Non-specific symptoms, as well as the lack of a cost-effective test to triage patients in primary care, has resulted in increased time-to-diagnosis and a poor prognosis for brain cancer patients. A ...rapid, cost-effective, triage test could significantly improve this patient pathway. A blood test using attenuated total reflection (ATR)-Fourier transform infrared (FTIR) spectroscopy for the detection of brain cancer, alongside machine learning technology, is advancing towards clinical translation. However, whilst the methodology is simple and does not require extensive sample preparation, the throughput of such an approach is limited. Here we describe the development of instrumentation for the analysis of serum that is able to differentiate cancer and control patients at a sensitivity and specificity of 93.2% and 92.8%. Furthermore, preliminary data from the first prospective clinical validation study of its kind are presented, demonstrating how this innovative technology can triage patients and allow rapid access to imaging.
It has recently been demonstrated that a spectroscopic test using blood-serum is able to effectively identify brain tumours in patients with sensitivities and specificities as high as 91.5% and 83% ...respectively. The approach employs Attenuated Total Reflectance - Fourier Transform Infrared (ATR-FTIR) spectroscopy to derive a disease specific spectroscopic signature, that using pattern recognition and machine learning algorithms is able to identify brain tumour cases. The ability to identify brain cancer cases based on serum samples alone raises the possibility of systematic screening prior to investigation with more expensive (MRI/CT imaging) and invasive (biopsy) tests. However, current methodology is currently limited to single patient analysis due to limitations in standard instrumentation. Here, we investigate the performance of a novel ATR-FTIR spectroscopic approach that allows automated, disposable, and multi-patient sampling. Our results indicate that this optimised approach is able to stratify brain tumour patients at performances equivalent to previous approaches, with sensitivities and specificities as high as 94.56% and 87.65% respectively. In advance of any prospective clinical study results being available, a cost-effectiveness analysis (CEA) was conducted to calculate the effects on health outcomes and health service costs of introducing this technology as a triage tool in primary and secondary care. Results indicate that using a serum spectroscopy test for brain tumours in both scenarios may be considered highly cost-effective in an HTA agency decision making process. Incremental cost-effectiveness ratios were well below standard threshold values of £20,000 to £30,000 per quality adjusted life year (QALY) gained used in the UK, and similar thresholds used internationally. In primary care, the test has the potential to be both more effective and cost saving for the health service.
Data quality and reproducibility are vital for robust, reliable and consistent diagnostic techniques within clinical environments. Most variance within clinical laboratories occur within the ...pre-analytical phase, prior to obtaining and analysing data. Herein, we investigate pre-analytical considerations for the spectroscopic analysis of blood serum for the purpose of clinical diagnostics.
Variables within sample collection, storage and preparation are explored in order to evaluate their effects on the spectral outcome, including; differences between sample collection tubes, centrifugal speed and time, short and long-term storage conditions, individual analyst technique, sample volumes, environment of sample batches, as well as various drying techniques. Exploratory data analysis using principal component analysis was implemented to unearth spectral variance not immediately observable.
Minor spectral variations were observed within each experiment; however, these were not considered significant differences as a result of these varying experimental factors. Variation between different operator techniques when preparing samples was observed, yet can be resolved with appropriate standard operating procedures, regardless of other factors such as sample volume and storage conditions. The findings within this report suggest that experimental variations within a laboratory, or between different laboratories, does not significantly affect the spectral outcome, and with good laboratory practice and careful sample handling results should be consistent and reliable.
This paper reports a study of the nutritive value of fertilized vs. unfertilized pasture herbage, with particular reference to the quality of the protein, as measured by comparative feeding trials. A ...technique for the management of growing rabbits as experimental animals for such tests is also described.Significant differences were found not only between certain pure species of grasses but also between the mixed herbage from fertilized and unfertilized pastures, which could not satisfactorily be explained on the basis of the usually advanced theories, viz., energy value, protein level and miner-al (Ca. and P.) content of these feeds. From the results obtained in these studies, the conclusions seem warranted that: (1) quality of protein (amino acid balance) may be an important factor determining the nutritive value of pasture herbage and (2) the improvement brought about through fertilization may be the result of a change in the constitution of its proteins.
Back pain is extremely common and causes more disability worldwide than any other condition.1 Up to 80% of individuals will experience back pain at some stage in their lives and as well as the burden ...to the individual there is also burden to the health service and economy. Generally, time, simple analgesia and gentle exercise will see most cases resolve. It is essential to differentiate between benign and serious causes for back pain. ‘Red flags’ should be identified within the presentation to try and exclude serious causes. Surgical treatment of back pain is reserved for persistent cases where conservative treatment has failed and there is a clear target for surgical intervention. This article discusses the clinical presentation, investigation and management of the common causes for back pain for the purpose of the MRCS examination.
Fluorescence lifetime imaging is a valuable technique for probing characteristics of wide ranging samples and sensing of the molecular environment. However, the desire to measure faster and reduce ...effects such as photo bleaching in optical photon-count measurements for lifetime estimation lead to inevitable effects of convolution with the instrument response functions and noise, causing a degradation of the lifetime accuracy and precision. To tackle the problem, this paper presents a robust and computationally efficient framework for recovering fluorophore sample decay from the histogram of photon-count arrivals modelled as a decaying single-exponential function. In the proposed approach, the temporal histogram data is first decomposed into multiple bins via an adaptive multi-bin signal representation. Then, at each level of the multi-resolution temporal space, decay information including both the amplitude and the lifetime of a single-exponential function is rapidly decoded based on a novel statistical estimator. Ultimately, a game-theoretic model consisting of two players in an "amplitude-lifetime" game is constructed to be able to robustly recover optimal fluorescence decay signal from a set of fused multi-bin estimates. In addition to theoretical demonstrations, the efficiency of the proposed framework is experimentally shown on both synthesised and real data in different imaging circumstances. On a challenging low photon-count regime, our approach achieves about 28% improvement in bias than the best competing method. On real images, the proposed method processes data on average around 63 times faster than the gold standard least squares fit. Implementation codes are available to researchers.
In collaboration with the Centers for Disease Control and Prevention, participating state and local health departments, universities, and community-based organizations applied venue-based, time-space ...sampling methods for the first wave of National HIV Behavioral Surveillance of men who have sex with men (NHBS-MSM). Conducted in 17 metropolitan areas in the United States and Puerto Rico from November 2003 through April 2005, NHBS-MSM methods included: (1) formative research to learn the venues, times, and methods to recruit MSM; (2) monthly sampling frames of eligible venues and day-time periods that met attendance, logistical, and safety criteria; and (3) recruitment of participants in accordance with randomly generated venue calendars. Participants were interviewed on HIV risk and prevention behaviors, referred to care when needed, and compensated for their time. By identifying the prevalence and trends of HIV risk and prevention behaviors, NHBS-MSM data may be used at local, state, and federal levels to help obtain, direct, and evaluate HIV prevention resources for MSM.
Pulmonary-resident memory T cells (T
) and B cells (B
) orchestrate protective immunity to reinfection with respiratory pathogens. Developing methods for the
detection of these populations would ...benefit both research and clinical settings.
To address this need, we developed a novel
immunolabelling approach combined with clinic-ready fibre-based optical endomicroscopy (OEM) to detect canonical markers of lymphocyte tissue residency
in human lungs undergoing
lung ventilation (EVLV).
Initially, cells from human lung digests (confirmed to contain T
/B
populations using flow cytometry) were stained with CD69 and CD103/CD20 fluorescent antibodies and imaged
using KronoScan, demonstrating it's ability to detect antibody labelled cells. We next instilled these pre-labelled cells into human lungs undergoing EVLV and confirmed they could still be visualised using both fluorescence intensity and lifetime imaging against background lung architecture. Finally, we instilled fluorescent CD69 and CD103/CD20 antibodies directly into the lung and were able to detect T
/B
following
labelling within seconds of direct
delivery of microdoses of fluorescently labelled antibodies.
, no wash, immunolabelling with
OEM imaging is a novel methodology with the potential to expand the experimental utility of EVLV and pre-clinical models.
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