Depth-resolved imaging and displacement measurement techniques viewed as linear filtering operations

The last 5 years have seen the emergence of a family of optical interferometric techniques that provide deformation measurements throughout three-dimensional (3-D) weakly scattering materials. They include wavelength scanning interferometry (WSI), tilt scanning interferometry (TSI), phase contrast spectral optical coherence tomography (PC SOCT) and hyperspectral interferometry (HSI) and can be thought of as a marriage between the phase sensing capabilities of Phase Shifting Interferometry and the depth-sensing capabilities of Optical Coherence Tomography. It was recently shown that some closely related 3-D optical imaging techniques can be treated as shift-invariant linear filtering operations. In this paper, we extend that work to include WSI, TSI, PC SOCT and HSI as spatial filtering operations and also relate the properties of their transfer functions in the spatial frequency domain to their spatial resolution and phase sensitivity, for depth-resolved displacement measurements

Suppression of ovine lymphocyte activation by Teladorsagia circumcincta larval excretory-secretory products

Teladorsagia circumcincta is an important pathogenic nematode of sheep. It has been demonstrated previously that stimulation of murine T lymphocytes with excretory-secretory (ES) products derived from fourth stage larvae of T. circumcincta (Tci-L4-ES) results in de novo expression of Foxp3, a transcription factor intimately involved in regulatory T cell function. In the current study, Foxp3(+) T cell responses in the abomasum and the effects of Tci-L4-ES on ovine peripheral blood mononuclear cells (PBMC) following T. circumcincta infection were investigated. T. circumcincta infection resulted in a significant increase in numbers of abomasal Foxp3(+) T cells, but not an increase in the proportion of T cells expressing Foxp3. Unlike in mice, Tci-L4-ES was incapable of inducing T cell Foxp3 expression but instead suppressed mitogen-induced and antigen-specific activation and proliferation of ovine PBMC in vitro. This effect was heat labile, suggesting that it is mediated by protein(s). Suppression was associated with up-regulation of interleukin-10 (IL-10) mRNA, and specific monoclonal antibody neutralisation of IL-10 resulted in a 50% reduction in suppression, indicating involvement of the IL-10 signaling pathway. Suppression was significantly reduced in PBMC isolated from T. circumcincta infected vs. helminth-naïve lambs, and this reduction in suppression was associated with an increase in Tci-L4-ES antigen-specific T cells within the PBMC. In conclusion, we have identified a mechanism by which T. circumcincta may modulate the host adaptive immune response, potentially assisting survival of the parasite within the host. However, the impact of Tci-L4-ES-mediated lymphocyte suppression during T. circumcincta infection remains to be determined

Perspectives on the diagnosis and management of functional cognitive disorder: An international Delphi study

Background: Current proposed criteria for functional cognitive disorder (FCD) have not been externally validated. We sought to analyse the current perspectives of cognitive specialists in the diagnosis and management of FCD in comparison with neurodegenerative conditions. Methods: International experts in cognitive disorders were invited to assess seven illustrative clinical vignettes containing history and bedside characteristics alone. Participants assigned a probable diagnosis and selected the appropriate investigation and treatment. Qualitative, quantitative and inter-rater agreement analyses were undertaken. Results: Eighteen diagnostic terminologies were assigned by 45 cognitive experts from 12 countries with a median of 13 years of experience, across the seven scenarios. Accurate discrimination between FCD and neurodegeneration was observed, independently of background and years of experience: 100% of the neurodegenerative vignettes were correctly classified and 75%–88% of the FCD diagnoses were attributed to non-neurodegenerative causes. There was <50% agreement in the terminology used for FCD, in comparison with 87%–92% agreement for neurodegenerative syndromes. Blood tests and neuropsychological evaluation were the leading diagnostic modalities for FCD. Diagnostic communication, psychotherapy and psychiatry referral were the main suggested management strategies in FCD. Conclusions: Our study demonstrates the feasibility of distinguishing between FCD and neurodegeneration based on relevant patient characteristics and history details. These characteristics need further validation and operationalisation. Heterogeneous labelling and framing pose clinical and research challenges reflecting a lack of agreement in the field. Careful consideration of FCD diagnosis is advised, particularly in the presence of comorbidities. This study informs future research on diagnostic tools and evidence-based interventions

Developments in functional analysis of ship dynamics

Mathematical .models of the motions of shins in yaw and sway are taken; and unified. The general model is multi-i_i_inite-dimensional: and nonlinear but it yields to stability analysis by methods which closely resemble those applied to finite-dimensional systems. A reduced version having the form,-r,.' a Ham;aerctcin operator' is proposed based on the assumption that' the nonlinear and linear behaviour may be observed separately and are respectively associated with the quasi-static and historical':asaects of the motion. Paramoterisations are avoided because little i~•.known about the fine structure of the system, so the suggested method of identification of the reduced model has two functional stages.A If the steady-state response function is' obtained by a conventional experiment, the linear ized operator may be identified after routine, tram formations. This procedure is appropriate for both stable and unstable ships. Extensive attention is devoted to the identification of the impulse response of the linear component. First it is desirable to optimize the identification by choice of an efficient t6st signal, and suitable criteria are deduced from the _tifi _ concept of information. Working first in a discrete environment it is shown that maximizing the mutual information between the impulse response and the observations' effectively optimizes the least-squares identification procedure. Extension to continuous signals enables the optimization criteria to be established.Input signals based on pseudo-random binary sequences are discussed tand their potential for near-optimal identification is emphasized. i Their, use may also enable contaminating signals to be removed before the solution for the impulse response is obtained. 'r. Algorithms for obtaining this solution from the Wiener-Hopf equation are considered and the classical 7eumann series is transformed into a preferred algorithm. This technique is iterative, convergence is strong and may be accelerated.Some experiments are described in which a pseudo-random binary sequence ::*as used to drive the rudder of a free-running ship model. The yaw rate impulse response function is computed and some simulations performed.</p

Africanized honey bee response to differences in reward frequency

Differences in predation pressure and floral resources exist among the endemic ranges of Apis mellifera subspecies. Those environmental differences should select for heterogeneity in forager flower fidelity among honey bee subspecies, particularly when reward frequency differences are associated with competing flower types. We tested that evolutionary model by examining the foraging behaviour of Africanized honey bees (AHB), and by comparing our observations with those recorded for Italian (A. m. ligustica) and Caucasian honey bees (A. m. caucasica). The response of AHB (A. m. scutellata hybrid/introgressant) to reward frequency differences among flower colours was examined using artificial flower patches. Each patch contained blue, white, and yellow flowers. When rewards offered by ail three flower-morphs were identical, some foragers restricted visitation to blue and white flowers, while others showed fidelity to yellow flowers. Bees visiting blue and white flowers did not show a preference for either the blue or white colour morph under those conditions. However, forager behaviour changed when they were presented with different reward frequencies associated with the alternative flower colours. Bees frequenting blue and white flowers favoured blue when it offered a reward more frequently than white, and favoured white when the reverse was true. That behaviour occurred not only when the more frequently rewarding flower colour offered a higher harvest rate, but also when harvest rates obtained from all flower colours were equal. A change in flower colour fidelity involving yellow vs. blue and white flowers was observed only when reward frequency difference was linked to maximizing harvest rate. Those results contrast sharply to reported A. m. ligustica and A. m. caucasica honey bee behaviour: neither Italian nor Caucasian bees respond to reward frequency differences among flower colours, even between blue and white flowers

Using indices of species’ potential range to inform conservation status

Assessments of conservation status are typically based on short-term extinction risk, but the value of indicators that compare the current state of species (e.g., abundance or distribution) to potential baselines is increasingly recognised. The use of baselines in conservation legislation is hindered by ambiguity in how baselines should be determined and interpreted, leading to inconsistent application. Here, we explored the use of species’ potential ranges as a consistent means of quantifying baselines for assessing species’ distributions, a key component of conservation status. Using breeding birds of Great Britain (GB) as a case study, we simulated where bird species would be expected to occur today in a modelled world without human land use. We calculated indices that contrasted these potential human-free ranges with realised ranges. Our analyses revealed that 42% of GB birds have wider realised than potential ranges and 28% have narrower realised than potential ranges. These indices could lead to reassessments of current conservation priorities. Eighteen species assigned ‘least concern’ status by the GB regional IUCN Red List had much narrower realised than potential ranges, suggesting that their ranges are in a more degraded state than currently recognised by Red List criteria. Some of these species are not under active conservation management and could be candidates for higher prioritisation. Our approach provides a systematic means of quantifying range baselines that is not reliant on variable historic data or expert opinion and, thereby, provides a step forward in resolving a major contemporary problem in conservation assessment: how to set baselines in conservation consistently. The insights produced are also of wider scientific and cultural relevance, revealing where species would likely exist today in the absence of historic human impacts. This could be used to identify areas where targeted restoration actions might lead to the return of historically extirpated species, or even to novel colonists

Prodrugs for colon-restricted delivery: Design, synthesis, and in vivo evaluation of colony stimulating factor 1 receptor (CSF1R) inhibitors.

The ability to restrict low molecular weight compounds to the gastrointestinal (GI) tract may enable an enhanced therapeutic index for molecular targets known to be associated with systemic toxicity. Using a triazolopyrazine CSF1R inhibitor scaffold, a broad range of prodrugs were synthesized and evaluated for enhanced delivery to the colon in mice. Subsequently, the preferred cyclodextrin prodrug moiety was appended to a number of CSF1R inhibitory active parent molecules, enabling GI-restricted delivery. Evaluation of a cyclodextrin prodrug in a dextran sodium sulfate (DSS)-induced mouse colitis model resulted in enhanced GI tissue levels of active parent. At a dose where no significant depletion of systemic monocytes were detected, the degree of pharmacodynamic effect-measured as reduction in macrophages in the colon-was inferior to that observed with a systemically available positive control. This suggests that a suitable therapeutic index cannot be achieved with CSF1R inhibition by using GI-restricted delivery in mice. However, these efforts provide a comprehensive frame-work in which to pursue additional gut-restricted delivery strategies for future GI targets

Cerebral and Retinal Infarction in Bicuspid Aortic Valve

Background Description of cerebral and retinal infarction in patients with bicuspid aortic valve (BAV) is limited to case reports. We aimed to characterize cerebral and retinal infarction and examine outcomes in patients with BAV. Methods and Results Consecutive patients from 1975 to 2015 with BAV (n=5401) were retrospectively identified from the institutional database; those with confirmed cerebral or retinal infarction were analyzed. Infarction occurring after aortic valve replacement was not included. Patients were grouped according to infarction pathogenesis: embolism from a degenerative calcific BAV (BAVi); non‐BAV, large artery atherosclerotic or lacunar infarction (LAi); and non‐BAV, non‐large artery embolic infarction (nLAi). There were 83/5401 (1.5%) patients, mean age 54±12 years and 28% female, with confirmed cerebral or retinal infarction (LAi 23/83 [28%]; nLAi 30/83 [36%]; BAVi 26/83 [31%]; other 4/83 [5%]). Infarction was embolic in 72/83 (87%), and 35/72 (49%) were cardioembolic. CHA2DS2‐VASc score was 1.4±1.2 in BAVi (P=0.188 versus nLAi) and 2.3±1.2 in LAi (P=0.005). Recurrent infarction occurred in 41% overall (50% BAVi, P=0.164 and 0.803 versus LAi and nLAi). BAVi was more commonly retinal (39% BAVi versus 13% LAi, P=0.044 versus 0% nLAi, P=0.002). Patients with BAVi and LAi were more likely to have moderate‐to‐severe aortic stenosis and undergo aortic valve replacement compared with patients with nLAi. Conclusions Cardioembolism, often from degenerative calcification of the aortic valve, is a predominant cause of cerebral and retinal infarction in patients with BAV and is frequently recurrent. Cerebral and retinal infarction should be regarded as a complication of BAV