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.

/pdf/a-flood-vulnerability-index-for-coastal-cities-and-its-use-ws959jml8h.pdf

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.

Putting vulnerability to climate change on the map: a review of approaches, benefits, and risks

Description and geoconservation assessment of a glacio-fluvial terrace at the Southwood development site, and possible equivalent terraces in the Huon River Valley

Shoreline Change at Roches Beach, South-Eastern Tasmania

Review of the National Coastal Geomorphic (Polygon) Map and Classification for the Australian Coastal Zone TECHNICAL REPORT

The original Lake Pedder was a
glacial lake of surpassing beauty and outstanding
natural value, set in the geographical heart of what
was, in the latter half of the twentieth century, one
of only three substantial temperate wilderness areas
remaining in the southern hemisphere (Neilson
1975). The full breadth and depth of Lake Pedder's
nature conservation values have seldom been fully
recognised, and one aim of this volume is to
describe some of those values. However, the
aesthetic and inspirational values of the lake and its
surrounding mountainous regions have been
illustrated and lyrically described by many of those
fortunate enough to have visited the original lake
(see for example Angus 1975, Neilson 1975,
Southwell 1983, Brown et al. 1985).
In 1972 Lake Pedder was flooded to create a new
and larger artificial lake as part of the Middle
Gordon hydro-electric power development. This
flooding occurred in the face of a public outcry
which was, for an environmental issue,
unprecedented in Australia's history, and that
heralded the beginning of a new phase in
Australian political history in which the
environment became a pervasive political issue
right up there alongside the economy and other
traditional issues. Although environmental
concerns had been expressed in Australian society
long before this time and earlier political battles
had been fought over environmental issues, few
would disagree with the assertion that it was the
flooding of Lake Pedder, more than any other
single event, that irrevocably brought the
environment into the general public consciousness
in Australia and made it a mainstream political
issue. It is noteworthy that it was an event at the
periphery of the Australian political scene, rather
than in the power centres of Melbourne and
Sydney, which challenged the established order and
wrought this profound change in the Australian
political landscape.

C Sharples

Papers

Description and geoconservation assessment of a glacio-fluvial terrace at the Southwood development site, and possible equivalent terraces in the Huon River Valley

Shoreline Change at Roches Beach, South-Eastern Tasmania

Review of the National Coastal Geomorphic (Polygon) Map and Classification for the Australian Coastal Zone TECHNICAL REPORT

Lake Pedder: Values and Restoration. Volume 27, Centre for Environmental Studies Occasional Paper

Magnesite Karst in Northwest Tasmania - Geology, Geomorphology and Hydrology