Modelling fine scale route choice of upstream migrating fish as they approach an instream structure

This study used pattern-oriented modelling (POM) to investigate the space use and behavioural response of upstream migrating European river lamprey (Lampetra fluviatilis) to the two-dimensional hydrodynamic conditions created by an instream structure (triangular profile gauging weir). Passive Integrated Transponder (PIT) and acoustic telemetry were used to map the spatial-temporal distribution patterns of lamprey as they migrated upstream. Acoustic Doppler velocimetry and computer modelling were used to quantify the hydrodynamic environment. In adherence with the POM methodology, multiple movement models, incorporating increasingly complex environmental feedback mechanisms and behavioural rules were created and systematically assessed to identify which factors might reproduce the observed patterns. The best model was a spatially explicit Eulerian-Lagrangian Individual Based Model (IBM) that included two simple behaviours: 1) tortuous non-directed swimming when in low flow velocity (< 0.1 m s−1) and 2) persistent directed (against the flow) swimming in moderate to high flow velocity (≥ 0.1 m s−1). The POM indicated that flow heterogeneity was an important influence of lamprey space use and that simple behavioural rules (i.e. two separate movement behaviours in response to flow velocity) were sufficient to reproduce the main movement pattern observed: avoidance of flow recirculating regions near the banks. The combination of field telemetry, hydrodynamic modelling and POM provided a useful framework for systematically identifying the key factors (hydrodynamic and behavioural) that governed the space use of the target species and would likely work well for investigating similar relationships in other aquatic species

Eye-movements reveal attention to social information in autism spectrum disorder

Autism spectrum disorder (ASD) is a neurodevelopmental condition in which children show reduced attention to social aspects of the environment. However in adults with ASD, evidence for social attentional deficits is equivocal. One problem is that many paradigms present social information in an unrealistic, isolated way. This study presented adults and adolescents, with and without ASD, with a complex social scene alongside another, non-social scene, and measured eye-movements during a 3-s viewing period. Analyses first identified viewing time to different regions and then investigated some more complex issues. These were: the location of the very first fixation in a trial (indicating attentional priority); the effect of a task instruction on scan paths; the extent to which gaze-following was evident; and the degree to which participants’ scan paths were influenced by the low-level properties of a scene. Results indicate a superficially normal attentional preference for social information in adults with ASD. However, more sensitive measures show that ASD does entail social attention problems across the lifespan, supporting accounts of the disorder which emphasise lifelong neurodevelopmental atypicalities. These subtle abnormalities may be sufficient to produce serious difficulties in real-life scenarios

Eligibility for vericiguat in a real-world heart failure population according to trial, guideline and label criteria:Data from the Swedish Heart Failure Registry

Aim: We investigated the eligibility for vericiguat in a real-world heart failure (HF) population based on trial, guideline and label criteria. Methods and results: From the Swedish HF registry, 23 573 patients with HF with reduced ejection fraction (HFrEF) enrolled between 2000 and 2018, with a HF duration ≥6 months, were considered. Eligibility for vericiguat was calculated based on criteria from (i) the Vericiguat Global Study in Subjects with Heart Failure and Reduced Ejection Fraction (VICTORIA) trial; (ii) European and American guidelines on HF; (iii) product labelling according to the Food and Drug Administration and European Medicines Agency. Estimated eligibility for vericiguat in the trial, guidelines, and label scenarios was 21.4%, 47.4%, and 47.4%, respectively. Prior HF hospitalization within 6 months was the criterion limiting eligibility the most in all scenarios (met by 49.1% of the population). In the trial scenario, other criteria meaningfully limiting eligibility were elevated N-terminal pro-B-type natriuretic peptide levels and nitrate use. In all scenarios, eligibility was higher among patients hospitalized for HF at baseline (44.3% vs. 21.4% [trial scenario] and 97.3% vs. 47.4% [guideline/label scenarios] for hospitalized vs. non-hospitalized patients). Overall, eligible patients were older, had more severe HF, more comorbidities, and consequently higher cardiovascular mortality and HF hospitalization rates compared with ineligible patients across all scenarios. Conclusion: In a large and contemporary real-world HFrEF cohort, we estimated that 21.4% of patients would be eligible for vericiguat according to the VICTORIA trial selection criteria, 47.4% based on guidelines and labelling. Eligibility for vericiguat translated into the selection of a population at high risk of morbidity/mortality.</p

Dark Energy Survey Year 1 Results: A Precise H0 Measurement from DES Y1, BAO, and D/H Data

We combine Dark Energy Survey Year 1 clustering and weak lensing data with baryon acoustic oscillations and Big Bang nucleosynthesis experiments to constrain the Hubble constant. Assuming a flat ΛCDM model with minimal neutrino mass (Σm υ = 0.06 eV), we find H 0 = 67.4 -1.2+1.1 km s -1 Mpc -1 (68 per cent CL). This result is completely independent of Hubble constant measurements based on the distance ladder, cosmic microwave background anisotropies (both temperature and polarization), and strong lensing constraints. There are now five data sets that: (a) have no shared observational systematics; and (b) each constrains the Hubble constant with fractional uncertainty at the few percent level. We compare these five independent estimates, and find that, as a set, the differences between them are significant at the 2.5σ level (χ 2 /dof = 24/11, probability to exceed = 1.1 per cent). Having set the threshold for consistency at 3σ, we combine all five data sets to arrive at H 0 = 69.3 -0.6+0.4 km s -1 Mpc -

The delivery of personalised, precision medicines via synthetic proteins

Introduction: The design of advanced drug delivery systems based on synthetic and su-pramolecular chemistry has been very successful. Liposomal doxorubicin (Caelyx®), and liposomal daunorubicin (DaunoXome®), estradiol topical emulsion (EstrasorbTM) as well as soluble or erodible polymer systems such as pegaspargase (Oncaspar®) or goserelin acetate (Zoladex®) represent considerable achievements. The Problem: As deliverables have evolved from low molecular weight drugs to biologics (currently representing approximately 30% of the market), so too have the demands made of advanced drug delivery technology. In parallel, the field of membrane trafficking (and endocytosis) has also matured. The trafficking of specific receptors i.e. material to be recycled or destroyed, as well as the trafficking of protein toxins has been well characterized. This, in conjunction with an ability to engineer synthetic, recombinant proteins provides several possibilities. The Solution: The first is using recombinant proteins as drugs i.e. denileukin diftitox (Ontak®) or agalsidase beta (Fabrazyme®). The second is the opportunity to use protein toxin architecture to reach targets that are not normally accessible. This may be achieved by grafting regulatory domains from multiple species to form synthetic proteins, engineered to do multiple jobs. Examples include access to the nucleocytosolic compartment. Herein the use of synthetic proteins for drug delivery has been reviewed