scholarly journals Multicenter External Validation of the Liverpool Uveal Melanoma Prognosticator Online: An OOG Collaborative Study

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 477 ◽  
Author(s):  
Alda Cunha Rola ◽  
Azzam Taktak ◽  
Antonio Eleuteri ◽  
Helen Kalirai ◽  
Heinrich Heimann ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
External Validation ◽  
Collaborative Study ◽  
Survival Rates ◽  
Choroidal Melanoma ◽  
External Data ◽  
Calibration Methods ◽  
Anonymized Data ◽  
Using Data ◽  
Disseminated Disease

Uveal melanoma (UM) is fatal in ~50% of patients as a result of disseminated disease. This study aims to externally validate the Liverpool Uveal Melanoma Prognosticator Online V3 (LUMPO3) to determine its reliability in predicting survival after treatment for choroidal melanoma when utilizing external data from other ocular oncology centers. Anonymized data of 1836 UM patients from seven international ocular oncology centers were analyzed with LUMPO3 to predict the 10-year survival for each patient in each external dataset. The analysts were masked to the patient outcomes. Model predictions were sent to an independent statistician to evaluate LUMPO3’s performance using discrimination and calibration methods. LUMPO3’s ability to discriminate between UM patients who died of metastatic UM and those who were still alive was fair-to-good, with C-statistics ranging from 0.64 to 0.85 at year 1. The pooled estimate for all external centers was 0.72 (95% confidence interval: 0.68 to 0.75). Agreement between observed and predicted survival probabilities was generally good given differences in case mix and survival rates between different centers. Despite the differences between the international cohorts of patients with primary UM, LUMPO3 is a valuable tool for predicting all-cause mortality in this disease when using data from external centers.

scholarly journals Validation of the BATT score for prehospital risk stratification of traumatic haemorrhagic death: usefulness for tranexamic acid treatment criteria

2021 ◽  
Vol 29 (1) ◽  
Author(s):  
Francois-Xavier Ageron ◽  
Timothy J. Coats ◽  
Vincent Darioli ◽  
Ian Roberts
Keyword(s):  
Tranexamic Acid ◽  
Acid Treatment ◽  
Injury Severity ◽  
External Validation ◽  
Research Network ◽  
Brier Score ◽  
Trauma Patients ◽  
Using Data ◽  
The Uk ◽  
The Impact

Abstract Background Tranexamic acid reduces surgical blood loss and reduces deaths from bleeding in trauma patients. Tranexamic acid must be given urgently, preferably by paramedics at the scene of the injury or in the ambulance. We developed a simple score (Bleeding Audit Triage Trauma score) to predict death from bleeding. Methods We conducted an external validation of the BATT score using data from the UK Trauma Audit Research Network (TARN) from 1st January 2017 to 31st December 2018. We evaluated the impact of tranexamic acid treatment thresholds in trauma patients. Results We included 104,862 trauma patients with an injury severity score of 9 or above. Tranexamic acid was administered to 9915 (9%) patients. Of these 5185 (52%) received prehospital tranexamic acid. The BATT score had good accuracy (Brier score = 6%) and good discrimination (C-statistic 0.90; 95% CI 0.89–0.91). Calibration in the large showed no substantial difference between predicted and observed death due to bleeding (1.15% versus 1.16%, P = 0.81). Pre-hospital tranexamic acid treatment of trauma patients with a BATT score of 2 or more would avoid 210 bleeding deaths by treating 61,598 patients instead of avoiding 55 deaths by treating 9915 as currently. Conclusion The BATT score identifies trauma patient at risk of significant haemorrhage. A score of 2 or more would be an appropriate threshold for pre-hospital tranexamic acid treatment.

scholarly journals Ischemia Is Related to Tumour Genetics in Uveal Melanoma

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1004 ◽  
Author(s):  
Niels J. Brouwer ◽  
Annemijn P. A. Wierenga ◽  
Gülçin Gezgin ◽  
Marina Marinkovic ◽  
Gregorius P. M. Luyten ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Messenger Rna ◽  
Tumour Size ◽  
Hypoxia Inducible Factor ◽  
The Cancer Genome Atlas ◽  
Basal Diameter ◽  
Von Hippel Lindau ◽  
The Status ◽  
Using Data ◽  
Tumour Genetics

Hypoxia-inducible factor 1-alpha (HIF1a) and its regulator von Hippel–Lindau protein (VHL) play an important role in tumour ischemia. Currently, drugs that target HIF1a are being developed to treat malignancies. Although HIF1a is known to be expressed in uveal melanoma (UM), it is as yet unknown which factors, such as tumour size or genetics, determine its expression. Therefore, we aimed to determine which tumour characteristics relate to HIF1a expression in UM. Data from 64 patients who were enucleated for UM were analysed. Messenger RNA (mRNA) expression was determined with the Illumina HT-12 v4 chip. In 54 cases, the status of chromosomes 3 and 8q, and BRCA1-associated protein 1 (BAP1) protein expression (immunohistochemistry) were determined. Findings were corroborated using data of 80 patients from the Cancer Genome Atlas (TCGA) study. A significantly increased expression of HIF1a, and a decreased expression of VHL were associated with monosomy 3/loss of BAP1 expression. The relationship between BAP1 loss and HIF1a expression was independent of chromosome 3. The largest basal diameter and tumour thickness showed no relationship with HIF1a. HIF1a expression related to an increased presence of infiltrating T cells and macrophages. From this study, we conclude that HIF1a is strongly related to tumour genetics in UM, especially to loss of BAP1 expression, and less to tumour size. Tumour ischemia is furthermore related to the presence of an inflammatory phenotype.

scholarly journals Fitness of breeders in social Damaraland mole-rats is independent of group size

2021 ◽  
Author(s):  
Jack Thorley ◽  
Hanna Bensch ◽  
Kyle Finn ◽  
Tim Clutton-Brock ◽  
Markus Zöttl
Keyword(s):  
Reproductive Success ◽  
Group Size ◽  
Survival Rates ◽  
Group Living ◽  
Adult Survival ◽  
High Survival ◽  
Successful Reproduction ◽  
Related Group ◽  
Group Members ◽  
Using Data

Damaraland mole-rats (Fukomys damarensis) are usually viewed as an obligatorily group living eusocial species in which successful reproduction is dependent on reproductive altruism of closely related group members. However, the reproductive ecology of social mole-rats in their natural environment remains poorly understood and it is unclear to what extent successful reproduction is dependent on assistance from other group members. Using data from a 7-year field study of marked individuals, we show that, after dispersal from their natal group, individuals typically settled alone in new burrow systems where they enjoyed high survival rates, and often remained in good body condition for several years before finding a mate. Unlike most other eusocial or singular cooperative breeders, we found that Damaraland mole-rats reproduced successfully in pairs without helpers and experimentally formed pairs had the same reproductive success as larger established groups. Overall there was only a weak increase in reproductive success with increasing group size and no effect of group size on adult survival rates across the population. Juveniles in large groups grew faster early in life but their growth rates declined subsequently so that they eventually plateaued at a lower maximum body mass than juveniles from small groups. Taken together, our data suggest that the fitness benefits of group living to breeders are small and we suggest that extended philopatry in Damaraland mole-rats has evolved because of the high costs and constraints of dispersal rather than because of strong indirect benefits accrued through cooperative behaviour.

scholarly journals Quantifying previous SARS-CoV-2 infection through mixture modelling of antibody levels

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
C. Bottomley ◽  
M. Otiende ◽  
S. Uyoga ◽  
K. Gallagher ◽  
E. W. Kagucia ◽  
...  
Keyword(s):  
Threshold Analysis ◽  
Vaccination Strategies ◽  
Mixture Modelling ◽  
External Data ◽  
Alternative Approach ◽  
Future Burden ◽  
Previous Infection ◽  
Using Data ◽  
Antibody Levels ◽  
Crude Estimate

AbstractAs countries decide on vaccination strategies and how to ease movement restrictions, estimating the proportion of the population previously infected with SARS-CoV-2 is important for predicting the future burden of COVID-19. This proportion is usually estimated from serosurvey data in two steps: first the proportion above a threshold antibody level is calculated, then the crude estimate is adjusted using external estimates of sensitivity and specificity. A drawback of this approach is that the PCR-confirmed cases used to estimate the sensitivity of the threshold may not be representative of cases in the wider population—e.g., they may be more recently infected and more severely symptomatic. Mixture modelling offers an alternative approach that does not require external data from PCR-confirmed cases. Here we illustrate the bias in the standard threshold-based approach by comparing both approaches using data from several Kenyan serosurveys. We show that the mixture model analysis produces estimates of previous infection that are often substantially higher than the standard threshold analysis.

scholarly journals Validation of parsimonious prognostic models for patients infected with COVID-19

2021 ◽  
Vol 28 (1) ◽  
pp. e100267
Author(s):  
Keerthi Harish ◽  
Ben Zhang ◽  
Peter Stella ◽  
Kevin Hauck ◽  
Marwa M Moussa ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Validation Cohort ◽  
External Validation ◽  
Clinical Decision ◽  
Prognostic Models ◽  
Clinical Prediction ◽  
Inclusion Criteria ◽  
Local Data ◽  
External Data ◽  
Operator Curve

ObjectivesPredictive studies play important roles in the development of models informing care for patients with COVID-19. Our concern is that studies producing ill-performing models may lead to inappropriate clinical decision-making. Thus, our objective is to summarise and characterise performance of prognostic models for COVID-19 on external data.MethodsWe performed a validation of parsimonious prognostic models for patients with COVID-19 from a literature search for published and preprint articles. Ten models meeting inclusion criteria were either (a) externally validated with our data against the model variables and weights or (b) rebuilt using original features if no weights were provided. Nine studies had internally or externally validated models on cohorts of between 18 and 320 inpatients with COVID-19. One model used cross-validation. Our external validation cohort consisted of 4444 patients with COVID-19 hospitalised between 1 March and 27 May 2020.ResultsMost models failed validation when applied to our institution’s data. Included studies reported an average validation area under the receiver–operator curve (AUROC) of 0.828. Models applied with reported features averaged an AUROC of 0.66 when validated on our data. Models rebuilt with the same features averaged an AUROC of 0.755 when validated on our data. In both cases, models did not validate against their studies’ reported AUROC values.DiscussionPublished and preprint prognostic models for patients infected with COVID-19 performed substantially worse when applied to external data. Further inquiry is required to elucidate mechanisms underlying performance deviations.ConclusionsClinicians should employ caution when applying models for clinical prediction without careful validation on local data.

Uncertainties of spectral in situ measurements in wastewater using different calibration approaches

2006 ◽  
Vol 53 (12) ◽  
pp. 187-197 ◽  
Author(s):  
L. Rieger ◽  
G. Langergraber ◽  
H. Siegrist
Keyword(s):  
Suspended Solids ◽  
Wastewater Treatment Plants ◽  
Total Suspended Solids ◽  
Data Sets ◽  
Global Calibration ◽  
Nitrite Nitrogen ◽  
Calibration Methods ◽  
Using Data ◽  
Nitrate And Nitrite

Three calibration methods were applied to UV/VIS spectra recorded in the influent of six wastewater treatment plants (WWTPs) to measure total COD (CODtot), filtered COD (CODfil), nitrate and nitrite nitrogen (NOx-N) and total suspended solids (TSS). It could be shown that a calibration of the sensor using data sets from four Swiss WWTPs leads to an improvement of the precision in comparison to the global calibration provided by the manufacturer. A calibration to the specific wastewater matrix always improves the results and gives the highest accuracy. For CODtot a mean coefficient of variation CVx of 12.5% could be reached, whereas for NOx-N only weak results were achieved (average CVx=36%).

scholarly journals Molecular Insights and Emerging Strategies for Treatment of Metastatic Uveal Melanoma

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2761
Author(s):  
Fabiana Mallone ◽  
Marta Sacchetti ◽  
Alessandro Lambiase ◽  
Antonietta Moramarco
Keyword(s):  
Clinical Trials ◽  
Uveal Melanoma ◽  
Treatment Options ◽  
Survival Rates ◽  
Metastatic Tumor ◽  
Clinical Use ◽  
Future Perspectives ◽  
Diagnosis And Prognosis ◽  
Novel Treatment ◽  
Combinational Therapies

Uveal melanoma (UM) is the most common intraocular cancer. In recent decades, major advances have been achieved in the diagnosis and prognosis of UM allowing for tailored treatments. However, nearly 50% of patients still develop metastatic disease with survival rates of less than 1 year. There is currently no standard of adjuvant and metastatic treatment in UM, and available therapies are ineffective resulting from cutaneous melanoma protocols. Advances and novel treatment options including liver-directed therapies, immunotherapy, and targeted-therapy have been investigated in UM-dedicated clinical trials on single compounds or combinational therapies, with promising results. Therapies aimed at prolonging or targeting metastatic tumor dormancy provided encouraging results in other cancers, and need to be explored in UM. In this review, the latest progress in the diagnosis, prognosis, and treatment of UM in adjuvant and metastatic settings are discussed. In addition, novel insights into tumor genetics, biology and immunology, and the mechanisms underlying metastatic dormancy are discussed. As evident from the numerous studies discussed in this review, the increasing knowledge of this disease and the promising results from testing of novel individualized therapies could offer future perspectives for translating in clinical use.

Pediatric Mucormycosis: A 10-Year Systematic Review of Reported Cases and Review of the Literature

2019 ◽  
Vol 8 (4) ◽  
pp. 342-350 ◽  
Author(s):  
William R Otto ◽  
Barbara A Pahud ◽  
Dwight E Yin
Keyword(s):  
Systematic Review ◽  
English Language ◽  
Hematologic Malignancy ◽  
Survival Rates ◽  
Clinical Manifestations ◽  
Severe Infection ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Sinus Disease ◽  
Disseminated Disease

AbstractMucormycosis is a severe infection that affects a variety of patients, including immunocompromised children and neonates. Given improved survival rates from advances in the treatment of malignancies, the population at risk for mucormycosis is increasing. We conducted a systematic review of cases of mucormycosis in children in the English-language literature reported between August 2008 and June 2017 and analyzed the clinical characteristics, diagnosis, management, and outcome of those infections. The most common underlying diagnoses included neutropenia (41%), hematologic malignancy (39%), prematurity (13%), and hematopoietic stem cell transplant (11%). Sinus disease (28%) and disseminated disease (24%) were the most common presentations. Rhizopus spp were the most common organisms isolated (22%). Amphotericin B remains the backbone of treatment and was prescribed in 86% of these cases. The resulting mortality rate remains high (32%). We provide here the results of a literature review of mucormycosis in children, including its epidemiology and clinical manifestations, and describe current advances in its diagnosis and treatment.

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