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

Ordovician sedimentary rocks in the Ida Bay area occur in 
a north-south trending Tabberabberan anticline, and in some further 
outcrops having doubtful structural relationships. Early 
Ordovician quartzites containing gastropods are overlain on Marble 
Hill by 350 metres of limestone ranging in age from Late Chazyan to 
Trentonian. 
Ten lithofacies are distinguished in the limestones on 
Marble Hill, most of which represent sediments deposited in 
depositional regression cycles in a prograding tidal flat 
environment. While the lower 240 metres of limestones represent 
supratidal-intertidal conditions, the upper 110 metres represent 
intertidal-subtidal conditions. 
Siliceous sediments on Coal Hill, north of the Lune River, 
appear to represent Ordovician Limestones which have been completely 
silicified, probably by a process related to silcrete horizon 
formation. 
A primary Ordovician magnetisation is no longer present in 
the limestones on Marble Hill; instead a secondary magnetisation 
of mid-Cretaceous age has overprinted previous magnetisations in 
the limestone, probably as a result of burial and increased heat 
flow related to the rifting of the Tasman Sea.

The Ordovician system in the Ida Bay area (Honours)

A Reconnaissance of Landforms and Geological Sites of Geoconservation Significance in the Western Derwent Forest District

Much attention is focussed on protecting built development and infrastructure in coastal areas as a
result of climate change and sea-level rise. In some cases, allowance for the coast to adjust
naturally to sea-level rise can provide substantial benefits in reduced protection costs and
preservation of natural features that underpin the appeal and value of the coast to residents and
visitors. Natural foredunes provide substantial protection for inland areas from storm surges. They
provide a buffer to reduce the immediate rate of erosion after a severe storm or series of lesser
storm events. Given adequate room to form and reform as sea levels change, they provide these
services at a minimal cost. Where the natural rate of adjustment may be slow and leave some hind
areas at risk, these processes may be assisted by augmentation/nourishment and revegetation
undertaken in a way to mimic or reinforce natural processes. All this may be at substantially lower
cost than man-made structures of rock, concrete or other responses, and often with greater appeal
to many in the community. Some other shoreline types are also prone to flooding, erosion and
slumping. In these cases too, provision of an unoccupied buffer zone between the shoreline and
development serves as a low cost form of protection from these coastal hazards while also
providing a coastal strip giving the social benefit of public access to the shore along with the
conservation benefits of retaining a natural coastal reserve. High value coastal ecosystems may
also make a claim on space to adjust. Areas that host shore feeding birds, wetlands that provide
habitat for migratory birds (RAMSAR sites) and other coastal habitat that host ecological
communities such as salt marsh which have declining areas available may have high ecological
value. If there were no coastal development, many of these ecosystems could migrate inland with
rising sea levels. Where landscape fragmentation due to roads or other forms of development
block this inland movement, or where natural landforms prevent this, these natural coastal
communities will be lost. Inventories of high value ecosystems that still have potential to move
inland are needed, so as to identify priority sites where allowance for inland migration over time
can be ensured.

The Changing Coast - Providing Room for Natural Adjustments

https://ro.uow.edu.au/cgi/viewcontent.cgi?article=1379&context=smhpapers1

Reply to: Punctuated transgression (?): Comment on Oliver, T.S.N., Donaldson, P., Sharples, C., Roach, M., and Woodroffe, C.D. “Punctuated progradation of the Seven Mile Beach Holocene barrier system, southeastern Tasmania”

Reconnaisance Geological Observations on Precambrian and Palaeozoic Rocks of the New and Salisbury Rivers, Southern Tasmania.

C Sharples

Papers

The Ordovician system in the Ida Bay area (Honours)

A Reconnaissance of Landforms and Geological Sites of Geoconservation Significance in the Western Derwent Forest District

The Changing Coast - Providing Room for Natural Adjustments

Reply to: Punctuated transgression (?): Comment on Oliver, T.S.N., Donaldson, P., Sharples, C., Roach, M., and Woodroffe, C.D. “Punctuated progradation of the Seven Mile Beach Holocene barrier system, southeastern Tasmania”

Reconnaisance geological observations on Precambrian and Palaeozoic rocks of the New and Salisbury Rivers, Southern Tasmania