Modelling of Tirapazamine effects on solid tumour morphology

Bioreductive drugs are in clinical practice to exploit the resistance from tumour microenvironments especially in the hypoxic region of tumour. We pre-sented a tumour treatment model to capture the pharmacology of one of the most prominent bioreductive drugs, Tirapazamine (TPZ) which is in clinical trials I and II. We calculated solid tumour mass in our previous work and then integrated that model with TPZ infusion. We calculated TPZ cytotoxicity, concentration, penetra-tion with increasing distance from blood vessel and offered resistance from micro-environments for drug penetration inside the tumour while considering each cell as an individual entity. The impact of these factors on tumour morphology is also showed to see the drug behaviour inside animals/humans tumours. We maintained the heterogeneity factors in presented model as observed in real tumour mass es-pecially in terms of cells proliferation, cell movement, extracellular matrix (ECM) interaction, and the gradients of partial oxygen pressure (pO2) inside tumour cells during the whole growth and treatment activity. The results suggest that TPZ high concentration in combination with chemotherapy should be given to get maximum abnormal cell killing. This model can be a good choice for oncologists and re-searchers to explore more about TPZ action inside solid tumour

Advance telephone calls ahead of reminder questionnaires increase response rate in non-responders compared to questionnaire reminders only : The RECORD phone trial

Peer reviewedPublisher PD

Perceptual Pluralism

Perceptual systems respond to proximal stimuli by forming mental representations of distal stimuli. A central goal for the philosophy of perception is to characterize the representations delivered by perceptual systems. It may be that all perceptual representations are in some way proprietarily perceptual and differ from the representational format of thought (Dretske 1981; Carey 2009; Burge 2010; Block ms.). Or it may instead be that perception and cognition always trade in the same code (Prinz 2002; Pylyshyn 2003). This paper rejects both approaches in favor of perceptual pluralism, the thesis that perception delivers a multiplicity of representational formats, some proprietary and some shared with cognition. The argument for perceptual pluralism marshals a wide array of empirical evidence in favor of iconic (i.e., image-like, analog) representations in perception as well as discursive (i.e., language-like, digital) perceptual object representations

A Mathematical Model of Liver Cell Aggregation In Vitro

The behavior of mammalian cells within three-dimensional structures is an area of intense biological research and underpins the efforts of tissue engineers to regenerate human tissues for clinical applications. In the particular case of hepatocytes (liver cells), the formation of spheroidal multicellular aggregates has been shown to improve cell viability and functionality compared to traditional monolayer culture techniques. We propose a simple mathematical model for the early stages of this aggregation process, when cell clusters form on the surface of the extracellular matrix (ECM) layer on which they are seeded. We focus on interactions between the cells and the viscoelastic ECM substrate. Governing equations for the cells, culture medium, and ECM are derived using the principles of mass and momentum balance. The model is then reduced to a system of four partial differential equations, which are investigated analytically and numerically. The model predicts that provided cells are seeded at a suitable density, aggregates with clearly defined boundaries and a spatially uniform cell density on the interior will form. While the mechanical properties of the ECM do not appear to have a significant effect, strong cell-ECM interactions can inhibit, or possibly prevent, the formation of aggregates. The paper concludes with a discussion of our key findings and suggestions for future work

Taxa‐dependent temporal trends in the abundance and size of sea urchins in subtropical eastern Australia

Subtropical reefs host a dynamic mix of tropical, subtropical, and temperate species that is changing due to shifts in the abundance and distribution of species in response to ocean warming. In these transitional communities, biogeographic affinity is expected to predict changes in species composition, with projected increases of tropical species and declines in cool-affinity temperate species. Understanding population dynamics of species along biogeographic transition zones is critical, especially for habitat engineers such as sea urchins that can facilitate ecosystem shifts through grazing. We investigated the population dynamics of sea urchins on coral-associated subtropical reefs at 7 sites in eastern Australia (28.196° S to 30.95° S) over 9 years (2010–2019), a period impacted by warming and heatwaves. Specifically, we investigated the density and population size structure of taxa with temperate (Centrostephanus rodgersii, Phyllacanthus parvispinus), subtropical (Tripneustes australiae) and tropical (Diadema spp.) affinities. Counter to expectation, biogeographic affinity did not explain shifts in species abundances in this region. Although we expected the abundance of tropical species to increase at their cold range boundaries, tropical Diadema species declined across all sites. The subtropical T. australiae also showed declines, while populations of the temperate C. rodgersii were remarkably stable throughout our study period. Our results show that temporal patterns of sea urchin populations in this region cannot be predicted by bio-geographic affinity alone and contribute critical information about the population dynamics of these important herbivores along this biogeographic transition zone

Synovial sepsis of unknown origin in the adult Thoroughbred racehorse

Background: Synovial sepsis of unknown origin is a rare cause of lameness in the adult horse, and a haematogenous pathogenesis has been proposed in previous cases. Objectives: To describe the features and outcome of synovial sepsis of unknown origin in adult Thoroughbred racehorses. Study design: Retrospective case series. Methods: Hospital records for admissions between 2005 and 2015 were reviewed to identify adult horses diagnosed with synovial sepsis of unknown origin. Presentation, clinicopathological, microbiological and diagnostic imaging findings were recorded. Treatment methods, surgical findings, complications and long-term outcome were evaluated. Results: Eleven cases were identified over the study period. Diagnosis was established from clinical examination and clinicopathologic findings, which were comparable to other aetiologies of synovial sepsis. Affected structures included synovial joints, tendon sheaths and bursae. Concurrent osteochondritis dissecans or articular cartilage lesions were evident during arthroscopic surgery in three cases. Significant intrasynovial haemorrhage was not identified. Microbial culture of synovial fluid or synovial biopsy was positive in 6/11 of cases, with all isolates being Gram-positive cocci. Of the 6 positive microbial cultures, all isolates demonstrated in vitro sensitivity to a cephalosporin antimicrobial agent. A concurrent remote wound was present in a single case. No other potential origins of bacteraemia were identified. Treatment methods included endoscopic surgery, standing multineedle lavage, intravenous regional limb perfusion, intrasynovial medication and/or systemic antimicrobial administration. All horses survived to hospital discharge. For the 6/11 cases that raced following synovial sepsis, the median period for return to racing was 221 days. Main limitations: A small study population, which was retrospectively reviewed. Conclusions: Synovial sepsis of unknown origin is rare in the adult Thoroughbred racehorse and can affect a range of synovial structures. A concurrent potential source of bacteraemia is rarely identified. With appropriate management, the prognosis to return to racing is fair

Higher serum immunoglobulin G3 levels may predict the development of multiple sclerosis in individuals with Clinically Isolated Syndrome

Clinically isolated syndrome (CIS) is a first episode of neurological symptoms that may precede a diagnosis of multiple sclerosis (MS). Therefore, studying individuals with CIS may lead to breakthroughs in understanding the development and pathogenesis of MS. In this study, serum levels of immunoglobulin (Ig)G, IgA, IgM, and IgG1–4 were measured in 20 people with CIS and compared with those in 10 healthy controls (HC) and 8 people with MS. Serum Ig levels in individuals with CIS were compared with (a) the time to their conversion from CIS to MS, (b) serum levels of antibodies to Epstein–Barr virus, (c) frequencies of T regulatory (Treg), T follicular regulatory (Tfr), and B cell subsets, and (d) Treg/Tfr expression of Helios. Serum IgG, IgM, and IgG2 levels were significantly lower in people with CIS than HC, and IgG, IgM, and IgG1 levels were significantly lower in people with CIS than MS. After adjusting for age, sex, and serum 25(OH) vitamin D3 [25(OH)D] levels, CIS was associated with lower serum levels of IgG and IgG2 compared with HC (p = 0.001 and p < 0.001, respectively). People with MS had lower IgG2 levels (p < 0.001) and IgG2 proportions (%IgG; p = 0.007) compared with HC. After adjusting for age, sex, and 25(OH)D, these outcomes remained, in addition to lower serum IgA levels (p = 0.01) and increased IgG3 levels (p = 0.053) in people with MS compared with HC. Furthermore, serum from people with MS had increased proportions of IgG1 and IgG3 (p = 0.03 and p = 0.02, respectively), decreased proportions of IgG2 (p = 0.007), and greater ratios of “upstream” to “downstream” IgG subclasses (p = 0.001) compared with HC. Serum IgG3 proportions (%IgG) from people with CIS correlated with the frequency of plasmablasts in peripheral blood (p = 0.02). Expression of Helios by Treg and Tfr cell subsets from individuals with CIS correlated with levels of serum IgG2 and IgG4. IgG3 levels and proportions of IgG3 (%IgG) in serum at CIS diagnosis were inversely correlated with the time until conversion to MS (p = 0.018 and p < 0.001, respectively), suggesting they may be useful prognostic markers of individuals with CIS who rapidly convert to MS

“That's cool, you’re a musician and you drink”: Exploring entertainers’ accounts of their unique workplace relationship with alcohol

This qualitative research investigates the alcohol experiences of entertainers who perform within licensed premises. Previous, mainly quantitative, studies have found that entertainers, specifically musicians, are an occupational group who drink excessively. This qualitative study draws on a wider sample of entertainers to examine their accounts of drinking in the workplace and the explanations they provide for this. We conducted individual semi-structured interviews (n = 24) with band-members, variety acts and DJs in Glasgow, Scotland. This revealed a workplace characterised by continual opportunities for often free alcohol consumption. Unlike most occupations, for entertainers ‘drinking-on-the-job’ was normative, expected, and sometimes encouraged by peers, the public, employers or sponsors. Entertainers also experienced performance-related incentives to drink before, during and/or after a show; including anxiety, matching their intoxication level to the audience's, and ‘reward-drinking’. This qualitative research confirms the unique nature of the entertainer-alcohol link, even in comparison to that found within other leisure industry occupations. While providing some explanation as to why entertainers might drink excessively, participants’ accounts also suggested potential strategies for avoiding the negative outcomes of workplace drinking

Magnetic trapping of ultracold neutrons

Three-dimensional magnetic confinement of neutrons is reported. Neutrons are loaded into an Ioffe-type superconducting magnetic trap through inelastic scattering of cold neutrons with 4He. Scattered neutrons with sufficiently low energy and in the appropriate spin state are confined by the magnetic field until they decay. The electron resulting from neutron decay produces scintillations in the liquid helium bath that results in a pulse of extreme ultraviolet light. This light is frequency downconverted to the visible and detected. Results are presented in which 500 +/- 155 neutrons are magnetically trapped in each loading cycle, consistent with theoretical predictions. The lifetime of the observed signal, 660 s +290/-170 s, is consistent with the neutron beta-decay lifetime.Comment: 17 pages, 18 figures, accepted for publication in Physical Review