Merchants of Doubt. How a Handful of Scientists Obscured the Truth on Issues from Tobacco Smoke to Global Warming

Oligonucleotides can be used to modulate gene expression via a range of processes including RNAi, target degradation by RNase H-mediated cleavage, splicing modulation, non-coding RNA inhibition, gene activation and programmed gene editing. As such, these molecules have potential therapeutic applications for myriad indications, with several oligonucleotide drugs recently gaining approval. However, despite recent technological advances, achieving efficient oligonucleotide delivery, particularly to extrahepatic tissues, remains a major translational limitation. Here, we provide an overview of oligonucleotide-based drug platforms, focusing on key approaches - including chemical modification, bioconjugation and the use of nanocarriers - which aim to address the delivery challenge.

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Advances in oligonucleotide drug delivery

Worldwide, there is a need to enhance our understanding of vulnerability and to develop methodologies and tools to assess vulnerability. One of the most important goals of assessing coastal flood vulnerability, in particular, is to create a readily understandable link between the theoretical concepts of flood vulnerability and the day-to-day decision-making process and to encapsulate this link in an easily accessible tool. This article focuses on developing a Coastal City Flood Vulnerability Index (CCFVI) based on exposure, susceptibility and resilience to coastal flooding. It is applied to nine cities around the world, each with different kinds of exposure. With the aid of this index, it is demonstrated which cities are most vulnerable to coastal flooding with regard to the system’s components, that is, hydro-geological, socio-economic and politico-administrative. The index gives a number from 0 to 1, indicating comparatively low or high coastal flood vulnerability, which shows which cities are most in need of further, more detailed investigation for decision-makers. Once its use to compare the vulnerability of a range of cities under current conditions has been demonstrated, it is used to study the impact of climate change on the vulnerability of these cities over a longer timescale. The results show that CCFVI provides a means of obtaining a broad overview of flood vulnerability and the effect of possible adaptation options. This, in turn, will allow for the direction of resources to more in-depth investigation of the most promising strategies.

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A flood vulnerability index for coastal cities and its use in assessing climate change impacts

Diabetes is one of the fastest growing diseases worldwide, projected to affect 693 million adults by 2045. Devastating macrovascular complications (cardiovascular disease) and microvascular complications (such as diabetic kidney disease, diabetic retinopathy and neuropathy) lead to increased mortality, blindness, kidney failure and an overall decreased quality of life in individuals with diabetes. Clinical risk factors and glycaemic control alone cannot predict the development of vascular complications; numerous genetic studies have demonstrated a clear genetic component to both diabetes and its complications. Early research aimed at identifying genetic determinants of diabetes complications relied on familial linkage analysis suited to strong-effect loci, candidate gene studies prone to false positives, and underpowered genome-wide association studies limited by sample size. The explosion of new genomic datasets, both in terms of biobanks and aggregation of worldwide cohorts, has more than doubled the number of genetic discoveries for both diabetes and diabetes complications. We focus herein on genetic discoveries for diabetes and diabetes complications, empowered primarily through genome-wide association studies, and emphasize the gaps in research for taking genomic discovery to the next level.

Genetics of diabetes mellitus and diabetes complications.

There is growing demand among stakeholders across public and private institutions for spatially-explicit information regarding vulnerability to climate change at the local scale. However, the challenges associated with mapping the geography of climate change vulnerability are non-trivial, both conceptually and technically, suggesting the need for more critical evaluation of this practice. Here, we review climate change vulnerability mapping in the context of four key questions that are fundamental to assessment design. First, what are the goals of the assessment? A review of published assessments yields a range of objective statements that emphasize problem orientation or decision-making about adaptation actions. Second, how is the assessment of vulnerability framed? Assessments vary with respect to what values are assessed (vulnerability of what) and the underlying determinants of vulnerability that are considered (vulnerability to what). The selected frame ultimately influences perceptions of the primary driving forces of vulnerability as well as preferences regarding management alternatives. Third, what are the technical methods by which an assessment is conducted? The integration of vulnerability determinants into a common map remains an emergent and subjective practice associated with a number of methodological challenges. Fourth, who participates in the assessment and how will it be used to facilitate change? Assessments are often conducted under the auspices of benefiting stakeholders, yet many lack direct engagement with stakeholders. Each of these questions is reviewed in turn by drawing on an illustrative set of 45 vulnerability mapping studies appearing in the literature. A number of pathways for placing vulnerability mapping on a more robust footing are also identified.

C Sharples

Papers

The Building and Ornamental Stone Resources of Tasmania

Circular Head Region Coastal Foreshore Habitats: Sea Level Rise Vulnerability Assessment

Reconnaissance Mapping of Soil Parent Materials in the East Florentine and Upper Tyenna Valleys

Shoreline Erosion and Coastal Geomorphic Processes at Cornelian Bay, Hobart: An Assessment of Causes and Response Options

West North West Tasmania Coastal Management Plan