Warmblood fragile foal syndrome type 1 mutation (PLOD1 c.2032G>A) is not associated with catastrophic breakdown and has a low allele frequency in the Thoroughbred breed.

BackgroundCatastrophic fractures are among the most common cause of fatalities in racehorses. Several factors, including genetics, likely contribute to increased risk for fatal injuries. A variant in the procollagen-lysine, 2-oxoglutarate 5-dioxygenase1 gene (PLOD1 c.2032G>A) was shown to cause Warmblood fragile foal syndrome type 1 (WFFS), a fatal recessive defect of the connective tissue. Screening of multiple horse breeds identified the presence of the WFFS allele in the Thoroughbred. PLOD1 is involved in cross-linking of collagen fibrils and thus could potentially increase the risk of catastrophic breakdown.ObjectivesEstimate the frequency of the WFFS allele (PLOD1 c.2032G>A) and determine if it is a risk factor for catastrophic breakdown in the Thoroughbred.Study designCase-control genetic study.MethodsGenomic DNA from hair and/or tissue samples was genotyped for the WFFS allele. Fisher's Exact tests were performed to compare allele and carrier frequencies between the case cohort (catastrophic breakdown, n = 22) and several cohorts with no record of injury (n = 138 raced/trained at same track and season and n = 185 older than 7 years and raced during same season), nonracers (n = 92), and a random sample without consideration for racing history (n = 279).ResultsThe frequency of the PLOD1 c.2032G>A variant in the Thoroughbred breed is low (1.2%). Seventeen of 716 Thoroughbreds tested were carriers (2.4%) and no WFFS homozygotes were detected. Only one catastrophic breakdown case carried the WFFS allele. No statistically significant difference in allele or carrier frequency was identified between case and control cohorts (P>0.05 in all comparisons performed).Main limitationsThis study evaluated cases from one single track.ConclusionsThis study demonstrated that the PLOD1 c.2032G>A associated with WFFS is present at very low frequency in Thoroughbreds and is not a genetic risk factor for catastrophic breakdown

Review of water supply-demand options for South East Queensland

This independent review aims to assess the Queensland Government's proposed strategy for meeting the long-term water supply-demand balance for South East Queensland, of which the Traveston Crossing scheme is a major and controversial component. The review, conducted by a team from the ISF at the UTS and Cardno, concludes that a diverse portfolio of options can ensure supply security for South East Queensland (SEQ) well into the future, certainly to 2050. Such options include: increasing water supply availability (supply-side options); decreasing the demand for water (demand-side options); and meeting water supply needs during deep droughts (drought response options). A number of the elements of such a portfolio are already being implemented as part of the current Queensland Government strategy. With the extension and addition of low unit cost demand-side options and supply-side drought response readiness options, a clear conclusion of this study is that the proposed dam at Traveston Crossing on the Mary River is neither necessary nor desirable as a part of the portfolio for ensuring supply security to 2050. The increase in supply from this proposed dam will not assist in the short-term during the current severe drought in which water (from savings and supply) is needed over the next two to three years. Planned completion of the Traveston Crossing Dam Stage 1 is in 2012. Additional time will be needed for the dam to fill, which could take an additional two years, resulting in the yield from this source only potentially being available in 2014. Neither is the Traveston Crossing scheme needed for supply-demand balance in the longer term with the suite of other more appropriate drought response measures being implemented by the Queensland Government and strategy being proposed as part of this study. The proposed dam at Traveston Crossing on the Mary River represents a high total cost, high unit cost, high risk and high environmental and social impact option

Use of whole-genome sequencing to identify clusters of Shigella flexneri associated with sexual transmission in men who have sex with men in England: a validation study using linked behavioural data

Since the 1970s, shigellosis has been reported as a sexually transmissible infection, and in recent years, genomic data have revealed the breadth of Shigella spp. transmission among global networks of men who have sex with men (MSM). In 2015, Public Health England (PHE) introduced routine whole-genome sequencing (WGS) of Shigella spp. to identify transmission clusters. However, limited behavioural information for the cases hampers interpretation. We investigated whether WGS can distinguish between clusters representing sexual transmission in MSM and clusters representing community (non-sexual) transmission to inform infection control. WGS data for Shigella flexneri from August 2015 to July 2017 were aggregated into single linkage clusters based on SNP typing using a range of SNP distances (the standard for Shigella surveillance at PHE is 10 SNPs). Clusters were classified as 'adult male', 'household', 'travel-associated' or 'community' using routine demographic data submitted alongside laboratory cultures. From August 2015 to March 2017, PHE contacted those with shigellosis as part of routine public-health follow-up and collected exposure data on a structured questionnaire, which for the first time included questions about sexual identity and behaviour. The questionnaire data were used to determine whether clusters classified as 'adult male' represented likely sexual transmission between men, thereby validating the use of the SNP clustering tool for informing appropriate public-health responses. Overall, 1006 S. flexneri cases were reported, of which 563 clustered with at least one other case (10-SNP threshold). Linked questionnaire data were available for 106 clustered cases, of which 84.0 % belonged to an 'adult male' cluster. At the 10-SNP threshold, 95.1 % [95 % confidence interval (CI) 88.0-98.1%] of MSM belonged to an 'adult male' cluster, while 73.2 % (95 % CI 49.1-87.5%) of non-MSM belonged to a 'community' or 'travel-associated' cluster. At the 25-SNP threshold, all MSM (95 % CI 96.0-100%) belonged to an 'adult male' cluster and 77.8 % (95 % CI 59.2-89.4%) of non-MSM belonged to a 'community' or 'travel-associated' cluster. Within one phylogenetic clade of S. flexneri, 9 clusters were identified (7 'adult male'; 2 'community') using a 10-SNP threshold, while a single 'adult male' cluster was identified using a 25-SNP threshold. Genotypic markers of azithromycin resistance were detected in 84.5 % (294/348) of 'adult male' cases and 20.9 % (9/43) of cases in other clusters (10-SNP threshold), the latter of which contained gay-identifying men who reported recent same-sex sexual contact. Our study suggests that SNP clustering can be used to identify Shigella clusters representing likely sexual transmission in MSM to inform infection control. Defining clusters requires a flexible approach in terms of genetic relatedness to ensure a clear understanding of underlying transmission networks

Luminosities of AGB Variables

The prevailing evidence suggests that most large-amplitude AGB variables follow the period luminosity (PL) relation that has been established for Miras in the LMC and galactic globular clusters. Hipparcos observations indicate that most Miras in the solar neighbourhood are consistent with such a relation. There are two groups of stars with luminosities that are apparently greater than the PL relation would predict: (1) in the LMC and SMC there are large amplitude variables, with long periods, P> 420 days, which are probably undergoing hot bottom burning, but which are very clearly more luminous than the PL relation (these are visually bright and are likely to be among the first stars discovered in more distant intermediate age populations); (2) in the solar neighbourhood there are short period, P<235 days, red stars which are probably more luminous than the PL relation. Similar short-period red stars, with high luminosities, have not been identified in the Magellanic Clouds.Comment: 8 pages, 2 figure, to be published in Mass-Losing Pulsating Stars and their Circumstellar Matter, Y. Nakada & M. Honma (eds) Kluwer ASSL serie

WHOPPA Enables Parallel Assessment of Leucine-Rich Repeat Kinase 2 and Glucocerebrosidase Enzymatic Activity in Parkinson's Disease Monocytes

Both leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GCase) are promising targets for the treatment of Parkinson's disease (PD). Evidence suggests that both proteins are involved in biological pathways involving the lysosome. However, studies to date have largely investigated the enzymes in isolation and any relationship between LRRK2 and GCase remains unclear. Both enzymes are highly expressed in peripheral blood monocytes and have been implicated in immune function and inflammation. To facilitate the standardized measurement of these readouts in large cohorts of samples collected from persons with PD across the globe, we developed and optimized a sample collection and processing protocol with parallel flow cytometry assays. Assay parameters were first optimized using healthy control peripheral blood mononuclear cells (PBMCs), and then LRRK2 and GCase activities were measured in immune cells from persons with idiopathic PD (iPD). We tested the ability of this protocol to deliver similar results across institutes across the globe, and named this protocol the Wallings-Hughes Optimized Protocol for PBMC Assessment (WHOPPA). In the application of this protocol, we found increased LRRK2 levels and stimulation-dependent enzymatic activity, and decreased GBA index in classical iPD monocytes, as well as increased cytokine release in PD PBMCs. WHOPPA also demonstrated a strong positive correlation between LRRK2 levels, pRab10 and HLA-DR in classical monocytes from subjects with iPD. These data support a role for the global use of WHOPPA and expression levels of these two PD-associated proteins in immune responses, and provide a robust assay to determine if LRRK2 and GCase activities in monocytes have potential utility as reliable and reproducible biomarkers of disease in larger cohorts of subjects with PD.Copyright © 2022 Wallings, Hughes, Staley, Simon, McFarland, Alcalay, Garrido, Martí, Sarró, Dzamko and Tansey

Monitoring ground movement at Volcán de Colima, Mexico, using Sentinel-1 data and SqueeSAR®

Volcán de Colima is a highly active stratovolcano in western Mexico which presents a significant hazard to over 300,000 people who live within ca 40 km of the volcano. Due to its persistent activity, the volcano is actively monitored and researched, and understanding the patterns of behaviour is vital to accurate hazard assessment. Sentinel-1 SAR images from ascending and descending orbits allow 1D and 2D ground motions to be retrieved using multi-interferogram techniques. SqueeSAR®’s unique processing allows a better characterisation of subtle ground movements in remote, rural mountainous areas compared to many other multi-interferogram techniques. A dataset of 147 SAR scenes (2017-2019) has been processed to show patterns of lava subsidence (<150 mm of downward vertical deformation over 2 years), as well as volcano deflation and apparent westward lateral movement. These data indicate that viscous andesitic lava flows may remain mobile for years following eruption and emplacement, and that the entire volcanic edifice is subsiding. Despite the apparent quiescence, volcanic edifices can remain highly dynamic after the termination of explosive or effusive activity. We interpret that the western flank of Volcán de Colima may become steeper with time and may be of long-term concern for hazard assessment activities. Thematic collection: This article is part of the Remote sensing for site investigations on Earth and other planets collection available at: https://www.lyellcollection.org/topic/collections/remote-sensing-for-site-investigations-on-earth-and-other-planet

Strongly linked current flow in polycrystalline forms of the new superconductor MgB2

The discovery of superconductivity at 39 K in MgB2[1] raises many issues. One of the central questions is whether this new superconductor resembles a high-temperature-cuprate superconductor or a low-temperature metallic superconductor in terms of its current carrying characteristics in applied magnetic fields. In spite of the very high transition temperatures of the cuprate superconductors, their performance in magnetic fields has several drawbacks[2]. Their large anisotropy restricts high bulk current densities to much less than the full magnetic field-temperature (H-T) space over which superconductivity is found. Further, weak coupling across grain boundaries makes transport current densities in untextured polycrystalline forms low and strongly magnetic field sensitive[3,4]. These studies of MgB2 address both issues. In spite of the multi-phase, untextured, nano-scale sub-divided nature of our samples, supercurrents flow throughout without the strong sensitivity to weak magnetic fields characteristic of Josephson-coupled grains[3]. Magnetization measurements over nearly all of the superconducting H-T plane show good temperature scaling of the flux pinning force, suggestive of a current density determined by flux pinning. At least two length scales are suggested by the magnetization and magneto optical (MO) analysis but the cause of this seems to be phase inhomogeneity, porosity, and minority insulating phase such as MgO rather than by weakly coupled grain boundaries. Our results suggest that polycrystalline ceramics of this new class of superconductor will not be compromised by the weak link problems of the high temperature superconductors, a conclusion with enormous significance for applications if higher temperature analogs of this compound can be discovered

Cataract surgery by appointment – a pilot study

BACKGROUND: "Cataract Surgery by Appointment" is a new method of delivery of cataract surgery that reduces the time a patient spends in hospital by their direct arrival at the operating theatre, having self-prepared for surgery, thus avoiding admission to the ward or time spent in the Day Case Unit. The patient can stay as little as 20 minutes from their arrival to going home. We describe the process in detail, and seek to evaluate the visual outcome, safety and patient satisfaction of same. METHODS: Visual outcome and safety data were obtained from patients' medical records, prospectively. Patients were also surveyed by a questionnaire to determine their satisfaction with the service and viability as a prospect for providing a more efficient cataract surgery service. RESULTS: In 2002, fifty-one eyes of 39 consecutive patients underwent "Cataract Surgery by Appointment". There were 16 male and 23 female. The pre-operative best-corrected visual acuity was 6/9 or better in 17 (33%) eyes. The post-operative best-corrected visual acuity was 6/9 or better in 44 (86%) eyes. There were no per-operative complications. Post-operative complications occurred in 3 (6%) eyes. The average number of days from surgery to final discharge was 14.5 days. Twenty-eight (72%) completed questionnaires were returned. The results show that the majority of patients were satisfied with their overall experience of this mode of delivery for cataract surgery. CONCLUSION: "Cataract Surgery by Appointment" performed under local anaesthesia by a skilled ophthalmic surgeon appears to be safe and effective for highly selected cases. This method of delivery gave a high level of patient satisfaction, and is the ultimate form of day case cataract surgery. The method may gain widespread use should per-operative intracameral pupil dilatation prove to be effective and acceptable. Attention should be paid to risk-stratification, so complex cases are allocated more time on the operating list