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Stevens, K.

Publications and source records attributed to Stevens, K..

3 recordsLinked to original sources
bioRxiv2017

Transmural unipolar electrogram morphology is achieved within 7s at the posterior left atrial wall during pulmonary vein isolation: VISITAG™ Module-based lesion assessment during radiofrequency ablation

AimsTo assess the occurrence of a histologically validated measure of transmural (TM) atrial ablation - pure R unipolar electrogram (UE) morphology change - at first-ablated left atrial posterior wall (LAPW) sites during contact force (CF)-guided pulmonary vein isolation (PVI).\n\nMethods and resultsExported VISITAG Module and CARTOREPLAY (Biosense Webster Inc.) UE morphology data was retrospectively analysed in 23 consecutive patients undergoing PVI under general anaesthesia. PVI without spontaneous / dormant recovery was achieved in all, employing 16.3[3.2] minutes (mean [SD]) of temperature-controlled RF at 30W. All first-ablated LAPW sites demonstrated RS UE morphology pre-ablation, with RF-induced pure R UE morphology change in 98%. Time to pure R UE morphology was significantly shorter at left-sided LAPW sites (4.9[2.1] s versus 6.7[2.5] s; p=0.02), with significantly greater impedance drop (median 13.5{Omega} versus 9.9{Omega}; p=0.003). Importantly, neither the first-site RF duration (14.9 versus 15.0s) nor the maximum ablation catheter tip distance moved (during RF) were significantly different, yet the mean CF was significantly higher at right-sided sites (16.5g versus 11.2g; p=0.002). Concurrent impedance and objectively annotated bipolar electrogram (BE) data demonstrated ~6-8{Omega} impedance drop and ~30% BE decrease at the time of first pure R UE morphology change.\n\nConclusionUsing objective ablation site annotation, TM UE morphology change was typically achieved within 7s at the LAPW, with significantly greater ablative effect evident at left-sided sites. The methodology described in this report represents a novel and scientifically more rigorous foundation towards future research into the biological effects of RF ablation in vivo.\n\nCondensed abstractThrough appropriate use of the VISITAG Module and CARTOREPLAY, unipolar electrogram morphology change indicative of histologically confirmed transmural atrial ablation in animal models, was proven to occur typically within 7s, during first-site contact force-guided ablation at the left atrial posterior wall during pulmonary vein isolation.

physiology↗
bioRxiv2017

Real-time genomic and epidemiological investigation of a multi-institution outbreak of KPC-producing Enterobacteriaceae: a translational study

BackgroundUntil recently, KPC-producing Enterobacteriaceae were rarely identified in Australia. Following an increase in the number of incident cases across the state of Victoria, we undertook a real-time combined genomic and epidemiological investigation. The scope of this study included identifying risk factors and routes of transmission, and investigating the utility of genomics to enhance traditional field epidemiology for informing management of established widespread outbreaks.\n\nMethods and FindingsAll KPC-producing Enterobacteriaceae isolates referred to the state reference laboratory from 2012 onwards were included. Whole-genome sequencing (WGS) was performed in parallel with a detailed descriptive epidemiological investigation of each case, using Illumina sequencing on each isolate. This was complemented with PacBio long-read sequencing on selected isolates to establish high-quality reference sequences and interrogate characteristics of KPC-encoding plasmids. Initial investigations indicated the outbreak was widespread, with 86 KPC-producing Enterobacteriaceae isolates (K. pneumoniae 92%) identified from 35 different locations across metropolitan and rural Victoria between 2012-2015. Initial combined analyses of the epidemiological and genomic data resolved the outbreak into distinct nosocomial transmission networks, and identified healthcare facilities at the epicentre of KPC transmission. New cases were assigned to transmission networks in real-time, allowing focussed infection control efforts. PacBio sequencing confirmed a secondary transmission network arising from inter-species plasmid transmission. Insights from Bayesian transmission inference and analyses of within-host diversity informed the development of state-wide public health and infection control guidelines, including interventions such as an intensive approach to screening contacts following new case detection to minimise unrecognised colonisation.\n\nConclusionsA real-time combined epidemiological and genomic investigation proved critical to identifying and defining multiple transmission networks of KPC Enterobacteriaceae, while data from either investigation alone were inconclusive. The investigation was fundamental to informing infection control measures in real-time and the development of state-wide public health guidelines on carbapenemase producing Enterobacteriaceae management.

genomics↗
bioRxiv2017

Olfactory Receptors Are Required For Social Behavior And Neural Plasticity In Ants, As Evidenced By CRISPR-Mediated Gene Knockout

The chemosensory system is key to establishing and maintaining social structure in eusocial insects. Ants exhibit cooperative colonial behaviors reflective of an advanced form of sociality with an extensive dependency on communication. Cuticular hydrocarbons (CHCs) serve as pheromones and cues that regulate multiple aspects of social interactions and behaviors in ants. The perception of CHCs entails odorant receptor neurons (ORNs) that express specific odorant receptors (ORs) encoded by a dramatically expanded Or gene family in ants. Until recently, studies of the biological functions of ORs in eusocial insects were stymied by the lack of genetic tools. In most eusocial insect species, only one or a few queens in a colony can transmit the genetic information to their progeny. In contrast, any worker in the ant Harpegnathos saltator can be converted into a gamergate (pseudo-queen), and used as a foundress to engender an entire new colony and be crossed for genetic experiments. This feature facilitated CRISPR-Cas9 gene targeting to generate a germline mutation in the orco gene that encodes the obligate co-receptor whose mutation should significantly impact ant olfaction. Our results show that Orco exhibits a conserved role in the perception of general odorants but also a role in reproductive physiology and social behavior plasticity in ants. Surprisingly, and in contrast to other insect systems, the loss of OR functionality also dramatically reduces the development of the ant antennal lobe where ORNs project. Taken together, these findings open the possibility of studying the genetics of eusociality and provide inroads towards understanding the function of the expanded ORs family in eusocial insects in regulating caste determination, social communication and neuronal plasticity.

neuroscience↗