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Human-shark conflict has been managed through catch-and-kill policies in most parts of the world. More recently, there has been a greater demand for shark bite mitigation measures to improve protection for water users whilst minimizing harm to non-target and target species, particularly White Sharks (Carcharodon carcharias), given their status as a Threatened, Endangered, or Protected (TEP) species. A new non-lethal shark bite mitigation method, known as the Shark-Management-Alert-in-Real-Time (SMART) drumline, alerts responders when an animal takes the bait and thereby provides an opportunity for rapid response to the catch and potentially to relocate, tag, and release sharks. Thirty-six White Sharks were caught on SMART drumlines in New South Wales, Australia, and tagged with dorsal fin-mounted satellite-linked radio transmitters (SLRTs) and acoustic tags before release. Thirty-one sharks were located within 10 days, 22 of which provided high-quality locations (classes 1 to 3) suitable for analysis. Twenty-seven percent and 59% of these sharks were first detected within 10 and 50 h of release, respectively. For the first three days post-release, sharks moved and mostly remained offshore (>3.5 km from the coast), irrespective of shark sex and length. Thereafter, tagged sharks progressively moved inshore; however, 77% remained more than 1.9 km off the coast and an average of 5 km away from the tagging location, 10 days post-release. Sharks were acoustically detected for an average of 591 days post-release (ranging from 45 to 1075 days). Although five of the 36 sharks were not detected on acoustic receivers, SLRT detections for these five sharks ranged between 43 and 639 days post-release, indicating zero mortality associated with capture. These results highlight the suitability of SMART drumlines as a potential non-lethal shark bite mitigation tool for TEP species such as White Sharks, as they initially move away from the capture site, and thereby this bather protection tool diminishes the immediate risk of shark interactions at that site.

Tetrodotoxin (TTX) is a highly specific voltage-gated sodium channel (VGSC) blocker in clinical evaluation as a peripheral-acting analgesic for chronic pain. This study presents the first published results of the safety including cardiac liability of TTX at therapeutic-relevant concentrations in twenty-five healthy adults. Randomized, double-blind, placebo-, and positive- (moxifloxacin) controlled study evaluated single ascending doses of 15 µg, 30 µg, and 45 µg TTX over 3 periods with a 7-day washout between each period. Subcutaneous injections of TTX were readily absorbed, reaching maximum plasma concentration (Cmax) within 1.5 h. Both extent of exposure (AUC) and Cmax increased in proportion to dose. No QT prolongation was identified by concentration-QTc analysis and the upper bounds of the two-sided 90% confidence interval of predicted maximum baseline and placebo corrected QTcF (ΔΔQTcF) value did not exceed 10 ms for all tetrodotoxin doses, thereby meeting the criteria of a negative QT study. Safety assessments showed no clinically relevant changes with values similar between all groups and no subject withdrawing due to adverse events. Paresthesia, oral-paresthesia, headache, dizziness, nausea, and myalgia were the most common TEAEs (overall occurrence ≥5%) in the TTX treatment groups. TTX doses investigated in this study are safe, well-tolerated, and lack proarrhythmic proclivity.

Understanding the movement dynamics of marine fish provides valuable information that can assist with species management, particularly regarding protection within marine protected areas (MPAs). We performed an acoustic tagging study implemented within the Port Stephens-Great Lakes Marine Park on the mid-north coast of New South Wales, Australia, to assess the movement patterns, home range and diel activity of snapper (Chrysophrys auratus; Sparidae); a species of significant recreational and commercial fishing importance in Australia. The study focused on C. auratus movements around Cabbage Tree Island, which is predominantly a no-take sanctuary zone (no fishing), with an array of acoustic stations deployed around the island and adjacent reefs and islands. Thirty C. auratus were tagged with internal acoustic tags in November 2010 with their movements recorded until September 2014. Both adult and juvenile C. auratus were observed to display strong site fidelity to Cabbage Tree Island with a mean 12-month residency index of 0.83 (range = 0 low to 1 high). Only three fish were detected on acoustic receivers away from Cabbage Tree Island, with one fish moving a considerable distance of ~ 290 kms over a short time frame (46 days). The longest period of residency recorded at the island was for three fish occurring regularly at the site for a period of 1249 days. Chrysophrys auratus displayed strong diurnal behaviour and detection frequency was significantly higher during the day than at night; however, there was no significant difference in detection frequency between different hours. This study demonstrates that even small-scale protected areas can benefit C. auratus during multiple life-history stages as it maintains a small home range and displays strong site fidelity over a period of 3 years.

Understanding and predicting the distribution of organisms in heterogeneous environments is a fundamental ecological question and a requirement for sound management. To implement effective conservation strategies for white shark Carcharodon carcharias populations, it is imperative to define drivers of their movement and occurrence patterns and to protect critical habitats. Here, we acoustically tagged 444 immature white sharks and monitored their presence in relation to environmental factors over a 3 yr period (2016–2019) using an array of 21 iridium satellite-linked (VR4G) receivers spread along the coast of New South Wales, Australia. Results of generalized additive models showed that all tested predictors (month, time of day, water temperature, tidal height, swell height, lunar phase) had a significant effect on shark occurrence. However, collectively, these predictors only explained 1.8% of deviance, suggesting that statistical significance may be rooted in the large sample size rather than biological importance. On the other hand, receiver location, which captures geographic fidelity and local conditions not captured by the aforementioned environmental variables, explained a sizeable 17.3% of de viance. Sharks tracked in this study hence appear to be tolerant to episodic changes in environmental conditions, and movement patterns are likely related to currently undetermined, location-specific habitat characteristics or biological components, such as local currents, prey availability or competition. Importantly, we show that performance of VR4G receivers can be strongly af fected by local environmental conditions, and provide an example of how a lack of range test controls can lead to misinterpretation and erroneous conclusions of acoustic detection data.

Developing new therapeutics presents formidable economic, scientific, and medical challenges that are exacerbated by special factors in neurotherapeutics development, e.g., the complexity of the CNS with its attendant need to sometimes affect multiple pathways, the lack of clarity of disease etiology, inadequacy of available animal models, and difficulties in defining disease populations and quantifying treatment response. This paper reviews the economic challenges faced by therapeutics developers in general and neurotherapeutics developers in particular. It discusses key scientific challenges, particularly those pertinent to neurotherapeutics development, as a background to proposing a different industrial strategy to drive future therapeutics development. This Biodesign strategy potentially surpasses previous paradigms by incorporating elements such as the use of disease modeling to select better targets and potential therapies, information science-based approaches to enhance small molecule chemistry, exploitation of the potential for biological technologies to rapidly generate mechanistic probes, and development of improved approaches for using animal models and studying human molecules mechanistically and biologically. Synergistic use of these elements can change the overall business model of companies engaged in neurotherapeutics development. The Biodesign paradigm has the potential to both markedly enhance the development of new therapies and to address some of the economic challenges facing healthcare systems and therapeutics developers alike.

Increased understanding of latitudinal gradients and patterns of biodiversity at a regional scale is important for many reasons (e.g. biodiversity conservation, species management, climate change). This study assessed rock pool fish assemblages and their relationship to latitude at 39 locations along 860 km of the New South Wales (NSW) coast, eastern Australia, from Sandon to Merimbula (29.67816°S to 36.90046°S). Thirty-minute deployments of miniature baited remote underwater video (mini-BRUV) were used to survey five or more replicates (rock pools) at each location for species richness and maximum number (MaxN) of individual fishes. A total of 371 rock pools were sampled, with 7070 fish recorded from 46 families and 115 species. Fish species richness was greatest in northern NSW, with a significant decline in species richness with increasing latitude, at a rate of 1.7 species per degree of latitude south. Tropical species were dominant in northern NSW (Coffs Harbour ∼30°S), whilst temperate species diversity was greatest towards central NSW (Port Stephens 32.7°S). Differences amongst rock pool assemblages were primarily driven by eight species from eight different families. This study documents latitudinal fish assemblage patterns along the east Australian coast and provides a baseline for elucidating future changes.

Issue Title: Drug Discovery for Disorders of the Central Nervous System

We tested the hypothesis that increases in tumor necrosis factor α (TNF-α) induced by human immunodeficiency virus (HIV) are associated with the increases in slow-wave sleep seen in early HIV infection and the decrease with sleep fragmentation seen in advanced HIV infection. Nocturnal sleep disturbances and associated fatigue contribute to the disability of HIV infection. TNF-α causes fatigue in clinical use and promotes slow-wave sleep in animal models. With slow progress toward a vaccine and weak effects from current therapies, efforts are directed toward extending productive life of HIV-infected individuals and shortening the duration of disability in terminal illness. We describe previously unrecognized nocturnal cyclic variations in plasma levels of TNF-α in all subjects. In 6 of 10 subjects (1 control subject, 3 HIV-seropositive patients with CD4+cell number >400 cells per μ l, and 2 HIV-positive patients with CD4+cell number <400 cells per μ l), these fluctuations in TNF-α were coupled to the known rhythm of electroencephalogram delta amplitude (square root of power) during sleep. This coupling was not present in 3 HIV-positive subjects with CD4+cell number <400 cells per μ l and 1 control subject. In 5 HIV subjects with abnormally low CD4+cell counts (<400 cells per μ l), the number of days since seroconversion correlated significantly with low correlation between TNF-α and delta amplitude. We conclude that a previously unrecognized normal, physiological coupling exists between TNF-α and delta amplitude during sleep and that the lessened likelihood of this coupling in progressive HIV infection may be important in understanding fatigue-related symptoms and disabilities.

Neuromagnetic fields were recorded from human subjects as they listened selectively to sequences of rapidly presented tones in one ear while ignoring tones of a different pitch in the opposite ear. Tones in the attended ear evoked larger magnetic brain responses than did unattended tones in the latency ranges 20-50 msec and 80-130 msec poststimulus. Source localization techniques in conjunction with magnetic resonance imaging placed the neural generators of these early attention-sensitive brain responses in auditory cortex on the supratemporal plane. These data demonstrate that focused auditory attention in humans can selectively modulate sensory processing in auditory cortex beginning as early as 20 msec poststimulus, thereby providing strong evidence for an \"early selection\" mechanism of auditory attention that can regulate auditory input at or before the initial stages of cortical analysis.

Understanding the movement dynamics of marine fish provides valuable information that can assist with species management, particularly regarding protection within marine protected areas (MPAs). We performed an acoustic tagging study implemented within the Port Stephens-Great Lakes Marine Park on the mid-north coast of New South Wales, Australia, to assess the movement patterns, home range and diel activity of snapper (Chrysophrys auratus; Sparidae); a species of significant recreational and commercial fishing importance in Australia. The study focused on C. auratus movements around Cabbage Tree Island, which is predominantly a no-take sanctuary zone (no fishing), with an array of acoustic stations deployed around the island and adjacent reefs and islands. Thirty C. auratus were tagged with internal acoustic tags in November 2010 with their movements recorded until September 2014. Both adult and juvenile C. auratus were observed to display strong site fidelity to Cabbage Tree Island with a mean 12-month residency index of 0.83 (range = 0 low to 1 high). Only three fish were detected on acoustic receivers away from Cabbage Tree Island, with one fish moving a considerable distance of ~ 290 kms over a short time frame (46 days). The longest period of residency recorded at the island was for three fish occurring regularly at the site for a period of 1249 days. Chrysophrys auratus displayed strong diurnal behaviour and detection frequency was significantly higher during the day than at night; however, there was no significant difference in detection frequency between different hours. This study demonstrates that even small-scale protected areas can benefit C. auratus during multiple life-history stages as it maintains a small home range and displays strong site fidelity over a period of 3 years.