How was it for you? Experiences of participatory design in the UK health service

Improving co-design methods implies that we need to understand those methods, paying attention to not only the effect of method choices on design outcomes, but also how methods affect the people involved in co-design. In this article, we explore participants' experiences from a year-long participatory health service design project to develop ‘Better Outpatient Services for Older People’. The project followed a defined method called experience-based design (EBD), which represented the state of the art in participatory service design within the UK National Health Service. A sample of participants in the project took part in semi-structured interviews reflecting on their involvement in and their feelings about the project. Our findings suggest that the EBD method that we employed was successful in establishing positive working relationships among the different groups of stakeholders (staff, patients, carers, advocates and design researchers), although conflicts remained throughout the project. Participants' experiences highlighted issues of wider relevance in such participatory design: cost versus benefit, sense of project momentum, locus of control, and assumptions about how change takes place in a complex environment. We propose tactics for dealing with these issues that inform the future development of techniques in user-centred healthcare design

A New Distance to The Antennae Galaxies (NGC 4038/39) Based on the Type Ia Supernova 2007sr

Traditionally, the distance to NGC 4038/39 has been derived from the systemic recession velocity, yielding about 20 Mpc for H_0 = 72 km/s/Mpc. Recently, this widely adopted distance has been challenged based on photometry of the presumed tip of the red giant branch (TRGB), which seems to yield a shorter distance of 13.3+-1.0 Mpc and, with it, nearly 1 mag lower luminosities and smaller radii for objects in this prototypical merger. Here we present a new distance estimate based on observations of the Type Ia supernova (SN) 2007sr in the southern tail, made at Las Campanas Observatory as part of the Carnegie Supernova Project. The resulting distance of D(SN Ia) = 22.3+-2.8 Mpc [(m-M)_0 = 31.74+-0.27 mag] is in good agreement with a refined distance estimate based on the recession velocity and the large-scale flow model developed by Tonry and collaborators, D(flow) = 22.5+-2.8 Mpc. We point out three serious problems that a short distance of 13.3 Mpc would entail, and trace the claimed short distance to a likely misidentification of the TRGB. Reanalyzing Hubble Space Telescope (HST) data in the Archive with an improved method, we find a TRGB fainter by 0.9 mag and derive from it a preliminary new TRGB distance of D(TRGB) = 20.0+-1.6 Mpc. Finally, assessing our three distance estimates we recommend using a conservative, rounded value of D = 22+-3 Mpc as the best currently available distance to The Antennae.Comment: 8 pages, 5 figures, 1 table (emulateapj; uses amsmath package). Accepted for publication in The Astronomical Journal, Vol. 136. Figs. 1 & 2 degraded to reduce file size

Star Clusters in the Nearby Late-Type Galaxy NGC 1311

Ultraviolet, optical and near infrared images of the nearby (D ~ 5.5 Mpc) SBm galaxy NGC 1311, obtained with the Hubble Space Telescope, reveal a small population of 13 candidate star clusters. We identify candidate star clusters based on a combination of their luminosity, extent and spectral energy distribution. The masses of the cluster candidates range from ~1000 up to ~100000 Solar masses, and show a strong positive trend of larger mass with increasing with cluster age. Such a trend follows from the fading and dissolution of old, low-mass clusters, and the lack of any young super star clusters of the sort often formed in strong starbursts. The cluster age distribution is consistent with a bursting mode of cluster formation, with active episodes of age ~10 Myr, ~100 Myr and ~1 Gyr. The ranges of age and mass we probe are consistent with those of the star clusters found in quiescent Local Group dwarf galaxies.Comment: 21 pages, 11 figures, accepted by A

A two-domain elevator mechanism for sodium/proton antiport

Sodium/proton (Na+/H+) antiporters, located at the plasma membrane in every cell, are vital for cell homeostasis1. In humans, their dysfunction has been linked to diseases, such as hypertension, heart failure and epilepsy, and they are well-established drug targets2. The best understood model system for Na+/H+ antiport is NhaA from Escherichia coli1, 3, for which both electron microscopy and crystal structures are available4, 5, 6. NhaA is made up of two distinct domains: a core domain and a dimerization domain. In the NhaA crystal structure a cavity is located between the two domains, providing access to the ion-binding site from the inward-facing surface of the protein1, 4. Like many Na+/H+ antiporters, the activity of NhaA is regulated by pH, only becoming active above pH 6.5, at which point a conformational change is thought to occur7. The only reported NhaA crystal structure so far is of the low pH inactivated form4. Here we describe the active-state structure of a Na+/H+ antiporter, NapA from Thermus thermophilus, at 3 Å resolution, solved from crystals grown at pH 7.8. In the NapA structure, the core and dimerization domains are in different positions to those seen in NhaA, and a negatively charged cavity has now opened to the outside. The extracellular cavity allows access to a strictly conserved aspartate residue thought to coordinate ion binding1, 8, 9 directly, a role supported here by molecular dynamics simulations. To alternate access to this ion-binding site, however, requires a surprisingly large rotation of the core domain, some 20° against the dimerization interface. We conclude that despite their fast transport rates of up to 1,500 ions per second3, Na+/H+ antiporters operate by a two-domain rocking bundle model, revealing themes relevant to secondary-active transporters in general

Engineered extracellular vesicle decoy receptor-mediated modulation of the IL6 trans-signalling pathway in muscle

The cytokine interleukin 6 (IL6) is a key mediator of inflammation that contributes to skeletal muscle pathophysiology. IL6 activates target cells by two main mechanisms, the classical and trans-signalling pathways. While classical signalling is associated with the anti-inflammatory activities of the cytokine, the IL6 trans-signalling pathway mediates chronic inflammation and is therefore a target for therapeutic intervention. Extracellular vesicles (EVs) are natural, lipid-bound nanoparticles, with potential as targeted delivery vehicles for therapeutic macromolecules. Here, we engineered EVs to express IL6 signal transducer (IL6ST) decoy receptors to selectively inhibit the IL6 trans-signalling pathway. The potency of the IL6ST decoy receptor EVs was optimized by inclusion of a GCN4 dimerization domain and a peptide sequence derived from syntenin-1 which targets the decoy receptor to EVs. The resulting engineered EVs were able to efficiently inhibit activation of the IL6 trans-signalling pathway in reporter cells, while having no effect on the IL6 classical signalling. IL6ST decoy receptor EVs, were also capable of blocking the IL6 trans-signalling pathway in C2C12 myoblasts and myotubes, thereby inhibiting the phosphorylation of STAT3 and partially reversing the anti-differentiation effects observed when treating cells with IL6/IL6R complexes. Treatment of a Duchenne muscular dystrophy mouse model with IL6ST decoy receptor EVs resulted in a reduction in STAT3 phosphorylation in the quadriceps and gastrocnemius muscles of these mice, thereby demonstrating in vivo activity of the decoy receptor EVs as a potential therapy. Taken together, this study reveals the IL6 trans-signalling pathway as a promising therapeutic target in DMD, and demonstrates the therapeutic potential of IL6ST decoy receptor EVs

Влияние количества биоптатов, взятых при таргетной биопсии предстательной железы, на вероятность положительного результата у пациентов с клинически значимым раком предстательной железы

Background. Targeted biopsy is proposed as a method of choice in the algorithm of prostate cancer diagnosis, but not all the features of method has been evaluated. Objective: determine the rational number of targeted biopsy samples in patients with clinically significant prostate cancer. Materials and methods. The magnetic resonance imaging and fusion biopsy data of 156 patients with suspected prostate cancer were retrospectively evaluated. Results and conclusion. In the study statistically significant dependence of the positive histological results in patients with clinically significant prostate cancer from the number of biopsy samples was found. The potential probability of a false negative histological examination with an insufficient number of biopsy samples was noted. These results confirm the latest published data of potential targeted biopsy false in true positive patients after multiparametric magnetic resonance imaging. An increase in the number of biopsy samples in the target lesion reduces the likelihood of false-negative results. The main causes of such discrepancy are some technical laxity and the heterogeneous histological structure of prostate cancer. Increase the number of biopsy cores can reduce the likelihood of false-negative results. © 2020 ABC-press Publishing House. All rights reserved

Evolution in the Disks and Bulges of Group Galaxies since z=0.4

We present quantitative morphology measurements of a sample of optically selected group galaxies at 0.3 < z < 0.55 using the Hubble Space Telescope (HST) Advanced Camera for Surveys (ACS) and the GIM2D surface brightness--fitting software package. The group sample is derived from the Canadian Network for Observational Cosmology Field Redshift survey (CNOC2) and follow-up Magellan spectroscopy. We compare these measurements to a similarly selected group sample from the Millennium Galaxy Catalogue (MGC) at 0.05 < z < 0.12. We find that, at both epochs, the group and field fractional bulge luminosity (B/T) distributions differ significantly, with the dominant difference being a deficit of disk--dominated (B/T < 0.2) galaxies in the group samples. At fixed luminosity, z=0.4 groups have ~ 5.5 +/- 2 % fewer disk--dominated galaxies than the field, while by z=0.1 this difference has increased to ~ 19 +/- 6 %. Despite the morphological evolution we see no evidence that the group environment is actively perturbing or otherwise affecting the entire existing disk population. At both redshifts, the disks of group galaxies have similar scaling relations and show similar median asymmetries as the disks of field galaxies. We do find evidence that the fraction of highly asymmetric, bulge--dominated galaxies is 6 +/- 3 % higher in groups than in the field, suggesting there may be enhanced merging in group environments. We replicate our group samples at z=0.4 and z=0 using the semi-analytic galaxy catalogues of Bower et al (2006). This model accurately reproduces the B/T distributions of the group and field at z=0.1. However, the model does not reproduce our finding that the deficit of disks in groups has increased significantly since z=0.4.Comment: Accepted for publication in MNRAS. 20 pages, 17 figure

Deficient spermiogenesis in mice lacking Rlim

The X-linked gene Rlim plays major roles in female mouse development and reproduction, where it is crucial for the maintenance of imprinted X chromosome inactivation in extraembryonic tissues of embryos. However, while females carrying a systemic Rlim knockout (KO) die around implantation, male Rlim KO mice appear healthy and are fertile. Here, we report an important role for Rlim in testis where it is highly expressed in post-meiotic round spermatids as well as in Sertoli cells. Systemic deletion of the Rlim gene results in lower numbers of mature sperm that contains excess cytoplasm, leading to decreased sperm motility and in vitro fertilization rates. Targeting the conditional Rlim cKO specifically to the spermatogenic cell lineage largely recapitulates this phenotype. These results reveal functions of Rlim in male reproduction specifically in round spermatids during spermiogenesis