Effects of growth factors and receptor blockade on gastrointestinal cancer

The advent of recombinant peptide technology offers the potential to use one or several peptides to treat a variety of gastrointestinal conditions. However, although cell culture and animal models have shown proof of concept, we are still at a relatively early stage in translating their use to standard clinical practice. Similarly, peptide and non-peptide antagonists of growth factor receptors show great potential as novel antichemotherapy agents. However, their actual place in clinical practice has yet to be established

Human transforming growth factor a (TGF-alpha) is digested to a smaller (1-43), less biologically active, form in acidic gastric juice

Publisher version: http://gut.bmj.com/content/51/6/787.full.pd

Non-invasive assessment of pulmonary vascular resistance in pulmonary hypertension: Current knowledge and future direction

Pulmonary Hypertension (PHT) is relatively common, dangerous and under-recognised. Pulmonary hypertension is not a diagnosis in itself; it is caused by a number of differing diseases each with different treatments and prognoses. Therefore, timely and accurate recognition of the underlying cause for PHT is essential for appropriate management. This is especially true for patients with Pulmonary Arterial Hypertension (PAH) in the current era of disease-specific drug therapy. Measurement of Pulmonary Vascular Resistance (PVR) helps separate pre-capillary from post-capillary PHT, and is measured with right heart catheterisation (RHC). Echocardiography has been used to derive a number of non-invasive surrogates for PVR, with varying accuracy. Ultimately, the goal of non-invasive assessment of PVR is to separate PHT due to left heart disease from PHT due to increased PVR, to help streamline investigation and subsequent treatment. In this review, we summarise the physiology and pathophysiology of pulmonary blood flow, the various causes of pulmonary hypertension, and non-invasive surrogates for PVR

Assessing a standardised approach to measuring corticospinal integrity after stroke with DTI

The structural integrity of the corticospinal tract (CST) after stroke is closely linked to the degree of motor impairment. Simple and reliable methods of assessing white matter integrity within the CST would facilitate the use of this measure in routine clinical practice. Commonly, diffusion tensor imaging is used to measure voxel-wise fractional anisotropy (FA) in a variety of regions of interest (ROIs) representing the CST. Several methods are currently in use with no consensus about which approach is best. ROIs are usually either the whole CST or the posterior limb of the internal capsule (PLIC). These are created manually on brain images or with reference to an individual's CST determined by tractography. Once the ROI has been defined, the FA can be reported as an absolute measure from the ipsilesional side or as a ratio in comparison to the contralesional side. Both corticospinal tracking and manual ROI definition in individual stroke patients are time consuming and subject to bias. Here, we investigated whether using a CST template derived from healthy volunteers was a feasible method for defining the appropriate ROI within which to measure changes in FA. We reconstructed the CST connecting the primary motor cortex to the ipsilateral pons in 23 age-matched control subjects and 21 stroke patients. An average healthy CST template was created from the 23 control subjects. For each patient, FA values were then calculated for both the template CST and for their own CST. We compared patients' FA metrics between the two tracts by considering four measures (FA in the ipsilesional side, FA in the contralesional side, FA ratio of the ipsilesional side to the contralesional side and FA asymmetry between the two sides) and in two tract-based ROIs (whole tract and tract section traversing the PLIC). There were no significant differences in FA metrics for either method, except for contralesional FA. Furthermore, we found that FA metrics relating to CST damage all correlated with motor ability post-stroke equally well. These results suggest that the healthy CST template could be a surrogate structure for defining tract-based ROIs with which to measure stroke patients' FA metrics, avoiding the necessity for CST tracking in individual patients. CST template-based automated quantification of structural integrity would greatly facilitate implementation of practical clinical applications of diffusion tensor imaging

Business Models in Emerging Online Services

Due to advances in technology and the rapid growth of online services, a significant number of new and inventive web-based service models and delivery methods have been introduced. Although online resources and services are having an impact on more traditional service delivery mechanisms, it is not yet clear how these emerging mechanisms for online service delivery will result in profitable business models. In this paper, we consider emerging business models for online services and their implications for how services are delivered, used, and paid for. We demonstrate the changing roles of user / consumer and provider / seller. We also discuss the applicability of different business models for various domains

Telerehabilitation for people with physical disabilities and movement impairment: development and evaluation of an online toolkit for practitioners and patients.

PURPOSE: Telerehabilitation has increasingly been used since the COVID-19 pandemic but with limited guidance available on undertaking physical assessments using remote methods. We aimed to provide such guidance by developing a Telerehab Toolkit, an online information and training resource for practitioners, patients, and carers on telerehabilitation for people with physical disabilities and movement impairment. MATERIALS AND METHODS: Development and evaluation of the toolkit were informed by the Knowledge to Action framework and took place iteratively in two phases-knowledge creation and action. Information was collated from various sources including literature review, online survey, service evaluation, and focus group discussions. The toolkit has been evaluated using think-aloud interviews, e-mail and social media feedback from users, and analytics data on user engagement with the website. RESULTS: The Telerehab Toolkit focuses on remote physical assessments, and contains information on technology, digital skills, remote assessment tools, information governance, and safety for telerehabilitation. Resources include top tips from practitioners and patients, how-to guides, checklists, videos, and links to evidence. CONCLUSIONS: The Telerehab Toolkit has been well-received by practitioners, healthcare students, patients, and carers, is being disseminated widely, and is freely available (www.plymouth.ac.uk/research/telerehab). IMPLICATIONS FOR REHABILITATIONTelerehabilitation has been increasingly used since the COVID-19 pandemic, but with limited guidance and training for practitioners on undertaking safe and effective remote physical assessments.The Telerehab Toolkit has been developed iteratively using the Knowledge to Action framework; it is a free online resource for practitioners and patients with specific guidance on telerehabilitation for physical disabilities and movement impairment.It is anticipated that the resource will help to improve the knowledge, skills, and confidence of the current and future rehabilitation workforce

Structure, spin correlations and magnetism of the S=1/2S = 1/2 square-lattice antiferromagnet Sr2_2CuTe1−x_{1-x}Wx_xO6_6 (0≤x≤10 \leq x \leq 1)

Quantum spin liquids are highly entangled magnetic states with exotic properties. The $S = 1/2$ square-lattice Heisenberg model is one of the foundational models in frustrated magnetism with a predicted, but never observed, quantum spin liquid state. Isostructural double perovskites Sr$_2$CuTeO$_6$ and Sr$_2$CuWO$_6$ are physical realizations of this model, but have distinctly different types magnetic order and interactions due to a $d^{10}/d^0$ effect. Long-range magnetic order is suppressed in the solid solution Sr$_2$CuTe$_{1-x}$W$_x$O$_6$ in a wide region of $x = 0.05-0.6$, where the ground state has been proposed to be a disorder-induced spin liquid. Here we show that the spin-liquid-like $x = 0.2$ and $x = 0.5$ samples have distinctly different local spin correlations, which suggests they have different ground states. Furthermore, the previously ignored interlayer coupling between the square-planes is likely to play a role in the suppression of magnetic order on the W-rich side at $x \approx 0.6$. These results highlight the complex magnetism of Sr$_2$CuTe$_{1-x}$W$_x$O$_6$ and hint at a new quantum critical point at $x \approx 0.3$.Comment: 19+8 pages, 6+8 figure

Prophylactic Intra-Aortic Balloon Counterpulsation in High Risk Cardiac Surgery: The PINBALL Pilot Multicentre, Registry-Linked, Randomised, Controlled Feasibility Trial

Background: Prophylactic intra-aortic balloon counterpulsation (IABC) is commonly used in selected patients undergoing coronary artery bypass graft (CABG) surgery, but definitive evidence is lacking. The aim of the multicentre PINBALL Pilot randomised controlled trial (RCT) was to assess the feasibility of performing a definitive trial to address this question. Methods: Patients listed for CABG surgery with impaired left ventricular function and at least one additional risk factor for postoperative low cardiac output syndrome were eligible for inclusion if the treating surgical team was uncertain as to the benefit of prophylactic IABC. The primary outcome of feasibility was based on exceeding a pre-specified recruitment rate, protocol compliance and follow-up. Results: The recruitment rate of 0.5 participants per site per month did not meet the feasibility threshold of two participants per site per month and the study was stopped early after enrolment of 24 out of the planned sample size of 40 participants. For 20/24 (83%) participants, preoperative IABC use occurred according to study assignment. Six (6)-month follow-up was available for all enrolled participants, [IABC 1 death (8%) vs. control 1 death (9%), p = 0.95]. Conclusion: The PINBALL Pilot recruitment rate was insufficient to demonstrate feasibility of a multicentre RCT of prophylactic IABC in high risk patients undergoing CABG surgery

Structure, Spin Correlations, and Magnetism of the S = 1/2 Square-Lattice Antiferromagnet Sr2CuTe1-xWxO6 (0 ≤ x ≤ 1)

Quantum spin liquids are highly entangled magnetic states with exotic properties. The S = 1/2 square-lattice Heisenberg model is one of the foundational models in frustrated magnetism with a predicted, but never observed, quantum spin liquid state. Isostructural double perovskites Sr2CuTeO6 and Sr2CuWO6 are physical realizations of this model but have distinctly different types of magnetic order and interactions due to a d10/d0 effect. Long-range magnetic order is suppressed in the solid solution Sr2CuTe1-xWxO6 in a wide region of x = 0.05-0.6, where the ground state has been proposed to be a disorder-induced spin liquid. Here, we present a comprehensive neutron scattering study of this system. We show using polarized neutron scattering that the spin liquid-like x = 0.2 and x = 0.5 samples have distinctly different local spin correlations, which suggests that they have different ground states. Low-temperature neutron diffraction measurements of the magnetically ordered W-rich samples reveal magnetic phase separation, which suggests that the previously ignored interlayer coupling between the square planes plays a role in the suppression of magnetic order at x ≈ 0.6. These results highlight the complex magnetism of Sr2CuTe1-xWxO6 and hint at a new quantum critical point between 0.2 &lt; x &lt; 0.4.</p