Discrete-valued Levy processes and low latency financial econometrics

Motivated by features of low latency data in finance we study in detail discrete-valued Levy processes as the basis of price processes for high frequency econometrics. An important case of this is a Skellam process, which is the difference of two independent Poisson processes. We propose a natural generalisation which is the difference of two negative binomial processes. We apply these models in practice to low latency data for a variety of different types of futures contracts.futures markets; high frequency econometrics; low latency data; negative binomial; Skellam distribution.

Inhalation therapy during acute asthma : the role of a combined steroid and beta-stimulant preparation

CITATION: Joubert, J. R., Burger, G. & Shephard, E. 1985. Inhalation therapy during acute asthma : the role of a combined steroid and beta-stimulant preparation. South African Medical Journal, 68:381-384.The original publication is available at http://www.samj.org.zaA compound consisting of a β-stimulant, salbutamol (100 μg/puff), and a steroid, beclomethasone diproprionate (50 μg/puff), was studied to test the hypothesis that the corticosteroid could enhance the bronchodilator proporties of the β-stimulant during chronic asthma and simulated acute attacks (antigen challenge). Conventional doses (200 μg and 100 μg of salbutamol and beclomethasone respectively) were compared using a schedule which included a second administration 1 hour later. The results obtained on the baseline bronchial responsiveness of chronic asthmatics and during the delayed asthmatic response (simulated acute asthma) were similar. The compound was as effective as salbutamol alone but not more so. A significantly greater bronchodilator response was recorded in all patients after the second administration of both the compound and salbutamol alone. The practical advantages of having one rather than two inhalers are evident, but the appropriate application of this compound agent, probably in a prophylactic role, must be defined.Publisher’s versio

Induction of HIV-1 Gag-specific memory T cells in Chacma baboons by MVA prime and VLP boost vaccine regimen

We previously reported induction of HIV-specific responses in Chacma baboons following immunization with SAAVI MVA-C (MVA) and HIV-1 Pr55 Gag virus-like particles (VLPs) in a prime-boost vaccination strategy. In the current study, we characterised the vaccine specific memory T cells by flow cytometry

Circum-Arctic mantle structure and long-wavelength topography since the Jurassic

The circum-Arctic is one of the most tectonically complex regions of the world, shaped by a history of ocean basin opening and closure since the Early Jurassic. The region is characterized by contemporaneous large-scale Cenozoic exhumation extending from Alaska to the Atlantic, but its driving force is unknown. We show that the mantle flow associated with subducted slabs of the South Anuyi, Mongol-Okhotsk, and Panthalassa oceans have imparted long-wavelength deflection on overriding plates. We identify the Jurassic-Cretaceous South Anuyi slab under present-day Greenland in seismic tomography and numerical mantle flow models. Under North America, we propose the “Farallon” slab results from Andean-style ocean-continent convergence around ~30°N and from a combination of ocean-continent and intraoceanic subduction north of 50°N. We compute circum-Arctic dynamic topography through time from subduction-driven convection models and find that slabs have imparted on average <1–16 m/Myr of dynamic subsidence across the region from at least 170 Ma to ~50 Ma. With the exception of Siberia, the main phase of circum-Arctic dynamic subsidence has been followed either by slowed subsidence or by uplift of <1–6 m/Myr on average to present day. Comparing these results to geological inferences suggest that subduction-driven dynamic topography can account for rapid Middle to Late Jurassic subsidence in the Slave Craton and North Slope (respectively, <15 and 21 m/Myr, between 170 and 130 Ma) and for dynamic subsidence (<7 m/Myr, ~170–50 Ma) followed by dynamic uplift (<6 m/Myr since 50 Ma) of the Barents Sea region. Combining detailed kinematic reconstructions with geodynamic modeling and key geological observations constitutes a powerful tool to investigate the origin of vertical motion in remote regions

HIV-1 sub-type C chimaeric VLPs boost cellular immune responses in mice

Several approaches have been explored to eradicate HIV; however, a multigene vaccine appears to be the best option, given their proven potential to elicit broad, effective responses in animal models. The Pr55Gag protein is an excellent vaccine candidate in its own right, given that it can assemble into large, enveloped, virus-like particles (VLPs) which are highly immunogenic, and can moreover be used as a scaffold for the presentation of other large non-structural HIV antigens. In this study, we evaluated the potential of two novel chimaeric HIV-1 Pr55Gag-based VLP constructs - C-terminal fusions with reverse transcriptase and a Tat::Nef fusion protein, designated GagRT and GagTN respectively - to enhance a cellular response in mice when used as boost components in two types of heterologous prime-boost vaccine strategies. A vaccine regimen consisting of a DNA prime and chimaeric HIV-1 VLP boosts in mice induced strong, broad cellular immune responses at an optimum dose of 100 ng VLPs. The enhanced cellular responses induced by the DNA prime-VLP boost were two- to three-fold greater than two DNA vaccinations. Moreover, a mixture of GagRT and GagTN VLPs also boosted antigen-specific CD8+ and CD4+ T-cell responses, while VLP vaccinations only induced predominantly robust Gag CD4+ T-cell responses. The results demonstrate the promising potential of these chimaeric VLPs as vaccine candidates against HIV-1

Abrogation of contaminating RNA activity in HIV-1 Gag VLPs

Background: HIV-1 Gag virus like particles (VLPs) used as candidate vaccines are regarded as inert particles as they contain no replicative nucleic acid, although they do encapsidate cellular RNAs. During HIV-1 Gag VLP production in baculovirus-based expression systems, VLPs incorporate the baculovirus Gp64 envelope glycoprotein, which facilitates their entry into mammalian cells. This suggests that HIV-1 Gag VLPs produced using this system facilitate uptake and subsequent expression of encapsidated RNA in mammalian cells - an unfavourable characteristic for a vaccine. Methods. HIV-1 Gag VLPs encapsidating reporter chloramphenicol acetyl transferase (CAT) RNA, were made in insect cells using the baculovirus expression system. The presence of Gp64 on the VLPs was verified by western blotting and RT-PCR used to detect and quantitate encapsidated CAT RNA. VLP samples were heated to inactivate CAT RNA. Unheated and heated VLPs incubated with selected mammalian cell lines and cell lysates tested for the presence of CAT protein by ELISA. Mice were inoculated with heated and unheated VLPs using a DNA prime VLP boost regimen. Results: HIV-1 Gag VLPs produced had significantly high levels of Gp64 (∼1650 Gp64 molecules/VLP) on their surfaces. The amount of encapsidated CAT RNA/g Gag VLPs ranged between 0.1 to 7 ng. CAT protein was detected in 3 of the 4 mammalian cell lines incubated with VLPs. Incubation with heated VLPs resulted in BHK-21 and HeLa cell lysates showing reduced CAT protein levels compared with unheated VLPs and HEK-293 cells. Mice inoculated with a DNA prime VLP boost regimen developed Gag CD8 and CD4 T cell responses to GagCAT VLPs which also boosted a primary DNA response. Heating VLPs did not abrogate these immune responses but enhanced the Gag CD4 T cell responses by two-fold. Conclusions: Baculovirus-produced HIV-1 Gag VLPs encapsidating CAT RNA were taken up by selected mammalian cell lines. The presence of CAT protein indicates that encapsidated RNA was expressed in the mammalian cells. Heat-treatment of the VLPs altered the ability of protein to be expressed in some cell lines tested but did not affect the ability of the VLPs to stimulate an immune response when inoculated into mice. © 2011 Valley-Omar et al; licensee BioMed Central Ltd

The porcine circovirus type 1 capsid gene promoter improves antigen expression and immunogenicity in a HIV-1 plasmid vaccine

Background. One of the promising avenues for development of vaccines against Human immunodeficiency virus type 1 (HIV-1) and other human pathogens is the use of plasmid-based DNA vaccines. However, relatively large doses of plasmid must be injected for a relatively weak response. We investigated whether genome elements from Porcine circovirus type 1 (PCV-1), an apathogenic small ssDNA-containing virus, had useful expression-enhancing properties that could allow dose-sparing in a plasmid vaccine. Results. The linearised PCV-1 genome inserted 5' of the CMV promoter in the well-characterised HIV-1 plasmid vaccine pTHgrttnC increased expression of the polyantigen up to 2-fold, and elicited 3-fold higher CTL responses in mice at 10-fold lower doses than unmodified pTHgrttnC. The PCV-1 capsid gene promoter (Pcap) alone was equally effective. Enhancing activity was traced to a putative composite host transcription factor binding site and a "Conserved Late Element" transcription-enhancing sequence previously unidentified in circoviruses. Conclusions. We identified a novel PCV-1 genome-derived enhancer sequence that significantly increased antigen expression from plasmids in in vitro assays, and improved immunogenicity in mice of the HIV-1 subtype C vaccine plasmid, pTHgrttnC. This should allow significant dose sparing of, or increased responses to, this and other plasmid-based vaccines. We also report investigations of the potential of other circovirus-derived sequences to be similarly used. © 2011 Tanzer et al; licensee BioMed Central Ltd

Autonomic dysregulation and self‐injurious thoughts and behaviours in children and young people: A systematic review and meta‐analysis

Background: self-injurious thoughts and behaviours (SITBs) have been associated with dysfunction of the Autonomic Nervous System (ANS) in children and young people, suggesting that objective ANS measures may aid assessment of suicide risk, but a systematic synthesis of this literature is currently lacking.Methods: following a pre-registered protocol (PROSPERO CRD42022327605), we conducted a systematic search of PubMed, Medline, Embase, PsycINFO, and Web of Science, for empirical studies published until 10th May 2022 that compared indices of ANS functioning in individuals aged 0–25 years with versus without SITBs, or reported continuous associations between ANS measures and SITBs. Study quality was assessed with the Newcastle-Ottawa Scales. Pooled effect sizes (Hedge's g) were estimated with random-effects meta-analytic models.Results: twenty studies (1979 participants) were included in our systematic review, with 16 included in meta-analyses. Results suggested that SITBs were associated with altered cardiac indices of arousal (g = −0.328, p &lt; 0.001), which was driven by lower heart rate variability in individuals with SITBs (g = −0.375, p = 0.025). Overall results for electrodermal activity were not significant (g = 0.026, p = 0.857), but subgroup analyses showed increased activity in studies of individuals who engaged specifically in non-suicidal self-harm (g = 0.249, p = 0.014) but decreased activity in the remaining studies (g = −0.567, p = 0.004).Conclusions: our systematic review and meta-analysis found evidence of reduced parasympathetic regulation as well as more tentative evidence of altered electrodermal activity in children and young people displaying SITBs. Future longitudinal studies should test the clinical utility of these markers for detecting and monitoring suicide risk

Miocene drainage reversal of the Amazon River driven by plate–mantle interaction

Northern South America experienced significant changes in drainage patterns during the opening of the South Atlantic Ocean. Disappearance of a mega-wetland in the western Amazonian basins was followed by the formation of the eastward-draining Amazon River, which has been attributed to Andean uplift. However, South America’s westward motion over cold, dense subducted slabs implies that regional subsidence and uplift east of the Andes may have been driven by mantle convection. Here we use a coupled model of mantle convection and plate kinematics to show that dynamic subsidence of up to 40 m Myr^(−1) initially formed the Amazonian mega-wetland. In our model, the sustained westward motion of continental South America over subducted slabs resulted in rebound of the Amazonian mega-wetland region at rates of up to 40 m Myr^(−1) after 30 million years ago, paired with continued subsidence of the eastern Amazonian sedimentary basins at 10–20 m Myr^(−1). The resulting progressive tilt of northern South America to the east enabled the establishment of the Amazon River, suggesting that mantle convection can profoundly affect the evolution of continental drainage systems

Oscillatory neural networks underlying resting-state, attentional control and social cognition task conditions in children with ASD, ADHD and ASD+ADHD

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are common and impairing neurodevelopmental disorders that frequently co-occur. The neurobiological mechanisms involved in ASD and ADHD are not fully understood. However, alterations in large-scale neural networks have been proposed as core deficits in both ASD and ADHD and may help to disentangle the neurobiological basis of these disorders and their co-occurrence. In this study, we examined similarities and differences in large-scale oscillatory neural networks between boys aged 8-13 years with ASD (n = 19), ADHD (n = 18), ASD + ADHD (n = 29) and typical development (Controls, n = 26). Oscillatory neural networks were computed using graph-theoretical methods from electroencephalographic (EEG) data collected during an eyes-open resting-state and attentional control and social cognition tasks in which we previously reported disorder-specific atypicalities in oscillatory power and event-related potentials (ERPs). We found that children with ASD showed significant hypoconnectivity in large-scale networks during all three task conditions compared to children without ASD. In contrast, children with ADHD showed significant hyperconnectivity in large-scale networks during the attentional control and social cognition tasks, but not during the resting-state, compared to children without ADHD. Children with co-occurring ASD + ADHD did not differ from children with ASD when paired with this group and vice versa when paired with the ADHD group, indicating that these children showed both ASD-like hypoconnectivity and ADHD-like hyperconnectivity. Our findings suggest that ASD and ADHD are associated with distinct alterations in large-scale oscillatory networks, and these atypicalities present together in children with both disorders. These alterations appear to be task-independent in ASD but task-related in ADHD, and may underlie other neurocognitive atypicalities in these disorders. [Abstract copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.