Navigating the path home:Pioneering hospital-to-home transitions for children with medical complexity

status: Published onlin

In-Vitro Differentiation of Mature Dendritic Cells From Human Blood Monocytes

Representing the most potent antigen-presenting cells, dendritic cells (DC) can now be generated from human blood monocytes. We recently presented a novel protocol employing GM-CSF, IL-4, and IFN-γ to differentiate monocyte-derived DC in vitro. Here, such cells are characterized in detail. Cells in culture exhibited both dendritic and veiled morphologies, the former being adherent and the latter suspended. Phenotypically, they were CD1a(-/dim), CD11a(+), CD11b(++), CD11c(+), CD14(dim/-), CD16(a-/dim), CD18(+), CD32(dim/-), CD33(+), CD40(+), CD45R0(+), CD50(+), CD54(+), CD64(-/dim), CD68(+), CD71(+), CD80(dim), CD86(+/++), MHC class I(++/+++) HLA-DR(++/+++) HLA-DP(+), and HLA-DQ(+). The DC stimulated a strong allogeneic T-cell response, and further evidence for their autologous antigen-specific stimulation is discussed. Although resembling a mature CD 11c(+)CD45R0(+) blood DC subset identified earlier, their differentiation in the presence of the Thl and Th2 cytokines IFN-γ and IL-4 indicates that these DC may conform to mature mucosal DC

Transverse Optical Mode Patterns for an RF Excited Ar-He-Xe Laser

Transverse optical modes for an RF excited Ar-He-Xe laser are studied both experimentally and theoretically. A diffraction model for a waveguide with a nonsaturable gain and refractive index gradients placed between two plane mirrors is formulated. The effects of gain and diffraction index gradients and of diffraction in free space are evaluated for typical experimental conditions. A direct comparison between theoretical mode patterns and experimentally measured ones at distances of 17 and 114 cm from the output mirror demonstrated a satisfactory agreement for various laser wavelengths and gas mixture composition

Endocytosed nanogold fiducials for improved in-situ cryo-electron tomography tilt-series alignment

Cryo-electron tomography (CET) on cryo-focused ion beam (FIB)-milled lamellae is becoming a powerful technique for determining the structure of macromolecular complexes in their native cellular environment. Prior to tomogram reconstruction, CET tilt-series recorded on FIB lamellae need to be aligned. Traditionally, CET tiltseries alignment is performed with 5-20 nm gold fiducials, but it has thus far proven difficult to apply this to FIB lamellae of eukaryotic cells. In here, we describe a simple method to allow uptake of bovine serum albumin (BSA)-gold fiducials into mammalian cells via endocytosis, which can subsequently be used as fiducials for tiltseries alignment of cryo-FIB lamellae. We compare the alignment of tilt-series with BSA-gold fiducials to fiducialless patch-tracking, and find better alignment results with BSA-gold. This technique can contribute to understand cells at a structural and ultrastructural level with both cryo- and room-temperature electron tomography. Furthermore, fluorescently labeled BSA-gold has the potential to be used as fiducials for correlative light and electron microscopy studies

Binding prediction of multi-domain cellulases with a dual-CNN

Cellulases hold great promise for the production of biofuels and biochemicals. However, they are modular enzymes acting on a complex heterogeneous substrate. Because of this complexity, the computational prediction of their catalytic properties remains scarce, which restricts both enzyme discovery and enzyme design. Here, we present a dual-input convolutional neural network to predict the binding of multi-domain enzymes. This regression model outperformed previous molecular dynamics-based methods for binding prediction for cellulases in a fraction of the time. Also, we show that when changed to a classification problem, the same network can be back-propagated to suggest mutations to improve enzyme binding. A similar approach could increase our understanding of the structure-activity relationship of enzymes, and suggest new promising mutations for enzyme design using explainable artificial intelligence

The provision of solar energy to rural households through a fee-for-service system

This baseline report is part of an evaluation commissioned by the Policy and Operations Evaluation Department (IOB) of the Netherlands Ministry of Foreign Affairs. It belongs to a series of impact evaluations of renewable energy and development programmes supported by the Netherlands, with a focus on the medium and long term effects of these programmes on end-users or final beneficiaries. A characteristic of these studies is the use of mixed methods, being quantitative research techniques, in combination with qualitative techniques, to get insight in the magnitude of effects. The purpose of the impact evaluations is to account for assistance provided and to draw lessons from the findings for improvement of policy and policy implementation. The results of these impact evaluations will be input to a policy evaluation of the “Promoting Renewable Energy Programme” (PREP) to be concluded in 2014

Attentional Bias for Pain and Sex, and Automatic Appraisals of Sexual Penetration:Differential Patterns in Dyspareunia vs Vaginismus?

Introduction: Current information processing models propose that heightened attention bias for sex-related threats (eg, pain) and lowered automatic incentive processes ("wanting") may play an important role in the impairment of sexual arousal and the development of sexual dysfunctions such as genitopelvic pain/penetration disorder (GPPPD). Differential threat and incentive processing may also help explain the stronger persistence of coital avoidance in women with vaginismus compared to women with dyspareunia.Aims: As the first aim, we tested if women with GPPPD show (1) heightened attention for pain and sex, and (2) heightened threat and lower incentive associations with sexual penetration. Second, we examined whether the stronger persistence of coital avoidance in vaginismus vs dyspareunia might be explained by a stronger attentional bias or more dysfunctional automatic threat/incentive associations.Methods: Women with lifelong vaginismus (n = 37), dyspareunia (n = 29), and a no-symptoms comparison group (n = 51) completed a visual search task to assess attentional bias, and single target implicit-association tests to measure automatic sex-threat and sex-wanting associations.Results: There were no group differences in attentional bias or automatic associations. Correlational analysis showed that slowed detection of sex stimuli and stronger automatic threat associations were related to lowered sexual arousal.Conclusion: The findings do not corroborate the view that attentional bias for pain or sex contributes to coital pain, or that differences in coital avoidance may be explained by differences in attentional bias or automatic threat/incentive associations. However, the correlational findings are consistent with the view that automatic threat associations and impaired attention for sex stimuli may interfere with the generation of sexual arousal. Copyright (C) 2016, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.</p

Switching from premixed insulin to glargine-based insulin regimen improves glycaemic control in patients with type 1 or type 2 diabetes: a retrospective primary care-based analysis

Background: Insulin glargine (glargine) and premixed insulins (premix) are alternative insulin treatments. This analysis evaluated glycaemic control in 528 patients with type 1 (n = 183) or type 2 (n = 345) diabetes, after switching from premix to a glargine-based regimen, using unselected general practice (GP) data. Methods: Data for this retrospective observational analysis were extracted from a UK GP database (The Health Improvement Network). Patients were required to have at least 12 months of available data, before and after, switching from premix to a glargine-based regimen. The principal analysis was the change in HbA1c after 12 months of treatment with glargine; secondary analyses included change in weight, bolus usage and total daily insulin dose. Inconsistent reporting of hypoglycemic episodes precludes reliable assessment of this outcome. Multivariate analyses were used to adjust for baseline characteristics and confounding variables. Results: Both cohorts showed significant reduction in mean HbA1c 12 months after the switch: by -0.67% (p < 0.001) in the type 1 cohort and by -0.53% (p < 0.001) in the type 2 cohort (adjusted data). The size of HbA1c improvement was positively correlated with baseline HbA1c; patients with a baseline HbA1c ≥ 10% had the greatest mean reduction in HbA1c, by -1.7% (p < 0.001) and -1.2% (p < 0.001), respectively. The proportion of patients receiving co-bolus prescriptions increased in the type 1 (mean 24.6% to 95.1%, p < 0.001) and type 2 (mean 16.2% to 73.9%, p < 0.001) cohorts. There was no significant change in weight in either cohort. Total mean insulin use increased in type 2 diabetes patients (from 0.67 ± 1.35 U/Kg to 0.88 ± 1.33 U/Kg, p < 0.001) with a slight decrease in type 1 diabetes patients (from 1.04 ± 2.51 U/Kg to 0.98 ± 2.58 U/Kg, p < 0.001). Conclusion: In everyday practice, patients with type 1 or type 2 diabetes inadequately controlled by premix insulins experienced significant improvement in glycaemic control over 12 months after switching to a glargine-based insulin regimen. These findings support the use of a basal-bolus glargine-based regimen in patients poorly controlled on premix.Peter Sharplin, Jason Gordon, John R Peters, Anthony P Tetlow, Andrea J Longman and Philip McEwa