The use of patient reported outcome measures might seem to be quite straightforward; however, a number of pitfalls await clinicians with limited expertise. Jill Dawson and colleagues provide a guide ...for individuals keen to use patient reported outcome measures at a local level
The thymic medulla provides a specialized microenvironment for the negative selection of T cells, with the presence of autoimmune regulator (Aire)-expressing medullary thymic epithelial cells (mTECs) ...during the embryonic-neonatal period being both necessary and sufficient to establish long-lasting tolerance. Here we showed that emergence of the first cohorts of Aire+ mTECs at this key developmental stage, prior to αβ T cell repertoire selection, was jointly directed by Rankl+ lymphoid tissue inducer cells and invariant Vγ5+ dendritic epidermal T cell (DETC) progenitors that are the first thymocytes to express the products of gene rearrangement. In turn, generation of Aire+ mTECs then fostered Skint-1-dependent, but Aire-independent, DETC progenitor maturation and the emergence of an invariant DETC repertoire. Hence, our data attributed a functional importance to the temporal development of Vγ5+ γδ T cells during thymus medulla formation for αβ T cell tolerance induction and demonstrated a Rank-mediated reciprocal link between DETC and Aire+ mTEC maturation.
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► Invariant Vγ5+ thymocytes regulate formation of Aire+ medullary thymic epithelium ► Generation of an invariant Vγ5+ T cell population requires thymus medulla development ► Skint-1-mediated Vγ5+ thymocyte development is Aire independent ► Dependency on Tnfrsf11a links γδ T cell and medullary epithelium development
Highlights • Ag doping of TiO2 results in a band gap shift towards the visible spectrum. • Small quantities of Ag–TiO2 have a bactericidal effect on S. mutans under visible light conditions. • ...Although reduced, the bactericidal effect was still observed when Ag–TiO2 was embedded in polymer.
Many attempts to predict the biotic responses to climate change rely on the 'climate envelope' approach, in which the current distribution of a species is mapped in climate-space and then, if the ...position of that climate-space changes, the distribution of the species is predicted to shift accordingly. The flaw in this approach is that distributions of species also reflect the influence of interactions with other species, so predictions based on climate envelopes may be very misleading if the interactions between species are altered by climate change. An additional problem is that current distributions may be the result of sources and sinks, in which species appear to thrive in places where they really persist only because individuals disperse into them from elsewhere,. Here we use microcosm experiments on simple but realistic assemblages to show how misleading the climate envelope approach can be. We show that dispersal and interactions, which are important elements of population dynamics, must be included in predictions of biotic responses to climate change.
Marine fjords along the northern Labrador coast of Arctic Canada are influenced by freshwater, nutrients, and sediment inputs from ice fields and rivers. These ecosystems, further shaped by both ...Atlantic and Arctic water masses, are important habitats for fishes, marine mammals, seabirds, and marine invertebrates and are vital to the Labrador Inuit who have long depended on these areas for sustenance. Despite their ecological and socio-cultural importance, these marine ecosystems remain largely understudied. Here we conducted the first quantitative underwater scuba surveys, down to 12 m, of the nearshore marine ecology of Nachvak Fjord, which is surrounded by Torngat Mountains National Park located in Nunatsiavut, the Indigenous lands claim region of northeastern Canada. Our goal was to provide the Nunatsiavut Government with a baseline of the composition and environmental influences on the subtidal community in this isolated region as they work towards the creation of an Indigenous-led National Marine Conservation Area that includes Nachvak Fjord. We identified four major benthic habitat types: (1) boulders (2) rocks with sediment, (3) sediment with rocks, and (4) unconsolidated sediments, including sand, gravel, and cobble. Biogenic cover (e.g., kelp, coralline algae, and sediment) explained much of the variability in megabenthic invertebrate community structure. The kelp species Alaria esculenta, Saccharina latissima, and Laminaria solidungula dominated the boulder habitat outside of the fjord covering 35%, 13%, and 11% of the sea floor, respectively. In contrast, the middle and inner portions of the fjord were devoid of kelp and dominated by encrusting coralline algae. More diverse megabenthic invertebrate assemblages were detected within the fjord compared to the periphery. Fish assemblages were depauperate overall with the shorthorn sculpin, Myoxocephalus scorpius, and the Greenland cod, Gadus ogac, dominating total fish biomass contributing 64% and 30%, respectively. Understanding the composition and environmental influences within this fjord ecosystem not only contributes towards the protection of this ecological and culturally important region but serves as a baseline in a rapidly changing climatic region.
The primary aim of this study was to develop a patient-reported Activity & Participation Questionnaire (the OKS-APQ) to supplement the Oxford knee score, in order to assess higher levels of activity ...and participation. The generation of items for the questionnaire involved interviews with 26 patients. Psychometric analysis (exploratory and confirmatory factor analysis and Rasch analysis) guided the reduction of items and the generation of a scale within a prospective study of 122 relatively young patients (mean age 61.5 years (42 to 71)) prior to knee replacement. A total of 99, completed pre-operative and six month post-operative assessments (new items, OKS, Short-Form 36 and American Knee Society Score). The eight-item OKS-APQ scale is unidimensional, reliable (Cronbach's alpha 0.85; intraclass correlation coefficient (ICC) 0.79; or 0.92 when one outlier was excluded), valid (r > 0.5 with related scales) and responsive (effect size 4.16). We recommend that it is used with the OKS with adults of all ages when further detail regarding the levels of activity and participation of a patient is required.
Mutations in the isocitrate dehydrogenase 1 (
) gene are found in a high proportion of diffuse gliomas. The presence of the
mutation is a valuable diagnostic, prognostic and predictive biomarker for ...the management of patients with glial tumours. Techniques involving vibrational spectroscopy, e.g., Fourier transform infrared (FTIR) spectroscopy, have previously demonstrated analytical capabilities for cancer detection, and have the potential to contribute to diagnostics. The implementation of FTIR microspectroscopy during surgical biopsy could present a fast, label-free method for molecular genetic classification. For example, the rapid determination of
status in a patient with a glioma diagnosis could inform intra-operative decision-making between alternative surgical strategies. In this study, we utilized synchrotron-based FTIR microanalysis to probe tissue microarray sections from 79 glioma patients, and distinguished the positive class (
-mutated) from the
-wildtype glioma, with a sensitivity and specificity of 82.4% and 83.4%, respectively. We also examined the ability of attenuated total reflection (ATR)-FTIR spectroscopy in detecting the biomolecular events and global epigenetic and metabolic changes associated with mutations in the
enzyme, in blood serum samples collected from an additional 72 brain tumour patients. Centrifugal filtration enhanced the diagnostic ability of the classification models, with balanced accuracies up to ~69%. Identification of the molecular status from blood serum prior to biopsy could further direct some patients to alternative treatment strategies.
Background: the recognition of stroke symptoms by the public and activation of the emergency medical services (EMS) are the most important factors in instigating pre-hospital stroke care. Studies ...have suggested that poor recognition of the warning signs of stroke is the main cause of delay in accessing the EMS. Methods: an integrative review of published studies about stroke knowledge and awareness was performed by searching online bibliographic databases, using keywords, from 1966 to 2008. Studies were included in the review if they focussed on risk factors, signs and symptoms, action and information. Each study was reviewed by two researchers (SJ and MJ). Results: we identified 169 studies of which 39 were included in the review. The ability to name one risk factor for stroke varied between studies, ranging from 18% to 94% when asked open-ended questions and from 42% to 97% when asked closed questions. The ability to name one symptom ranged from 25% to 72% when asked open-ended questions and from 95% to 100% when asked closed questions. When asked what action people would take if they thought they were having a stroke, between 53% and 98% replied that they would call the EMS. People generally obtained information about stroke from family and friends. Older members of the population, ethnic minority groups and those with lower levels of education had consistently poor levels of stroke knowledge. Conclusions: generally, levels of knowledge about recognising and preventing stroke were poor. Nevertheless, most participants stated they would contact the EMS at the onset of stroke symptoms.
Vedolizumab is an anti-a4b7 monoclonal antibody that is licensed for the treatment of moderate to severe Crohn's disease and ulcerative colitis. The aims of this study were to establish the ...real-world effectiveness and safety of vedolizumab for the treatment of inflammatory bowel disease.
This was a retrospective study involving seven NHS health boards in Scotland between June 2015 and November 2017. Inclusion criteria included: a diagnosis of ulcerative colitis or Crohn's disease with objective evidence of active inflammation at baseline (Harvey-Bradshaw IndexHBI ≥5/Partial Mayo ≥2 plus C-reactive protein CRP >5 mg/L or faecal calprotectin ≥250 µg/g or inflammation on endoscopy/magnetic resonance imaging MRI); completion of induction; and at least one clinical follow-up by 12 months. Kaplan-Meier survival analysis was used to establish 12-month cumulative rates of clinical remission, mucosal healing, and deep remission clinical remission plus mucosal healing. Rates of serious adverse events were described quantitatively.
Our cohort consisted of 180 patients with ulcerative colitis and 260 with Crohn's disease. Combined median follow-up was 52 weeks (interquartile range IQR 26-52 weeks). In ulcerative colitis, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 57.4%, 47.3%, and 38.5%, respectively. In Crohn's disease, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 58.4%, 38.9%, and 28.3% respectively. The serious adverse event rate was 15.6 per 100 patient-years of follow-up.
Vedolizumab is a safe and effective treatment for achieving both clinical remission and mucosal healing in ulcerative colitis and Crohn's disease.
Deformable image registration is an important tool in medical image analysis. In the case of lung computed tomography (CT) registration there are three major challenges: large motion of small ...features, sliding motions between organs, and changing image contrast due to compression. Recently, Markov random field (MRF)-based discrete optimization strategies have been proposed to overcome problems involved with continuous optimization for registration, in particular its susceptibility to local minima. However, to date the simplifications made to obtain tractable computational complexity reduced the registration accuracy. We address these challenges and preserve the potentially higher quality of discrete approaches with three novel contributions. First, we use an image-derived minimum spanning tree as a simplified graph structure, which copes well with the complex sliding motion and allows us to find the global optimum very efficiently. Second, a stochastic sampling approach for the similarity cost between images is introduced within a symmetric, diffeomorphic B-spline transformation model with diffusion regularization. The complexity is reduced by orders of magnitude and enables the minimization of much larger label spaces. In addition to the geometric transform labels, hyper-labels are introduced, which represent local intensity variations in this task, and allow for the direct estimation of lung ventilation. We validate the improvements in accuracy and performance on exhale-inhale CT volume pairs using a large number of expert landmarks.
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