The current state of biomarker research for Friedreich's ataxia: a report from the 2018 FARA biomarker meeting

The 2018 FARA Biomarker Meeting highlighted the current state of development of biomarkers for Friedreich's ataxia. A mass spectroscopy assay to sensitively measure mature frataxin (reduction of which is the root cause of disease) is being developed. Biomarkers to monitor neurological disease progression include imaging, electrophysiological measures and measures of nerve function, which may be measured either in serum and/or through imaging-based technologies. Potential pharmacodynamic biomarkers include metabolic and protein biomarkers and markers of nerve damage. Cardiac imaging and serum biomarkers may reflect cardiac disease progression. Considerable progress has been made in the development of biomarkers for various contexts of use, but further work is needed in terms of larger longitudinal multisite studies, and identification of novel biomarkers for additional use cases

Implications of the PEGASUS-TIMI 54 Trial for US Clinical Practice

Objectives This study aims to determine the proportion of real-world patients with myocardial infarction (MI) who would have been eligible for the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54) trial, to characterise their current use of P2Y12 inhibitors and to explore the estimated costs and ischaemic event consequences of increasing P2Y12 inhibitor use among these patients. Methods In the US national ACTION Registry–GWTG (Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With The Guidelines), we identified 273 328 patients with MI and determined the proportion that would have met the eligibility criteria for the PEGASUS trial. We described longitudinal P2Y12 inhibitor use among patients eligible for PEGASUS and estimated the cost and ischaemic consequences of increasing P2Y12 use among eligible patients. Results A total of 112 222 (41.1%) patients with MI in ACTION Registry–GWTG met eligibility for the PEGASUS trial. Among 83 871 eligible patients with pharmacy claims data, 23 042 (27.5%) were on a P2Y12 inhibitor at 1 year, 9661 (11.5%) at 2 years and 5246 (6.3%) at 3 years, with the majority (79.2%) of these patients on clopidogrel. The use of ticagrelor in eligible patients not yet on a P2Y12 inhibitor at 1 year post-MI would cost an estimated US$885 000 per MI, stroke or cardiovascular death averted over a 3-year time horizon, while the use of clopidogrel would cost an estimated US$19 800 per ischaemic event averted. Conclusion In contemporary clinical practice, a minority of patients are on a P2Y12 inhibitor beyond 1-year post-MI. Applying PEGASUS trial findings to clinical practice would result in a large increase in P2Y12 inhibitor use, with a cost per ischaemic event averted that is strongly influenced by the choice of therapy

Ultrathin Oxide Films by Atomic Layer Deposition on Graphene

In this paper, a method is presented to create and characterize mechanically robust, free standing, ultrathin, oxide films with controlled, nanometer-scale thickness using Atomic Layer Deposition (ALD) on graphene. Aluminum oxide films were deposited onto suspended graphene membranes using ALD. Subsequent etching of the graphene left pure aluminum oxide films only a few atoms in thickness. A pressurized blister test was used to determine that these ultrathin films have a Young's modulus of 154 \pm 13 GPa. This Young's modulus is comparable to much thicker alumina ALD films. This behavior indicates that these ultrathin two-dimensional films have excellent mechanical integrity. The films are also impermeable to standard gases suggesting they are pinhole-free. These continuous ultrathin films are expected to enable new applications in fields such as thin film coatings, membranes and flexible electronics.Comment: Nano Letters (just accepted

WARNING: Physics Envy May Be Hazardous To Your Wealth!

The quantitative aspirations of economists and financial analysts have for many years been based on the belief that it should be possible to build models of economic systems - and financial markets in particular - that are as predictive as those in physics. While this perspective has led to a number of important breakthroughs in economics, "physics envy" has also created a false sense of mathematical precision in some cases. We speculate on the origins of physics envy, and then describe an alternate perspective of economic behavior based on a new taxonomy of uncertainty. We illustrate the relevance of this taxonomy with two concrete examples: the classical harmonic oscillator with some new twists that make physics look more like economics, and a quantitative equity market-neutral strategy. We conclude by offering a new interpretation of tail events, proposing an "uncertainty checklist" with which our taxonomy can be implemented, and considering the role that quants played in the current financial crisis.Comment: v3 adds 2 reference

From Pig to Pacifier: Chitterling-Associated Yersiniosis Outbreak among Black Infants

In this case-control study of Yersinia enterocolitica infections among black infants, chitterling preparation was significantly associated with illness (p<0.001). Of 13 samples of chitterlings tested, 2 were positive for Yersinia intermedia and 5 for Salmonella. Decontamination of chitterlings before sale with methods such as irradiation should be strongly considered

Complementary genetic and genomic approaches help characterize the linkage group I seed protein QTL in soybean

Background: The nutritional and economic value of many crops is effectively a function of seed protein and oil content. Insight into the genetic and molecular control mechanisms involved in the deposition of these constituents in the developing seed is needed to guide crop improvement. A quantitative trait locus (QTL) on Linkage Group I (LG I) of soybean (Glycine max (L.) Merrill) has a striking effect on seed protein content. Results: A soybean near-isogenic line (NIL) pair contrasting in seed protein and differing in an introgressed genomic segment containing the LG I protein QTL was used as a resource to demarcate the QTL region and to study variation in transcript abundance in developing seed. The LG I QTL region was delineated to less than 8.4 Mbp of genomic sequence on chromosome 20. Using Affymetrix® Soy GeneChip and high-throughput Illumina® whole transcriptome sequencing platforms, 13 genes displaying significant seed transcript accumulation differences between NILs were identified that mapped to the 8.4 Mbp LG I protein QTL region. Conclusions: This study identifies gene candidates at the LG I protein QTL for potential involvement in the regulation of protein content in the soybean seed. The results demonstrate the power of complementary approaches to characterize contrasting NILs and provide genome-wide transcriptome insight towards understanding seed biology and the soybean genome

Systematic review of communication technologies to promote access and engagement of young people with diabetes into healthcare

Background: Research has investigated whether communication technologies (e.g. mobile telephony, forums, email) can be used to transfer digital information between healthcare professionals and young people who live with diabetes. The systematic review evaluates the effectiveness and impact of these technologies on communication. Methods: Nine electronic databases were searched. Technologies were described and a narrative synthesis of all studies was undertaken. Results: Of 20,925 publications identified, 19 met the inclusion criteria, with 18 technologies assessed. Five categories of communication technologies were identified: video-and tele-conferencing (n = 2); mobile telephony (n = 3); telephone support (n = 3); novel electronic communication devices for transferring clinical information (n = 10); and web-based discussion boards (n = 1). Ten studies showed a positive improvement in HbA1c following the intervention with four studies reporting detrimental increases in HbA1c levels. In fifteen studies communication technologies increased the frequency of contact between patient and healthcare professional. Findings were inconsistent of an association between improvements in HbA1c and increased contact. Limited evidence was available concerning behavioural and care coordination outcomes, although improvement in quality of life, patientcaregiver interaction, self-care and metabolic transmission were reported for some communication technologies. Conclusions: The breadth of study design and types of technologies reported make the magnitude of benefit and their effects on health difficult to determine. While communication technologies may increase the frequency of contact between patient and health care professional, it remains unclear whether this results in improved outcomes and is often the basis of the intervention itself. Further research is needed to explore the effectiveness and cost effectiveness of increasing the use of communication technologies between young people and healthcare professionals

The genome of cowpea (Vigna unguiculata [L.] Walp.)

[EN] Cowpea (Vigna unguiculata [L.] Walp.) is a major crop for worldwide food and nutritional security, especially in sub-Saharan Africa, that is resilient to hot and drought-prone environments. An assembly of the single-haplotype inbred genome of cowpea IT97K-499-35 was developed by exploiting the synergies between single-molecule real-time sequencing, optical and genetic mapping, and an assembly reconciliation algorithm. A total of 519 Mb is included in the assembled sequences. Nearly half of the assembled sequence is composed of repetitive elements, which are enriched within recombination-poor pericentromeric regions. A comparative analysis of these elements suggests that genome size differences between Vigna species are mainly attributable to changes in the amount of Gypsy retrotransposons. Conversely, genes are more abundant in more distal, high-recombination regions of the chromosomes; there appears to be more duplication of genes within the NBS-LRR and the SAUR-like auxin superfamilies compared with other warm-season legumes that have been sequenced. A surprising outcome is the identification of an inversion of 4.2 Mb among landraces and cultivars, which includes a gene that has been associated in other plants with interactions with the parasitic weed Striga gesnerioides. The genome sequence facilitated the identification of a putative syntelog for multiple organ gigantism in legumes. A revised numbering system has been adopted for cowpea chromosomes based on synteny with common bean (Phaseolus vulgaris). An estimate of nuclear genome size of 640.6 Mbp based on cytometry is presentedS