Blood flow and diameter effect in the navigation process of magnetic nanocarriers inside the carotid artery.

BACKGROUND AND OBJECTIVE: Serious side effects are occurred during the cancer therapy. Magnetic driving of nanoparticles is a novel method for the elimination of these effects by supplying with anticancer drug or increase the temperature of the infected area. For this reason, a numerical model for optimal guidance of nanoparticles, through the gradient magnetic field, inside the human artery system is presented in this study. METHODS: The present method couples Computational Fluid Dynamics (CFD) and Discrete Element Method (DEM) techniques. In addition, the optimum magnetic intensity each time is evaluated by using the covariance matrix adaptation evolution strategy (CMA-ES). Under five feature blood flow velocities in cardiac cycle, the developed method evaluate and select the optimum gradient magnetic field in order to eliminate the deviation of the guided nanoparticles from a pre-described trajectory. RESULTS: Results of the simulations indicate both the influence of the blood flow and the volume of nanocarriers in the magnetic driving process in real conditions. Specifically, the blood flow and the volume of particles are inversely proportional parameters in the magnetic navigation process. As the blood flow is decreased, the deviation of nanoparticles compared to the desired path is minimized. On the contrary, the decrease of the volume of nanocarriers increase the distance of particles from the described trajectory. However, greater magnetic gradient values are needed as the blood flow is increased. Furthermore, the imposed gradient magnetic values are strongly connected with the position of the nanoparticles and the blood blow velocity. CONCLUSIONS: Based on the results of the present study, the most important parameter in the navigation process is the magnetic volume of particles. Under real conditions, the effect of the blood flow is insignificant compared to the volume of particles in the navigation process. In addition, great differences in the optimized magnetic sequence are presented both among the different blood flows and the volume of particles.

Top 10 priorities for future infertility research: an international consensus development study.

STUDY QUESTION: Can the priorities for future research in infertility be identified? SUMMARY ANSWER: The top 10 research priorities for the four areas of male infertility, female and unexplained infertility, medically assisted reproduction, and ethics, access, and organization of care for people with fertility problems were identified. WHAT IS KNOWN ALREADY: Many fundamental questions regarding the prevention, management, and consequences of infertility remain unanswered. This is a barrier to improving the care received by those people with fertility problems. STUDY DESIGN, SIZE, DURATION: Potential research questions were collated from an initial international survey, a systematic review of clinical practice guidelines, and Cochrane systematic reviews. A rationalized list of confirmed research uncertainties was prioritized in an interim international survey. Prioritized research uncertainties were discussed during a consensus development meeting. Using a formal consensus development method, the modified nominal group technique, diverse stakeholders identified the top 10 research priorities for each of the categories male infertility, female and unexplained infertility, medically assisted reproduction, and ethics, access, and organization of care. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, people with fertility problems, and others (healthcare funders, healthcare providers, healthcare regulators, research funding bodies and researchers) were brought together in an open and transparent process using formal consensus methods advocated by the James Lind Alliance. MAIN RESULTS AND THE ROLE OF CHANCE: The initial survey was completed by 388 participants from 40 countries, and 423 potential research questions were submitted. Fourteen clinical practice guidelines and 162 Cochrane systematic reviews identified a further 236 potential research questions. A rationalized list of 231 confirmed research uncertainties were entered into an interim prioritization survey completed by 317 respondents from 43 countries. The top 10 research priorities for each of the four categories male infertility, female and unexplained infertility (including age-related infertility, ovarian cysts, uterine cavity abnormalities, and tubal factor infertility), medically assisted reproduction (including ovarian stimulation, IUI, and IVF), and ethics, access, and organization of care, were identified during a consensus development meeting involving 41 participants from 11 countries. These research priorities were diverse and seek answers to questions regarding prevention, treatment, and the longer-term impact of infertility. They highlight the importance of pursuing research which has often been overlooked, including addressing the emotional and psychological impact of infertility, improving access to fertility treatment, particularly in lower resource settings, and securing appropriate regulation. Addressing these priorities will require diverse research methodologies, including laboratory-based science, qualitative and quantitative research, and population science. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods, which have inherent limitations, including the representativeness of the participant sample, methodological decisions informed by professional judgement, and arbitrary consensus definitions. WIDER IMPLICATIONS OF THE FINDINGS: We anticipate that identified research priorities, developed to specifically highlight the most pressing clinical needs as perceived by healthcare professionals, people with fertility problems, and others, will help research funding organizations and researchers to develop their future research agenda. STUDY FUNDING/ COMPETING INTEREST(S): The study was funded by the Auckland Medical Research Foundation, Catalyst Fund, Royal Society of New Zealand, and Maurice and Phyllis Paykel Trust. Geoffrey Adamson reports research sponsorship from Abbott, personal fees from Abbott and LabCorp, a financial interest in Advanced Reproductive Care, committee membership of the FIGO Committee on Reproductive Medicine, International Committee for Monitoring Assisted Reproductive Technologies, International Federation of Fertility Societies, and World Endometriosis Research Foundation, and research sponsorship of the International Committee for Monitoring Assisted Reproductive Technologies from Abbott and Ferring. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and editor for the Cochrane Gynaecology and Fertility Group. Hans Evers reports being the Editor Emeritus of Human Reproduction. Andrew Horne reports research sponsorship from the Chief Scientist's Office, Ferring, Medical Research Council, National Institute for Health Research, and Wellbeing of Women and consultancy fees from Abbvie, Ferring, Nordic Pharma, and Roche Diagnostics. M. Louise Hull reports grants from Merck, grants from Myovant, grants from Bayer, outside the submitted work and ownership in Embrace Fertility, a private fertility company. Neil Johnson reports research sponsorship from Abb-Vie and Myovant Sciences and consultancy fees from Guerbet, Myovant Sciences, Roche Diagnostics, and Vifor Pharma. José Knijnenburg reports research sponsorship from Ferring and Theramex. Richard Legro reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. Ben Mol reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. Ernest Ng reports research sponsorship from Merck. Craig Niederberger reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. Jane Stewart reports being employed by a National Health Service fertility clinic, consultancy fees from Merck for educational events, sponsorship to attend a fertility conference from Ferring, and being a clinical subeditor of Human Fertility. Annika Strandell reports consultancy fees from Guerbet. Jack Wilkinson reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. Andy Vail reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and of the journal Reproduction. His employing institution has received payment from HFEA for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. Lan Vuong reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the present work. All authors have completed the disclosure form. TRIAL REGISTRATION NUMBER: Not applicable.

On the magnetic aggregation of Fe3O4 nanoparticles.

Background and objective In-vivo MRI-guided drug delivery concept is a personalized technique towards cancer treatment. A major bottleneck of this method, is the weak magnetic response of nanoparticles. A crucial improvement is the usage of paramagnetic nanoparticles aggregates since they can easier manipulated in human arteries than isolated particles. However its significance, not a comprehensive study to estimate the mean length and time to aggregate exists. Methods The present detailed numerical study includes all major discrete and continues forces and moments of the nanoscale in a global model. The effort is given in summarizing the effects of particle diameter and concentration, and magnetic field magnitude to comprehensive relations. Therefore, several cases with nanoparticles having various diameters and concentrations are simulated as magnetic field increases. Results It is found that aggregations with maximum length equal to 2000nm can be formed. In addition, the increase of the concentration leads to a decrease in the amount of the isolated particles. Consequently, 33% of the particles are isolated for the concentration of 2.25mg/ml while 13% for the concentration of 10mg/ml. Moreover, the increase of the permanent magnetic field and diameter of particles gives rise to an asymptotic behavior in the number of isolated particles. Furthermore, the mean length of aggregates scales linear with diameter and magnetic field, however, concentration increase results in a weaker effect. The larger aggregation that is formed is composed by 21 particles. Smaller time is needed for the completion of the aggregation process with larger particles. Additionally, the increase of the magnitude of the magnetic field leads to a decrease in the aggregation time process. Therefore, 8.5ms are needed for the completion of the aggregation process for particles of 100nm at B0=0.1T while 7ms at B0=0.9T. Surprisedly, the mean time to aggregate is of the same order as in microparticles, although, with an opposite trend. Conclusions In this study, the evolution of the mean length of aggregations as well as the completion time of the aggregation process in the nano and micro range is evaluated. The present results could be useful to improve the magnetic nanoparticles assisted drug delivery method in order to minimize the side effects from the convectional cancer treatments like radiation and chemotherapy.

Top 10 priorities for future infertility research: an international consensus development study† ‡.

STUDY QUESTION: Can the priorities for future research in infertility be identified? SUMMARY ANSWER: The top 10 research priorities for the four areas of male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care for people with fertility problems were identified. WHAT IS KNOWN ALREADY: Many fundamental questions regarding the prevention, management and consequences of infertility remain unanswered. This is a barrier to improving the care received by those people with fertility problems. STUDY DESIGN, SIZE, DURATION: Potential research questions were collated from an initial international survey, a systematic review of clinical practice guidelines and Cochrane systematic reviews. A rationalized list of confirmed research uncertainties was prioritized in an interim international survey. Prioritized research uncertainties were discussed during a consensus development meeting. Using a formal consensus development method, the modified nominal group technique, diverse stakeholders identified the top 10 research priorities for each of the categories male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, people with fertility problems and others (healthcare funders, healthcare providers, healthcare regulators, research funding bodies and researchers) were brought together in an open and transparent process using formal consensus methods advocated by the James Lind Alliance. MAIN RESULTS AND THE ROLE OF CHANCE: The initial survey was completed by 388 participants from 40 countries, and 423 potential research questions were submitted. Fourteen clinical practice guidelines and 162 Cochrane systematic reviews identified a further 236 potential research questions. A rationalized list of 231 confirmed research uncertainties was entered into an interim prioritization survey completed by 317 respondents from 43 countries. The top 10 research priorities for each of the four categories male infertility, female and unexplained infertility (including age-related infertility, ovarian cysts, uterine cavity abnormalities and tubal factor infertility), medically assisted reproduction (including ovarian stimulation, IUI and IVF) and ethics, access and organization of care were identified during a consensus development meeting involving 41 participants from 11 countries. These research priorities were diverse and seek answers to questions regarding prevention, treatment and the longer-term impact of infertility. They highlight the importance of pursuing research which has often been overlooked, including addressing the emotional and psychological impact of infertility, improving access to fertility treatment, particularly in lower resource settings and securing appropriate regulation. Addressing these priorities will require diverse research methodologies, including laboratory-based science, qualitative and quantitative research and population science. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods, which have inherent limitations, including the representativeness of the participant sample, methodological decisions informed by professional judgment and arbitrary consensus definitions. WIDER IMPLICATIONS OF THE FINDINGS: We anticipate that identified research priorities, developed to specifically highlight the most pressing clinical needs as perceived by healthcare professionals, people with fertility problems and others, will help research funding organizations and researchers to develop their future research agenda. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Auckland Medical Research Foundation, Catalyst Fund, Royal Society of New Zealand and Maurice and Phyllis Paykel Trust. G.D.A. reports research sponsorship from Abbott, personal fees from Abbott and LabCorp, a financial interest in Advanced Reproductive Care, committee membership of the FIGO Committee on Reproductive Medicine, International Committee for Monitoring Assisted Reproductive Technologies, International Federation of Fertility Societies and World Endometriosis Research Foundation, and research sponsorship of the International Committee for Monitoring Assisted Reproductive Technologies from Abbott and Ferring. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and editor for the Cochrane Gynaecology and Fertility Group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. A.W.H. reports research sponsorship from the Chief Scientist's Office, Ferring, Medical Research Council, National Institute for Health Research and Wellbeing of Women and consultancy fees from AbbVie, Ferring, Nordic Pharma and Roche Diagnostics. M.L.H. reports grants from Merck, grants from Myovant, grants from Bayer, outside the submitted work and ownership in Embrace Fertility, a private fertility company. N.P.J. reports research sponsorship from AbbVie and Myovant Sciences and consultancy fees from Guerbet, Myovant Sciences, Roche Diagnostics and Vifor Pharma. J.M.L.K. reports research sponsorship from Ferring and Theramex. R.S.L. reports consultancy fees from AbbVie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. E.H.Y.N. reports research sponsorship from Merck. C.N. reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring and retains a financial interest in NexHand. J.S. reports being employed by a National Health Service fertility clinic, consultancy fees from Merck for educational events, sponsorship to attend a fertility conference from Ferring and being a clinical subeditor of Human Fertility. A.S. reports consultancy fees from Guerbet. J.W. reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. A.V. reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and the journal Reproduction. His employing institution has received payment from Human Fertilisation and Embryology Authority for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the present work. All authors have completed the disclosure form. TRIAL REGISTRATION NUMBER: N/A.

Effect of fractal-shaped outer boundary of glioblastoma multiforme on drug delivery.

BACKGROUND AND OBJECTIVE: The present study investigates the transport of drugs in the proximity of the glioblastoma multiforme, a brain neoplasm which is regarded to be the most aggressive type of cancer. In such a small distance from the tumor, diffusion dominates and is driven by the concentration gradient of drug that acquires its maximum at regions where the drugs are released and its minimum at the cancer cell boundary. Undoubtedly, the morphology of the aforementioned boundary is going to play a crucial role in the drug delivery and should be taken into account for the optimal design of the treatment. As first step in order to simulate the topography of glioblastoma multiforme, a fractal boundary is examined which mimics an acceptable model-problem for prognosis and diagnosis of a number of cancer tumors in breast, lungs and brain. METHODS: The drug diffusion is investigated for two concentrations, namely a strong and a mild diffusion, while the outer boundary of the glioblastoma multiforme is approximated via triangular Von Koch shapes. Besides, a Finite Element Method is utilized via FEniCS, which is a Python-based open-source computing platform. Finally, after ascertaining the accuracy of the present numerical model, the concentration of the drug, the entropy production and the mass fluxes in the horizontal and vertical directions are estimated up to the fifth order of Von Koch fractal iterations. RESULTS: It is ascertained that as the boundaries become more and more irregular, the entropy production in specific areas increases and as a consequence the delivery of the drug is facilitated. Hence, the mass fluxes in these sites appear to be larger comparing to the rest of the boundary and increase, as expected, for the case of strong diffusion. CONCLUSIONS: These active regions, which are referred as "hot spots", are of great importance since they seem to be the sites where the drug ultimately penetrates the glioblastoma. This first-principles investigation is anticipated to shed light on a very significant part of drug delivery, which deals with the vicinity of the glioblastoma multiforme, stress the importance of the topography and give rise to future studies to be conducted based on subject-specific geometries.

Development of a new theoretical model for blood-CNTs effective thermal conductivity pertaining to hyperthermia therapy of glioblastoma multiform.

BACKGROUND AND OBJECTIVE: The present study deals with the hyperthermia therapy, which is the type of treatment in which tissues are exposed to high temperatures in order to destroy cancer cells with minimal injury to healthy tissues. In particular, it focuses on glioblastoma multiform, which is the most aggressive cancer that begins within the brain. Conventional treatments display limitations that can be overcome by using nanoparticles for targeted heating. Out of the proposed nanoparticles, this investigation focuses on a new field that utilizes carbon nanotubes (CNTs) which are able to selectively heat the cancer cells since they can convert near infrared light into heat. In the absence of any experiment or theoretical model for the estimation of an effective thermal conductivity of blood and CNTs, a first principle model is developed in this study which takes into account the blood micro-structure. Besides, a number of factors are included, namely the shape and the size of the nanoparticles, the interfacial layer formed around them and their volume fraction. METHODS: Firstly, assuming that the blood consists of blood cells and plasma, the thermal conductivity of the former is estimated. Then, the effective thermal conductivity of plasma/CNTs is calculated for various parameters. Finally, the resulting "bio-nanofluid" consisting of plasma/CNTs and blood cells is formed. RESULTS: It is ascertained that thin and elongated CNTs with relatively large nanolayer thickness as well as large concentrations of CNTs contribute to the increase of the thermal conductivity and, thus, in the enhancement of the heat transfer. CONCLUSIONS: Investigating of how design parameters pertaining to CNTs, such as their size and shape, affect the effective thermal conductivity of blood-CNTs, possible regulating ways are suggested regarding the hyperthermic treatment. Finally, the present simple estimation of the effective thermal conductivity can be used as an effective property of the nanofluid when it comes to numerical investigations regarding heat transfer occurring during hyperthermia or other potential clinical uses (for example targeted heat of living tissues).

A numerical model for aggregations formation and magnetic driving of spherical particles based on OpenFOAM®.

BACKGROUND AND OBJECTIVE: This work presents a numerical model for the formation of particle aggregations under the influence of a permanent constant magnetic field and their driving process under a gradient magnetic field, suitably created by a Magnetic Resonance Imaging (MRI) device. METHODS: The model is developed in the OpenFOAM platform and it is successfully compared to the existing experimental and numerical results in terms of aggregates size and their motion in water solutions. Furthermore, several series of simulations are performed for two common types of particles of different diameter in order to verify their aggregation and flow behaviour, under various constant and gradient magnetic fields in the usual MRI working range. Moreover, the numerical model is used to measure the mean length of aggregations, the total time needed to form and their mean velocity under different permanent and gradient magnetic fields. RESULTS: The present model is found to predict successfully the size, velocity and distribution of aggregates. In addition, our simulations showed that the mean length of aggregations is proportional to the permanent magnetic field magnitude and particle diameter according to the relation : l¯a=7.5B0di3/2. The mean velocity of the aggregations is proportional to the magnetic gradient, according to : u¯a=6.63G˜B0 and seems to reach a steady condition after a certain period of time. The mean time needed for particles to aggregate is proportional to permanent magnetic field magnitude, scaled by the relationship : t¯a∝7B0. CONCLUSIONS: A numerical model to predict the motion of magnetic particles for medical application is developed. This model is found suitable to predict the formation of aggregations and their motion under the influence of permanent and gradient magnetic fields, respectively, that are produced by an MRI device. The magnitude of the external constant magnetic field is the most important parameter for the aggregations formation and their driving.

Topical use of tranexamic acid to control perioperative local bleeding in gynaecology patients with clotting disorders: two cases.

Operating on patients with abnormal coagulation is a challenge frequently faced by surgeons. Achieving haemostasis perioperatively can involve bleeding points that would not ordinarily present a problem with intact clotting function. Here we present two women with localised wound bleeding following a gynaecological surgery in the presence of a clotting disorder. Haemostasis was successfully achieved with tropical use of tranexamic acid. These two cases illustrate a novel use for this antifibrinolytic agent. We suggest that there is a role for topical use of tranexamic acid in perioperative haemostasis in patients with clotting disorders.

Suture anchor repair of ulnar-sided triangular fibrocartilage complex tears.

Traditional open repair of traumatic triangular fibrocartilage complex (TFCC) tears requires a relatively extensive exposure, and arthroscopic repair, though conceptually simple, can be technically demanding. We describe a mini-open suture anchor technique that, while minimally invasive, is easier to perform than previously described open or arthroscopic techniques. Results achieved using this technique in eight cases compare favourably with those reported for other techniques.

MRI of mycetoma of the foot: two cases demonstrating the dot-in-circle sign.

Radiological and histological findings of two patients with fungal mycetoma of the foot are presented. MRI revealed multiple 2-5 mm lesions of high signal intensity interspersed within a low-intensity matrix. Within many of the lesions a minute low-intensity focus was identified. Ultrasound showed distinct hyperechoic foci within a hypoechoic mass. We speculate that the low-signal matrix represents fibrous tissue, the high-intensity lesions correspond to granulomata and the central low-signal focus to the characteristic organised fungal elements (grains) present in this condition. This "dot-in-circle sign" on MRI reflects the unique pathological features of mycetoma and is likely to be a highly specific sign for this lesion.

An allograft salvage technique for failure of the Darrach procedure: a report of four cases.

We report on four patients with failed resections of the distal ulna causing instability and impingement, who were treated with a tendon allograft to stabilize and buffer the ulnar stump. In three of the four patients the outcome was excellent. We believe that this new technique holds promise as an alternative salvage procedure for the failed Darrach resection.

Revision of failed hemiarthroplasty for fractures at the hip.

The records of 56 patients in whom a hemiarthroplasty, carried out for a femoral neck fracture, had been revised to a total hip replacement, were reviewed. The mode of failure was femoral loosening in 21, acetabular erosion in 26 and both in 5. Loosening tended to occur earlier than acetabular erosion. The median time to the onset of symptoms was 12 months and to revision 33 months. There were 38 major operative or postoperative complications at revision in 27 of the patients (48%).