablation, the median time to symptoms and the median time to diagnosis were 18 (7.75, 25; range: 0-60) days and 21 (15, 29.5; range: 2-63) days, respectively. The median time from symptom onset to oesophageal fistula diagnosis was 3 (1, 9; range: 0-42) days. The most common initial symptom was fever (59.3%). The diagnosis was established by chest computed tomography in 80.2% of patients. Oesophageal surgery was performed in 47.4% and direct endoscopic treatment in 19.8% and conservative treatment in 32.8% of patients. The overall mortality was 65.8%. Mortality following surgical (51.9%) or endoscopic treatment (56.5%) was significantly lower as compared to conservative management (89.5%) [odds ratio 7.463 (2.414, 23.072) P < 0.001]. CONCLUSION Oesophageal fistula after catheter ablation of atrial fibrillation is rare and occurs mostly with the use of radiofrequency energy rather than cryoenergy. Mortality without surgical or endoscopic intervention is exceedingly high

Identifying an indoor air exposure limit for formaldehyde considering both irritation and cancer hazards

Formaldehyde is a well-studied chemical and effects from inhalation exposures have been extensively characterized in numerous controlled studies with human volunteers, including asthmatics and other sensitive individuals, which provide a rich database on exposure concentrations that can reliably produce the symptoms of sensory irritation. Although individuals can differ in their sensitivity to odor and eye irritation, the majority of authoritative reviews of the formaldehyde literature have concluded that an air concentration of 0.3 ppm will provide protection from eye irritation for virtually everyone. A weight of evidence-based formaldehyde exposure limit of 0.1 ppm (100 ppb) is recommended as an indoor air level for all individuals for odor detection and sensory irritation. It has recently been suggested by the International Agency for Research on Cancer (IARC), the National Toxicology Program (NTP), and the US Environmental Protection Agency (US EPA) that formaldehyde is causally associated with nasopharyngeal cancer (NPC) and leukemia. This has led US EPA to conclude that irritation is not the most sensitive toxic endpoint and that carcinogenicity should dictate how to establish exposure limits for formaldehyde. In this review, a number of lines of reasoning and substantial scientific evidence are described and discussed, which leads to a conclusion that neither point of contact nor systemic effects of any type, including NPC or leukemia, are causally associated with exposure to formaldehyde. This conclusion supports the view that the equivocal epidemiology studies that suggest otherwise are almost certainly flawed by identified or yet to be unidentified confounding variables. Thus, this assessment concludes that a formaldehyde indoor air limit of 0.1 ppm should protect even particularly susceptible individuals from both irritation effects and any potential cancer hazard

Methodological Review and Revision of the Global Hunger Index

The Global Hunger Index (GHI) is a multidimensional measure of hunger that considers three dimensions: (1) inadequate dietary energy supply, (2) child undernutrition, and (3) child mortality. The initial version of the index included the following three, equally weighted, non-standardized (i.e. unscaled) indicators that are expressed in percent: the proportion of the population that is calorie deficient (FAO's prevalence of undernourishment); the prevalence of underweight in children under five; and the under-five mortality rate. Several decisions regarding the original formulation of the GHI are reconsidered in light of recent discussions in the nutrition community and suggestions by other researchers, namely the choice of the prevalence of child underweight for the child undernutrition dimension, the use of the under-five mortality rate from all causes for the child mortality dimension, and the decision not to standardize the component indicators prior to aggregation. Based on an exploration of the literature, data availability and comparability across countries, and correlation analyses with indicators of micronutrient deficiencies, the index is revised as follows: (1) The child underweight indicator is replaced with child stunting and child wasting; (2) The weight of one third for the child undernutrition dimension is shared equally between the two new indicators; and (3) The component indicators of the index are standardized prior to aggregation, using fixed thresholds set above the maximum values observed in the data set. The under-five mortality rate from all causes is retained, because estimating under-five mortality attributable to nutritional deficiencies would be very costly and make the production of the GHI dependent on statistics about cause-specific mortality rates by country and year that are published irregularly, while the expected benefits are limited

Between Hope and Hype: Traditional Knowledge(s) Held by Marginal Communities

Traditional Knowledge (TK) systems have always been integral to the survival and adaptation of human societies. Yet, they enjoy a fairly recent recognition and popularization by scientists, the media, politicians, corporates and the wider public. In this paper we present a typology of key driving forces behind the popularization of TK held by marginal communities: an equality preference motive, a value motive, a compliance motive, a scarcity motive and a strategic motive. Secondly, through the use of a simple model, we discuss the hype's impact on marginal communities. Moreover, we critically assess the outcome of a number of policy instruments that intend, in part, to protect traditional knowledge bases of such communities. Our analysis primarily draws upon secondary literature; policy documents and case studies within economics, the social sciences, conservation biology and legal studies. We argue that whilst the public and institutional hype around TK may have resulted in its prioritization within international conventions and frameworks, its institutionalization may have adversely impacted marginalized communities, and in particular contexts, unintentionally led to the creation of 'new' marginals. We purport that the traditional innovation incentive motive does not hold for protecting TK within a private property regime. Instead we identify a conservation incentive motive and a distribution motive that justify deriving policy instruments that focus on TK to protect marginal communities

Food and Nutrition Security Indicators: A Review

In this paper, we review existing food and nutrition security indicators, discuss some of their advantages and disadvantages, and finally classify them and describe their relationships and overlaps. In order to achieve this, the paper makes reference to the existing definitions of food and nutrition security (FNS), in particular as they have been agreed upon and implemented in the FoodSecure project (www.foodsecure.eu). The main existing conceptual frameworks of FNS predating the present paper are also used as guidelines and briefly discussed. Finally, we make recommendations in terms of the most appropriate FNS indicators to quantify the impacts of various shocks and interventions on food and nutrition security outcomes

Institutional Environments for Enabling Agricultural Technology Innovations: The Role of Land Rights in Ethiopia, Ghana, India and Bangladesh

Land rights are essential assets for improving the livelihoods of the rural poor. This literature based paper shed light to some land rights issues that are crucial for the effectiveness and sustainability of implementing technological innovations in marginalized rural areas of Ethiopia, Ghana, India and Bangladesh. By analysing country specific land right regimes, this paper aims to understand what institutional conditions might constitute barriers to the effective implementation of technological innovations and how they might be overcome. Land rights issues considered in this paper include public and private ownership of land in Ethiopia, customary and statutory law in Ghana, and gender equality and land rights in India and Bangladesh. A better understanding of institutional barriers for the effective implementation of technological innovations is a precondition for complementing technological with enabling institutional innovations and for improving priority setting, targeting and sequencing in the implementation of productivity increasing development measures

Social Safety Nets for Food and Nutritional Security in India

This paper brings together existing literature on the Mahatma Gandhi National Rural Employment Guarantee Act (MGNRGEA) and the Public Distribution System (PDS) in India, offering a narrative review of the evidence on impacts on food security, health and nutrition of beneficiaries. Both programs operate on a large scale and have the capacity to impact the factors leading to undernutrition. It is evident that despite the deficiencies in implementation, both the MGNREGA and the PDS are inclusive and reach the poor and the marginalized who are likely to also experience greater undernutrition and poor health. Data challenges have however prevented researchers from conducting studies that assess the ultimate impact of these two large-scale programs on health and nutrition. The evidence that exists suggests largely positive impacts indicating a clear potential to make these programs more nutrition sensitive not just by incorporating elements that would explicitly address nutritional concerns but also by directing specific attention to innovations that strengthen critical complementarities and synergies that exist between the two programs