Mathematical modelling of nanoparticle delivery to vascular tumours

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.The goal of any cancer therapy is to achieve efficient, tissue-specific targeting of drugs to cancer cells. However, most anticancer agents act on healthy and malignant tissue alike, potentially resulting in side effects to healthy tissue. This has motivated the development of treatment strategies that are cancer-cell specific; one approach uses biomimetic polymer vesicles (BPV) to deliver chemotherapeutic drugs into cells before releasing them. BPVs are synthetic membrane enclosed, nanometre-sized structures, and provide ideal drug delivery vectors because specific targeting to cancer cells can be achieved by coating with tumourspecific molecules. We present several mathematical models covering a wide range of length-scales pertinent to BPV-mediated delivery protocols and focus on capturing the in vivo environment by evaluating the impact of the underlying vascular structure upon the governing transport mechanisms. Firstly, we present models of specific binding of BPVs to cancer cells. Subsequently we examine the implications of these model outputs in the contexts of both discrete capillary architectures and higher level homogenized-models that track blood and BPV transport at the tissue scale (both intra- and extra-tumorally). Numerical solutions are discussed, and recommendations are presented on that optimal integration of the models to generate quantitative predictions associated with BPV treatment efficacy

Ordered groupoids and the holomorph of an inverse semigroup

We present a construction for the holomorph of an inverse semigroup, derived from the cartesian closed structure of the category of ordered groupoids. We compare the holomorph with the monoid of mappings that preserve the ternary heap operation on an inverse semigroup: for groups these two constructions coincide. We present detailed calculations for semilattices of groups and for the polycyclic monoids.Comment: 16 page

The extraordinary evolutionary history of the reticuloendotheliosis viruses

The reticuloendotheliosis viruses (REVs) comprise several closely related amphotropic retroviruses isolated from birds. These viruses exhibit several highly unusual characteristics that have not so far been adequately explained, including their extremely close relationship to mammalian retroviruses, and their presence as endogenous sequences within the genomes of certain large DNA viruses. We present evidence for an iatrogenic origin of REVs that accounts for these phenomena. Firstly, we identify endogenous retroviral fossils in mammalian genomes that share a unique recombinant structure with REVs—unequivocally demonstrating that REVs derive directly from mammalian retroviruses. Secondly, through sequencing of archived REV isolates, we confirm that contaminated Plasmodium lophurae stocks have been the source of multiple REV outbreaks in experimentally infected birds. Finally, we show that both phylogenetic and historical evidence support a scenario wherein REVs originated as mammalian retroviruses that were accidentally introduced into avian hosts in the late 1930s, during experimental studies of P. lophurae, and subsequently integrated into the fowlpox virus (FWPV) and gallid herpesvirus type 2 (GHV-2) genomes, generating recombinant DNA viruses that now circulate in wild birds and poultry. Our findings provide a novel perspective on the origin and evolution of REV, and indicate that horizontal gene transfer between virus families can expand the impact of iatrogenic transmission events

A new resorbable device for ligation of blood vessels - A pilot study

<p>Abstract</p> <p>Background</p> <p>During surgery, controlled haemostasis to prevent blood loss is vital for a successful outcome. It can be difficult to ligate vessels located deep in the abdomen. A device that is easy to use and enables secure ligatures could be beneficial. Cable ties made of nylon have been used for ligation but the non-resorbable material caused tissue reactions. The objective of this study was to use a resorbable material to construct a device with a self-locking mechanism and to test its mechanical strength and ligation efficiency.</p> <p>Methods</p> <p>The device was manufactured by injection moulding of polydioxanone, a resorbable polymer used for suture materials. Polydioxanone with inherent viscosities of 1.9 dL/g and 1.3 dL/g were tested. The device consisted of a perforated flexible band which could be pulled through a case with a locking mechanism. After a first version of the device had been tested, some improvements were made. The locking case was downsized, corners were rounded off, the band was made thicker and the mould was redesigned to produce longer devices. Tensile tests were performed with the second version.</p> <p>The first version of the device was used to ligate the ovarian pedicle in a euthanized dog and to test echogenicity of the device with ultrasound. Compression of vessels of the ovarian pedicle was examined by histology. Both versions of the device were tested for haemostasis of and tissue grip on renal arteries in six anaesthetised pigs.</p> <p>Results</p> <p>The tensile strength of the flexible band of the devices with inherent viscosity of 1.9 dL/g was 50.1 ± 5.5 N (range 35.2-62.9 N, <it>n </it>= 11) and the devices with inherent viscosity of 1.3 dL/g had a tensile strength of 39.8 ± 8.1 N (range 18.6-54.2 N, <it>n </it>= 11). Injection moulding of the polymer with lower inherent viscosity resulted in a longer flow distance.</p> <p>Both versions of the device had an effective tissue grip and complete haemostasis of renal arteries was verified. The device attached to the ovarian pedicle could be seen with ultrasound, and vessel compression and occlusion were verified by histology.</p> <p>Conclusions</p> <p>Tests of functionality of the device showed complete haemostasis and good tissue grip. Devices with a band of sufficient length were easily applied and tightened in tissue.</p

Treatment of mastitis during lactation

Treatment of mastitis should be based on bacteriological diagnosis and take national and international guidelines on prudent use of antimicrobials into account. In acute mastitis, where bacteriological diagnosis is not available, treatment should be initiated based on herd data and personal experience. Rapid bacteriological diagnosis would facilitate the proper selection of the antimicrobial. Treating subclinical mastitis with antimicrobials during lactation is seldom economical, because of high treatment costs and generally poor efficacy. All mastitis treatment should be evidence-based, i.e., the efficacy of each product and treatment length should be demonstrated by scientific studies. Use of on-farm written protocols for mastitis treatment promotes a judicious use of antimicrobials and reduces the use of antimicrobials

Why simulation can be efficient: on the preconditions of efficient learning in complex technology based practices

<p>Abstract</p> <p>Background</p> <p>It is important to demonstrate learning outcomes of simulation in technology based practices, such as in advanced health care. Although many studies show skills improvement and self-reported change to practice, there are few studies demonstrating patient outcome and societal efficiency.</p> <p>The objective of the study is to investigate if and why simulation can be effective and efficient in a hi-tech health care setting. This is important in order to decide whether and how to design simulation scenarios and outcome studies.</p> <p>Methods</p> <p>Core theoretical insights in Science and Technology Studies (STS) are applied to analyze the field of simulation in hi-tech health care education. In particular, a process-oriented framework where technology is characterized by its devices, methods and its organizational setting is applied.</p> <p>Results</p> <p>The analysis shows how advanced simulation can address core characteristics of technology beyond the knowledge of technology's functions. Simulation's ability to address skilful device handling as well as purposive aspects of technology provides a potential for effective and efficient learning. However, as technology is also constituted by organizational aspects, such as technology status, disease status, and resource constraints, the success of simulation depends on whether these aspects can be integrated in the simulation setting as well. This represents a challenge for future development of simulation and for demonstrating its effectiveness and efficiency.</p> <p>Conclusion</p> <p>Assessing the outcome of simulation in education in hi-tech health care settings is worthwhile if core characteristics of medical technology are addressed. This challenges the traditional technical versus non-technical divide in simulation, as organizational aspects appear to be part of technology's core characteristics.</p

Reproductive performance of Norwegian cattle from 1985 to 2005: trends and seasonality

Declining reproductive performance is a serious breeding concern in many countries. To reveal the situation in Norwegian cattle, trends in reproductive performance were studied using insemination reports from 1985 to 2005 and data based on herd recording files from 1989 to 2005. The total number of first services was 469.765 in 1985 declining to 335.712 in 2005. The number of recorded herds and animals declined from 21.588 to 14.718 and 360.289 to 309.452 from 1989 to 2005, respectively. Sixty days non-return rate after single inseminations (NR60) increased from 68.1 in 1985 to 72.7% in 2005 (p < 0.001) and the number of services per inseminated animal (NIA) decreased from 1.8 to 1.6 (p < 0.001) from 1985 to 2005. However, return rates 0–3 days post insemination (RR0-3) increased from 6 to 12% in the same period (p < 0.001). NR60 was higher and the RR0-3 was lower in the summer season compared to the winter season during the whole period. A fertility index (FS), has been calculated from the herd recording files each year from 1989 to 2005. The average FS-index did not show a significant trend and the calving interval was also fairly constant between 12.4 and 12.6 months during this period. The average interval from calving to first and last insemination, respectively, increased from a low of 79 and 102 days in 1990 to a high of 86 and 108 days in 2005. Both intervals were consistently longer for cows in first lactation than for cows in later lactations. The percentage of inseminated animals reported culled because of poor fertility decreased from 6.0% in 1989 to 4.6% in 1996 and thereafter again increased to 6% in 2005. In conclusion, most fertility measures, mainly comprising the Norwegian Red (NRF) breed, show a relatively high level of reproductive performance with a positive or a relatively constant trend during the last two decades

Global Monitoring of Fault Zones and Volcanoes with Sentinel-1

Sentinel-1 represents a major step forward in enabling us to monitor the Earth's hazardous tectonic and volcanic zones. Here, we present the latest progress from the Centre for the Observation and Modelling of Earthquakes, Volcanoes and Tectonics (COMET), where we provide deformation results to the community for volcanoes and the tectonic belts. For the estimation of seismic hazard, we require relative accuracy on the order of 1 mm/yr between points 100 km apart. This requires mass processing of long time series of radar acquisitions. As of January 2018, we are producing in-terferograms systematically for the entire Alpine-Himalayan belt (~9000 × 2000 km) and the majority of subaerial volcanoes. Currently we make interferograms and coherence products available to the community, but we plan to also provide average deformation rates and displacement time series, in the future. The results are made available through a dedicated COMET portal, and we are in the process of linking them to the ESA G-TEP and EPOS. COMET also responds routinely to significant continental earthquakes, larger than ~Mw 6.0. The short repeat interval of Sentinel-1, together with the rapid availability of the data, allows us to do this within a few days for most earthquakes. For example, after the Mw 7.8 Kaikoura earthquake we supplied a processed interferogram to the community just 5 hours and 37 minutes after the Sentinel-1 acquisition. In this paper we provide an overview of some of the latest results for tectonics and volcanism and discuss how the accuracy of these products will improve as the number of data products acquired by Sentinel-1 increases

Lithic technological responses to Late Pleistocene glacial cycling at Pinnacle Point Site 5-6, South Africa

There are multiple hypotheses for human responses to glacial cycling in the Late Pleistocene, including changes in population size, interconnectedness, and mobility. Lithic technological analysis informs us of human responses to environmental change because lithic assemblage characteristics are a reflection of raw material transport, reduction, and discard behaviors that depend on hunter-gatherer social and economic decisions. Pinnacle Point Site 5-6 (PP5-6), Western Cape, South Africa is an ideal locality for examining the influence of glacial cycling on early modern human behaviors because it preserves a long sequence spanning marine isotope stages (MIS) 5, 4, and 3 and is associated with robust records of paleoenvironmental change. The analysis presented here addresses the question, what, if any, lithic assemblage traits at PP5-6 represent changing behavioral responses to the MIS 5-4-3 interglacial-glacial cycle? It statistically evaluates changes in 93 traits with no a priori assumptions about which traits may significantly associate with MIS. In contrast to other studies that claim that there is little relationship between broad-scale patterns of climate change and lithic technology, we identified the following characteristics that are associated with MIS 4: increased use of quartz, increased evidence for outcrop sources of quartzite and silcrete, increased evidence for earlier stages of reduction in silcrete, evidence for increased flaking efficiency in all raw material types, and changes in tool types and function for silcrete. Based on these results, we suggest that foragers responded to MIS 4 glacial environmental conditions at PP5-6 with increased population or group sizes, 'place provisioning', longer and/or more intense site occupations, and decreased residential mobility. Several other traits, including silcrete frequency, do not exhibit an association with MIS. Backed pieces, once they appear in the PP5-6 record during MIS 4, persist through MIS 3. Changing paleoenvironments explain some, but not all temporal technological variability at PP5-6.Social Science and Humanities Research Council of Canada; NORAM; American-Scandinavian Foundation; Fundacao para a Ciencia e Tecnologia [SFRH/BPD/73598/2010]; IGERT [DGE 0801634]; Hyde Family Foundations; Institute of Human Origins; National Science Foundation [BCS-9912465, BCS-0130713, BCS-0524087, BCS-1138073]; John Templeton Foundation to the Institute of Human Origins at Arizona State Universit