Simulating the Geometric Growth of the Marine Sponge Crella Incrustans

Simulating marine sponge growth helps marine biologists analyze, measure, and predict the effects that the marine environment has on marine sponges, and vice versa. This paper describes a way to simulate and grow geometric models of the marine sponge Crella incrustans while considering environmental factors including fluid flow and nutrients. The simulation improves upon prior work by changing the skeletal architecture of the sponge in the growth model to better suit the structure of Crella incrustans. The change in skeletal architecture and other simulation parameters are then evaluated qualitatively against photos of a real-life Crella incrustans sponge. The results support the hypothesis that changing the skeletal architecture from radiate accretive to Halichondrid produces a sponge model which is closer in resemblance to Crella incrustans than the prior work.Comment: 5 pages, 5 figures, IEEE VIS 2023, short paper, 9 supplementary figures, 1 supplementary tabl

Characterization of a murine mixed neuron-glia model and cellular responses to regulatory T cell-derived factors

Abstract One of the unmet clinical needs in demyelinating diseases such as Multiple Sclerosis (MS) is to provide therapies that actively enhance the process of myelin regeneration (remyelination) in the central nervous system (CNS). Oligodendrocytes, the myelinating cells of the CNS, play a central role in remyelination and originate from oligodendrocyte progenitor cells (OPCs). We recently showed that depletion of regulatory T cells (Treg) impairs remyelination in vivo, and that Treg-secreted factors directly enhance oligodendrocyte differentiation. Here we aim to further characterize the dynamics of Treg-enhanced oligodendrocyte differentiation as well as elucidate the cellular components of a murine mixed neuron-glia model. Murine mixed neuron-glia cultures were generated from P2–7 C57BL/6 mice and characterized for percentage of neuronal and glial cell populations prior to treatment at 7 days in vitro (div) as well as after treatment with Treg-conditioned media at multiple timepoints up to 12 div. Mixed neuron-glia cultures consisted of approximately 30% oligodendroglial lineage cells, 20% neurons and 10% microglia. Furthermore, a full layer of astrocytes, that could not be quantified, was present. Treatment with Treg-conditioned media enhanced the proportion of MBP+ oligodendrocytes and decreased the proportion of PDGFRα+ OPCs, but did not affect OPC proliferation or survival. Treg-enhanced oligodendrocyte differentiation was not caused by Treg polarizing factors, was dependent on the number of activation cycles Treg underwent and was robustly achieved by using 5% conditioned media. These studies provide in-depth characterization of a murine mixed neuron-glia model as well as further insights into the dynamics of Treg-enhanced oligodendrocyte differentiation

European badger (Meles meles) responses to low-intensity, selective culling: using mark recapture and relatedness data to assess social perturbation

Publication history: Accepted - 20 June 2022; Published online - 28 July 2022Culling the main wildlife host of bovine tuberculosis in Great Britain (GB) and Ireland, the European badger (Meles meles), has been employed in both territories to reduce infections in cattle. In GB, this has been controversial, with results suggesting that culling induces disturbance to badger social structure, facilitating wider disease dissemination. Previous analyses hypothesized that even very low-level, selective culling may cause similar deleterious effects by increasing ranging of individuals and greater mixing between social groups. To assess this hypothesis, a novel, prospective, landscape-scale ‘before-and-after’ Test and Vaccinate or Remove (TVR) study was implemented. Test-positive badgers were culled and test-negative badgers were Bacillus Calmette–Guérin (BCG) vaccinated and released. Mark–recapture metrics of badger ranging and genetic metrics of social group relatedness did not change significantly over the study period. However, selective culling was associated with a localized reduction in social group relatedness in culled groups. Ecological context is important; extrapolation across territories and other disease epidemiological systems (epi-systems) is likely to be challenging. However, we demonstrate that small-scale, selective removal of test-positive badgers was not associated with metrics of increased ranging but was associated with localized changes in social group relatedness. This adds to the evidence base on badger control options for policy makers.Department of Agriculture, Environment and Rural Affairs (DAERA) N

Using the net benefit regression framework to construct cost-effectiveness acceptability curves: an example using data from a trial of external loop recorders versus Holter monitoring for ambulatory monitoring of "community acquired" syncope

BACKGROUND: Cost-effectiveness acceptability curves (CEACs) describe the probability that a new treatment or intervention is cost-effective. The net benefit regression framework (NBRF) allows cost-effectiveness analysis to be done in a simple regression framework. The objective of the paper is to illustrate how net benefit regression can be used to construct a CEAC. METHODS: One hundred patients referred for ambulatory monitoring with syncope or presyncope were randomized to a one-month external loop recorder (n = 49) or 48-hour Holter monitor (n = 51). The primary endpoint was symptom-rhythm correlation during monitoring. Direct costs were calculated based on the 2003 Ontario Health Insurance Plan (OHIP) fee schedule combined with hospital case costing of labour, materials, service and overhead costs for diagnostic testing and related equipment. RESULTS: In the loop recorder group, 63.27% of patients (31/49) had symptom recurrence and successful activation, compared to 23.53% in the Holter group (12/51). The cost in US dollars for loop recording was $648.50 and$212.92 for Holter monitoring. The incremental cost-effectiveness ratio (ICER) of the loop recorder was $1,096 per extra successful diagnosis. The probability that the loop recorder was cost-effective compared to the Holter monitor was estimated using net benefit regression and plotted on a CEAC. In a sensitivity analysis, bootstrapping was used to examine the effect of distributional assumptions. CONCLUSION: The NBRF is straightforward to use and interpret. The resulting uncertainty surrounding the regression coefficient relates to the CEAC. When the link from the regression's p-value to the probability of cost-effectiveness is tentative, bootstrapping may be used

Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD

Expert Status and Performance

Expert judgements are essential when time and resources are stretched or we face novel dilemmas requiring fast solutions. Good advice can save lives and large sums of money. Typically, experts are defined by their qualifications, track record and experience [1], [2]. The social expectation hypothesis argues that more highly regarded and more experienced experts will give better advice. We asked experts to predict how they will perform, and how their peers will perform, on sets of questions. The results indicate that the way experts regard each other is consistent, but unfortunately, ranks are a poor guide to actual performance. Expert advice will be more accurate if technical decisions routinely use broadly-defined expert groups, structured question protocols and feedback

Inflammatory biomarkers in Alzheimer's disease plasma.

INTRODUCTION: Plasma biomarkers for Alzheimer's disease (AD) diagnosis/stratification are a "Holy Grail" of AD research and intensively sought; however, there are no well-established plasma markers. METHODS: A hypothesis-led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL; 259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed. RESULTS: Ten analytes showed significant intergroup differences. Logistic regression identified five (FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APOε4 adjusted, optimally differentiated AD and CTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI (AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Two analytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71). DISCUSSION: Plasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation

Design and synthesis of novel bicalutamide and enzalutamide derivatives as antiproliferative agents for the treatment of prostate cancer

Prostate cancer (PC) is one of the major causes of male death worldwide and the development of new and more potent anti-PC compounds is a constant requirement. Among the current treatments, (R)-bicalutamide and enzalutamide are non-steroidal androgen receptor antagonist drugs approved also in the case of castration-resistant forms. Both these drugs present a moderate antiproliferative activity and their use is limited due to the development of resistant mutants of their biological target. Insertion of fluorinated and perfluorinated groups in biologically active compounds is a current trend in medicinal chemistry, applied to improve their efficacy and stability profiles. As a means to obtain such effects, different modifications with perfluoro groups were rationally designed on the bicalutamide and enzalutamide structures, leading to the synthesis of a series of new antiproliferative compounds. Several new analogues displayed improved in vitro activity towards four different prostate cancer cell lines, while maintaining full AR antagonism and therefore representing promising leads for further development. Furthermore, a series of molecular modelling studies were performed on the AR antagonist conformation, providing useful insights on potential protein-ligand interactions