Development of a compact fluorescence spectroscopy sensor for non-invasive monitoring gut function

Monitoring gut permeability is currently either invasive, inaccurate or difficult to perform in infants. We present a compact fluorescence sensor that overcomes some of these limitations, paving the way for non-invasive gut permeability monitoring

Quantifying hypoxia with diffuse reflectance spectroscopy for advanced prognostication and real-time response monitoring in rectal cancer: an in vivo feasibility study

Tumour hypoxia is a critical factor in treatment failure and resistance, and its accurate measurement with diffuse reflectance spectroscopy (DRS) could be used for prognostic and response monitoring purposes. In this in vivo characterisation study, we sequentially measured oxygenation trends over the entire course of tumour growth in mice using a multi-depth, fibre-optic DRS probe. Results demonstrated a clear downtrend in oxygenation over time. This progression was not always linear, with significant heterogeneity over time and between mice. Our findings will be further validated against gold standards prior to investigating whether hypoxia can be used to predict radiotherapy responses

Non-invasive assessment of intestinal permeability in healthy volunteers using transcutaneous fluorescence spectroscopy

The permeability of the intestinal barrier is altered in a multitude of gastrointestinal conditions such as Crohn's and coeliac disease. However, the clinical utility of gut permeability is currently limited due to a lack of reliable diagnostic tests. To address this issue, we report a novel technique for rapid, non-invasive measurement of gut permeability based on transcutaneous ('through-the-skin') fluorescence spectroscopy. In this approach, participants drink an oral dose of a fluorescent dye (fluorescein) and a fibre-optic fluorescence spectrometer is attached to the finger to detect permeation of the dye from the gut into the blood stream in a non-invasive manner. To validate this technique, clinical trial measurements were performed in 11 healthy participants. First, after 6 h of fasting, participants ingested 500 mg of fluorescein dissolved in 100 ml of water and fluorescence measurements were recorded at the fingertip over the following 3 h. All participants were invited back for a repeat study, this time ingesting the same solution but with 60 g of sugar added (known to transiently increase intestinal permeability). Results from the two study datasets (without and with sugar respectively) were analysed and compared using a number of analysis procedures. This included both manual and automated calculation of a series of parameters designed for assessment of gut permeability. Calculated values were compared using Student's T-tests, which demonstrated significant differences between the two datasets. Thus, transcutaneous fluorescence spectroscopy shows promise in non-invasively discriminating between two differing states of gut permeability, demonstrating potential for future clinical use

Lumen shape reconstruction using a soft robotic balloon catheter and electrical impedance tomography

Incorrectly sized balloon catheters can lead to increased post-surgical complications, yet even with preoperative imaging, correct selection remains a challenge. With limited feedback during surgery, it is difficult to verify correct deployment. We propose the use of integrated impedance measurements and Electrical Impedance Tomography (EIT) imaging to assess the deformation of the balloon and determine the size and shape of the surrounding lumen. Previous work using single impedance measurements, or pressure data and analytical models, whilst demonstrating high sizing accuracy, have assumed a circular cross section. Here we extend these methods by adding a multitude of electrodes to detect elliptical and occluded lumen and obtain EIT images to localise deformations. Using a 14 Fr (5.3 mm) catheter as an example, numerical simulations were performed to find the optimal electrode configuration of two rings of 8 electrodes spaced 10 mm apart. The simulations predicted that the maximum detectable aspect ratio decreased from 0.9 for a 14mm balloon to 0.5 at 30mm. The sizing and ellipticity detection results were verified experimentally. A prototype robotic balloon catheter was constructed to automatically inflate a compliant balloon while simultaneously recording EIT and pressure data. Data were collected in experiments replicating stenotic vessels with an elliptical and asymmetrical profile, and the widening of a lumen during angioplasty. After calibration, the system was able to correctly localise the occlusion and detect aspect ratios of 0.75. EIT images further localised the occlusion and visualised the dilation of the lumen during balloon inflation

The Heavenly Sanctuary/Temple Motif in the Hebrew Bible : Function and Relationship to the Earthly Counterparts

The present dissertation investigates the function of the heavenly sanctuary/temple and its relationship to the earthly counterparts, as reflected in forty-three passages of Hebrew Bible. Following an introductory chapter, the second chapter of this dissertation is devoted to a survey of the heavenly sanctuary/temple motif in the ANE literature, as represented by Sumerian, Akkadian, Hittite, Ugaritic, and Egyptian texts. The investigation of these texts reveals that the heavenly sanctuary/temple motif was part of the worldview of the ANE, where the heavenly sanctuary was not only assumed as existing in heaven, but also as functioning in close relationship to the earthly counterparts. Chapters 3, 4, and 5 are devoted to the exegesis of heavenly sanctuary/temple passages in the Hebrew Scriptures, according to the canonical divisions of the Hebrew Bible (namely Torah, Prophets, and Writings). This investigation reveals the pervasive presence of the heavenly sanctuary/temple motif in the Hebrew Bible and provides a broad delineation of its function and relationship to the earthly counterparts. It has been found that the heavenly sanctuary temple functions as a place of divine activities where YHWH supervises the cosmos, performs acts of judgment (sometimes conceived as a two-stage activity in which the execution of the sentence was preceded by an investigative phase), hears the prayers of the needy, and bestows atonement and forgiveness upon the sinners. The perception also emerged of the heavenly sanctuary/temple as a place of worship, a meeting place for the heavenly council, and an object of attack by anti-YHWH forces, thus playing a pivotal role in the cosmic battle between good and evil. In terms of its relationship to the earthly counterparts, it becomes apparent that the heavenly sanctuary/temple was understood to operate in structural and functional correspondence to the earthly counterparts. Moreover, some texts reveal a dynamic interaction between heavenly and earthly sanctuaries/temples, inasmuch as the activities of one could affect the other. Chapter 6 presents a theological synthesis of the heavenly sanctuary/temple motif based on the previous chapters. Some consideration is given to the similarities and differences between the heavenly sanctuary/temple motif as found in the Hebrew Bible and in its ANE background. Next, attention is devoted to some theological implications of the heavenly sanctuary/temple motif for the notions of judgment, cosmic battle, and covenant. To conclude, the Hebrew Bible conceives of the heavenly sanctuary/temple in functional and structural correspondence with its earthly counterpart with both sanctuaries/temples operating in dynamic interaction

The Functional PTPN22 Variant R620W Is Strongly Associated With Giant Cell Artetitis Predisposition

Pathophysiology and treatment of rheumatic disease

Identification of the PTPN22 functional variant R620W as susceptibility genetic factor for giant cell arteritis

Pathophysiology and treatment of rheumatic disease