Implementing streamlined radiology reporting and clinical results management in low-dose CT screening for lung cancer

Lung cancer kills more people in the UK than any other cancer. Mortality rates are poor, with fewer than 10% of people alive 10 years after diagnosis. Lung Cancer Screening (LCS) with low-dose CT (LDCT) is effective at reducing lung cancer mortality when employed in at-risk populations; because of this, in the US, LCS has been implemented as a national programme. The UK does not currently screen for lung cancer, but in 2019 NHS England announced a pilot scheme to implement lung health checks (LHC) in areas with the poorest lung cancer outcomes. Despite these advances in LCS in the UK, there are outstanding questions about how LCS could be implemented safely and effectively, which this thesis, based on experience and data from the SUMMIT Study, aims to investigate. To provide screening safely, implementation of any study or programme must focus on maintaining a favourable cost to benefit ratio. This is particularly true in LCS where high false positive and overdiagnosis rates, as well as considerable levels of incidental findings, lead to possible psychological stress, needless investigations and interventions, making provision challenging to both screenees and healthcare providers. The SUMMIT Study investigates how to deliver evidence-based LCS in a large population (25,000), and this thesis in particular focusses on how LCS can be streamlined through proformatisation of radiological data collection, clinical actioning of results and standardised communication with general practitioners (GPs) and participants. This thesis explains the approach to managing pulmonary nodules and incidental findings detected at LDCT in SUMMIT, and how these findings are collected, triaged, and communicated in a way that is both efficient and safe. Early data from SUMMIT is presented to understand how evidence-based proformas may enable streamlined clinical management, data collection and results communications, while decreasing the burden on healthcare professionals and participants alike

Return and volatility reactions to monthly announcements of business cycle forecasts : an event study based on high-frequency data

This article contributes to the literature on macroeconomic announcements and their impact on asset prices by investigating how the 15-second Xetra DAX returns reflect the monthly announcements of the two best known business cycle forecasts for Germany, i.e. the ifo Business Climate Index and the ZEW Indicator of Economic Sentiment. From the methodological point of view, the main innovation lies in disentangling "good" macroeconomics news from "bad" news, and, simultaneously, considering time intervals with and without confounding announcements from other sources. Releases from both institutes lead to an immediate response of returns occurring 15 seconds after the announcements, i.e. within the first possible time interval. Announcements of both institutes are also clearly and immediately reflected in the volatility, which remains at a significantly higher level for approximately two minutes slightly elevated for approximately 15 minutes. Combining returns and volatility in a GARCH(1,1)-model, the paper reveals that significant increases in volatility only show up in the presence of simultaneous news released by other sources, whereas return reactions can be observed irrespective of whether confounding announcements are published or not

FACS purification and transcriptome analysis of drosophila neural stem cells reveals a role for Klumpfuss in self-renewal

Drosophila neuroblasts (NBs) have emerged as a model for stem cell biology that is ideal for genetic analysis but is limited by the lack of cell-type-specific gene expression data. Here, we describe a method for isolating large numbers of pure NBs and differentiating neurons that retain both cell-cycle and lineage characteristics. We determine transcriptional profiles by mRNA sequencing and identify 28 predicted NB-specific transcription factors that can be arranged in a network containing hubs for Notch signaling, growth control, and chromatin regulation. Overexpression and RNA interference for these factors identify Klumpfuss as a regulator of self-renewal. We show that loss of Klumpfuss function causes premature differentiation and that overexpression results in the formation of transplantable brain tumors. Our data represent a valuable resource for investigating Drosophila developmental neurobiology, and the described method can be applied to other invertebrate stem cell lineages as well

Rigid thinking about deformables: do children sometimes overgeneralize the shape bias?

Young children learning English are biased to attend to the shape of solid rigid objects when learning novel names. This study seeks further understanding of the processes that support this behavior by examining a previous finding that three-year-old children are also biased to generalize novel names for objects made from deformable materials by shape, even after the materials are made salient. In two experiments, we examined the noun generalizations of 72 two-, three- and four-year- old children with rigid and deformable stimuli. Data reveal that three-year-old, but not two- or four-year-old, children generalize names for deformable things by shape, and that this behavior is not due to the syntactic context of the task. We suggest this behavior is an overgeneralization of three-year-old children’s knowledge of how rigid things are named and discuss the implications of this finding for a developmental account of the origins of the shape bias

Working Memory Alterations After a Romantic Relationship Breakup

Experiencing stress can have a disadvantageous effect on mental well-being. Additional to the relation between suffering from chronic stress and depression, both stress (acute and chronic) and depression are associated with cognitive alterations, including working memory. The breakup of a relationship is considered to be a stressful event that can lead to symptoms of depression in otherwise healthy people. Additional to elevated depression scores, stress-related cognitive alterations may occur in this population as well. Therefore, in the present fMRI study we investigated whether experiencing a relationship breakup is associated with working memory alterations and whether this is related to depressive symptom severity. A three workload version of the n-back task (0-back, 1-back, 2-back) was used to measure working memory in subjects who experienced a breakup in the preceding 6 months ("heartbreak group", n = 70) and subjects in a romantic relationship ("relationship group", n = 46). Behavioral task performance was compared between the two groups. Functional MRI scans were analyzed using General Linear Model (GLM) activation analyses. Workload conditions were contrasted to each other and to baseline and group differences were assessed. To investigate whether brain networks are associated with depressive symptom severity within the heartbreak group specifically, a post hoc feature-based Independent Component Analysis was performed on the 2-back > 0-back contrast images to identify brain regions that covaried across subjects. Behaviorally, the heartbreak group performed similar at high workload (i.e., 2-back) and better at moderate workload (i.e., 1-back) than the relationship group. GLM analysis revealed an interaction between group and 2-back > 0-back, 2-back > 1-back and 2-back > baseline; the heartbreak group showed less precuneus activation compared to the relationship group. Furthermore, within the heartbreak group, we found a negative association between depressive symptom severity and a brain network representing mostly the precuneus, anterior cingulate gyrus and supplementary motor cortex. Our findings suggest that the effect of a breakup is accompanied by workload-dependent working memory alterations. Therefore, we propose that this population can potentially be used to investigate the interplay between stress, cognitive functioning and depression