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

A New Differential Positioning Method using Modulation Correlation of Signals of Opportunity

Global Navigation Satellite Systems (GNSS) have become the positioning systems of choice for many applications. However, GNSS signals are susceptible to obstruction, interference and jamming. Therefore, to maximize robustness and integrity, it is necessary to employ a dissimilar positioning technology that can operate independently and back-up GNSS. One such technology exploits 'signals of opportunity' - signals that are designed for purposes other than navigation.This paper presents a system that uses amplitude modulation (AM) radio broadcasts in the medium frequency (MF) band. At these frequencies, the predominant ground-wave propagation mode offers better coverage in remote areas and over sea than is achievable with higher frequency signals.The system is differential and operates by correlating modulation information between the reference and user receivers. A system of this form mitigates the deterioration in and around buildings encountered in prior systems and can provide absolute position using fewer signals than a system using only carrier phase.The system presented in this paper uses generalized cross correlation to obtain time difference of arrival measurements that are subsequently used for position determination. Preliminary results indicate the system provides a robust position solution. Moreover, the system offers the potential to be combined with carrier phase measurements to achieve enhanced performance, while the modulation correlation technique is readily extendable to other types of signal

The Eating Behaviours, Quality of Life and Cardiometabolic Risks of Adults with Type 1 Diabetes using Continuous Subcutaneous Insulin Infusion Therapy

Evidence suggests continuous subcutaneous insulin infusion (CSII) is an effective method of achieving glycaemic control in those with Type 1 diabetes (T1D). Among the advantages of CSII is the opportunity for patients to potentially discard the dietary inflexibility imposed by other regimes such as multiple daily injections (MDI). There are also reported improvements in quality of life. Furthermore, patients with T1D who achieve good glycaemic control may present a normal quantitative lipid profile; however, various qualitative atherogenic lipid abnormalities may exist, potentially leading to increased cardiometabolic (CM) risks. Literature investigating this in those using CSII is sparse and frequently dated; as is evidence regarding their eating behaviours and quality of life and is therefore worthy of further research. To investigate these issues an initial audit of CSII patients’ medical records spanning 8 years was performed, with a focus on routinely measured clinical markers of risk (n = 260). Then a cross-sectional study was carried out to compare those using CSII (n = 40) vs. MDI (n = 40). This involved the use of a food diaries and food frequency questionnaires to determine eating behaviours; semi-structured interviews and questionnaires were used to ascertain quality of life and CM risks were assessed by further interrogating participants’ medical records and analysing a sample of plasma for lipoprotein quality. Finally, using similar methods, longitudinal case studies (n = 5) were performed to elucidate the transition from MDI onto CSII over one year. The results indicated that upon commencing CSII HbA1c was significantly reduced from 8.3 to 7.6% (p = <0.001) and insulin dose significantly lowered from 54.5 to 46.4 IU (p = <0.001) after using CSII for 12 months and these improvements were maintained over the following 3 years. There were few changes in both quantitative and qualitative lipids; however, systolic blood pressure decreased significantly and unexpectedly both over the 4 year audit period (128.2 to 122.1 mmHg; p = 0.003) and when comparing those using CSII against their MDI counterparts (123.5 mmHg vs. 135.3 mmHg; p = 0.023). Significant reductions were also shown in diastolic blood pressure (75.2 to 72.0 mmHg; p = 0.027). There was little variance in the diets of the two treatment groups; however, subtle differences existed and the intake of certain nutrients such as fibre and iron in females failed to meet the RNI. Many qualitative themes emerged from the interviews regarding participants’ quality of life and in particular highlighted how the device was largely held in positive regard for its ability to improve glycaemic control and offer unprecedented flexibility which allowed a largely unrestricted lifestyle. Despite limitations, this study offers useful information for those working in the field, allowing, for the first time, a deep insight into the eating behaviours, cardiometabolic risks and quality of life of a group of patients using contemporary CSII therapy. It is hoped these findings will assist with decision making processes in clinical practice, thus improving the lives of those with T1D

A Differential Positioning System Using Modulation Correlation of Signals of Opportunity

Global Navigation Satellite Systems (GNSS) have become the positioning systems of choice for many applications. However, GNSS signals are susceptible to obstruction, interference and jamming. Therefore, to maximize robustness and integrity, it is necessary to employ a dissimilar positioning technology that can operate independently and back-up GNSS. One such technology exploits ‘signals of opportunity’ – signals that are designed for purposes other than navigation. This paper presents a system that uses amplitude modulation (AM) radio broadcasts in the medium frequency (MF) band. At these frequencies, the predominant ground-wave propagation mode offers better coverage in remote areas and over sea than is achievable with higher frequency signals. The system is differential and operates by correlating modulation information between the reference and user receivers. A system of this form mitigates the deterioration in and around buildings encountered in prior systems and can provide absolute position using fewer signals than a system using only carrier phase. The system presented in this paper uses generalized cross correlation to obtain time difference of arrival measurements that are subsequently used for position determination. Preliminary results indicate the system provides a robust position solution. Moreover, the system offers the potential to be combined with carrier phase measurements to achieve enhanced performance, while the modulation correlation technique is readily extendable to other types of signal

Beyond the barrier: Female Genital Schistosomiasis as a potential risk factor for HIV-1 acquisition.

Female genital schistosomiasis (FGS) results from egg-deposition in the female reproductive tract primarily by the waterborne parasite Schistosoma (S.) haematobium, and less commonly by Schistosoma (S.) mansoni. FGS affects an estimated 20-56 million women worldwide, mostly in sub-Saharan Africa. There is cross-sectional evidence of increased HIV-1 prevalence in schistosomiasis-infected women, but a causal relationship between FGS and either HIV-1 acquisition or transmission has not been fully established. Beyond the pathognomonic breach in the cervicovaginal barrier caused by FGS, this narrative review explores potential mechanisms for a synergistic relationship between S. haematobium infection, FGS, and HIV-1 acquisition through vaginal inflammation and target cell recruitment

The nonlinear anomalous lattice elasticity associated with the high-pressure phase transition in spodumene: A high precission static compression study

The high-pressure behavior of the lattice elasticity of spodumene, LiAlSi2O6, was studied by static compression in a diamond-anvil cell up to 9.3 GPa. Investigations by means of single-crystal XRD and Raman spectroscopy within the hydrostatic limits of the pressure medium focus on the pressure ranges around similar to 3.2 and similar to 7.7 GPa, which have been reported previously to comprise two independent structural phase transitions. While our measurements confirm the well-established first-order C2/c-P2(1)/c transformation at 3.19 GPa (with 1.2% volume discontinuity and a hysteresis between 0.02 and 0.06 GPa), both unit-cell dimensions and the spectral changes observed in high-pressure Raman spectra give no evidence for structural changes related to a second phase transition. Monoclinic lattice parameters and unit-cell volumes at in total 59 different pressure points have been used to re-calculate the lattice-related properties of spontaneous strain, volume strain, and the bulk moduli as a function of pressure across the transition. A modified Landau free energy expansion in terms of a one component order parameter has been developed and tested against these experimentally determined data. The Landau solution provides a much better reproduction of the observed anomalies than any equation-of-state fit to data sets truncated below and above P (tr), thus giving Landau parameters of K (0) = 138.3(2) GPa, K' = 7.46(5), lambda (V) = 33.6(2) GPa, a = 0.486(3), b = -29.4(6) GPa and c = 551(11) GPa

Long-term Variability Properties and Periodicity Analysis for Blazars

In this paper, the compiled long-term optical and infrared measurements of some blazars are used to analyze the variation properties and the optical data are used to search for periodicity evidence in the lightcurve by means of the Jurkevich technique and the discrete correlation function (DCF) method. Following periods are found: 4.52-year for 3C 66A; 1.56 and 2.95 years for AO 0235+164; 14.4, 18.6 years for PKS 0735+178; 17.85 and 24.7 years for PKS 0754+100; 5.53 and 11.75 for OJ 287. 4.45, and 6.89 years for PKS 1215; 9 and 14.84 years for PKS 1219+285; 2.0, 13.5 and 22.5 for 3C273; 7.1 year for 3C279; 6.07 for PKS 1308+326; 3.0 and 16.5 years for PKS 1418+546; 2.0 and 9.35 years for PKS 1514-241; 18.18 for PKS 1807+698; 4.16 and 7.0 for 2155-304; 14 and 20 years for BL Lacertae. Some explanations have been discussed.Comment: 10 pages, 2 table, no figure, a proceeding paper for Pacific Rim Conference on Stellar Astrophysics, Aug. 1999, HongKong, Chin