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

Area of review: how large is large enough for carbon storage?

The Texas Gulf Coast is an attractive target for carbon storage. Stacked sand-shale layers provide large potential storage volumes and defense-in-depth leakage protection. However, multiple perforations resulting from intensive hydrocarbon exploration and production have weakened seal integrity in many favorable locations. If the ultimate goal of carbon storage is to isolate large volumes of CO2 for hundreds to thousands of years, plume migration will encounter inadequately completed wells miles away from the injection zone. Moreover, the detrimental impact of CO2 on cement could undermine the structural integrity of all contacted wells, although pressure effects subside quickly after injection. Even wells abandoned to current standards cannot be guaranteed leak-free in the long term. We describe spatial statistics extracted from the Texas RRC Well Bore database as applied to carbon storage. Although the Area of Review (AOR) has been traditionally defined by a fixed radius with the strong regulatory requirement that the injectate stays within the injection layer, buoyancy is a major characteristic of CO2 that introduces a third dimension into the Area of Review process. Using simple geological mapping to characterize structural traps, we determine the likely pathway and the contacted volume of a migrating plume. The latter can be as large as a fault compartment with dimensions of 20 km × 20 km. However, the contacted volume is ultimately a function of the total injected volume, and the specifics of each project should dictate the dimensions of the zone of endangering influence (ZEI). An option, viable for the Texas Gulf Coast, to reduce geologic uncertainty, to decrease the impact of wells, and to limit the amount of information to be collected, is to inject CO2 below the maximum penetration of most wells.Bureau of Economic Geolog

Quasilocal energy for rotating charged black hole solutions in general relativity and string theory

We explore the (non)-universality of Martinez's conjecture, originally proposed for Kerr black holes, within and beyond general relativity. The conjecture states that the Brown-York quasilocal energy at the outer horizon of such a black hole reduces to twice its irreducible mass, or equivalently, to \sqrt{A} /(2\sqrt{pi}), where `A' is its area. We first consider the charged Kerr black hole. For such a spacetime, we calculate the quasilocal energy within a two-surface of constant Boyer-Lindquist radius embedded in a constant stationary-time slice. Keeping with Martinez's conjecture, at the outer horizon this energy equals the irreducible mass. The energy is positive and monotonically decreases to the ADM mass as the boundary-surface radius diverges. Next we perform an analogous calculation for the quasilocal energy for the Kerr-Sen spacetime, which corresponds to four-dimensional rotating charged black hole solutions in heterotic string theory. The behavior of this energy as a function of the boundary-surface radius is similar to the charged Kerr case. However, we show that in this case it does not approach the expression conjectured by Martinez at the horizon.Comment: 15 page

Identification of senescent cells in multipotent mesenchymal stromal cell cultures: Current methods and future directions

Regardless of their tissue of origin, multipotent mesenchymal stromal cells (MSCs) are commonly expanded in vitro for several population doublings, in order to achieve a sufficient number of cells for therapy. Prolonged MSC expansion has shown to result in phenotypical, morphological and gene expression changes in MSCs, which ultimately lead to the state of senescence. The presence of senescent cells in therapeutic MSC batches is undesirable, as it reduces their viability, differentiation potential and trophic capabilities. Additionally, senescent cells acquire senescence-activated secretory phenotype, which may not only induce apoptosis in the neighbouring host cells following MSC transplantation, but also trigger local inflammatory reactions. This review outlines the current and promising new methodologies for the identification of senescent cells in MSC cultures, with a particular emphasis on non-destructive and label-free methodologies. Technologies allowing identification of individual senescent cells, based on new surface markers, offer potential advantage for targeted senescent cell removal using new-generation senolytic agents, and subsequent production of therapeutic MSC batches fully devoid of senescent cells. Methods or a combination of methods that are non-destructive and label-free, for example involving cell size and spectroscopic measurements, could be the best way forward as they do not modify the cells of interest thus maximising the final output of therapeutic-grade MSC cultures. The further incorporation of machine learning methods has also recently shown promise in facilitating, automating and enhancing the analysis of these measured data

Process evaluation of student health promotion programmes in rural Sabah

The Faculty of Medicine & health sciences, UMS has implemented a co-curricular programme which is aimed to be improving rural health and reducing inequalities of health in Sabah. Groups of medical students are formed and distributed in various areas of rural remote areas in Sabah. Based on the observation and interview findings, each student group conducted health promotion activities with the limited resources. Various health problems were explored in different areas and different ethnic groups of Sabah and students conducted their health promotion activities .There are some questions “Are they effective, how it works in implementation?” Poor implementation can lead to errors in outcome of the programmes. In this paper we focus on process evaluation for measuring the degree to which Health promotion programmes were implemented as designed by using determinant framework (active implementation framework) and process evaluation tools in yearly health promotion programmes from 2009-2018. Methods: The study measures the implementation of programmes with active implementation framework (Exploration, Installation, Initial implementation, Full implementation) and process evaluation tools such as validation of implementation integrity using specification of intervention areas, making guidelines and manual for intervention protocol, competency of students and supervisors and fidelity monitoring. We used 7 components of process evaluation particularly in context( Environmental influences), reach (Target participation), dose delivered (Lectures), dose received (learned by students with assessment methods), fidelity (Adherence to intervention delivery protocol), implementation (rating of execution and receipt of intervention) and recruitment (participant engagement). Results: It was found that fidelity, implementation strategies and some lessons learned after outreach programmes are importantly influence in implementing the programmes. Conclusion: The study shows process evaluation strategies is ideal tool for conducting the rural outreach health promotion programme to reduce the errors and obstacles in implementing the programmes to maintain the better quality of the projects

Factors Affecting Continued Participation in Tuberculosis Contact Investigation in a Low-Income, High-Burden Setting

ABSTRACT Setting: Outpatient clinics, Kota Kinabalu, Malaysia; January–April 2018. Objectives: To identify barriers to full participation in tuberculosis (TB) contact investigation. Methods: Cross-sectional study of knowledge, perceptions, and behaviours among TB contacts. This study was conducted among contacts who attended an initial clinic visit to explore retention in care. During this first visit, contacts were approached for participation in a questionnaire at a follow-up visit. Contacts who consented but did not subsequently attend were interviewed at home. Associations between questionnaire findings and attendance were tested using logistic regression. Results: Of the total 1436 identified contacts, 800 (56%) attended an initial clinic visit. Of 237 consenting TB contacts, 207 (87%) attended their follow-up appointment. In univariable analyses, the odds of attendance were highest for people notified to attend the TB clinic directly by a health inspector; close relatives of TB patients; non-students; people with higher incomes and smaller households; older individuals; males; and people not perceiving TB as stigmatising. In multivariable analysis, mode of notification to attend and having a close relative with TB remained significant. Conclusions: Health inspectors provide an effective role in TB contact investigation through direct personal communication to encourage the completion of the TB screening process, but this requires further integration with clinical processes, and with workplace and school-based investigations