Development and evaluation of a patient decision aid for patients considering ongoing medical or surgical treatment options for ulcerative colitis using a mixed-methods approach : protocol for DISCUSS study

Introduction: Approximately 20%–30% of patients with ulcerative colitis (UC) require surgery, the majority of these being elective due to chronic symptoms refractory to medical treatment. The decision for surgery is difficult and dependent on patient preferences. Current resources for patients considering surgery have been found not to meet minimum international standards. The overall aim of the ‘DISCUSS’ study is to develop and evaluate a new patient decision aid (PtDA) for patients considering surgery for UC created in line with international minimum standards. Methods and analysis: This is a prospective mixed-methods study of adults (18+ years) who are considering surgical intervention for UC across two regional centres in Yorkshire, UK. This study is in three stages. In stage 1 we will develop the PtDA and its content via systematic reviews and a patient questionnaire. In stage 2 we will assess the face validity of the PtDA using mixed-methods on key stakeholders using both semistructured interviews and questionnaires, following which the PtDA will be refined. In stage 3 we will assess the acceptability of using the PtDA in clinical practice. This will use a mixed-methods approach on clinicians and patients who are considering undergoing elective surgery. Questionnaires including the Preparation for Decision-Making Scale, a measure of anxiety and decisional conflict will be analysed at two timepoints using paired sample t-tests and CIs. Interviews with patients and clinicians will be analysed using thematic analysis. Ethics and dissemination: Research ethics approval from North East–Tyne & Wear South Research Ethics Committee (Ref: 19/NE/0073) and Health Research Authority approval (Ref: 257044) have been granted. Results will be published in open access peer-reviewed journals, presented in conferences and distributed through the Crohn’s and Colitis UK charity. External endorsement will be sought from the International Patient Decision Aid Standards Collaboration inventory of PtDAs

Relaxation Methods for Mixed-Integer Optimal Control of Partial Differential Equations

We consider integer-restricted optimal control of systems governed by abstract semilinear evolution equations. This includes the problem of optimal control design for certain distributed parameter systems endowed with multiple actuators, where the task is to minimize costs associated with the dynamics of the system by choosing, for each instant in time, one of the actuators together with ordinary controls. We consider relaxation techniques that are already used successfully for mixed-integer optimal control of ordinary differential equations. Our analysis yields sufficient conditions such that the optimal value and the optimal state of the relaxed problem can be approximated with arbitrary precision by a control satisfying the integer restrictions. The results are obtained by semigroup theory methods. The approach is constructive and gives rise to a numerical method. We supplement the analysis with numerical experiments

18S rRNA is a reliable normalisation gene for real time PCR based on influenza virus infected cells

Background: One requisite of quantitative reverse transcription PCR (qRT-PCR) is to normalise the data with an internal reference gene that is invariant regardless of treatment, such as virus infection. Several studies have found variability in the expression of commonly used housekeeping genes, such as beta-actin (ACTB) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), under different experimental settings. However, ACTB and GAPDH remain widely used in the studies of host gene response to virus infections, including influenza viruses. To date no detailed study has been described that compares the suitability of commonly used housekeeping genes in influenza virus infections. The present study evaluated several commonly used housekeeping genes [ACTB, GAPDH, 18S ribosomal RNA (18S rRNA), ATP synthase, H+ transporting, mitochondrial F1 complex, beta polypeptide (ATP5B) and ATP synthase, H+ transporting, mitochondrial Fo complex, subunit C1 (subunit 9) (ATP5G1)] to identify the most stably expressed gene in human, pig, chicken and duck cells infected with a range of influenza A virus subtypes. Results: The relative expression stability of commonly used housekeeping genes were determined in primary human bronchial epithelial cells (HBECs), pig tracheal epithelial cells (PTECs), and chicken and duck primary lung-derived cells infected with five influenza A virus subtypes. Analysis of qRT-PCR data from virus and mock infected cells using NormFinder and BestKeeper software programmes found that 18S rRNA was the most stable gene in HBECs, PTECs and avian lung cells. Conclusions: Based on the presented data from cell culture models (HBECs, PTECs, chicken and duck lung cells) infected with a range of influenza viruses, we found that 18S rRNA is the most stable reference gene for normalising qRT-PCR data. Expression levels of the other housekeeping genes evaluated in this study (including ACTB and GPADH) were highly affected by influenza virus infection and hence are not reliable as reference genes for RNA normalisation

Phase transition enhanced thermoelectric figure-of-merit in copper chalcogenides

While thermoelectric materials can be used for solid state cooling, waste heat recovery, and solar electricity generation, low values of the thermoelectric figure of merit, zT, have led to an efficiency too low for widespread use. Thermoelectric effects are characterized by the Seebeck coefficient or thermopower, which is related to the entropy associated with charge transport. For example, coupling spin entropy with the presence of charge carriers has enabled the enhancement of zT in cobalt oxides. We demonstrate that the coupling of a continuous phase transition to carrier transport in Cu 2Se over a broad (360–410 K) temperature range results in a dramatic peak in thermopower, an increase in phonon and electron scattering, and a corresponding doubling of zT (to 0.7 at 406 K), and a similar but larger increase over a wider temperature range in the zT of Cu 1.97 Ag .03Se (almost 1.0 at 400 K). The use of structural entropy for enhanced thermopower could lead to new engineering approaches for thermoelectric materials with high zT and new green applications for thermoelectrics

Coronal X-Ray Emission from Nearby, Low-Mass, Exoplanet Host Stars Observed by the MUSCLES and Mega-MUSCLES HST Treasury Survey Projects

The high energy X-ray and ultraviolet (UV) radiation fields of exoplanet host stars play a crucial role in controlling the atmospheric conditions and the potential habitability of exoplanets. Major surveys of the X-ray/UV emissions from late-type (K and M spectral type) exoplanet hosts have been conducted by the MUSCLES and Mega-MUSCLES Hubble Space Telescope (HST) Treasury programs. These samples primarily consist of relatively old, ``inactive'', low mass stars. In this paper we present results from X-ray observations of the coronal emission from these stars obtained using the Chandra X-ray Observatory, the XMM-Newton Observatory, and the Neil Gehrels Swift Observatory. The stars effectively sample the coronal activity of low-mass stars at a wide range of masses and ages. The vast majority (21 of 23) of the stars are detected and their X-ray luminosities measured. Short-term flaring variability is detected for most of the fully-convective (M $\leq$ 0.35 M$_{\odot}$) stars but not for the more massive M dwarfs during these observations. Despite this difference, the mean X-ray luminosities for these two sets of M dwarfs are similar with more massive (0.35 M$_{\odot}$ $\leq$ M $\leq$ 0.6 M$_{\odot}$) M dwarfs at $\sim$5 $\times$ 10$^{26}$ erg s$^{-1}$ compared to $\sim$2 $\times$ 10$^{26}$ erg s$^{-1}$ for fully-convective stars older than 1 Gyr. Younger, fully-convective M dwarfs have X-ray luminosities between 3 and 6 $\times$ 10$^{27}$ erg s$^{-1}$.The coronal X-ray spectra have been characterized and provide important information that is vital for the modeling of the stellar EUV spectra.Comment: 39 pages, 15 figures. Accepted for publication in The Astronomical Journa

Evaluating annual severe coral bleaching risk for marine protected areas across Indonesia

Coral reefs face an uncertain future under global climate change, with thermal-induced bleaching increasing in frequency such that corals will soon experience annual severe bleaching (ASB). Marine Protected Areas (MPAs) are therefore becoming increasingly important as a conservation tool. Here we evaluate (i) Indonesia’s coral reefs’ spatial variation in ASB, (ii) whether reefs projected to have a later onset of ASB (i.e. possible climate refugia) are protected within MPAs, and (iii) the ASB risk profiles for reefs related to MPAs receiving priority investments. Our results highlight considerable variability across Indonesia’s reefs being at risk of ASB. The ASB risk before 2028 is greater for coral reefs protected by MPAs versus those outside MPA boundaries. The ASB risk before 2025 is greater for coral reefs protected by priority MPAs versus those protected by non-priority MPAs. Overall, our results show that only ∼45% of the coral reef areas that are currently located within MPAs will likely act as thermal refugia (ASB > 2044). This is unsurprising given that the MPA network in Indonesia has been established over many decades, with most MPAs designated before suitable bleaching risk projections were available to inform MPA placement. Our results highlight the scope to further incorporate potential climate refugia for reefs into new MPA designations. This study also provides strategic information, which can support the development of Indonesia’s long-term MPA and coral reef conservation strategy to effectively manage, mitigate, and adapt to the impacts of climate change on coral reefs

Influenza nucleoprotein delivered with aluminium salts protects mice from an influenza virus that expresses an altered nucleoprotein sequence

Influenza virus poses a difficult challenge for protective immunity. This virus is adept at altering its surface proteins, the proteins that are the targets of neutralizing antibody. Consequently, each year a new vaccine must be developed to combat the current recirculating strains. A universal influenza vaccine that primes specific memory cells that recognise conserved parts of the virus could prove to be effective against both annual influenza variants and newly emergent potentially pandemic strains. Such a vaccine will have to contain a safe and effective adjuvant that can be used in individuals of all ages. We examine protection from viral challenge in mice vaccinated with the nucleoprotein from the PR8 strain of influenza A, a protein that is highly conserved across viral subtypes. Vaccination with nucleoprotein delivered with a universally used and safe adjuvant, composed of insoluble aluminium salts, provides protection against viruses that either express the same or an altered version of nucleoprotein. This protection correlated with the presence of nucleoprotein specific CD8 T cells in the lungs of infected animals at early time points after infection. In contrast, immunization with NP delivered with alum and the detoxified LPS adjuvant, monophosphoryl lipid A, provided some protection to the homologous viral strain but no protection against infection by influenza expressing a variant nucleoprotein. Together, these data point towards a vaccine solution for all influenza A subtypes