Using two large datasets from Dorset, we previously reported an internally validated multivariable risk model for predicting the risk of GI malignancy in IDA-the IDIOM score. The aim of this ...retrospective observational study was to validate the IDIOM model using two independent external datasets.
The external validation datasets were collected, in a secondary care setting, by different investigators from cohorts in Oxford and Sheffield derived under different circumstances, comprising 1117 and 474 patients with confirmed IDA respectively. The data were anonymised prior to analysis. The predictive performance of the original model was evaluated by estimating measures of calibration, discrimination and clinical utility using the validation datasets.
The discrimination of the original model using the external validation data was 70% (95% CI 65, 75) for the Oxford dataset and 70% (95% CI 61, 79) for the Sheffield dataset. The analysis of mean, weak, flexible and across the risk groups' calibration showed no tendency for under or over-estimated risks in the combined validation data. Decision curve analysis demonstrated the clinical value of the IDIOM model with a net benefit that is higher than 'investigate all' and 'investigate no-one' strategies up to a threshold of 18% in the combined validation data, using a risk cut-off of around 1.2% to categorise patients into the very low risk group showed that none of the patients stratified in this risk group proved to have GI cancer on investigation in the validation datasets.
This external validation exercise has shown promising results for the IDIOM model in predicting the risk of underlying GI malignancy in independent IDA datasets collected in different clinical settings.
Patients with cancer are purported to have poor COVID-19 outcomes. However, cancer is a heterogeneous group of diseases, encompassing a spectrum of tumour subtypes. The aim of this study was to ...investigate COVID-19 risk according to tumour subtype and patient demographics in patients with cancer in the UK.
We compared adult patients with cancer enrolled in the UK Coronavirus Cancer Monitoring Project (UKCCMP) cohort between March 18 and May 8, 2020, with a parallel non-COVID-19 UK cancer control population from the UK Office for National Statistics (2017 data). The primary outcome of the study was the effect of primary tumour subtype, age, and sex and on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevalence and the case–fatality rate during hospital admission. We analysed the effect of tumour subtype and patient demographics (age and sex) on prevalence and mortality from COVID-19 using univariable and multivariable models.
319 (30·6%) of 1044 patients in the UKCCMP cohort died, 295 (92·5%) of whom had a cause of death recorded as due to COVID-19. The all-cause case–fatality rate in patients with cancer after SARS-CoV-2 infection was significantly associated with increasing age, rising from 0·10 in patients aged 40–49 years to 0·48 in those aged 80 years and older. Patients with haematological malignancies (leukaemia, lymphoma, and myeloma) had a more severe COVID-19 trajectory compared with patients with solid organ tumours (odds ratio OR 1·57, 95% CI 1·15–2·15; p<0·0043). Compared with the rest of the UKCCMP cohort, patients with leukaemia showed a significantly increased case–fatality rate (2·25, 1·13–4·57; p=0·023). After correction for age and sex, patients with haematological malignancies who had recent chemotherapy had an increased risk of death during COVID-19-associated hospital admission (OR 2·09, 95% CI 1·09–4·08; p=0·028).
Patients with cancer with different tumour types have differing susceptibility to SARS-CoV-2 infection and COVID-19 phenotypes. We generated individualised risk tables for patients with cancer, considering age, sex, and tumour subtype. Our results could be useful to assist physicians in informed risk–benefit discussions to explain COVID-19 risk and enable an evidenced-based approach to national social isolation policies.
University of Birmingham and University of Oxford.
Patients with cancer have been shown to have increased risk of COVID-19 severity. We previously built and validated the COVID-19 Risk in Oncology Evaluation Tool (CORONET) to predict the likely ...severity of COVID-19 in patients with active cancer who present to hospital. We assessed the differences in presentation and outcomes of patients with cancer and COVID-19, depending on the wave of the pandemic. We examined differences in features at presentation and outcomes in patients worldwide, depending on the waves of the pandemic: wave 1 D614G (n = 1430), wave 2 Alpha (n = 475), and wave 4 Omicron variant (n = 63, UK and Spain only). The performance of CORONET was evaluated on 258, 48, and 54 patients for each wave, respectively. We found that mortality rates were reduced in subsequent waves. The majority of patients were vaccinated in wave 4, and 94% were treated with steroids if they required oxygen. The stages of cancer and the median ages of patients significantly differed, but features associated with worse COVID-19 outcomes remained predictive and did not differ between waves. The CORONET tool performed well in all waves, with scores in an area under the curve (AUC) of >0.72. We concluded that patients with cancer who present to hospital with COVID-19 have similar features of severity, which remain discriminatory despite differences in variants and vaccination status. Survival improved following the first wave of the pandemic, which may be associated with vaccination and the increased steroid use in those patients requiring oxygen. The CORONET model demonstrated good performance, independent of the SARS-CoV-2 variants.
Both clinical and experimental studies have reported that mild traumatic brain injury (mTBI) can result in cognitive impairments in the absence of overt brain damage. Whether these impairments result ...from neuronal dysfunction/altered plasticity is an area that has received limited attention. In this study, we recorded activity of neurons in the cornu Ammonis (CA)1 subfield of the hippocampus in sham and mild lateral fluid percussion injured (mFPI) rats while these animals were performing an object location task. Electrophysiology results showed that the number of excitatory neurons encoding spatial information (i.e., place cells) was reduced in mFPI rats, and that these cells had broader and less stable place fields. Additionally, the in-field firing rate of place cells in sham operated, but not in mFPI, animals increased when objects within the testing arena were moved. Immunostaining indicated no visible damage or overall neuronal loss in mFPI brain sections. However, a reduction in the number of parvalbumin-positive inhibitory neurons in the CA1 subfield of mFPI animals was observed, suggesting that this reduction could have influenced place cell physiology. Alterations in spatial information content, place cell stability, and activity in mFPI rats coincided with poor performance in the object location task. These results indicate that altered place cell physiology may underlie the hippocampus-dependent cognitive impairments that result from mTBI.
Growing recognition of persistent cognitive defects associated with electroconvulsive therapy (ECT), a highly effective and commonly used antidepressant treatment, has spurred interest in identifying ...its mechanism of action to guide development of safer treatment options. However, as repeated seizure activity elicits a bewildering array of electrophysiological and biochemical effects, this goal has remained elusive. We have examined whether deletion of Narp, an immediate early gene induced by electroconvulsive seizures (ECS), blocks its antidepressant efficacy. Based on multiple measures, we infer that Narp knockout mice undergo normal seizure activity in this paradigm, yet fail to display antidepressant-like behavioral effects of ECS. Although Narp deletion does not suppress ECS-induced proliferation in the dentate gyrus, it blocks dendritic outgrowth of immature granule cell neurons in the dentate molecular layer induced by ECS. Taken together, these findings indicate that Narp contributes to the antidepressant action of ECT and implicate the ability of ECS to induce dendritic arborization of differentiating granule cells as a relevant step in eliciting this response.
TWO'S COMPANY / Maynard FERGUSON et Chris CONNOR Wilder, Alec (1907-1980). Auteur ou responsable intellectuel; Sundgaard, Arnold (1909-2006). Auteur ou responsable intellectuel; Sondheim, Stephen (1930-....). Auteur ou responsable intellectuel ...
1962
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Provider: - Institution: - Data provided by Europeana Collections- Titre uniforme : West Side story. Extrait- Titre uniforme : West Side story. Extrait- Comprend : I FEEL A SONG COMING ON / OPPENHEIM ...- McHUGH et D. FIELDS - THE WIND / Russt FREEMAN - NEW-YORK'S MY HOME / Gordon JENKINS - GUESS WHO I SAW TO-DAY / GRAND et BOYD - WHEN THE SUN COMES OUT / ARLEN et KOEHLER - SEND FOR ME / Ollie JONES - WHERE DO YOU GO ? / WILDER et SUNDGAARD - SOMETHING'S COMING : extrait de "WEST SIDE STORY", comédie musicale / L. BERNSTEIN et SONDHEIM - DEEP SONG / CORY et CROSS - CAN'T GET OUT OF THIS MOOD / LOESSER et McHUGH- BnF-Partenariats, Collection sonore - Believe- BnF-Partenariats, Collection sonore - Believe- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
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