Review of unmanned aircraft system technologies to enable beyond visual line of sight (BVLOS) operations

The need to develop and deploy Beyond Visual Line of Sight (BVLOS) aerial vehicles has intensified over the last decade. As the demand for Unmanned Aircraft Systems (UAS) has increased, so too has the regulations that surrounds the industry. Strict regulations are currently in place but differ from country to country. Due to these regulations BVLOS innovators have been posed the task of exploring the means of operating flight missions with the UAV out of the sight of the pilot. Autonomous flight capability is not only fundamental to BVLOS operations for UAS but also likely to have a significant impact on the future development of passenger carrying autonomous aircraft. This review explores the technologies that have been developed to date that enable BVLOS applications. BVLOS flight operations have the potential to open a huge area of commercial opportunity however, there remain many concerns about the current capabilities of UAS to detect and avoid manned and unmanned airborne hazards that may pose a significant safety risk

Genetic enhancement of behavioral itch responses in mice lacking phosphoinositide 3-kinase-γ (PI3Kγ)

Phosphoinositide 3-kinases (PI3Ks) are important for synaptic plasticity and various brain functions. The only class IB isoform of PI3K, PI3Kγ, has received the most attention due to its unique roles in synaptic plasticity and cognition. However, the potential role of PI3Kγ in sensory transmission, such as pain and itch has not been examined. In this study, we present the evidence for the first time, that genetic deletion of PI3Kγ enhanced scratching behaviours in histamine-dependent and protease-activated receptor 2 (PAR-2)-dependent itch. In contrast, PI3Kγ-deficient mice did not exhibit enhanced scratching in chloroquine-induced itch, suggesting that PI3Kγ selectively contributes to certain types of behavioal itch response. Furthermore, PI3Kγ-deficient mice exhibited normal acute nociceptive responses to thermal and mechanical noxious stimuli. Behavioral licking responses to intraplantar injections of formalin and mechanical allodynia in a chronic inflammatory pain model (CFA) were also not affected by PI3Kγ gene deletion. Our findings indicate that PI3Kγ selectively contributes to behavioral itching induced by histamine and PAR-2 agonist, but not chloroquine agonist

Impaired learning and memory in CD38 null mutant mice

CD38 is an enzyme that catalyzes the formation of cyclic ADP ribose and nicotinic acid adenine dinucleotide phosphate, both of which are involved in the mobilization of Ca2+ from intracellular stores. Recently, CD38 has been shown to regulate oxytocin release from hypothalamic neurons. Importantly, CD38 mutations are associated with autism spectrum disorders (ASD) and CD38 knockout (CD38(-/-)) mice display ASD-like behavioral phenotypes including deficient parental behavior and poor social recognition memory. Although ASD and learning deficits commonly co-occur, the role of CD38 in learning and memory has not been investigated. We report that CD38(-/-)mice show deficits in various learning and memory tasks such as the Morris water maze, contextual fear conditioning, and the object recognition test. However, either long-term potentiation or long-term depression is not impaired in the hippocampus of CD38(-/-)mice. Our results provide convincing evidence that CD38(-/-)mice show deficits in various learning and memory tasks including spatial and non-spatial memory tasks. Our data demonstrate that CD38 is critical for regulating hippocampus-dependent learning and memory without modulating synaptic plasticity.open1

The application of Diffusive Gradients in Thin Films (DGT) for improved understanding of metal behaviour at marine disposal sites

Assessment of the effects of sediment metal contamination on biological assemblages and function remains a key question in marine management, especially in relation to disposal activities. However, the appropriate description of bioavailable metal concentrations within pore-waters has rarely been reported. Here, metal behaviour and availability at contaminated dredged material disposal sites within UK waters were investigated using Diffusive Gradient in Thin films (DGT). Three stations, representing contrasting history and presence of dredge disposal were studied. Depth profiles of five metals were derived using DGT probes as well as discrete analysis of total metal concentrations from sliced cores. The metals analysed were: iron and manganese, both relevant to sediment biogeochemistry; cadmium, nickel and lead, classified as priority pollutants. DGT time-integrated labile flux profiles of the metals display behaviour consistent with increasingly reduced conditions at depth and availability to DGT (iron and manganese), subsurface peaks and a potential sedimentary source to the water column related to the disposal activity (lead and nickel) and release to pore-water linked to decomposition of enriched phytodetritus (cadmium). DGT data has the potential to improve our current understanding of metal behaviour at impacted sites and is suitable as a monitoring tool. DGT data can provide information on metal availability and fluxes within the sediment at high depth-resolution (5 mm steps). Differences observed in the resulting profiles between DGT and conventional total metal analysis illustrates the significance of considering both total metals and a potentially labile fraction. The study outcomes can help to inform and improve future disposal site impact assessment, and could be complemented with techniques such as Sediment Profile Imagery for improved biologically relevance, spatial coverage and cost-effective monitoring and sampling of dredge material disposal sites. Additionally, the application of this technology could help improve correlative work on biological impacts under national and international auspices when linking biological effects to more biologically relevant metal concentrations

Enhanced firing of locus coeruleus neurons and SK channel dysfunction are conserved in distinct models of prodromal Parkinson's disease

Parkinson’s disease (PD) is clinically defined by the presence of the cardinal motor symptoms, which are associated with a loss of dopaminergic nigrostriatal neurons in the substantia nigra pars compacta (SNpc). While SNpc neurons serve as the prototypical cell-type to study cellular vulnerability in PD, there is an unmet need to extent our efforts to other neurons at risk. The noradrenergic locus coeruleus (LC) represents one of the first brain structures affected in Parkinson’s disease (PD) and plays not only a crucial role for the evolving non-motor symptomatology, but it is also believed to contribute to disease progression by efferent noradrenergic deficiency. Therefore, we sought to characterize the electrophysiological properties of LC neurons in two distinct PD models: (1) in an in vivo mouse model of focal α-synuclein overexpression; and (2) in an in vitro rotenone-induced PD model. Despite the fundamental differences of these two PD models, α-synuclein overexpression as well as rotenone exposure led to an accelerated autonomous pacemaker frequency of LC neurons, accompanied by severe alterations of the afterhyperpolarization amplitude. On the mechanistic side, we suggest that Ca(2+)-activated K(+) (SK) channels are mediators of the increased LC neuronal excitability, as pharmacological activation of these channels is sufficient to prevent increased LC pacemaking and subsequent neuronal loss in the LC following in vitro rotenone exposure. These findings suggest a role of SK channels in PD by linking α-synuclein- and rotenone-induced changes in LC firing rate to SK channel dysfunction

Reconstructing the three-dimensional GABAergic microcircuit of the striatum

A system's wiring constrains its dynamics, yet modelling of neural structures often overlooks the specific networks formed by their neurons. We developed an approach for constructing anatomically realistic networks and reconstructed the GABAergic microcircuit formed by the medium spiny neurons (MSNs) and fast-spiking interneurons (FSIs) of the adult rat striatum. We grew dendrite and axon models for these neurons and extracted probabilities for the presence of these neurites as a function of distance from the soma. From these, we found the probabilities of intersection between the neurites of two neurons given their inter-somatic distance, and used these to construct three-dimensional striatal networks. The MSN dendrite models predicted that half of all dendritic spines are within 100 mu m of the soma. The constructed networks predict distributions of gap junctions between FSI dendrites, synaptic contacts between MSNs, and synaptic inputs from FSIs to MSNs that are consistent with current estimates. The models predict that to achieve this, FSIs should be at most 1% of the striatal population. They also show that the striatum is sparsely connected: FSI-MSN and MSN-MSN contacts respectively form 7% and 1.7% of all possible connections. The models predict two striking network properties: the dominant GABAergic input to a MSN arises from neurons with somas at the edge of its dendritic field; and FSIs are interconnected on two different spatial scales: locally by gap junctions and distally by synapses. We show that both properties influence striatal dynamics: the most potent inhibition of a MSN arises from a region of striatum at the edge of its dendritic field; and the combination of local gap junction and distal synaptic networks between FSIs sets a robust input-output regime for the MSN population. Our models thus intimately link striatal micro-anatomy to its dynamics, providing a biologically grounded platform for further study

Developing an exploratory framework linking Australian Aboriginal peoples\u27 connection to country and concepts of wellbeing

Aboriginal people across Australia suffer significant health inequalities compared with the non-Indigenous population. Evidence indicates that inroads can be made to reduce these inequalities by better understanding social and cultural determinants of health, applying holistic notions of health and developing less rigid definitions of wellbeing. The following article draws on qualitative research on Victorian Aboriginal peoples\u27 relationship to their traditional land (known as Country) and its link to wellbeing, in an attempt to tackle this. Concepts of wellbeing, Country and nature have also been reviewed to gain an understanding of this relationship. An exploratory framework has been developed to understand this phenomenon focusing on positive (e.g., ancestry and partnerships) and negative (e.g., destruction of Country and racism) factors contributing to Aboriginal peoples\u27 health. The outcome is an explanation of how Country is a fundamental component of Aboriginal Victorian peoples\u27 wellbeing and the framework articulates the forces that impact positively and negatively on this duality. This review is critical to improving not only Aboriginal peoples\u27 health but also the capacity of all humanity to deal with environmental issues like disconnection from nature and urbanisation

Determinants of facility delivery after implementation of safer mother programme in Nepal: A prospective cohort study

Background: There are several barriers for pregnant women to deliver in a health care facility. This prospective cohort study investigated factors affecting facility delivery and reasons for unplanned place of delivery after implementation of the safer mother programme in Nepal. Methods: Baseline interviews using a validated questionnaire were conducted on a sample of 700 pregnant women representative of the Kaski district in central Nepal. Follow-up interviews of the cohort were then conducted within 45 days postpartum. Stepwise logistic regression analysis was performed to determine factors associated with the facility delivery outcome. Results: Of the 644 pregnant women whose delivery location had been identified, 547 (85%) gave birth in a health care facility. Women were more likely to deliver in a health facility if they were educated especially with higher secondary or above qualification (adjusted odds ratio (OR) 12.39, 95% confidence interval (CI) 5.09 to 30.17), attended 4 or more antenatal care visits (OR 2.15, 95% CI 1.25 to 3.69), and lived within 30 minutes to the facility (OR 11.61, 95% CI 5.77 to 24.04). For the 97 women who delivered at home, 72 (74.2%) were unplanned, mainly due to quick precipitation of labour making it impossible to reach a health facility. Conclusions: It appeared that facility delivery occurs more frequent among educated women and those who live nearby, even though maternity services are now freely available in Nepal. Because of the difficult terrain and transportation problem in rural areas, interventions that make maternity service physically accessible during antenatal period are needed to increase the utilisation of health facility for child birth

Implanted reuptake-deficient or wild-type dopaminergic neurons improve ON l-dopa dyskinesias without OFF-dyskinesias in a rat model of Parkinson's disease

OFF-l-dopa dyskinesias have been a surprising side-effect of intrastriatal foetal ventral mesencephalic transplantation in patients with Parkinson's disease. It has been proposed that excessive and unregulated dopaminergic stimulation of host post-synaptic striatal neurons by the grafts could be responsible for these dyskinesias. To address this issue we transplanted foetal dopaminergic neurons from mice lacking the dopamine transporter (DATKO) or from wild-type mice, into a rat model of Parkinson's disease and l-dopa-induced dyskinesias. Both wild-type and DATKO grafts reinnervated the host striatum to a similar extent, but DATKO grafts produced a greater and more diffuse increase in extra-cellular striatal dopamine levels. Interestingly, grafts containing wild-type dopaminergic neurons improved parkinsonian signs to a similar extent as DATKO grafts, but provided a more complete reduction of l-dopa induced dyskinesias. Neither DATKO nor wild-type grafts induced OFF-l-dopa dyskinesias. Behavioural and receptor autoradiography analyses demonstrated that DATKO grafts induced a greater normalization of striatal dopaminergic receptor supersensitivity than wild-type grafts. Both graft types induced a similar downregulation and normalization of PEnk and fosb/Δfosb in striatal neurons. In summary, DATKO grafts causing high and diffuse extra-cellular dompamine levels do not per se alter graft-induced recovery or produce OFF-l-dopa dyskinesias. Wild-type dopaminergic neurons appear to be the most effective neuronal type to restore function and reduce l-dopa-induced dyskinesias