Audiogenic reflex seizures in cats

This study aims at characterizing feline audiogenic reflex seizures (FARS). An online questionnaire was developed to capture information from owners with cats suffering FARS. This was collated with the medical records from the primary veterinarian. Ninety-six cats were included. Myoclonic seizures were one of the cardinal signs of this syndrome (90/96), frequently occurring prior to generalized tonic-clonic seizures (GTCS) in this population. Other features include a late-onset (median 15 years) and absence seizures (6/96), with most seizures triggered by high frequency sounds amid occasional spontaneous seizures (up to 20%). Half the population (48/96) had hearing impairment or were deaf. One third of cats (35/96) had concurrent diseases, most likely reflecting the age distribution. Birmans were strongly represented (30/96). Levetiracetam gave good seizure control. The course of the epilepsy was non-progressive in the majority (68/96) with an improvement over time in some (23/96). Only 33/96 and 11/90 owners respectively felt the GTCS and myoclonic seizures affected their cat’s quality of life (QoL). Despite this, many owners (50/96) reported a slow decline in their cat’s health becoming less responsive (43/50), not jumping (41/50), uncoordinated or weak in the pelvic limbs (24/50), and exhibiting dramatic weight loss (39/50). These signs were exclusively reported in cats experiencing seizures for >2 years with 42/50 owners stating these signs affected their cat’s QoL. In gathering data on audiogenic seizures in cats, we have identified a new epilepsy syndrome named FARS with a geriatric-onset. Further studies are warranted to investigate potential genetic predispositions to this condition

Automated and reproducible cell identification in mass cytometry using neural networks

The principal use of mass cytometry is to identify distinct cell types and changes in their composition, phenotype and function in different samples and conditions. Combining data from different studies has the potential to increase the power of these discoveries in diverse fields such as immunology, oncology and infection. However, current tools are lacking in scalable, reproducible and automated methods to integrate and study data sets from mass cytometry that often use heterogenous approaches to study similar samples. To address these limitations, we present two novel developments: (1) a pre-trained cell identification model named Immunopred that allows automated identification of immune cells without user-defined prior knowledge of expected cell types and (2) a fully automated cytometry meta-analysis pipeline built around Immunopred. We evaluated this pipeline on six COVID-19 study data sets comprising 270 unique samples and uncovered novel significant phenotypic changes in the wider immune landscape of COVID-19 that were not identified when each study was analyzed individually. Applied widely, our approach will support the discovery of novel findings in research areas where cytometry data sets are available for integration

i-Tracker: For quantitative proteomics using iTRAQ (TM)

Background: iTRAQ(TM) technology for protein quantitation using mass spectrometry is a recent, powerful means of determining relative protein levels in up to four samples simultaneously. Although protein identification of samples generated using iTRAQ may be carried out using any current identification software, the quantitation calculations have been restricted to the ProQuant software supplied by Applied Biosciences. i- Tracker software has been developed to extract reporter ion peak ratios from non-centroided tandem MS peak lists in a format easily linked to the results of protein identification tools such as Mascot and Sequest. Such functionality is currently not provided by ProQuant, which is restricted to matching quantitative information to the peptide identifications from Applied Biosciences' Interrogator T software.|Results: i- Tracker is shown to generate results that are consistent with those produced by ProQuant, thus validating both systems.|Conclusion: i- Tracker allows quantitative information gained using the iTRAQ protocol to be linked with peptide identifications from popular tandem MS identification tools and hence is both a timely and useful tool for the proteomics community

Analysis of mental and physical disorders associated with COVID-19 in online health forums: a natural language processing study

Objectives Online health forums provide rich and untapped real-time data on population health. Through novel data extraction and natural language processing (NLP) techniques, we characterise the evolution of mental and physical health concerns relating to the COVID-19 pandemic among online health forum users. Setting and design We obtained data from three leading online health forums: HealthBoards, Inspire and HealthUnlocked, from the period 1 January 2020 to 31 May 2020. Using NLP, we analysed the content of posts related to COVID-19. Primary outcome measures (1) Proportion of forum posts containing COVID-19 keywords; (2) proportion of forum users making their very first post about COVID-19; (3) proportion of COVID-19-related posts containing content related to physical and mental health comorbidities. Results Data from 739 434 posts created by 53 134 unique users were analysed. A total of 35 581 posts (4.8%) contained a COVID-19 keyword. Posts discussing COVID-19 and related comorbid disorders spiked in early March to mid-March around the time of global implementation of lockdowns prompting a large number of users to post on online health forums for the first time. Over a quarter of COVID-19-related thread titles mentioned a physical or mental health comorbidity. Conclusions We demonstrate that it is feasible to characterise the content of online health forum user posts regarding COVID-19 and measure changes over time. The pandemic and corresponding public response has had a significant impact on posters’ queries regarding mental health. Social media data sources such as online health forums can be harnessed to strengthen population-level mental health surveillance

Reconstructing kinase network topologies from phosphoproteomics data reveals cancer-associated rewiring

Understanding how oncogenic mutations rewire regulatory-protein networks is important for rationalizing the mechanisms of oncogenesis and for individualizing anticancer treatments. We report a chemical phosphoproteomics method to elucidate the topology of kinase-signaling networks in mammalian cells. We identified >6,000 protein phosphorylation sites that can be used to infer >1,500 kinase–kinase interactions and devised algorithms that can reconstruct kinase network topologies from these phosphoproteomics data. Application of our methods to primary acute myeloid leukemia and breast cancer tumors quantified the relationship between kinase expression and activity, and enabled the identification of hitherto unknown kinase network topologies associated with drug-resistant phenotypes or specific genetic mutations. Using orthogonal methods we validated that PIK3CA wild-type cells adopt MAPK-dependent circuitries in breast cancer cells and that the kinase TTK is important in acute myeloid leukemia. Our phosphoproteomic signatures of network circuitry can identify kinase topologies associated with both phenotypes and genotypes of cancer cells

Longevity and mortality of cats attending primary care veterinary practices in England

Enhanced knowledge on longevity and mortality in cats should support improved breeding, husbandry, clinical care and disease prevention strategies. The VetCompass research database of primary care veterinary practice data offers an extensive resource of clinical health information on companion animals in the UK. This study aimed to characterise longevity and mortality in cats, and to identify important demographic risk factors for compromised longevity. Crossbred cats were hypothesised to live longer than purebred cats. Descriptive statistics were used to characterise the deceased cats. Multivariable linear regression methods investigated risk factor association with longevity in cats that died at or after 5 years of age. From 118,016 cats attending 90 practices in England, 4009 cats with confirmed deaths were randomly selected for detailed study. Demographic characterisation showed that 3660 (91.7%) were crossbred, 2009 (50.7%) were female and 2599 (64.8%) were neutered. The most frequently attributed causes of mortality in cats of all ages were trauma (12.2%), renal disorder (12.1%), non-specific illness (11.2%), neoplasia (10.8%) and mass lesion disorders (10.2%). Overall, the median longevity was 14.0 years (interquartile range [IQR] 9.0–17.0; range 0.0–26.7). Crossbred cats had a higher median longevity than purebred cats (median [IQR] 14.0 years [9.1–17.0] vs 12.5 years [6.1–16.4]; P \u3c0.001), but individual purebred cat breeds varied substantially in longevity. In cats dying at or after 5 years (n = 3360), being crossbred, having a lower bodyweight, and being neutered and non-insured were associated with increased longevity. This study described longevity in cats and identified important causes of mortality and breed-related associations with compromised longevity

Levetiracetam in the management of feline audiogenic reflex seizures: a randomised, controlled, open-label study

OBJECTIVES: Currently, there are no published randomised, controlled veterinary trials evaluating the efficacy of antiepileptic medication in the treatment of myoclonic seizures. Myoclonic seizures are a hallmark of feline audiogenic seizures (FARS). METHODS: This prospective, randomised, open-label trial compared the efficacy and tolerability of levetiracetam (20-25 mg/kg q8h) with phenobarbital (3-5 mg/kg q12h) in cats with suspected FARS that experienced myoclonic seizures. Cats were included that had ⩾12 myoclonic seizure days during a prospective 12 week baseline period. This was followed by a 4 week titration phase (until a therapeutic serum concentration of phenobarbital was achieved) and a 12 week treatment phase. RESULTS: Fifty-seven cats completed the study: 28 in the levetiracetam group and 29 in the phenobarbital group. A reduction of ⩾50% in the number of myoclonic seizure days was seen in 100% of patients in the levetiracetam group and in 3% of patients in the phenobarbital group (P <0.001) during the treatment period. Levetiracetam-treated cats had higher freedom from myoclonic seizures (50.0% vs 0%; P <0.001) during the treatment period. The most common adverse events were lethargy, inappetence and ataxia, with no difference in incidence between levetiracetam and phenobarbital. Adverse events were mild and transient with levetiracetam but persistent with phenobarbital. CONCLUSIONS AND RELEVANCE: These results suggest that levetiracetam is an effective and well-tolerated treatment for cats with myoclonic seizures and is more effective than phenobarbital. Whether it will prevent the occurrence of generalised tonic-clonic seizures and other forebrain signs if used early in the course of FARS is not yet clear

Listening and learning : the reciprocal relationship between worker and client

The relationship between worker and client has for the best part of 100 years been the mainstay of probation, and yet has recently been eroded by an increased emphasis on punishment, blame and managerialism. The views of offenders are in direct contradiction to these developments within the criminal justice system and this article argues that only by taking account of the views of those at the 'coal face' will criminologists, policy makers and practitioners be able to effect real change in crime rates. The article thus focuses on the views of a sample of previously persistent offenders in Scotland about offending, desistance and how the system can help them. It explores not only their need for friendship and support in youth but also the close association between relationships and the likelihood of offending. It also demonstrates the views of offenders themselves about the importance of the working relationship with supervising officers in helping them desist from crime. The article concludes that the most effective way of reducing offending is to re-engage with the message of the Probation Act of 100 years ago, namely, to 'advise, assist and befriend' offenders rather than to 'confront, challenge and change' offending behaviour

Development of medical point-of-care applications for renal medicine and tuberculosis based on electronic nose technology

Introduction: Current clinical diagnostics are based on biochemical, immunological or microbiological methods. However, these methods are operator dependent, time consuming, expensive and require special skills, and are therefore not suitable for point-of-care testing. Recent developments in gas-sensing technology and pattern recognition methods make electronic nose technology an interesting alternative for medical point-of-care devices. Methods: We applied a gas sensor array based on 14 conducting polymers to monitor haemodialysis in vitro and to detect pulmonary tuberculosis in both culture and sputum. Results and discussion: The electronic nose is able to distinguish between control blood and “uraemic” blood. Furthermore, the gas sensor array is not only capable of discriminating pre- from post-dialysis blood (97% accuracy) but also can follow the volatile shift occurring during a single haemodialysis session. The electronic nose can be used for both dialysate side and blood-side monitoring of haemodialysis. The pattern observed for post- and pre-dialysis blood might reflect the health status of the patients and can therefore be related to the long-term outcome. Furthermore, the gas sensor array was also able to discriminate between Mycobacterium spp. and other lung pathogens such as Pseudomonas aeruginosa. More importantly the gas sensor array was capable of resolving different Mycobacterium spp. such as Mycobacterium tuberculosis, M. scrofulaceum, and M. avium in both liquid culture and spiked sputum samples. The detection limit for M. tuberculosis in both sputum and liquid culture is 1 x 104 mycobacteria ml-1 and therefore partially fulfils the requirement set by the WHO. The gas sensor array was able to detect culture proven TB with a sensitivity of 89% and a specificity of 91%. Conclusions: In conclusion, this study has shown the ability of an electronic nose as a point-of-care device in these areas.EThOS - Electronic Theses Online ServiceGBUnited Kingdo