Deep Learning versus Classical Regression for Brain Tumor Patient Survival Prediction

Deep learning for regression tasks on medical imaging data has shown promising results. However, compared to other approaches, their power is strongly linked to the dataset size. In this study, we evaluate 3D-convolutional neural networks (CNNs) and classical regression methods with hand-crafted features for survival time regression of patients with high grade brain tumors. The tested CNNs for regression showed promising but unstable results. The best performing deep learning approach reached an accuracy of 51.5% on held-out samples of the training set. All tested deep learning experiments were outperformed by a Support Vector Classifier (SVC) using 30 radiomic features. The investigated features included intensity, shape, location and deep features. The submitted method to the BraTS 2018 survival prediction challenge is an ensemble of SVCs, which reached a cross-validated accuracy of 72.2% on the BraTS 2018 training set, 57.1% on the validation set, and 42.9% on the testing set. The results suggest that more training data is necessary for a stable performance of a CNN model for direct regression from magnetic resonance images, and that non-imaging clinical patient information is crucial along with imaging information.Comment: Contribution to The International Multimodal Brain Tumor Segmentation (BraTS) Challenge 2018, survival prediction tas

Carboxyhaemoglobin levels and their determinants in older British men

Background: Although there has been concern about the levels of carbon monoxide exposure, particularly among older people, little is known about COHb levels and their determinants in the general population. We examined these issues in a study of older British men.Methods: Cross-sectional study of 4252 men aged 60-79 years selected from one socially representative general practice in each of 24 British towns and who attended for examination between 1998 and 2000. Blood samples were measured for COHb and information on social, household and individual factors assessed by questionnaire. Analyses were based on 3603 men measured in or close to (< 10 miles) their place of residence.Results: The COHb distribution was positively skewed. Geometric mean COHb level was 0.46% and the median 0.50%; 9.2% of men had a COHb level of 2.5% or more and 0.1% of subjects had a level of 7.5% or more. Factors which were independently related to mean COHb level included season (highest in autumn and winter), region (highest in Northern England), gas cooking (slight increase) and central heating (slight decrease) and active smoking, the strongest determinant. Mean COHb levels were more than ten times greater in men smoking more than 20 cigarettes a day (3.29%) compared with non-smokers (0.32%); almost all subjects with COHb levels of 2.5% and above were smokers (93%). Pipe and cigar smoking was associated with more modest increases in COHb level. Passive cigarette smoking exposure had no independent association with COHb after adjustment for other factors. Active smoking accounted for 41% of variance in COHb level and all factors together for 47%.Conclusion: An appreciable proportion of men have COHb levels of 2.5% or more at which symptomatic effects may occur, though very high levels are uncommon. The results confirm that smoking (particularly cigarette smoking) is the dominant influence on COHb levels

A systematic review of studies measuring and reporting hearing aid usage in older adults since 1999: a descriptive summary of measurement tools

Objective: A systematic review was conducted to identify and quality assess how studies published since 1999 have measured and reported the usage of hearing aids in older adults. The relationship between usage and other dimensions of hearing aid outcome, age and hearing loss are summarised. Data sources: Articles were identified through systematic searches in PubMed/MEDLINE, The University of Nottingham Online Catalogue, Web of Science and through reference checking. Study eligibility criteria: (1) participants aged fifty years or over with sensori-neural hearing loss, (2) provision of an air conduction hearing aid, (3) inclusion of hearing aid usage measure(s) and (4) published between 1999 and 2011. Results: Of the initial 1933 papers obtained from the searches, a total of 64 were found eligible for review and were quality assessed on six dimensions: study design, choice of outcome instruments, level of reporting (usage, age, and audiometry) and cross validation of usage measures. Five papers were rated as being of high quality (scoring 10–12), 35 papers were rated as being of moderate quality (scoring 7–9), 22 as low quality (scoring 4–6) and two as very low quality (scoring 0–2). Fifteen different methods were identified for assessing the usage of hearing aids. Conclusions: Generally, the usage data reviewed was not well specified. There was a lack of consistency and robustness in the way that usage of hearing aids was assessed and categorised. There is a need for more standardised level of reporting of hearing aid usage data to further understand the relationship between usage and hearing aid outcomes

Is group cognitive behaviour therapy for postnatal depression evidence-based practice? A systematic review

Background: There is evidence that psychological therapies including cognitive behaviour therapy (CBT) may be effective in reducing postnatal depression (PND) when offered to individuals. In clinical practice, this is also implemented in a group therapy format, which, although not recommended in guidelines, is seen as a cost-effective alternative. To consider the extent to which group methods can be seen as evidence-based, we systematically review and synthesise the evidence for the efficacy of group CBT compared to currently used packages of care for women with PND, and we discuss further factors which may contribute to clinician confidence in implementing an intervention. Methods: Seventeen electronic databases were searched. All full papers were read by two reviewers and a third reviewer was consulted in the event of a disagreement on inclusion. Selected studies were quality assessed, using the Cochrane Risk of Bias Tool, were data extracted by two reviewers using a standardised data extraction form and statistically synthesised where appropriate using the fixed-effect inverse-variance method. Results: Seven studies met the inclusion criteria. Meta-analyses showed group CBT to be effective in reducing depression compared to routine primary care, usual care or waiting list groups. A pooled effect size of d = 0.57 (95% CI 0.34 to 0.80, p < 0.001) was observed at 10–13 weeks post-randomisation, reducing to d = 0.28 (95% CI 0.03 to 0.53, p = 0.025) at 6 months. The non-randomised comparisons against waiting list controls at 10–13 weeks was associated with a larger effect size of d = 0.94 (95% CI 0.42 to 1.47, p < 0.001). However due to the limitations of the available data, such as ill-specified definitions of the CBT component of the group programmes, these results should be interpreted with caution. Conclusions: Although the evidence available is limited, group CBT was shown to be effective. We argue, therefore, that there is sufficient evidence to implement group CBT, conditional upon routinely collected outcomes being benchmarked against those obtained in trials of individual CBT, and with other important factors such as patient preference, clinical experience, and information from the local context taken into account when making the treatment decision

A Mass Spectrometry-Based Approach for Mapping Protein Subcellular Localization Reveals the Spatial Proteome of Mouse Primary Neurons

We previously developed a mass spectrometry-based method, Dynamic Organellar Maps, for the determination of protein subcellular localisation, and the identification of translocation events in comparative experiments. The use of metabolic labelling for quantification (SILAC) renders the method best suited to cells grown in culture. Here we have adapted the workflow to both label-free quantification (LFQ) and chemical labelling/multiplexing strategies (Tandem Mass Tagging, TMT). Both new methods are highly effective for generation of organellar maps and capture of protein translocations. Furthermore, application of label-free organellar mapping to acutely isolated mouse primary neurons provided subcellular localisation and copy number information for over 8,000 proteins, allowing a detailed analysis of organellar organisation. Our study extends the scope of Dynamic Organellar Maps to any cell type or tissue, and also to high throughput screening.This work was funded by the German Research Foundation (DFG/Gottfried Wilhelm Leibniz Prize MA 1764/2-1), the Louis-Jeantet Foundation, the Max Planck Society for the Advancement of Science, a Wellcome Trust Senior Clinical Research Fellowship 108070/Z/15/Z (to M.P.W.), and a strategic award to Cambridge Institute for Medical Research from the Wellcome Trust (100140)

Expression of HIWI in human esophageal squamous cell carcinoma is significantly associated with poorer prognosis

<p>Abstract</p> <p>Background</p> <p>HIWI, the human homologue of Piwi family, is present in CD34⁺hematopoietic stem cells and germ cells, but not in well-differentiated cell populations, indicating that HIWI may play an impotent role in determining or maintaining stemness of these cells. That HIWI expression has been detected in several type tumours may suggest its association with clinical outcome in cancer patients.</p> <p>Methods</p> <p>With the methods of real-time PCR, western blot, immunocytochemistry and immunohistochemistry, the expression of HIWI in three esophageal squamous cancer cell lines KYSE70, KYSE140 and KYSE450 has been characterized. Then, we investigated HIWI expression in a series of 153 esophageal squamous cell carcinomas using immunohistochemistry and explored its association with clinicopathological features.</p> <p>Results</p> <p>The expression of HIWI was observed in tumour cell nuclei or/and cytoplasm in 137 (89.5%) cases, 16 (10.5%) cases were negative in both nuclei and cytoplasm. 86 (56.2%) were strongly positive in cytoplasm, while 49 (32.0%) were strongly positive in nuclei. The expression level of HIWI in cytoplasm of esophageal cancer cells was significantly associated with histological grade (<it>P </it>= 0.011), T stage (<it>P </it>= 0.035), and clinic outcome (<it>P </it>< 0.001), while there was no correlation between the nuclear HIWI expression and clinicopathological features.</p> <p>Conclusion</p> <p>The expression of HIWI in the cytoplasm of esophageal cancer cells is significantly associated with higher histological grade, clinical stage and poorer clinical outcome, indicating its possible involvement in cancer development.</p

Numerical Algebraic Geometry: A New Perspective on String and Gauge Theories

The interplay rich between algebraic geometry and string and gauge theories has recently been immensely aided by advances in computational algebra. However, these symbolic (Gr\"{o}bner) methods are severely limited by algorithmic issues such as exponential space complexity and being highly sequential. In this paper, we introduce a novel paradigm of numerical algebraic geometry which in a plethora of situations overcomes these short-comings. Its so-called 'embarrassing parallelizability' allows us to solve many problems and extract physical information which elude the symbolic methods. We describe the method and then use it to solve various problems arising from physics which could not be otherwise solved.Comment: 36 page

Network model of immune responses reveals key effectors to single and co-infection dynamics by a respiratory bacterium and a gastrointestinal helminth

Co-infections alter the host immune response but how the systemic and local processes at the site of infection interact is still unclear. The majority of studies on co-infections concentrate on one of the infecting species, an immune function or group of cells and often focus on the initial phase of the infection. Here, we used a combination of experiments and mathematical modelling to investigate the network of immune responses against single and co-infections with the respiratory bacterium Bordetella bronchiseptica and the gastrointestinal helminth Trichostrongylus retortaeformis. Our goal was to identify representative mediators and functions that could capture the essence of the host immune response as a whole, and to assess how their relative contribution dynamically changed over time and between single and co-infected individuals. Network-based discrete dynamic models of single infections were built using current knowledge of bacterial and helminth immunology; the two single infection models were combined into a co-infection model that was then verified by our empirical findings. Simulations showed that a T helper cell mediated antibody and neutrophil response led to phagocytosis and clearance of B. bronchiseptica from the lungs. This was consistent in single and co-infection with no significant delay induced by the helminth. In contrast, T. retortaeformis intensity decreased faster when co-infected with the bacterium. Simulations suggested that the robust recruitment of neutrophils in the co-infection, added to the activation of IgG and eosinophil driven reduction of larvae, which also played an important role in single infection, contributed to this fast clearance. Perturbation analysis of the models, through the knockout of individual nodes (immune cells), identified the cells critical to parasite persistence and clearance both in single and co-infections. Our integrated approach captured the within-host immuno-dynamics of bacteria-helminth infection and identified key components that can be crucial for explaining individual variability between single and co-infections in natural populations

Measurement of the Rates of Synthesis of Three Components of Ribosomes of Mycobacterium fortuitum: A Theoretical Approach to qRT-PCR Experimentation

BACKGROUND: Except for the ribosomal protein L12 (rplL), ribosomal proteins are present as one copy per ribosome; L12 (rplL) is unusual because it is present as four copies per ribosome. Thus, the strategies used by Mycobacterium fortuitum to regulate ribosomal protein synthesis were investigated, including evaluations of the rates of chain elongations of 16S rRNA, rplL and ribosomal protein S12 (rpsL). METHODOLOGY: RNA was isolated from cell cultures and cDNA was prepared. The numbers of cDNA copies of 16S rRNA, precursor-16S rRNA and transcripts of rpsL and rplL were quantified by qRT-PCR and then related to the rates of 16S rRNA, rpsL and rplL chain elongations by means of a mathematical framework for coupled transcription/translation. PRINCIPAL FINDINGS: The rates of synthesis of 16S rRNA, rpsL and rplL respectively were found to be approximately 50 x 10(3) nucleotides h(-1), 1.6 x 10(3) amino acid residues h(-1) and 3.4 x 10(3) amino acid residues h(-1). The number of transcripts of rplL was approximately twice that of rpsL. These data account for the presence of one copy of rpsL and four copies of rplL per ribosome, and reveal that the rate of M. fortuitum ribosome synthesis was closer to that of M. tuberculosis than to E. coli. Except for rplJ, the elongation rate obtained for rpsL was inferred to be appropriate for all other proteins present as one copy per ribosome. SIGNIFICANCE: The results obtained provide the basis for a comprehensive view of the kinetics of ribosome synthesis, and of the ways that bacterial cells utilize genes encoding ribosomal proteins. The methodology also applies to proteins involved in transcription, energy generation and to bacterial proteins in general. The method proposed for measuring the fidelity of cDNA preparations is intrinsically much more sensitive than procedures that measure the integrity of 16S rRNA