Project description:Automatic video tracking has become a standard tool for investigating the social behaviour of insects. The recent integration of computer vision in tracking technologies will probably lead to fully automated behavioural pattern classification within the next few years. However, many current systems rely on offline data analysis and use computationally expensive techniques to track pre-recorded videos. To address this gap, we developed BACH (Behaviour Analysis maCHine), a software that performs video tracking of insect groups in real time. BACH uses object recognition via convolutional neural networks and identifies individually tagged insects via an existing matrix code recognition algorithm. We compared the tracking performances of BACH and a human observer (HO) across a series of short videos of ants moving in a two-dimensional arena. We found that BACH detected ant shapes only slightly worse than the HO. However, its matrix code-mediated identification of individual ants only attained human-comparable levels when ants moved relatively slowly, and fell when ants walked relatively fast. This happened because BACH had a relatively low efficiency in detecting matrix codes in blurry images of ants walking at high speeds. BACH needs to undergo hardware and software adjustments to overcome its present limits. Nevertheless, our study emphasizes the possibility of, and the need for, further integrating real-time data analysis into the study of animal behaviour. This will accelerate data generation, visualization and sharing, opening possibilities for conducting fully remote collaborative experiments.
Project description:Expression profiling of superficial bladder tumours to delineate the expression pattern differences between non-recurring and recurring tumours. Keywords = bladder cancer, superficial, recurrence, prediction Keywords: other
Project description:Patients who were previously treated for prostate cancer with radiation therapy are monitored at regular intervals using a laboratory test called Prostate Specific Antigen (PSA). If the value of the PSA test starts to rise, this is an indication that the prostate cancer is more likely to recur, and the patient may wish to initiate new treatments. Such patients could be helped in making medical decisions by an accurate estimate of the probability of recurrence of the cancer in the next few years. In this article, we describe the methodology for giving the probability of recurrence for a new patient, as implemented on a web-based calculator. The methods use a joint longitudinal survival model. The model is developed on a training dataset of 2386 patients and tested on a dataset of 846 patients. Bayesian estimation methods are used with one Markov chain Monte Carlo (MCMC) algorithm developed for estimation of the parameters from the training dataset and a second quick MCMC developed for prediction of the risk of recurrence that uses the longitudinal PSA measures from a new patient.
Project description:The lack of relevant pre-clinical animal models incorporating the clinical scenario of Glioblastoma multiforme (GBM) resection and recurrence has contributed significantly to the inability to successfully treat GBM. A multi-modality imaging approach that allows real-time assessment of tumor resection during surgery and non-invasive detection of post-operative tumor volumes is urgently needed. In this study, we report the development and implementation of an optical imaging and magnetic resonance imaging (MRI) approach to guide GBM resection during surgery and track tumor recurrence at multiple resolutions in mice. Intra-operative fluorescence-guided surgery allowed real-time monitoring of intracranial tumor removal and led to greater than 90 % removal of established intracranial human GBM. The fluorescent signal clearly delineated tumor margins, residual tumor, and correlated closely with the clinically utilized fluorescence surgical marker 5-aminolevulinic acid/porphyrin. Post-operative non-invasive optical imaging and MRI confirmed near-complete tumor removal, which was further validated by immunohistochemistry (IHC). Longitudinal non-invasive imaging and IHC showed rapid recurrence of multi-focal tumors that exhibited a faster growth rate and altered blood-vessel density compared to non-resected tumors. Surgical tumor resection significantly extended long-term survival, however mice ultimately succumbed to the recurrent GBM. This multi-modality imaging approach to GBM resection and recurrence in mice should provide an important platform for investigating multiple aspects of GBM and ultimately evaluating novel therapeutics.
Project description:High-resolution real-time tomography of scattering tissues is important for many areas of medicine and biology1-6. However, the compromise between transverse resolution and depth-of-field in addition to low sensitivity deep in tissue continue to impede progress towards cellular-level volumetric tomography. Computed imaging has the potential to solve these long-standing limitations. Interferometric synthetic aperture microscopy (ISAM)7-9 is a computed imaging technique enabling high-resolution volumetric tomography with spatially invariant resolution. However, its potential for clinical diagnostics remains largely untapped since full volume reconstructions required lengthy postprocessing, and the phase-stability requirements have been difficult to satisfy in vivo. Here we demonstrate how 3-D Fourier-domain resampling, in combination with high-speed optical coherence tomography (OCT), can achieve high-resolution in vivo tomography. Enhanced depth sensitivity was achieved over a depth-of-field extended in real time by more than an order of magnitude. This work lays the foundation for high-speed volumetric cellular-level tomography.
Project description:IntroductionThe main goal of brain tumour surgery is to maximize tumour resection while avoiding neurological deficits. Accurate characterization of tissue and delineation of resection margins are, therefore, essential to achieve optimal surgical results.ObjectivesThe primary objective of this study was to develop and validate a mass spectrometry- based technique for the molecular characterization of high- and low-grade glioma tissue during surgery.MethodsAn electrosurgical knife is connected to a mass spectrometer (iKnife). Using this system, an aerosol created during electrosurgical resection is aspirated to a mass spectrometer to determine the molecular profile of the tissue within seconds. This rapid evaporative ionization mass spectrometry (REIMS) technique is used to create a chemical profile database and develop a real-time tissue recognition system based on machine learning.ResultsClassification models were built by analysing biopsies from 36 patients who underwent brain tumour resection. Our multivariate statistical model could differentiate between astrocytoma grade II and III, glioblastoma, oligodendroglioma grade II and III, and normal brain tissue with an 88% overall accuracy. Astrocytoma and oligodendroglioma grade II were separated from normal brain with a 96% correct classification rate. REIMS could differentiate between different percentages of GBM with 99.2% sensitivity and different percentages of astrocytoma grade II with 97.5% sensitivity.ConclusionReal-time information during electrosurgical dissection can improve intra-operative decision-making, leading to a more accurate tumour removal for different glioma subtypes.
Project description:To evaluate the use of endovascular coils as markers for respiratory motion correction during high-dose stereotactic radiotherapy with the CyberKnife, an image-guided linear accelerator mounted on a robotic arm. Endovascular platinum embolisation coils were used to mark intrapulmonary lesions. The coils were placed in subsegmental pulmonary artery branches in close proximity to the target tumour. This procedure was attempted in 25 patients who were considered unsuitable candidates for standard transthoracic percutaneous insertion. Vascular coils (n = 87) were successfully inserted in 23 of 25 patients. Only minor complications were observed: haemoptysis during the procedure (one patient), development of pleural pain and fever on the day of procedure (one patient), and development of small infiltrative changes distal to the vascular coil (five patients). Fifty-seven coils (66% of total inserted number) could be used as tumour markers for delivery of biologically highly effective radiation doses with automated tracking during CyberKnife radiotherapy. Endovascular markers are safe and allow high-dose radiotherapy of lung tumours with CyberKnife, also in patients who are unsuitable candidates for standard transthoracic percutaneous marker insertion.
Project description:Deciphering molecular mechanisms underlying the division of hematopoietic stem cells (HSCs) and malignant precursors would improve our understanding of the basis of stem cell-fate decisions and oncogenic transformation.Using a novel reporter of hematopoietic precursor, Evi1-GFP, we tracked the division of hematopoietic precursors in culture in real time.First, we confirmed that Evi1-GFP is a faithful reporter of HSC activity and identified three dividing patterns of HSCs: symmetric renewal, symmetric differentiation, and asymmetric division. Moreover, we found that the cytokine and growth factor combination (STIF) promotes symmetric renewal, whereas OP9 stromal cells balance symmetric renewal and differentiation of HSCs ex vivo. Interestingly, we found that Tet2 knockout HSCs underwent more symmetric differentiation in culture compared with the wild-type control. Intriguingly, OP9 stromal cells reverse the phenotype of Tet2 knockout HSCs ex vivo. Furthermore, we demonstrated that Tet2 -/- ;Flt3ITD acute myeloid leukemia (AML) precursors primarily underwent symmetric renewal divisions in culture. Mechanistically, we demonstrated that inhibiting DNA methylation can reverse the aberrant division phenotypes of Tet2 -/- and Tet2 -/- ;FLT3ITD precursors, suggesting that abnormal DNA methylation plays an important role in controlling (pre-)leukemic precursor fate decision ex vivo.Our study exploited a new system to explore the molecular mechanisms of the regulation of benign and malignant hematopoietic precursor division ex vivo. The knowledge learned from these studies will provide new insights into the molecular mechanisms of HSC fate decision and leukemogenesis.
Project description:ObjectivesMechanical ventilation of patients with acute respiratory distress syndrome should balance lung and diaphragm protective principles, which may be difficult to achieve in routine clinical practice. Through a Phase I clinical trial, we sought to determine whether a computerized decision support-based protocol (real-time effort-driven ventilator management) is feasible to implement, results in improved acceptance for lung and diaphragm protective ventilation, and improves clinical outcomes over historical controls.DesignInterventional nonblinded pilot study.SettingPICU.PatientsMechanically ventilated children with acute respiratory distress syndrome.InterventionsA computerized decision support tool was tested which prioritized lung-protective management of peak inspiratory pressure-positive end-expiratory pressure, positive end-expiratory pressure/FIO2, and ventilatory rate. Esophageal manometry was used to maintain patient effort in a physiologic range. Protocol acceptance was reported, and enrolled patients were matched 4:1 with respect to age, initial oxygenation index, and percentage of immune compromise to historical control patients for outcome analysis.Measurements and main resultsThirty-two patients were included. Acceptance of protocol recommendations was over 75%. One-hundred twenty-eight matched historical controls were used for analysis. Compared with historical controls, patients treated with real-time effort-driven ventilator management received lower peak inspiratory pressure-positive end-expiratory pressure and tidal volume, and higher positive end-expiratory pressure when FIO2 was greater than 0.60. Real-time effort-driven ventilator management was associated with 6 more ventilator-free days, shorter duration until the first spontaneous breathing trial and 3 fewer days on mechanical ventilation among survivors (all p ≤ 0.05) in comparison with historical controls, while maintaining no difference in the rate of reintubation.ConclusionsA computerized decision support-based protocol prioritizing lung-protective ventilation balanced with reduction of controlled ventilation to maintain physiologic levels of patient effort can be implemented and may be associated with shorter duration of ventilation.