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"Sturdy, Lauren"
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Risk-prediction models in postmenopausal patients with symptoms of suspected ovarian cancer in the UK (ROCkeTS): a multicentre, prospective diagnostic accuracy study
2024
Multiple risk-prediction models are used in clinical practice to triage patients as being at low risk or high risk of ovarian cancer. In the ROCkeTS study, we aimed to identify the best diagnostic test for ovarian cancer in symptomatic patients, through head-to-head comparisons of risk-prediction models, in a real-world setting. Here, we report the results for the postmenopausal cohort.
In this multicentre, prospective diagnostic accuracy study, we recruited newly presenting female patients aged 16–90 years with non-specific symptoms and raised CA125 or abnormal ultrasound results (or both) who had been referred via rapid access, elective clinics, or emergency presentations from 23 hospitals in the UK. Patients with normal CA125 and simple ovarian cysts of smaller than 5 cm in diameter, active non-ovarian malignancy, or previous ovarian malignancy, or those who were pregnant or declined a transvaginal scan, were ineligible. In this analysis, only postmenopausal participants were included. Participants completed a symptom questionnaire, gave a blood sample, and had transabdominal and transvaginal ultrasounds performed by International Ovarian Tumour Analysis consortium (IOTA)-certified sonographers. Index tests were Risk of Malignancy 1 (RMI1) at a threshold of 200, Risk of Malignancy Algorithm (ROMA) at multiple thresholds, IOTA Assessment of Different Neoplasias in the Adnexa (ADNEX) at thresholds of 3% and 10%, IOTA SRRisk model at thresholds of 3% and 10%, IOTA Simple Rules (malignant vs benign, or inconclusive), and CA125 at 35 IU/mL. In a post-hoc analysis, the Ovarian Adnexal and Reporting Data System (ORADS) at 10% was derived from IOTA ultrasound variables using established methods since ORADS was described after completion of recruitment. Index tests were conducted by study staff masked to the results of the reference standard. The comparator was RMI1 at the 250 threshold (the current UK National Health Service standard of care). The reference standard was surgical or biopsy tissue histology or cytology within 3 months, or a self-reported diagnosis of ovarian cancer at 12 month follow-up. The primary outcome was diagnostic accuracy at predicting primary invasive ovarian cancer versus benign or normal histology, assessed by analysing the sensitivity, specificity, C-index, area under receiver operating characteristic curve, positive and negative predictive values, and calibration plots in participants with conclusive reference standard results and available index test data. This study is registered with the International Standard Randomised Controlled Trial Number registry (ISRCTN17160843).
Between July 13, 2015, and Nov 30, 2018, 1242 postmenopausal patients were recruited, of whom 215 (17%) had primary ovarian cancer. 166 participants had missing, inconclusive, or other reference standard results; therefore, data from a maximum of 1076 participants were used to assess the index tests for the primary outcome. Compared with RMI1 at 250 (sensitivity 82·9% [95% CI 76·7 to 88·0], specificity 87·4% [84·9 to 89·6]), IOTA ADNEX at 10% was more sensitive (difference of –13·9% [–20·2 to –7·6], p<0·0001) but less specific (difference of 28·5% [24·7 to 32·3], p<0·0001). ROMA at 29·9 had similar sensitivity (difference of –3·6% [–9·1 to 1·9], p=0·24) but lower specificity (difference of 5·2% [2·5 to 8·0], p=0·0001). RMI1 at 200 had similar sensitivity (difference of –2·1% [–4·7 to 0·5], p=0·13) but lower specificity (difference of 3·0% [1·7 to 4·3], p<0·0001). IOTA SRRisk model at 10% had similar sensitivity (difference of –4·3% [–11·0 to –2·3], p=0·23) but lower specificity (difference of 16·2% [12·6 to 19·8], p<0·0001). IOTA Simple Rules had similar sensitivity (difference of –1·6% [–9·3 to 6·2], p=0·82) and specificity (difference of –2·2% [–5·1 to 0·6], p=0·14). CA125 at 35 IU/mL had similar sensitivity (difference of –2·1% [–6·6 to 2·3], p=0·42) but higher specificity (difference of 6·7% [4·3 to 9·1], p<0·0001). In a post-hoc analysis, when compared with RMI1 at 250, ORADS achieved similar sensitivity (difference of –2·1%, 95% CI –8·6 to 4·3, p=0·60) and lower specificity (difference of 10·2%, 95% CI 6·8 to 13·6, p<0·0001).
In view of its higher sensitivity than RMI1 at 250, despite some loss in specificity, we recommend that IOTA ADNEX at 10% should be considered as the new standard-of-care diagnostic in ovarian cancer for postmenopausal patients.
UK National Institute for Health and Care Research.
Journal Article
579 Refining ovarian cancer test accuracy scores: a multicentre, prospective cohort study investigating diagnostic accuracy in women with symptoms of suspected ovarian cancer (the ROCkeTS study): results for post-menopausal women
2024
Introduction/BackgroundROCkeTS investigated accuracy of risk prediction models for diagnosing ovarian cancer (OC); no previous studies investigate all tests as head-to-head comparisons.MethodologyRecruitment: ROCkeTS recruited newly presenting women with non-specific symptoms and raised CA125 and/or abnormal imaging to donate blood and undergo ultrasound scan performed mainly by sonographers. Sonographers achieved certification in IOTA models pre-participation and underwent quality assurance.Index tests: IOTA ADNeX model 3% and 10% thresholds, RMI1 at 200, ROMA at >14.4%, >25.3%, >27.7%, > 29.9% (manufacturer recommended threshold) and CA125 at 35 IU/ml.Comparator: RMI1 at 250 threshold.Reference standard: Tissue biopsy/cytology or follow-up at 12 monthPrimary outcome: accuracy defined as primary invasive OC versus benign or normalSecondary outcomes: accuracy defined as primary invasive OC, secondary malignant, borderline and neoplasms of uncertain behaviour versus benign or normalStudy sample size required 150 OCs to detect 13% sensitivity improvement from 70% to 84% with 90% power, assuming positive correlation of test errors.Sensitivity, specificity, c-index (area under Receiver operating characteristic (ROC) curve), PPV and Negative Predictive value (NPV) were reported with calibration plots.Results1242 postmenopausal women recruited from 23 hospitals. For primary outcome, comparing RMI 1 250, sensitivity 82.9% (95% CI: 76.7 to 88.0), specificity 87.4% (95% CI: 84.9 to 89.6), IOTA ADNeX 10% was more sensitive 96.1% (95% CI: 92.2 to 98.4) and less specific 58.5% (95% CI: 54.7 TO 62.1), p< 0.001, whilst sensitivity of ROMA at 29.9% was comparable 88.0% (95% CI: 82.5 to 92.2) with lower specificity 79.9% (95% CI: 76.9 to 82.7), p=0.0001. Analysis of secondary outcome was similar. (table 1).Abstract 579 Table 1Diagnostic performance statistics of index test combinations by secondary outcomes definition of cancerConclusionAcross all analyses, IOTA ADNeX had highest sensitivity but lower specificity. ROMA at 29.9 had marginal improvement of sensitivity over RMI 250 but reduction in specificity. IOTA ADNEX at 10% should be standard of care diagnostic in OC for postmenopausal women.DisclosuresDavenport C, Rai N, Sharma P, Deeks JJ, Berhane S, Mallett S, Saha P, Champaneria R, Bayliss SE, Snell KIE, Sundar S. Menopausal status, ultrasound and biomarker tests in combination for the diagnosis of ovarian cancer in symptomatic women. Cochrane Database of Systematic Reviews 2022, Issue 7. Art. No.: CD011964. DOI: 10.1002/14651858.CD011964.pub2. Accessed 30 November 2023.
Journal Article
Symptom-triggered testing detects early stage and low volume resectable advanced stage ovarian cancer
2026
ObjectiveSymptom-triggered testing for ovarian cancer was introduced to the UK whereby symptomatic women undergo an ultrasound scan and serum CA125, and are referred to hospital within 2 weeks if these are abnormal. The potential value of symptom-triggered testing in the detection of early-stage disease or low tumor burden remains unclear in women with high grade serous ovarian cancer. In this descriptive study, we report on the International Federation of Gynecology and Obstetrics (FIGO) stage, disease distribution, and complete cytoreduction rates in women presenting via the fast-track pathway and who were diagnosed with high grade serous ovarian cancer.MethodsWe analyzed the dataset from Refining Ovarian Cancer Test accuracy Scores (ROCkeTS), a single-arm prospective diagnostic test accuracy study recruiting from 24 hospitals in the UK. The aim of ROCkeTS is to validate risk prediction models in symptomatic women. We undertook an opportunistic analysis for women recruited between June 2015 to July 2022 and who were diagnosed with high grade serous ovarian cancer via the fast-track pathway. Women presenting with symptoms suspicious for ovarian cancer receive a CA125 blood test and an ultrasound scan if the CA125 level is abnormal. If either of these is abnormal, women are referred to secondary care within 2 weeks. Histology details were available on all women who underwent surgery or biopsy within 3 months of recruitment. Women who did not undergo surgery or biopsy at 3 months were followed up for 12 months as per the national guidelines in the UK. In this descriptive study, we report on patient demographics (age and menopausal status), WHO performance status, FIGO stage at diagnosis, disease distribution (low/pelvic confined, moderate/extending to mid-abdomen, high/extending to upper abdomen) and complete cytoreduction rates in women who underwent surgery.ResultsOf 1741 participants recruited via the fast-track pathway, 119 (6.8%) were diagnosed with high grade serous ovarian cancer. The median age was 63 years (range 32–89). Of these, 112 (94.1%) patients had a performance status of 0 and 1, 30 (25.2%) were diagnosed with stages I/II, and the disease distribution was low-to-moderate in 77 (64.7%). Complete and optimal cytoreduction were achieved in 73 (61.3%) and 18 (15.1%). The extent of disease was low in 43 of 119 (36.1%), moderate in 34 of 119 (28.6%), high in 32 of 119 (26.9%), and not available in 10 of 119 (8.4%). Nearly two thirds, that is 78 of 119 (65.5%) women with high grade serous ovarian cancer, underwent primary debulking surgery, 36 of 119 (30.3%) received neoadjuvant chemotherapy followed by interval debulking surgery, and 5 of 119 (4.2%) women did not undergo surgery.ConclusionOur results demonstrate that one in four women identified with high grade serous ovarian cancer through the fast-track pathway following symptom-triggered testing was diagnosed with early-stage disease. Symptom-triggered testing may help identify women with a low disease burden, potentially contributing to high complete cytoreduction rates.
Journal Article
Coating Characterization with the Quartz Crystal Microbalance
2016
The quartz crystal microbalance is a sensitive tool that can be used to measure the mass, modulus and phase angle of films of appropriate thicknesses. It is can be applied to systems with very varied properties, from liquid to solid, and under many different conditions. In this thesis its capabilities have been used to study the properties of several different systems of relevance to the coatings, art conservation, and rubber communities, in the process of which new techniques and tools were developed to analyze data and improve QCM data collection and experimental design. Alkyd resins, which have been used in artists' paints since the twentieth century, are the subject of the first studies. Alkyds are oil-modified polyesters. These resins are of interest because of their relatively recent use in art and how little is known of the mechanical properties in the early stages of cure. The QCM was shown to be sensitive to the curing process, changes in temperature, and mass change due to exposure to water. Kinetic studies during the first days of curing showed that the curing process can be divided into three regions. The first is dominated by solvent evaporation. In the second, oxygen absorption dominates and the mechanical properties change rapidly. The final stage extends from when the film is touch dry after about a day to years and is characterized by mass loss and continued increases in the modulus. Studying the curing at different temperatures revealed that the reactions do proceed much more rapidly at higher temperatures and an overall energy of activation was calculated for the curing process. The mechanical properties of alkyd resins containing zinc oxide, a white pigment, were studied with the QCM, nanoindentation and dynamic mechanical analysis. These measurements showed increases in the modulus with the inclusion of zinc oxide, and the QCM data showed that the second region started at earlier times as the pigment concentration was increased. Linseed oil is one of the starting materials for many alkyd resins and should cure similarly since the primary curing mechanisms are the same. It takes longer to cure than alkyds because it begins with no initial polymerization. Linseed oil was harder to study, as obtaining even films was difficult, multiple peaks at a single harmonic were observed, and the material properties during the early stages of curing led to a region where viscoelastic properties could not be calculated. To facilitate studying linseed oil, a multiple peak fitting method was developed to extract data from unusual peak shapes. With this ability, measurements at short times could be obtained despite poor film quality. Although linseed oil begins as a softer material than alkyds, its curing follows the same patterns as alkyd resins, exhibiting mass gain followed by mass loss, and sharp increases in modulus and decreases in phase angle during the early stages of curing. Having demonstrated the ability of the QCM to monitor curing, the QCM was also applied to uncrosslinked rubber systems. Rubbers, like the drying oils, contain double bonds which can react with oxygen, so first the oxidation of these materials was studied. In further studies oxidation was undesirable, so protocols were developed to limit oxidation. Measurements were made of homopolymers at different temperatures and the QCM measurements appear to be consistent with time-temperature superposition results obtained at lower frequencies. Blends of the various rubbers were studied and compared with models. The mechanical properties measured by the QCM were between the Voigt and Reuss predictions for most blends studied. Modeling the expected QCM response of layered rubbers matched the predictions of the Reuss model but not the measured values of the rubber blends, suggesting that the QCM is sensitive to different morphologies. Measurements with the QCM expanded our understanding of a variety of systems and proved to be a useful tool to measure mechanical changes during processes which are difficult to study by other methods.
Dissertation
Sometimes slower is better: slow-exploring birds are more sensitive to changes in a vocal discrimination task
by
Hoeschele, Marisa
,
Reddon, Adam R.
,
Sturdy, Christopher B.
in
Animal Personality
,
Animals
,
Auditory Perception - physiology
2011
Animal personality, defined as consistent individual differences across context and time, has attracted much recent research interest in the study of animal behaviour. More recently, this field has begun to examine how such variation arose and is maintained within populations. The habitat-dependent selection hypothesis, which posits that animals with differing personality types may fare better (i.e. have a fitness advantage) in different habitats, suggests one possible mechanism. In the current experiment, we tested whether slow- and fast-exploring black-capped chickadees (Poecile atricapillus), determined by performance in a novel environment exploration task, perform differentially when the demands of an acoustic operant discrimination (cognitive) task were altered following successful task acquisition. We found that slow-exploring birds learn to reverse previously learned natural category rules more quickly than faster exploring conspecifics. In accordance with the habitat-dependent selection hypothesis, and previous work with great tits (Parus major), a close relative of the black-capped chickadee, our results suggest that fast-exploring birds may perform better in stable, predictable environments where forming a routine is advantageous, while slow-exploring birds are favoured in unstable, unpredictable environments, where task demands often change. Our results also support a hypothesis derived from previous work with great tits; slow-exploring birds may be generally more flexible (i.e. able to modify their behaviour in accordance with changes in environmental stimuli) in some learning tasks.
Journal Article
Individual differences in learning speed, performance accuracy and exploratory behaviour in black-capped chickadees
2015
Cognitive processes are important to animals because they not only influence how animals acquire, store and recall information, but also may underpin behaviours such as deciding where to look for food, build a nest, or with whom to mate. Several recent studies have begun to examine the potential interaction between variation in cognition and variation in personality traits. One hypothesis proposed that there is a speed–accuracy trade-off in cognition ability that aligns with a fast–slow behaviour type. Here, we explicitly examined this hypothesis by testing wild-caught black-capped chickadees in a series of cognitive tasks that assessed both learning speed (the number of trials taken to learn) and accuracy (post-acquisition performance when tested with un-trained exemplars). Chickadees’ exploration scores were measured in a novel environment task. We found that slow-exploring chickadees demonstrated higher accuracy during the test phase, but did not learn the initial task in fewer trials compared to fast-exploring chickadees, providing partial support for the proposed link between cognition and personality. We report positive correlations in learning speed between different phases within cognitive tasks, but not between the three cognitive tasks suggesting independence in underlying cognitive processing. We discuss different rule-based strategies that may contribute to differential performance accuracy in cognitive tasks and provide suggestions for future experimentation to examine mechanisms underlying the relationship between cognition and personality.
Journal Article
ZENK Activation in the Nidopallium of Black-Capped Chickadees in Response to Both Conspecific and Heterospecific Calls
by
Hoeschele, Marisa
,
Owens, Jessica L.
,
Avey, Marc T.
in
Acoustic Stimulation
,
Acoustics
,
Activation
2014
Neuronal populations in the songbird nidopallium increase in activity the most to conspecific vocalizations relative to heterospecific songbird vocalizations or artificial stimuli such as tones. Here, we tested whether the difference in neural activity between conspecific and heterospecific vocalizations is due to acoustic differences or to the degree of phylogenetic relatedness of the species producing the vocalizations. To compare differences in neural responses of black-capped chickadees, Poecile atricapillus, to playback conditions we used a known marker for neural activity, ZENK, in the caudal medial nidopallium and caudomedial mesopallium. We used the acoustically complex 'dee' notes from chick-a-dee calls, and vocalizations from other heterospecific species similar in duration and spectral features. We tested the vocalizations from three heterospecific species (chestnut-backed chickadees, tufted titmice, and zebra finches), the vocalizations from conspecific individuals (black-capped chickadees), and reversed versions of the latter. There were no significant differences in the amount of expression between any of the groups except in the control condition, which resulted in significantly less neuronal activation. Our results suggest that, in certain cases, neuronal activity is not higher in response to conspecific than in response to heterospecific vocalizations for songbirds, but rather is sensitive to the acoustic features of the signal. Both acoustic features of the calls and the phylogenetic relationship between of the signaler and the receiver interact in the response of the nidopallium.
Journal Article
Among-individual differences in auditory and physical cognitive abilities in zebra finches
by
Lambert, Connor T.
,
Sahu, Prateek K.
,
Sturdy, Christopher B.
in
Acoustics
,
Animals
,
Auditory discrimination
2022
Among-individual variation in performance on cognitive tasks is ubiquitous across species that have been examined, and understanding the evolution of cognitive abilities requires investigating among-individual variation because natural selection acts on individual differences. However, relatively little is known about the extent to which individual differences in cognition are determined by domain-specific compared with domain-general cognitive abilities. We examined individual differences in learning speed of zebra finches across seven different tasks to determine the extent of domain-specific versus domain-general learning abilities, as well as the relationship between learning speed and learning generalization. Thirty-two zebra finches completed a foraging board experiment that included visual and structural discriminations, and then these same birds went through an acoustic operant discrimination experiment that required discriminating between different natural categories of acoustic stimuli. We found evidence of domain-general learning abilities as birds’ relative performance on the seven learning tasks was weakly repeatable and a principal components analysis found a first principal component that explained 36% of the variance in performance across tasks with all tasks loading unidirectionally on this component. However, the few significant correlations between tasks and high repeatability within each experiment suggest the potential for domain-specific abilities. Learning speed did not influence an individual’s ability to generalize learning. These results suggest that zebra finch performance across visual, structural, and auditory learning relies upon some common mechanism; some might call this evidence of “general intelligence”(
g
), but it is also possible that this finding is due to other noncognitive mechanisms such as motivation.
Journal Article
Unifying Psychological and Biological Approaches to Understanding Animal Cognition
2020
This special issue has two main aims. The first aim is to broaden the scope of the Canadian Journal of Experimental Psychology. This aim is motivated by the simple fact that the journal’s mandate includes comparative psychology, but many of the articles published in the journal are currently, and have been for some time, mainly human cognitive in nature. The second aim of this issue is one that we take very seriously, and that is to promote not only comparative cognition and cognitive ecology research but research from a diverse group of scientists. Although the global diversity in this special issue is not exhaustive, there is work highlighted from scientists at institutions in Canada, Germany, Italy, the Netherlands, Spain, the United Kingdom, and the United States. (PsycInfo Database Record (c) 2025 APA, all rights reserved)
Journal Article