Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Plugging the leaks Making the most of every pound that enters your local economy

Includes bibliographical references. Co-published by: Countryside AgencyAvailable from British Library Document Supply Centre- DSC:m03/16902 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Cognitive strategy use by children with Asperger's syndrome during intervention for motor-based goals

Cognitive Orientation for (daily) Occupational Performance (CO-OP) is a cognitive approach utilised by occupational therapists to help guide children in the discovery of appropriate strategies for effective task performance through a structured problem-solving process. There has been limited research into its utility for children with Asperger's syndrome (AS). These children often present with motor difficulties, although these are not required for diagnosis of the syndrome. A recent study found that children with AS were able to use the CO-OP framework to enhance their performance of motor-based goals.This paper presents two case studies demonstrating the use of CO-OP with children with AS, and explores the global and domain-specific strategies and types of guidance utilised to improve their task performance. Two children with AS, aged 9 and 11, with above average intellectual ability, engaged in 10 sessions of CO-OP. All sessions were videotaped. One hundred minutes of randomly selected footage were coded per child using the Observer Software Package version 5.0.The mean interrater agreement for the two children was 94.06% and 89.30%. Both children (i) utilised the global strategies 'do', followed by 'plan' and 'check', (ii) used at least three domain-specific strategies in each session with 'task specification/modification' and 'body position' utilised most, and (iii) used limited verbal self-guidance.These two children with AS were able to utilise cognitive strategies to effectively solve their motor performance problems. Children with AS and those with DCD used similar strategies to achieve motor goals. CO-OP appears to have potential as an effective intervention for children with AS. Study limitations, clinical implications and directions for future research are discussed

Cognitive Orientation to (daily) Occupational Performance (CO-OP) with children with Asperger's syndrome who have motor-based occupational performance goals

Motor difficulties associated with Asperger's syndrome (AS) are commonly reported, despite these not being diagnostically significant. Cognitive Orientation to daily Occupational Performance (CO-OP) is a verbal problem-solving intervention developed for use with children with developmental coordination disorder to address their motor-based difficulties. This paper reports on two case studies of children with AS illustrating the outcomes of CO-OP to address motor-based occupational performance goals.A case study approach was used to document how two children with AS engaged in 10 weekly sessions of CO-OP addressing child-chosen motor-based occupational performance goals and the outcomes of this intervention.Pre and post-intervention assessment using the Canadian Occupational Performance Measure, Vineland Adaptive Behaviour Scales and the Performance Quality Rating Scale indicated that both children were able to engage in CO-OP intervention to successfully improve their occupational performance.Further research into the application of CO-OP with children with AS is warranted based on preliminary positive findings regarding the efficacy of this intervention to address motor-based performance difficulties in two children with AS

Crime and Ornament : The Arts and Popular Culture in the Shadow of Adolf Loos

The editors of this collection have assembled 16 essays in response to Adolf Loos’ seminal essay on modern architecture “Crime and Ornament” (also included). As Ward and Miller note, some of the authors address Loos’ text directly, investigating the extent to which ornament problematizes form and function, while others use "ornament" as a vehicle for reflecting on issues related to contemporary art and culture. Notes on contributors. 193 bibl. ref

The Effect of Diurnal Sea Surface Temperature Warming on Climatological Air–Sea Fluxes

Diurnal sea surface warming affects the fluxes of latent heat, sensible heat, and upwelling longwave radiation. Diurnal warming most typically reaches maximum values of 3°C, although very localized events may reach 7°–8°C. An analysis of multiple years of diurnal warming over the global ice-free oceans indicates that heat fluxes determined by using the predawn sea surface temperature can differ by more than 100% in localized regions over those in which the sea surface temperature is allowed to fluctuate on a diurnal basis. A comparison of flux climatologies produced by these two analyses demonstrates that significant portions of the tropical oceans experience differences on a yearly average of up to 10 W m[superscript −2]. Regions with the highest climatological differences include the Arabian Sea and the Bay of Bengal, as well as the equatorial western and eastern Pacific Ocean, the Gulf of Mexico, and the western coasts of Central America and North Africa. Globally the difference is on average 4.45 W m[superscript −2]. The difference in the evaporation rate globally is on the order of 4% of the total ocean–atmosphere evaporation. Although the instantaneous, year-to-year, and seasonal fluctuations in various locations can be substantial, the global average differs by less than 0.1 W m[superscript −2] throughout the entire 10-yr time period. A global heat budget that uses atmospheric datasets containing diurnal variability but a sea surface temperature that has removed this signal may be underestimating the flux to the atmosphere by a fairly constant value.American Society for Engineering Education. National Defense Science and Engineering Graduate FellowshipUnited States. National Aeronautics and Space Administration. Graduate Student Researchers Progra