Cassini observations of the thermal plasma in the vicinity of Saturn's main rings and the F and G rings

The ion mass spectrometer on Cassini detected enhanced ion flux near Saturn's main rings that is consistent with the presence of atomic and molecular oxygen ions in the thermal plasma. The ring "atmosphere'' and "ionosphere'' are likely produced by UV photosputtering of the icy rings and subsequent photoionization of O-2. The identification of the O+ and O-2(+) ions is made using time-of-flight analysis and densities and temperatures are derived from the ion counting data. The ion temperatures over the main rings are a minimum near synchronous orbit and increase with radial distance from Saturn as expected from ion pick up in Saturn's magnetic field. The O-2(+) temperatures provide an estimate of the neutral O-2 temperature over the main rings. The ion mass spectrometer also detected significant O-2(+) outside of the main rings, near the F ring. It is concluded that between the F and G rings, the heavy ion population most likely consists of an admixture of O-2(+) and water group ions O+, OH+, and H2O+

Incentivizing research into the effectiveness of medical devices

Introduction Medical devices (MDs) often obtain market authorization with much less clinical evidence than other health technologies, especially pharmaceuticals. This is due to a number of reasons. First, in contrast to pharmaceuticals, there is no legal requirement to conduct adequately controlled clinical studies, other than for ‘high-risk’ devices in some jurisdictions. In the US for example, high-risk devices and innovative lower-risk devices are required to demonstrate ‘reasonable assurance of safety and effectiveness’, which may imply clinical evidence based on randomized studies in many instances. In contrast, in the EU the requirement is to demonstrate adequate performance and safety, which can often be achieved by conducting observational studies such as registries [1, 2]. Secondly, the devices industry comprises many small and medium-size enterprises (SMEs), which would find the cost of conducting clinical studies, especially randomized controlled trials, prohibitive. However, although some larger manufacturers do undertake clinical studies of some of their products, manufacturers with similar products (called ‘fast-followers’) can often claim ‘substantial equivalence’ to a product that already has market authorization, thus avoiding the need to conduct costly and timeconsuming clinical studies. Since regulatory agencies often accept these claims of equivalence, for example under the 510(k) process in the US [3], this further reduces the incentives for manufacturers to conduct expensive clinical studies. Therefore, although device manufacturers have patent protection, they are often not granted data exclusivity in the same way as pharmaceutical manufacturers. Finally, unlike pharmaceuticals, devices are often modified once on the market, meaning that even if clinical evidence was available for the original version of the product, it may not necessarily be available for the version currently being marketed. For example in the US, one analysis showed that for 77 original market authorization applications for cardiac implantable electronic devices (e.g., pacemakers, implantable cardioverter-defibrillators) since 1979, the FDA approved 5829 ‘supplements’ reflecting product modifications in the period up until 2012. Of course, many of these product modifications were minor and unlikely to affect the performance of the device, but 37 % involved a change to the device’s design. In the vast majority of these cases the FDA deemed that new clinical data were not necessary for approval [4]. The lack of clinical evidence prior to product launch, especially evidence of comparative effectiveness, limits the possibilities for health technology assessment [2]. However, it should be remembered that clinical evidence can be gathered both pre-market (i.e., through conducting controlled clinical trials in an experimental setting), and postmarket, through clinical studies undertaken in regular clinical practice. Post-market effectiveness research may be more important for MDs than pharmaceuticals, as the performance of the device often depends on the interaction with the user (the so-called learning curve) [5]. This suggests that solutions to the problem of inadequate clinical evidence should address the issue of conducting clinical research in both the pre- and post-market phase. In this editorial we consider ways in which MD manufacturers could be incentivized to produce more clinical evidence to facilitate health technology assessments, including economic evaluations

Cassini in situ observations of long duration magnetic reconnection in Saturn’s magnetotail

Magnetic reconnection is a fundamental process in solar system and astrophysical plasmas, through which stored magnetic energy associated with current sheets is converted into thermal, kinetic and wave energy1, 2, 3, 4. Magnetic reconnection is also thought to be a key process involved in shedding internally produced plasma from the giant magnetospheres at Jupiter and Saturn through topological reconfiguration of the magnetic field5, 6. The region where magnetic fields reconnect is known as the diffusion region and in this letter we report on the first encounter of the Cassini spacecraft with a diffusion region in Saturn’s magnetotail. The data also show evidence of magnetic reconnection over a period of 19?h revealing that reconnection can, in fact, act for prolonged intervals in a rapidly rotating magnetosphere. We show that reconnection can be a significant pathway for internal plasma loss at Saturn6. This counters the view of reconnection as a transient method of internal plasma loss at Saturn5, 7. These results, although directly relating to the magnetosphere of Saturn, have applications in the understanding of other rapidly rotating magnetospheres, including that of Jupiter and other astrophysical bodies

Screening for coping style increases the power of gene expression studies

Background: Individuals of many vertebrate species show different stress coping styles and these have a striking influence on how gene expression shifts in response to a variety of challenges. Principal Findings: This is clearly illustrated by a study in which common carp displaying behavioural predictors of different coping styles (characterised by a proactive, adrenaline-based or a reactive, cortisol-based response) were subjected to inflammatory challenge and specific gene transcripts measured in individual brains. Proactive and reactive fish differed in baseline gene expression and also showed diametrically opposite responses to the challenge for 80% of the genes investigated. Significance: Incorporating coping style as an explanatory variable can account for some the unexplained variation that is common in gene expression studies, can uncover important effects that would otherwise have passed unnoticed and greatly enhances the interpretive value of gene expression data

Pattern scaling using ClimGen: monthly-resolution future climate scenarios including changes in the variability of precipitation

Development, testing and example applications of the pattern-scaling approach for generating future climate change projections are reported here, with a focus on a particular software application called “ClimGen”. A number of innovations have been implemented, including using exponential and logistic functions of global-mean temperature to represent changes in local precipitation and cloud cover, and interpolation from climate model grids to a finer grid while taking into account land-sea contrasts in the climate change patterns. Of particular significance is a new approach for incorporating changes in the inter-annual variability of monthly precipitation simulated by climate models. This is achieved by diagnosing simulated changes in the shape of the gamma distribution of monthly precipitation totals, applying the pattern-scaling approach to estimate changes in the shape parameter under a future scenario, and then perturbing sequences of observed precipitation anomalies so that their distribution changes according to the projected change in the shape parameter. The approach cannot represent changes to the structure of climate timeseries (e.g. changed autocorrelation or teleconnection patterns) were they to occur, but is shown here to be more successful at representing changes in low precipitation extremes than previous pattern-scaling methods

Evidence for solar cycles in a late Holocene speleothem record from Dongge Cave, China

The association between solar activity and Asian monsoon (AM) remains unclear. Here we evaluate the possible connection between them based on a precisely-dated, high-resolution speleothem oxygen isotope record from Dongge Cave, southwest China during the past 4.2 thousand years (ka). Without being adjusted chronologically to the solar signal, our record shows a distinct peak-to-peak correlation with cosmogenic nuclide 14C, total solar irradiance (TSI) and sunspot number (SN) at multi-decadal to centennial timescales. Further cross-wavelet analyses between our calcite δ18O and atmospheric 14C show statistically strong coherence at three typical periodicities of ~80, 200 and 340 years, suggesting important roles of solar activities in modulating AM changes at those timescales. Our result has further indicated a better correlation between our calcite δ18O record and atmospheric 14C than between our record and TSI. This better correlation may imply that the Sun–monsoon connection is dominated most likely by cosmic rays and oceanic circulation (both associated to atmospheric 14C), instead of the direct solar heating (TSI)

Predicting cell types and genetic variations contributing to disease by combining GWAS and epigenetic data

Genome-wide association studies (GWASs) identify single nucleotide polymorphisms (SNPs) that are enriched in individuals suffering from a given disease. Most disease-associated SNPs fall into non-coding regions, so that it is not straightforward to infer phenotype or function; moreover, many SNPs are in tight genetic linkage, so that a SNP identified as associated with a particular disease may not itself be causal, but rather signify the presence of a linked SNP that is functionally relevant to disease pathogenesis. Here, we present an analysis method that takes advantage of the recent rapid accumulation of epigenomics data to address these problems for some SNPs. Using asthma as a prototypic example; we show that non-coding disease-associated SNPs are enriched in genomic regions that function as regulators of transcription, such as enhancers and promoters. Identifying enhancers based on the presence of the histone modification marks such as H3K4me1 in different cell types, we show that the location of enhancers is highly cell-type specific. We use these findings to predict which SNPs are likely to be directly contributing to disease based on their presence in regulatory regions, and in which cell types their effect is expected to be detectable. Moreover, we can also predict which cell types contribute to a disease based on overlap of the disease-associated SNPs with the locations of enhancers present in a given cell type. Finally, we suggest that it will be possible to re-analyze GWAS studies with much higher power by limiting the SNPs considered to those in coding or regulatory regions of cell types relevant to a given disease