Proximity sensors provide an accurate alternative for measuring maternal pedigree of lambs in Australian sheep flocks under commercial conditions

Context: Proximity sensors were used recently to determine the maternal pedigree of lambs on a small plot with high accuracy. If this accuracy is maintained under commercial grazing conditions, this method could be a useful alternative to improving genetic gain in sheep, including reproduction traits. Aims: To investigate using proximity sensors to determine the maternal pedigree of lambs and to define the level of interactions required to determine maternal pedigree confidently irrespective of differences in ewe age, lamb age, birth type, paddock size, flock size or stocking rate under commercial grazing conditions. Methods: We compared maternal pedigree determined using the proximity sensors to DNA profiling (n = 10 flocks) and lambing rounds (n = 16 flocks). Ewes (n = 7315) and lambs (n = 8058) were fitted with proximity sensors under normal grazing conditions for each property for 1–3 days. Flocks varied in ewe age (adults, hoggets and ewe lambs), lamb age (up to 100 days old, except for 1 flock), birth type (singles, multiples), paddock size (0.25–320 ha), flock size (37–420 lambs) and stocking rate (2–100 dry sheep equivalents/ha, except for 1 flock). Key results: An interaction ratio of >2 was required for a confident ewe–lamb match (ewe with the most interactions compared with the ewe with the second-most interactions for each lamb). Using this criterion, the average success of proximity sensors at matching a lamb to a ewe was 95% and the sensors were 97% accurate when compared with the pedigree results from lambing rounds or DNA. For lambs matched successfully, over 90% of this success was achieved in the first 7 h and over 99% in the first 20 h. While the success rate of matching a lamb to a ewe was not influenced significantly by ewe age, birth type, paddock size, flock size or stocking rate, the time to achieve sensor success was significantly quicker for singles than for twins and sensor accuracy was significantly higher for smaller paddocks with higher stocking rates. Conclusions: Our results showed that proximity sensors can establish maternal pedigree effectively and accurately across a range of conditions experienced on commercial properties. Implications: Private industry can now develop more cost-effective sensor technologies with greater confidence that will enhance recording of maternal pedigree and, hence, the rate of genetic gain across the sheep industry

The Impact of the Level of Feed-On-Offer Available to Merino Ewes During Winter-Spring on the Wool Production of Their Progeny as Adults

New opportunities for developing optimum ewe management systems, based on achieving liveweight and body condition score (CS) targets at critical stages of the reproductive cycle, have emerged from the acceptance that nutrition during pregnancy can have substantial impacts on the lifetime wool performance of the progeny (Kelly et al,. 1996). However, most studies of the impacts of nutrition on foetal growth and development tended to focus on late pregnancy and have also only considered extreme nutritional regimes often outside the boundaries of commercial reality. Hence, the Lifetime Wool team (Thompson & Oldham, 2004) conducted dose-response experiments to determine the levels of feed-on-offer (FOO; kg dry matter/ha; Hyder et al., 2004) needed at different stages of the reproductive cycle to optimise both wool and meat production per ha in the short term and the lifetime performance of the progeny in the long term. This paper reports the response in the first two years of the experiment of clean fleece weight (CFW) and fibre diameter (FD) of the progeny as adults to the level of FOO available to their mother in late pregnancy and lactation

Borrelia valaisiana resist complement-mediated killing independently of the recruitment of immune regulators and inactivation of complement components

Spirochetes belonging to the Borrelia (B.) burgdorferi sensu lato complex differ in their resistance to complement-mediated killing, particularly in regard to human serum. In the present study, we elucidate the serum and complement susceptibility of B. valaisiana, a genospecies with the potential to cause Lyme disease in Europe as well as in Asia. Among the investigated isolates, growth of ZWU3 Ny3 was not affected while growth of VS116 and Bv9 was strongly inhibited in the presence of 50% human serum. Analyzing complement activation, complement components C3, C4 and C6 were deposited on the surface of isolates VS116 and Bv9, and similarly the membrane attack complex was formed on their surface. In contrast, no surface-deposited components and no aberrations in cell morphology were detected for serum-resistant ZWU3 Ny3. While further investigating the protective role of bound complement regulators in mediating complement resistance, we discovered that none of the B. valaisiana isolates analyzed bound complement regulators Factor H, Factor H-like protein 1, C4b binding protein or C1 esterase inhibitor. In addition, B. valaisiana also lacked intrinsic proteolytic activity to degrade complement components C3, C3b, C4, C4b, and C5. Taken together, these findings suggest that certain B. valaisiana isolates differ in their capability to resist complement-mediating killing by human serum. The molecular mechanism utilized by B. valaisiana to inhibit bacteriolysis appears not to involve binding of the key host complement regulators of the alternative, classical, and lectin pathways as already known for serum-resistant Lyme disease or relapsing fever borreliae

A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.Comment: 41 page

Topological data analysis reveals genotype-phenotype relationships in primary ciliary dyskinesia

Background: Primary ciliary dyskinesia (PCD) is a heterogeneous inherited disorder caused by mutations in approximately 50 cilia-related genes. PCD genotype-phenotype relationships have mostly arisen from small case series because existing statistical approaches to investigate relationships have been unsuitable for rare diseases. / Methods: We applied a topological data analysis (TDA) approach to investigate genotype-phenotype relationships in PCD. Data from separate training and validation cohorts included 396 genetically defined individuals carrying pathogenic variants in PCD genes. To develop the TDA models, twelve clinical and diagnostic variables were included. TDA-driven hypotheses were subsequently tested using traditional statistics. / Results: Disease severity at diagnosis measured by FEV1 z-score was (i) significantly worse in individuals with CCDC39 mutations compared to other gene mutations and (ii) better in those with DNAH11 mutations; the latter also reported less neonatal respiratory distress. Patients without neonatal respiratory distress had better preserved FEV1 at diagnosis. Individuals with DNAH5 mutations were phenotypically diverse. Cilia ultrastructure and beat pattern defects correlated closely to specific causative gene groups, confirming these tests can be used to support a genetic diagnosis. / Conclusions: This large scale multi-national study presents PCD as a syndrome with overlapping symptoms and variation in phenotype, according to genotype. TDA modelling confirmed genotype-phenotype relationships reported by smaller studies (e.g. FEV1 worse with CCDC39 mutations), and identified new relationships, including FEV1 preservation with DNAH11 mutations and diversity of severity with DNAH5 mutations

Severe course of Lyme neuroborreliosis in an HIV-1 positive patient; case report and review of the literature

<p>Abstract</p> <p>Background</p> <p>Lyme Neuroborreliosis (LNB) in a human immunodeficiency virus (HIV) positive patient is a rare co-infection and has only been reported four times in literature. No case of an HIV patient with a meningoencephalitis due to LNB in combination with HIV has been described to date.</p> <p>Case presentation</p> <p>A 51 year old woman previously diagnosed with HIV presented with an atypical and severe LNB. Diagnosis was made evident by several microbiological techniques. Biochemical and microbiological recovery during treatment was rapid, however after treatment the patient suffered from severe and persistent sequelae.</p> <p>Conclusions</p> <p>A clinician should consider LNB when being confronted with an HIV patient with focal encephalitis, without any history of Lyme disease or tick bites, in an endemic area. Rapid diagnosis and treatment is necessary in order to minimize severe sequelae.</p

Sheep Updates 2006 - part 4

This session covers seven papers from different authors: MANAGEMENT 1. Wool and meat traits in Merino flocks in different regions, K.G. Geenty, A.A. Swan, A.J. Smith, J.L. Smith, Sheep CRC and CSIRO Livestock Industries, Armidale 2. Fat score or Condition score? - It all depends on what you want to do! Chris Oldham, Department of Agriculture and Food Western Australia 3. Sheep worm control - the latest for Western Australia, RG Woodgate, RA Love, E Dobbe, HM Hoult, J Pearson, S Hill, A van Burgel and RB Besier, Department of Agriculture and Food Western Australia PASTURES 4. Rethinking pasture production - STEPS to greater productivity with perennials, R. Warburton, Farmer, Mobrup, WA, L. Mathwin, Farmer Kojonup WA, D. Rogers, E. Crossley, Department of Agriculture and Food Western Australia 5. Sheep Returnes from Saltland Pastures, Allan Herbert, Department of Agriculture and Food Western Australia 6. Pasture legumes and grasses from saline land, Phil Nichols, Tony Albertsen, Darryl McClements, Department of Agriculture and Food Western Australia, & Cooperative Research Centre for Plant-based Management of Dryland Salinity MERINO INNOVATION DAY 7. Towards \u27clean, green and ethical\u27 sheep production, Graeme Martin, Penny Hawken, Carolina Viñoles, Beth Paganoni and Dominique Blache, School of Animal Biology, Faculty of Natural & Agricultural Sciences, The University of Western Australi

Rapid Response to Remdesivir in Hospitalised COVID-19 Patients:A Propensity Score Weighted Multicentre Cohort Study

Introduction: Remdesivir is a registered treatment for hospitalised patients with COVID-19 that has moderate clinical effectiveness. Anecdotally, some patients’ respiratory insufficiency seemed to recover particularly rapidly after initiation of remdesivir. In this study, we investigated if this rapid improvement was caused by remdesivir, and which patient characteristics might predict a rapid clinical improvement in response to remdesivir. Methods: This was a multicentre observational cohort study of hospitalised patients with COVID-19 who required supplemental oxygen and were treated with dexamethasone. Rapid clinical improvement in response to treatment was defined by a reduction of at least 1 L of supplemental oxygen per minute or discharge from the hospital within 72 h after admission. Inverse probability of treatment-weighted logistic regression modelling was used to assess the association between remdesivir and rapid clinical improvement. Secondary endpoints included in-hospital mortality, ICU admission rate and hospitalisation duration. Results: Of 871 patients included, 445 were treated with remdesivir. There was no influence of remdesivir on the occurrence of rapid clinical improvement (62% vs 61% OR 1.05, 95% CI 0.79–1.40; p = 0.76). The in-hospital mortality was lower (14.7% vs 19.8% OR 0.70, 95% CI 0.48–1.02; p = 0.06) for the remdesivir-treated patients. Rapid clinical improvement occurred more often in patients with low C-reactive protein (≤ 75 mg/L) and short duration of symptoms prior to hospitalisation (&lt; 7 days) (OR 2.84, 95% CI 1.07–7.56). Conclusion: Remdesivir generally does not increase the incidence of rapid clinical improvement in hospitalised patients with COVID-19, but it might have an effect in patients with short duration of symptoms and limited signs of systemic inflammation.</p

How Do Dual Long-Acting Bronchodilators Prevent Exacerbations of Chronic Obstructive Pulmonary Disease?

Decreasing the frequency and severity of exacerbations is one of the main goals of treatment for patients with chronic obstructive pulmonary disease. Several studies have documented that long-acting bronchodilators can reduce exacerbation rate and/or severity, and others have shown that combinations of long-acting β2-adrenergic agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) provide greater reductions in exacerbation frequency than either their monocomponents or LABA/inhaled corticosteroid combinations in patients at low and high risk for these events. In this review, small groups of experts critically evaluated mechanisms potentially responsible for the increased benefit of LABA/LAMA combinations over single long-acting bronchodilators or LABA/inhaled corticosteroids in decreasing exacerbation. These included effects on lung hyperinflation and mechanical stress, inflammation, excessive mucus production with impaired mucociliary clearance, and symptom severity. The data assembled and analyzed by each group were reviewed by all authors and combined into this manuscript. Available clinical results support the possibility that effects of LABA/LAMA combinations on hyperinflation, mucociliary clearance, and symptom severity may all contribute to decreasing exacerbations. Although preclinical studies suggest LABAs and LAMAs have antiinflammatory effects, such effects have not been demonstrated yet in patients with chronic obstructive pulmonary disease