THE EVALUATION OF ALTERNATIVE TOXINS TO SODIUM MONOFLUOROACETATE (1080) FOR POSSUM CONTROL

Possum control in New Zealand is dependent on the use of sodium monofluroacetate (1080) and cyanide. Although 1080 is highly effective, its use is restricted to government staff. Cyanide is available for a wider group of licensed operators, but cyanide shyness reduces its effectiveness. An acute toxicity program has been set up to identify nonanticoagulant toxins that could be used safely by farmers. Dose-ranging studies showed that possums are susceptible to cholecalciferol, calciferol, gliftor, alpha-chloralose, and nicotine, but not to bromethalin. As lethal doses for these toxins have been ascertained, which of them are likely to be cost-effective and safe alternatives to 1080 now needs to be established. Bait palatability and field studies will then be undertaken with the most promising candidates

Benefits and risks of including the bromoform containing seaweed Asparagopsis in feed for the reduction of methane production from ruminants

The agricultural production of ruminants is responsible for 24% of global methane emissions, contributing 39% of emissions of this greenhouse gas from the agricultural sector. Strategies to mitigate ruminant methanogenesis include the use of methanogen inhibitors. For example, the seaweeds Asparagopsis taxiformis and Asparagopsis armata included at low levels in the feed of cattle and sheep inhibit methanogenesis by up to 98%, with evidence of improvements in feed utilisation efficiency. This has resulted in an increasing interest in and demand for these seaweeds globally. In response, research is progressing rapidly to facilitate Asparagopsis cultivation at large scale, and to develop aquaculture production systems to enable a high quality and consistent supply chain. In addition to developing robust strategies for sustainable production, it is important to consider and evaluate the benefits and risks associated with its production and subsequent use as an antimethanogenic feed ingredient for ruminant livestock. This review focuses on the relevant ruminal biochemical pathways, degradation, and toxicological risks associated with bromoform (CHBr3), the major active ingredient for inhibition of methanogenesis in Asparagopsis, and the effects that production of Asparagopsis and its use as a ruminant feed ingredient might have on atmospheric chemistry

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

General anaesthetic and airway management practice for obstetric surgery in England: a prospective, multi-centre observational study

There are no current descriptions of general anaesthesia characteristics for obstetric surgery, despite recent changes to patient baseline characteristics and airway management guidelines. This analysis of data from the direct reporting of awareness in maternity patients' (DREAMY) study of accidental awareness during obstetric anaesthesia aimed to describe practice for obstetric general anaesthesia in England and compare with earlier surveys and best-practice recommendations. Consenting patients who received general anaesthesia for obstetric surgery in 72 hospitals from May 2017 to August 2018 were included. Baseline characteristics, airway management, anaesthetic techniques and major complications were collected. Descriptive analysis, binary logistic regression modelling and comparisons with earlier data were conducted. Data were collected from 3117 procedures, including 2554 (81.9%) caesarean deliveries. Thiopental was the induction drug in 1649 (52.9%) patients, compared with propofol in 1419 (45.5%). Suxamethonium was the neuromuscular blocking drug for tracheal intubation in 2631 (86.1%), compared with rocuronium in 367 (11.8%). Difficult tracheal intubation was reported in 1 in 19 (95%CI 1 in 16-22) and failed intubation in 1 in 312 (95%CI 1 in 169-667). Obese patients were over-represented compared with national baselines and associated with difficult, but not failed intubation. There was more evidence of change in practice for induction drugs (increased use of propofol) than neuromuscular blocking drugs (suxamethonium remains the most popular). There was evidence of improvement in practice, with increased monitoring and reversal of neuromuscular blockade (although this remains suboptimal). Despite a high risk of difficult intubation in this population, videolaryngoscopy was rarely used (1.9%)

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

TOXIC BAIT AND BAITING STRATEGIES FOR FERAL CATS

To improve feral cat control we developed a dry pelleted toxic bait and evaluated the potential of lures. A polymer fish meal bait was preferred by cats from a range of bait types tested. L-alanine further increased bait acceptance by cats in pen trials and catnip may have the potential to increase field acceptance and target specificity. An oral LD90 of 0.38 mg/ kg was established for sodium monofluoroacetate (1080) in feral cats voluntarily eating surface-loaded baits. Acute toxicity to cats of warfarin, cholecalciferol, and gliftor was tested. However, because the cat proved highly sensitive to 1080, we recommend its use at a dose of 2 mg per cat bait. In preliminary field trials of bait acceptance using non-toxic polymer bait (without flavors or attractants), marked with the plasma marker iophenoxic acid 50% of 39 cats caught within 3 weeks of laying the baits were marked. Subsequently polymer bait, surface coated with 1080 was used in the successful eradication of feral cats from Matakohe Island (37 ha) Whangarei Harbour, New Zealand

DEVELOPING A NEW TOXIN FOR POTENTIAL CONTROL OF FERAL CATS, STOATS, AND WILD DOGS IN NEW ZEALAND

The endemic fauna of New Zealand evolved in the absence of mammalian predators and their introduction has been responsible for many extinctions and declines. Predator control will have to be on-going if some native species are to survive on the mainland. Currently, predator control relies largely on labourintensive trapping, so the development of humane predator-specific toxins would provide valuable additional control methods. Para-aminopropiophenone (PAPP) is being investigated as a toxin for feral cats (Felis catus), stoats (Mustela erminea), and wild dogs (Canis familiaris). Carnivores appear to be much more susceptible to PAPP than birds, so it potentially has a high target specificity, at least in the New Zealand context. Pen trials with 20 feral cats, 15 stoats, and 14 dogs have been undertaken using meat baits containing a proprietary formulation of PAPP. A PAPP dose of 20-34 mg/kg was lethal for feral cats, 37-95 mg/kg was lethal for stoats, and 26-43 mg/kg was lethal for dogs. Our results suggest that PAPP is a humane and effective toxin for control of feral cats and stoats, and possibly for wild dogs. We are now continuing studies towards product registration, which will include the assessment of non-target effects, particularly on birds