Improving regulatory standards for clearing facilities

Clearinghouses (Banking) ; Payment systems

When participants get involved: reconsidering patient and public involvement in clinical trials at the MRC Clinical Trials Unit at UCL.

BACKGROUND: Patient and public involvement (PPI) in clinical trials aims to ensure that research is carried out collaboratively with patients and/or members of the public. However, current guidance on involving clinical trial participants in PPI activities is not consistent. METHODS: We reviewed the concept of participant involvement, based on our experience. Two workshops were held at the MRCCTU at UCL with the aim of defining participant involvement, considering its rationale; benefits and challenges; and identifying appropriate models for participant involvement in clinical trials. We considered how participant involvement might complement the involvement of other public contributors. Both workshops were attended by two patient representatives and seven staff members with experience of PPI in trials. Two of the staff members had also been involved in studies that had actively involved participants. They shared details of that work to inform discussions. RESULTS: We defined trial participants as individuals taking part in the study in question, including those who had already completed their trial treatment and/or follow-up. Because of their direct experience, involving participants may offer advantages over other public contributors; for example, in studies of new interventions or procedures, and where it is hard to identify or reach patient or community groups that include or speak for the study population. Participant involvement is possible at all stages of a trial; however, because there are no participants to involve during the design stage of a trial, prior to enrolment, participant involvement should complement and not replace involvement of PPI stakeholders. A range of models, including those with managerial, oversight or responsive roles are appropriate for involving participants; however, involvement in data safety and monitoring committees may not be appropriate where there is a potential risk of unblinding. Involvement of participants can improve the trial experience for other participants; optimising study procedures, improving communications; however, there are some specific, notably, managing participant confidentiality and practicalities relating to payments. CONCLUSIONS: Participant involvement in clinical trials is feasible and complements other forms of PPI in clinical trials. Involving active participants offers significant advantages, particularly in circumstances where trials are assessing new, or otherwise unavailable, therapies or processes. We recommend that current guidance on PPI should be updated to routinely consider including participants as valid stakeholders in PPI and potentially useful approach to PPI

A Decision Tool to Identify Population Management Strategies for Common Ravens and Other Avian Predators

Some avian species have developed the capacity to leverage resource subsidies associated with human manipulated landscapes to increase population densities in habitats with naturally low carrying capacities. Elevated corvid densities and new territory establishment have led to an unsustainable increase in depredation pressure on sympatric native wildlife prey populations as well as in crop damage. Yet, subsidized predator removal programs aimed at reducing densities are likely most effective longer-term when conducted in tandem with subsidy control, habitat management, and robust assessment monitoring programs. We developed decision support software that leverages stage structured Lefkovitch population matrices to compare and identify treatment strategies that reduce subsidized avian predator densities most efficiently, in terms of limiting both cost and take levels. The StallPOPd (Version 4; available at https://doi.org/10.7298/sk2e-0c38.4) software enables managers to enter the area of their management stratum and the demographic properties (vital rates) of target bird population(s) of interest to evaluate strategies to decrease or curtail further population growth. Strategies explicitly include the reduction in fertility (i.e., eggs hatched) and/or the culling of hatchlings, non-breeders and/or breeders, but implicitly comprise reduction in survival or reproduction through subsidy denial. We illustrate the utilities of the software with examples using common ravens (Corvus corax; ravens) in the Mojave Desert of California, USA. Unfortunately, the survival and reproduction effects of each unit of a particular subsidy in that system have remained elusive, though this is the priority of current research. Because the software leverages a life history representation that is known to characterize hundreds of wildlife species in addition to ravens, the work expands the suite of tools available to wildlife managers and agricultural industry specialists to abate bird damage and impacts on sensitive wildlife in habitats with persistent human subsidies

Bostonia: The Boston University Alumni Magazine. Volume 10

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

Bostonia: The Boston University Alumni Magazine. Volume 12

Founded in 1900, Bostonia magazine is Boston University’s main alumni publication

SOX9 predicts progression towards cirrhosis in patients while its loss protects against liver fibrosis

Fibrosis and organ failure is a common endpoint for many chronic liver diseases. Much is known about the upstream inflammatory mechanisms provoking fibrosis and downstream potential for tissue remodeling. However, less is known about the transcriptional regulation in vivo governing fibrotic matrix deposition by liver myofibroblasts. This gap in understanding has hampered molecular predictions of disease severity and clinical progression and restricted targets for antifibrotic drug development. In this study we show the prevalence of SOX9 in biopsies from patients with chronic liver disease correlated with fibrosis severity and accurately predicted disease progression towards cirrhosis. Inactivation of Sox9 in mice protected against both parenchymal and biliary fibrosis, improved liver function and ameliorated chronic inflammation. SOX9 was downstream of mechanosignaling factor, YAP1. These data demonstrate a role for SOX9 in liver fibrosis and open the way for the transcription factor and its dependent pathways as new diagnostic, prognostic and therapeutic targets in patients with liver fibrosis

TGF-b2 induction regulates invasiveness of theileria-transformed leukocytes and disease susceptibility

Theileria parasites invade and transform bovine leukocytes causing either East Coast fever (T. parva), or tropical theileriosis (T. annulata). Susceptible animals usually die within weeks of infection, but indigenous infected cattle show markedly reduced pathology, suggesting that host genetic factors may cause disease susceptibility. Attenuated live vaccines are widely used to control tropical theileriosis and attenuation is associated with reduced invasiveness of infected macrophages in vitro. Disease pathogenesis is therefore linked to aggressive invasiveness, rather than uncontrolled proliferation of Theileria-infected leukocytes. We show that the invasive potential of Theileria-transformed leukocytes involves TGF-b signalling. Attenuated live vaccine lines express reduced TGF-b2 and their invasiveness can be rescued with exogenous TGF-b. Importantly, infected macrophages from disease susceptible Holstein-Friesian (HF) cows express more TGF-b2 and traverse Matrigel with great efficiency compared to those from disease-resistant Sahiwal cattle. Thus, TGF-b2 levels correlate with disease susceptibility. Using fluorescence and time-lapse video microscopy we show that Theileria-infected, disease-susceptible HF macrophages exhibit increased actin dynamics in their lamellipodia and podosomal adhesion structures and develop more membrane blebs. TGF-b2-associated invasiveness in HF macrophages has a transcription-independent element that relies on cytoskeleton remodelling via activation of Rho kinase (ROCK). We propose that a TGF-b autocrine loop confers an amoeboid-like motility on Theileria-infected leukocytes, which combines with MMP-dependent motility to drive invasiveness and virulence

Bostonia: The Boston University Alumni Magazine. Volume 9

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

A risk prediction model for the assessment and triage of women with hypertensive disorders of pregnancy in low-resourced settings: the miniPIERS (Pre-eclampsia Integrated Estimate of RiSk) multi-country prospective cohort study.

BACKGROUND: Pre-eclampsia/eclampsia are leading causes of maternal mortality and morbidity, particularly in low- and middle- income countries (LMICs). We developed the miniPIERS risk prediction model to provide a simple, evidence-based tool to identify pregnant women in LMICs at increased risk of death or major hypertensive-related complications. METHODS AND FINDINGS: From 1 July 2008 to 31 March 2012, in five LMICs, data were collected prospectively on 2,081 women with any hypertensive disorder of pregnancy admitted to a participating centre. Candidate predictors collected within 24 hours of admission were entered into a step-wise backward elimination logistic regression model to predict a composite adverse maternal outcome within 48 hours of admission. Model internal validation was accomplished by bootstrapping and external validation was completed using data from 1,300 women in the Pre-eclampsia Integrated Estimate of RiSk (fullPIERS) dataset. Predictive performance was assessed for calibration, discrimination, and stratification capacity. The final miniPIERS model included: parity (nulliparous versus multiparous); gestational age on admission; headache/visual disturbances; chest pain/dyspnoea; vaginal bleeding with abdominal pain; systolic blood pressure; and dipstick proteinuria. The miniPIERS model was well-calibrated and had an area under the receiver operating characteristic curve (AUC ROC) of 0.768 (95% CI 0.735-0.801) with an average optimism of 0.037. External validation AUC ROC was 0.713 (95% CI 0.658-0.768). A predicted probability ≥25% to define a positive test classified women with 85.5% accuracy. Limitations of this study include the composite outcome and the broad inclusion criteria of any hypertensive disorder of pregnancy. This broad approach was used to optimize model generalizability. CONCLUSIONS: The miniPIERS model shows reasonable ability to identify women at increased risk of adverse maternal outcomes associated with the hypertensive disorders of pregnancy. It could be used in LMICs to identify women who would benefit most from interventions such as magnesium sulphate, antihypertensives, or transportation to a higher level of care