Simulation study of three instrument displays to assist in airplane thrust management

Simulation study of three instrument displays to assist airplane thrust managemen

Estrogen blocks the protective action of melatonin in a behavioral model of ethanol-induced hangover in mice

Melatonin has antioxidant and neuroprotective properties in human beings and experimental models, as well as 'anti-estrogenic' effects. Ethanol (EtOH) affects various behavioral parameters during a period known as ethanol-induced hangover. Our study evaluated the neuroprotective effect of melatonin on motor performance during ethanol hangover in male and female Swiss mice. The females were subjected to specific hormonal states: ovariectomized (OVX) and OVX estrogenized (OVX-E2). Mice received melatonin (25μg/ml) or vehicle in their drinking water for seven days and were given intraperitoneal (i.p.) injections of EtOH (3.8g/kg) or saline on the morning of the eighth day. Motor performance was evaluated by the tightrope test 6h after EtOH exposure (hangover onset). During ethanol hangover, males exhibited lower motor performance than controls (p<0.01) but pretreatment with melatonin significantly improved performance during hangover (p<0.05). In females, melatonin treatment before ethanol-induced hangover led to a better motor performance in OVX compared with intact females (p<0.01) and a lower performance in OVX-E2 compared with not-estrogenized OVX (p<0.05). Consequently, estrogen reversed the motor performance enhancement afforded by melatonin. We conclude that estrogen interferes with the protective action of melatonin on motor performance during ethanol hangover.Fil: Karadayian, A. G.. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Mc Laughlin, M. A.. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Cutrera, Rodolfo Angel. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Minimization of Radiation Exposure due to Computed Tomography in Inflammatory Bowel Disease

Patient awareness and concern regarding the potential health risks from ionizing radiation have peaked recently (Coakley et al., 2011) following widespread press and media coverage of the projected cancer risks from the increasing use of computed tomography (CT) (Berrington et al., 2007). The typical young and educated patient with inflammatory bowel disease (IBD) may in particular be conscious of his/her exposure to ionising radiation as a result of diagnostic imaging. Cumulative effective doses (CEDs) in patients with IBD have been reported as being high and are rising, primarily due to the more widespread and repeated use of CT (Desmond et al., 2008). Radiologists, technologists, and referring physicians have a responsibility to firstly counsel their patients accurately regarding the actual risks of ionizing radiation exposure; secondly to limit the use of those imaging modalities which involve ionising radiation to clinical situations where they are likely to change management; thirdly to ensure that a diagnostic quality imaging examination is acquired with lowest possible radiation exposure. In this paper, we synopsize available evidence related to radiation exposure and risk and we report advances in low-dose CT technology and examine the role for alternative imaging modalities such as ultrasonography or magnetic resonance imaging which avoid radiation exposure

Scalar transport in compressible flow

Transport of scalar fields in compressible flow is investigated. The effective equations governing the transport at scales large compared to those of the advecting flow are derived by using multi-scale techniques. Ballistic transport generally takes place when both the solenoidal and the potential components of the velocity do not vanish, despite of the fact that it has zero average value. The calculation of the effective ballistic velocity $V_b$ is reduced to the solution of one auxiliary equation. An analytic expression for $V_b$ is derived in some special instances, i.e. flows depending on a single coordinate, random with short correlation times and slightly compressible cellular flow. The effective mean velocity $V_b$ vanishes for velocity fields which are either incompressible or potential and time-independent. For generic compressible flow, the most general conditions ensuring the absence of ballistic transport are isotropy and/or parity invariance. When $V_b$ vanishes (or in the frame of reference moving with velocity $V_b$), standard diffusive transport takes place. It is known that diffusion is always enhanced by incompressible flow. On the contrary, we show that diffusion is depleted in the presence of time-independent potential flow. Trapping effects due to potential wells are responsible for this depletion. For time-dependent potential flow or generic compressible flow, transport rates are enhanced or depleted depending on the detailed structure of the velocity field.Comment: 27 pages, submitted to Physica

Population pharmacokinetics of TLD-1, a novel liposomal doxorubicin, in a phase I trial

Study objectives TLD-1 is a novel pegylated liposomal doxorubicin (PLD) formulation aiming to optimise the PLD efficacy-toxicity ratio. We aimed to characterise TLD-1’s population pharmacokinetics using non-compartmental analysis and nonlinear mixed-effects modelling. Methods The PK of TLD-1 was analysed by performing a non-compartmental analysis of longitudinal doxorubicin plasma concentration measurements obtained from a clinical trial in 30 patients with advanced solid tumours across a 4.5-fold dose range. Furthermore, a joint parent-metabolite PK model of doxorubicinentrapped, doxorubicinfree, and metabolite doxorubicinol was developed. Interindividual and interoccasion variability around the typical PK parameters and potential covariates to explain parts of this variability were explored. Results Medians +- standard deviations of dose-normalised doxorubicinentrapped+free Cmax and AUC0−∞ were 0.342 +- 0.134 mg/L and 40.1 +- 18.9 mg·h/L, respectively. The median half-life (95 h) was 23.5 h longer than the half-life of currently marketed PLD. The novel joint parent-metabolite model comprised a one-compartment model with linear release (doxorubicinentrapped), a two-compartment model with linear elimination (doxorubicinfree), and a one-compartment model with linear elimination for doxorubicinol. Body surface area on the volumes of distribution for free doxorubicin was the only significant covariate. Conclusion The population PK of TLD-1, including its release and main metabolite, were successfully characterised using non-compartmental and compartmental analyses. Based on its long half-life, TLD-1 presents a promising candidate for further clinical development. The PK characteristics form the basis to investigate TLD-1 exposure-response (i.e., clinical efficacy) and exposure-toxicity relationships in the future. Once such relationships have been established, the developed population PK model can be further used in model-informed precision dosing strategies. Clinical trial registration ClinicalTrials.gov–NCT03387917–January 2, 201

Easing Legal News Monitoring with Learning to Rank and BERT

While ranking approaches have made rapid advances in the Web search, systems that cater to the complex information needs in professional search tasks are not widely developed, common issues and solutions typically rely on dedicated search strategies backed by ad-hoc retrieval models. In this paper we present a legal search problem where professionals monitor news articles with constant queries on a periodic basis. Firstly, we demonstrate the effectiveness of using traditional retrieval models against the Boolean search of documents in chronological order. In an attempt to capture the complex information needs of users, a learning to rank approach is adopted with user specified relevance criteria as features. This approach, however, only achieves mediocre results compared to the traditional models. However, we find that by fine-tuning a contextualised language model (e.g. BERT), significantly improved retrieval performance can be achieved, providing a flexible solution to satisfying complex information needs without explicit feature engineering

Laws of biology: why so few?

Finding fundamental organizing principles is the current intellectual front end of systems biology. From a hydrogen atom to the whole cell level, organisms manage massively parallel and massively interactive processes over several orders of magnitude of size. To manage this scale of informational complexity it is natural to expect organizing principles that determine higher order behavior. Currently, there are only hints of such organizing principles but no absolute evidences. Here, we present an approach as old as Mendel that could help uncover fundamental organizing principles in biology. Our approach essentially consists of identifying constants at various levels and weaving them into a hierarchical chassis. As we identify and organize constants, from pair-wise interactions to networks, our understanding of the fundamental principles in biology will improve, leading to a theory in biology

Plasma concentration guided dosing of drugs used for the treatment of childhood leukaemias: protocol for a systematic review

Introduction: Childhood leukaemia is the most common type of cancer in children and represents among 25% of the diagnoses in children <15 years old. Childhood survival rates have significantly improved within the last 40 years due to a rapid advancement in therapeutic interventions. However, in high-risk groups, survival rates remain poor. Pharmacokinetic (PK) data of cancer medications in children are limited and thus current dosing regimens are based on studies with small sample sizes. In adults, large variability in PK is observed and dose individualisation (plasma concentration guided dosing) has been associated with improved clinical outcomes; whether this is true for children is still unknown. This provides an opportunity to explore this strategy in children to potentially reduce toxicities and ensure optimal dosing. This paper will provide a protocol to systematically review studies that have used dose individualisation of drugs used in the treatment of childhood leukaemias. Methods and analysis: Systematic review methodology will be applied to identify, select and extract data from published plasma guided dosing studies conducted in a paediatric leukaemia cohort. Databases (eg, Ovid Embase, Ovid MEDLINE, Ovid Cochrane) and clinical trial registries (CENTRAL, ClinicalTrials.gov and ISRCTN) will be used to perform the systematic literature search (up until February 2021). Only full empirical studies will be included, with primary clinical outcomes (progression-free survival, toxicities, minimal residual disease status, complete cytogenetic response, partial cytogenetic response and major molecular response) being used to decide whether the study will be included. The quality of included studies will be undertaken, with a subgroup analysis where appropriate. Ethics and dissemination: This systematic review will not require ethics approval as there will not be collection of primary data. Findings of this review will be made available through publications in peer-reviewed journals and conference presentations. Gaps will be identified in current literature to inform future-related research. PROSPERO registration number CRD42021225045