Ten women's decision-making experiences in threatened preterm labour: Qualitative findings from the EQUIPTT trial.

BACKGROUND: Clinical triage of women in threatened preterm labour (TPTL) could be improved through utilising the QUiPP App, as symptoms alone are poor predictors of early delivery. As most women in TPTL ultimately deliver at term, they must weigh this likelihood with their own personal considerations, and responsibilities. The importance of personal considerations was highlighted by the 2015 Montgomery ruling, and the significance of shared decision-making. AIMS: Through qualitative interviews, the primary aim was to explore women's decision-making experiences in TPTL through onset of symptoms, triage, clinical assessment, and discharge. METHODS: Qualitative interviews were undertaken as part of the EQUIPTT study (REC: 17/LO/1802) using a semi-structured interview schedule. Descriptive labels of the coding scheme were applied to the raw transcript data. This coding scheme was then increasingly refined into key themes and allowed parallels to be made within and between cases. RESULTS: Ten ethnically diverse women who presented at six different London hospitals sites in TPTL were interviewed. Three final themes emerged from the data incorporating 10 sub-themes, 'Seeking help', 'Being "assessed" vs making clinical decisions together', and 'End result.' CONCLUSION: Women described their busy lives and the need to juggle their commitments. Participants drew comparisons between their TPTL symptoms and 'period pain,' contrasting to typical medical terminology. Shared decision-making and the clinician-patient relationship could be improved through clinicians utilizing terminology women understand and relate to. Women used language that highlighted the clinician-patient power balance. While not fully involved in shared decision-making, women were overall satisfied with their care

Clinicians' experiences of using and implementing a medical mobile phone app (QUiPP V2) designed to predict the risk of preterm birth and aid clinical decision making.

BACKGROUND: As the vast majority of women who present in threatened preterm labour (TPTL) will not deliver early, clinicians need to balance the risks of over-medicalising the majority of women, against the potential risk of preterm delivery for those discharged home. The QUiPP app is a free, validated app which can support clinical decision-making as it produces individualised risks of delivery within relevant timeframes. Recent evidence has highlighted that clinicians would welcome a decision-support tool that accurately predicts preterm birth. METHODS: Qualitative interviews were undertaken as part of the EQUIPTT study (The Evaluation of the QUiPP app for Triage and Transfer) (REC: 17/LO/1802) which aimed to evaluate the impact of the QUiPP app on management of TPTL. Individual semi-structured telephone interviews were used to explore clinicians' (obstetricians' and midwives') experiences of using the QUiPP app and how it was implemented at their hospital sites. Thematic analysis was chosen to explore the meaning of the data, through a framework approach. RESULTS: Nineteen participants from 10 hospital sites in England took part. Data analysis revealed three overarching themes which were: 'experience of using the app', 'how QUiPP risk changes practice' and 'successfully adopting QUiPP: context is everything'. With these final themes we appeared to have achieved our aim of exploring the clinicians' experiences of using and implementing the QUiPP app. CONCLUSION: This study explored different clinician's experiences of implementing the app. The organizational and cultural context at different sites appeared to have a large impact on how well the QUiPP app was implemented. Future work needs to be undertaken to understand how best to embed the intervention within different settings. This will inform scale up of QUiPP app use across the UK and ensure that clinicians have access to this free, easy-to-use tool which can positively aid clinical decision making when caring for women in TPTL. CLINICAL TRIAL REGISTRY AND REGISTRATION NUMBER: ISRCTN 17846337, registered 08th January 2018, https://doi.org/10.1186/ISRCTN17846337

Amorfrutin B is an efficient natural peroxisome proliferator-activated receptor gamma (PPARgamma) agonist with potent glucose-lowering properties

AIMS/HYPOTHESIS: The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) is an important gene regulator in glucose and lipid metabolism. Unfortunately, PPARgamma-activating drugs of the thiazolidinedione class provoke adverse side effects. As recently shown, amorfrutin A1 is a natural glucose-lowering compound that selectively modulates PPARgamma. In this study we aimed to characterise, in vitro, a large spectrum of the amorfrutins and similar molecules, which we isolated from various plants. We further studied in vivo the glucose-lowering effects of the so far undescribed amorfrutin B, which featured the most striking PPARgamma-binding and pharmacological properties of this family of plant metabolites. METHODS: Amorfrutins were investigated in vitro by binding and cofactor recruitment assays and by transcriptional activation assays in primary human adipocytes and murine preosteoblasts, as well as in vivo using insulin-resistant high-fat-diet-fed C57BL/6 mice treated for 27 days with 100 mg kg(-1) day(-1) amorfrutin B. RESULTS: Amorfrutin B showed low nanomolar binding affinity to PPARgamma, and micromolar binding to the isotypes PPARalpha and PPARbeta/delta. Amorfrutin B selectively modulated PPARgamma activity at low nanomolar concentrations. In insulin-resistant mice, amorfrutin B considerably improved insulin sensitivity, glucose tolerance and blood lipid variables after several days of treatment. Amorfrutin B treatment did not induce weight gain and furthermore showed liver-protecting properties. Additionally, amorfrutins had no adverse effects on osteoblastogenesis and fluid retention. CONCLUSIONS/INTERPRETATION: The application of plant-derived amorfrutins or synthetic analogues thereof constitutes a promising approach to prevent or treat complex metabolic diseases such as insulin resistance or type 2 diabetes

Induction of antibody-mediated neutralization in SIVmac239 by a naturally acquired V3 mutation

AbstractAchieving humoral immunity against human immunodeficiency virus (HIV) is a major obstacle in AIDS vaccine development. Despite eliciting robust humoral responses to HIV, exposed hosts rarely produce broadly neutralizing antibodies. The present study utilizes simian immunodeficiency virus (SIV) to identify viral epitopes that conferred antibody neutralization to clone SIV/17E-CL, an in vivo variant derived from neutralization resistant SIVmac239. Neutralization assays using rhesus macaque monoclonal antibodies were performed on viruses engineered to express single or multiple amino acid mutations. Results identified a single amino acid mutation, P334R, in the carboxy-terminal half of the V3 loop as a critical residue that induced neutralization while retaining normal glycoprotein expression on the surface of the virus. Furthermore, the R334 residue yielded neutralization sensitivity by antibodies recognizing diverse conformational and linear epitopes of gp120, suggesting that neutralization phenotype was a consequence of global structural changes of the envelope protein rather than a specific site epitope

Normative resistance to responsibility to protect in times of emerging multipolarity: the cases of Brazil and Russia

This article assesses the normative resistance to Responsibility to Protect adopted by Brazil and Russia against the backdrop of their international identities and self-assigned roles in a changing global order. Drawing upon the framework of Bloomsfield's norm dynamics role spectrum, it argues that while the ambiguous Russian role regarding this principle represents an example of 'norm antipreneurship', particularities of Brazil's resistance are better grasped by a new category left unaccounted for by this model, which this study portrays as 'contesting entrepreneur'.- (undefined

Shape model, reference system definition, and cartographic mapping standards for comet 67P/Churyumov-Gerasimenko - Stereo-photogrammetric analysis of Rosetta/OSIRIS image data

We analyzed more than 200 OSIRIS NAC images with a pixel scale of 0.9-2.4 m/pixel of comet 67P/Churyumov-Gerasimenko (67P) that have been acquired from onboard the Rosetta spacecraft in August and September 2014 using stereo-photogrammetric methods (SPG). We derived improved spacecraft position and pointing data for the OSIRIS images and a high-resolution shape model that consists of about 16 million facets (2 m horizontal sampling) and a typical vertical accuracy at the decimeter scale. From this model, we derive a volume for the northern hemisphere of 9.35 km3 ± 0.1 km3. With the assumption of a homogeneous density distribution and taking into account the current uncertainty of the position of the comet's center-of-mass, we extrapolated this value to an overall volume of 18.7 km3± 1.2 km3, and, with a current best estimate of 1.0 × 1013 kg for the mass, we derive a bulk density of 535 kg/m3± 35 kg/m3. Furthermore, we used SPG methods to analyze the rotational elements of 67P. The rotational period for August and September 2014 was determined to be 12.4041 ± 0.0004 h. For the orientation of the rotational axis (z-axis of the body-fixed reference frame) we derived a precession model with a half-cone angle of 0.14°, a cone center position at 69.54°/64.11° (RA/Dec J2000 equatorial coordinates), and a precession period of 10.7 days. For the definition of zero longitude (x-axis orientation), we finally selected the boulder-like Cheops feature on the big lobe of 67P and fixed its spherical coordinates to 142.35° right-hand-rule eastern longitude and -0.28° latitude. This completes the definition of the new Cheops reference frame for 67P. Finally, we defined cartographic mapping standards for common use and combined analyses of scientific results that have been obtained not only within the OSIRIS team, but also within other groups of the Rosetta mission

Comet 67P/Churyumov-Gerasimenko: Constraints on its origin from OSIRIS observations

Context. One of the main aims of the ESA Rosetta mission is to study the origin of the solar system by exploring comet 67P/Churyumov-Gerasimenko at close range. Aims. In this paper we discuss the origin and evolution of comet 67P/Churyumov-Gerasimenko in relation to that of comets in general and in the framework of current solar system formation models. Methods. We use data from the OSIRIS scientific cameras as basic constraints. In particular, we discuss the overall bi-lobate shape and the presence of key geological features, such as layers and fractures. We also treat the problem of collisional evolution of comet nuclei by a particle-in-a-box calculation for an estimate of the probability of survival for 67P/Churyumov-Gerasimenko during the early epochs of the solar system. Results. We argue that the two lobes of the 67P/Churyumov-Gerasimenko nucleus are derived from two distinct objects that have formed a contact binary via a gentle merger. The lobes are separate bodies, though sufficiently similar to have formed in the same environment. An estimate of the collisional rate in the primordial, trans-planetary disk shows that most comets of similar size to 67P/Churyumov-Gerasimenko are likely collisional fragments, although survival of primordial planetesimals cannot be excluded. Conclusions. A collisional origin of the contact binary is suggested, and the low bulk density of the aggregate and abundance of volatile species show that a very gentle merger must have occurred. We thus consider two main scenarios: the primordial accretion of planetesimals, and the re-accretion of fragments after an energetic impact onto a larger parent body. We point to the primordial signatures exhibited by 67P/Churyumov-Gerasimenko and other comet nuclei as critical tests of the collisional evolution

Double-Positive CD21+CD27+ B Cells Are Highly Proliferating Memory Cells and Their Distribution Differs in Mucosal and Peripheral Tissues

Several B-cell defects arise in HIV infected patients, particularly in patients with chronic infection and high viral load. Loss of memory B cells (CD27(+) B cells) in peripheral blood and lymphoid tissues is one of the major B cell dysfunctions in HIV and simian immunodeficiency virus (SIV) infection. Despite several studies, definitive identification of memory B cells based on CD27 surface expression has not been described. Similarly, the rates of cell turnover in different B cell subpopulation from lymphoid and mucosal tissues have not been well documented. In this study, we demonstrate the presence of memory B cell populations and define their distribution, frequency and immunophenotype with regards to activation, proliferation, maturation, and antibody production in normal rhesus macaques from different lymphoid tissues.Thirteen healthy, uninfected rhesus macaques were selected for this study. CD20(+) B cells were isolated from peripheral blood and sorted based on CD27 and CD21 surface markers to define memory B cell population. All the B cell subpopulation was further characterized phenotypically and their cell turnover rates were evaluated in vivo following bromodeoxyuridine (BrdU) inoculation. Double positive (DP) CD21(+)CD27(+) B cells in both peripheral and lymphoid tissues are memory B cells, able to produce antibody by polyclonal activation, and without T cell help. Peripheral and lymphoid DP CD21(+)CD27(+) B cells were also able to become activated and proliferate at higher rates than other B cell subpopulations. Increased turnover of tonsillar memory B cells were identified compared to other tissues examined.We suggest that this DP memory B cells play a major role in the immune system and their function and proliferation might have an important role in HIV/SIV mediated B cell dysregulation and pathogenesis

The rotation state of 67P/Churyumov-Gerasimenko from approach observations with the OSIRIS cameras on Rosetta

Aims. Approach observations with the Optical, Spectroscopic, and Infrared Remote Imaging System (OSIRIS) experiment onboard Rosetta are used to determine the rotation period, the direction of the spin axis, and the state of rotation of comet 67P's nucleus. Methods. Photometric time series of 67P have been acquired by OSIRIS since the post wake-up commissioning of the payload in March 2014. Fourier analysis and convex shape inversion methods have been applied to the Rosetta data as well to the available ground-based observations. Results. Evidence is found that the rotation rate of 67P has significantly changed near the time of its 2009 perihelion passage, probably due to sublimation-induced torque. We find that the sidereal rotation periods P1 = 12.76129 ± 0.00005 h and P2 = 12.4043 ± 0.0007 h for the apparitions before and after the 2009 perihelion, respectively, provide the best fit to the observations. No signs of multiple periodicity are found in the light curves down to the noise level, which implies that the comet is presently in a simple rotation state around its axis of largest moment of inertia. We derive a prograde rotation model with spin vector J2000 ecliptic coordinates λ = 65° ± 15°, β = + 59° ± 15°, corresponding to equatorial coordinates RA = 22°, Dec = + 76°. However, we find that the mirror solution, also prograde, at λ = 275° ± 15°, β = + 50° ± 15° (or RA = 274°, Dec = + 27°), is also possible at the same confidence level, due to the intrinsic ambiguity of the photometric problem for observations performed close to the ecliptic plane

The global meter-level shape model of comet 67P/Churyumov-Gerasimenko

We performed a stereo-photogrammetric (SPG) analysis of more than 1500 Rosetta/OSIRIS NAC images of comet 67P/Churyumov-Gerasimenko (67P). The images with pixel scales in the range 0.2-3.0 m/pixel were acquired between August 2014 and February 2016. We finally derived a global high-resolution 3D description of 67P's surface, the SPG SHAP7 shape model. It consists of about 44 million facets (1-1.5 m horizontal sampling) and a typical vertical accuracy at the decimeter scale. Although some images were taken after perihelion, the SPG SHAP7 shape model can be considered a pre-periheliondescription and replaces the previous SPG SHAP4S shape model. From the new shape model, some measures for 67P with very low 3σ uncertainties can be retrieved: 18.56 km3 ± 0.02 km3 for the volume and 537.8 kg/m3 ± 0.7 kg/m3 for the mean density assuming a mass value of 9.982 × 1012 kg