Familial hypercholesterolaemia: challenges in primary care

Familial hypercholesterolaemia remains largely unrecognised and undertreated in Australian primary care. A new approach involving increased awareness, early detection, lifelong treatment and cascade testing of relatives is essential to improve outcomes of patients with this disorder. Key Points Familial hypercholesterolaemia (FH) is a relatively common inherited disorder of high cholesterol levels. FH can lead to atherosclerosis, premature coronary artery disease and early death if left untreated. Cascade testing of relatives of patients with FH is cost- effective and necessary as one in two will have the condition. Innovations in primary care can improve FH detection in the community. An integrated approach to FH detection involving GPs, specialists and pathology laboratories is recommended. Primary care teams are well positioned to provide a sustainable approach to FH diagnosis and management but greater awareness of this condition is needed

The RadFxSat-2 Mission to Measure SEU Rates in FinFET Microelectronics

The RadFxSat-2 mission was launched January 17, 2021 with Virgin Orbit\u27s LauncherOne under the NASA ELaNa-20 initiative. RadFxSat-2 carries a radiation effects payload designed to investigate single event upsets (SEUs) in sub-65 nm commercial memories, including a FinFET-based memory. Sub-65 nm technologies have demonstrated enhanced sensitivity to low-energy protons, but current models have not considered low-energy protons as a source of SEUs. Missions utilizing the latest commercial technologies could experience a higher error rate than predicted. RadFxSat-2 was designed to assess SEU rates for FinFET SRAMs operated in low-Earth orbit (LEO), a proton-heavy environment. Details of the mission and data collected over the previous two years are presented. Results from RadFxSat-2 suggest that FinFET-based microelectronic technologies are suitable for high-performance, high-density storage in LEO

Relative Oscillation Theory, Weighted Zeros of the Wronskian, and the Spectral Shift Function

We develop an analog of classical oscillation theory for Sturm-Liouville operators which, rather than measuring the spectrum of one single operator, measures the difference between the spectra of two different operators. This is done by replacing zeros of solutions of one operator by weighted zeros of Wronskians of solutions of two different operators. In particular, we show that a Sturm-type comparison theorem still holds in this situation and demonstrate how this can be used to investigate the finiteness of eigenvalues in essential spectral gaps. Furthermore, the connection with Krein's spectral shift function is established.Comment: 26 page

On Fourier transforms of radial functions and distributions

We find a formula that relates the Fourier transform of a radial function on $\mathbf{R}^n$ with the Fourier transform of the same function defined on $\mathbf{R}^{n+2}$. This formula enables one to explicitly calculate the Fourier transform of any radial function $f(r)$ in any dimension, provided one knows the Fourier transform of the one-dimensional function $t\to f(|t|)$ and the two-dimensional function $(x_1,x_2)\to f(|(x_1,x_2)|)$. We prove analogous results for radial tempered distributions.Comment: 12 page

Planet Hunters. VIII. Characterization of 41 Long-Period Exoplanet Candidates from Kepler Archival Data

The census of exoplanets is incomplete for orbital distances larger than 1 AU. Here, we present 41 long-period planet candidates in 38 systems identified by Planet Hunters based on Kepler archival data (Q0-Q17). Among them, 17 exhibit only one transit, 14 have two visible transits and 10 have more than three visible transits. For planet candidates with only one visible transit, we estimate their orbital periods based on transit duration and host star properties. The majority of the planet candidates in this work (75%) have orbital periods that correspond to distances of 1-3 AU from their host stars. We conduct follow-up imaging and spectroscopic observations to validate and characterize planet host stars. In total, we obtain adaptive optics images for 33 stars to search for possible blending sources. Six stars have stellar companions within 4". We obtain high-resolution spectra for 6 stars to determine their physical properties. Stellar properties for other stars are obtained from the NASA Exoplanet Archive and the Kepler Stellar Catalog by Huber et al. (2014). We validate 7 planet candidates that have planet confidence over 0.997 (3-{\sigma} level). These validated planets include 3 single-transit planets (KIC-3558849b, KIC-5951458b, and KIC-8540376c), 3 planets with double transits (KIC-8540376b, KIC-9663113b, and KIC-10525077b), and 1 planet with 4 transits (KIC-5437945b). This work provides assessment regarding the existence of planets at wide separations and the associated false positive rate for transiting observation (17%-33%). More than half of the long-period planets with at least three transits in this paper exhibit transit timing variations up to 41 hours, which suggest additional components that dynamically interact with the transiting planet candidates. The nature of these components can be determined by follow-up radial velocity and transit observations.Comment: Published on ApJ, 815, 127 Notations of validated planets are changed in accordance with naming convention of NASA Exoplanet Archiv

Adjuvant drugs for peripheral nerve blocks: The role of nmda antagonists, neostigmine, epinephrine, and sodium bicarbonate

The potential for misuse, overdose, and chronic use has led researchers to look for other methods to decrease opioid consumption in patients with acute and chronic pain states. The use of peripheral nerve blocks for surgery has gained increasing popularity as it minimizes peripheral pain signals from the nociceptors of local tissue sustaining trauma and inflammation from surgery. The individualization of peripheral nerve blocks using adjuvant drugs has the potential to improve patient outcomes and reduce chronic pain. The major limitations of peripheral nerve blocks are their limited duration of action and dose-dependent adverse effects. Adjuvant drugs for peripheral nerve blocks show increasing potential as a solution for postoperative and chronic pain with their synergistic effects to increase the duration of action and decrease the required dosage of local anesthetic. N-methyl-d-aspartate (NMDA) receptor antagonists are a viable option for patients with opioid resistance and neuropathic pain due to their affinity to the neurotransmitter glutamate, which is released when patients experience a noxious stimulus. Neostigmine is a cholinesterase inhibitor that exerts its effect by competitively binding at the active site of acetylcholinesterase, which prevents the hydrolysis of acetylcholine and subsequently retaining acetylcholine at the nerve terminal. Epinephrine, also known as adrenaline, can potentially be used as an adjuvant to accelerate and prolong analgesic effects in digital nerve blocks. The theorized role of sodium bicarbonate in local anesthetic preparations is to increase the pH of the anesthetic. The resulting alkaline solution enables the anesthetic to more readily exist in its un-ionized form, which more efficiently crosses lipid membranes of peripheral nerves. However, more research is needed to show the efficacy of these adjuvants for nerve block prolongation as studies have been either mixed or have small sample sizes

Assessing the impact of comparative genomic sequence data on the functional annotation of the Drosophila genome

BACKGROUND: It is widely accepted that comparative sequence data can aid the functional annotation of genome sequences; however, the most informative species and features of genome evolution for comparison remain to be determined. RESULTS: We analyzed conservation in eight genomic regions (apterous, even-skipped, fushi tarazu, twist, and Rhodopsins 1, 2, 3 and 4) from four Drosophila species (D. erecta, D. pseudoobscura, D. willistoni, and D. littoralis) covering more than 500 kb of the D. melanogaster genome. All D. melanogaster genes (and 78-82% of coding exons) identified in divergent species such as D. pseudoobscura show evidence of functional constraint. Addition of a third species can reveal functional constraint in otherwise non-significant pairwise exon comparisons. Microsynteny is largely conserved, with rearrangement breakpoints, novel transposable element insertions, and gene transpositions occurring in similar numbers. Rates of amino-acid substitution are higher in uncharacterized genes relative to genes that have previously been studied. Conserved non-coding sequences (CNCSs) tend to be spatially clustered with conserved spacing between CNCSs, and clusters of CNCSs can be used to predict enhancer sequences. CONCLUSIONS: Our results provide the basis for choosing species whose genome sequences would be most useful in aiding the functional annotation of coding and cis-regulatory sequences in Drosophila. Furthermore, this work shows how decoding the spatial organization of conserved sequences, such as the clustering of CNCSs, can complement efforts to annotate eukaryotic genomes on the basis of sequence conservation alone

Finishing a whole-genome shotgun: Release 3 of the Drosophila melanogaster euchromatic genome sequence

BACKGROUND: The Drosophila melanogaster genome was the first metazoan genome to have been sequenced by the whole-genome shotgun (WGS) method. Two issues relating to this achievement were widely debated in the genomics community: how correct is the sequence with respect to base-pair (bp) accuracy and frequency of assembly errors? And, how difficult is it to bring a WGS sequence to the accepted standard for finished sequence? We are now in a position to answer these questions. RESULTS: Our finishing process was designed to close gaps, improve sequence quality and validate the assembly. Sequence traces derived from the WGS and draft sequencing of individual bacterial artificial chromosomes (BACs) were assembled into BAC-sized segments. These segments were brought to high quality, and then joined to constitute the sequence of each chromosome arm. Overall assembly was verified by comparison to a physical map of fingerprinted BAC clones. In the current version of the 116.9 Mb euchromatic genome, called Release 3, the six euchromatic chromosome arms are represented by 13 scaffolds with a total of 37 sequence gaps. We compared Release 3 to Release 2; in autosomal regions of unique sequence, the error rate of Release 2 was one in 20,000 bp. CONCLUSIONS: The WGS strategy can efficiently produce a high-quality sequence of a metazoan genome while generating the reagents required for sequence finishing. However, the initial method of repeat assembly was flawed. The sequence we report here, Release 3, is a reliable resource for molecular genetic experimentation and computational analysis