Magnetic drug targeting: Preclinical in vivo studies, mathematical modeling, and extrapolation to humans

A sound theoretical rationale for the design of a magnetic nanocarrier capable of magnetic capture in vivo after intravenous administration could help elucidate the parameters necessary for in vivo magnetic tumor targeting. In this work, we utilized our long-circulating polymeric magnetic nanocarriers, encapsulating increasing amounts of superparamagnetic iron oxide nanoparticles (SPIONs) in a biocompatible oil carrier, to study the effects of SPION loading and of applied magnetic field strength on magnetic tumor targeting in CT26 tumor-bearing mice. Under controlled conditions, the in vivo magnetic targeting was quantified and found to be directly proportional to SPION loading and magnetic field strength. Highest SPION loading, however, resulted in a reduced blood circulation time and a plateauing of the magnetic targeting. Mathematical modeling was undertaken to compute the in vivo magnetic, viscoelastic, convective, and diffusive forces acting on the nanocapsules (NCs) in accordance with the Nacev–Shapiro construct, and this was then used to extrapolate to the expected behavior in humans. The model predicted that in the latter case, the NCs and magnetic forces applied here would have been sufficient to achieve successful targeting in humans. Lastly, an in vivo murine tumor growth delay study was performed using docetaxel (DTX)-encapsulated NCs. Magnetic targeting was found to offer enhanced therapeutic efficacy and improve mice survival compared to passive targeting at drug doses of ca. 5–8 mg of DTX/kg. This is, to our knowledge, the first study that truly bridges the gap between preclinical experiments and clinical translation in the field of magnetic drug targeting

Differences in access and patient outcomes across antiretroviral treatment clinics in the Free State province: A prospective cohort study

Objective. To assess differences in access to antiretroviral treatment (ART) and patient outcomes across public sector treatment facilities in the Free State province, South Africa. Design. Prospective cohort study with retrospective database linkage. We analysed data on patients enrolled in the treatment programme across 36 facilities between May 2004 and December 2007, and assessed percentage initiating ART and percentage dead at 1 year after enrolment. Multivariable logistic regression was used to estimate associations of facility-level and patient-level characteristics with both mortality and treatment status. Results. Of 44 866 patients enrolled, 15 219 initiated treatment within 1 year; 8 778 died within 1 year, 7 286 before accessing ART. Outcomes at 1 year varied greatly across facilities and more variability was explained by facility-level factors than by patient-level factors. The odds of starting treatment within 1 year improved over calendar time. Patients enrolled in facilities with treatment initiation available on site had higher odds of starting treatment and lower odds of death at 1 year compared with those enrolled in facilities that did not offer treatment initiation. Patients were less likely to start treatment if they were male, severely immunosuppressed (CD4 count ≤50 cells/µl), or underweight

Standardisation of magnetic nanoparticles in liquid suspension

Suspensions of magnetic nanoparticles offer diverse opportunities for technology innovation, spanning a large number of industry sectors from imaging and actuation based applications in biomedicine and biotechnology, through large-scale environmental remediation uses such as water purification, to engineering-based applications such as position-controlled lubricants and soaps. Continuous advances in their manufacture have produced an ever-growing range of products, each with their own unique properties. At the same time, the characterisation of magnetic nanoparticles is often complex, and expert knowledge is needed to correctly interpret the measurement data. In many cases, the stringent requirements of the end-user technologies dictate that magnetic nanoparticle products should be clearly defined, well characterised, consistent and safe; or to put it another way—standardised. The aims of this document are to outline the concepts and terminology necessary for discussion of magnetic nanoparticles, to examine the current state-of-the-art in characterisation methods necessary for the most prominent applications of magnetic nanoparticle suspensions, to suggest a possible structure for the future development of standardisation within the field, and to identify areas and topics which deserve to be the focus of future work items. We discuss potential roadmaps for the future standardisation of this developing industry, and the likely challenges to be encountered along the way

Lethal coalitionary attacks of chimpanzees (Pan troglodytes troglodytes) on gorillas (Gorilla gorilla gorilla) in the wild

Intraspecies violence, including lethal interactions, is a relatively common phenomenon in mammals. Contrarily, interspecies violence has mainly been investigated in the context of predation and received most research attention in carnivores. Here, we provide the first information of two lethal coalitionary attacks of chimpanzees (Pan troglodytes troglodytes) on another hominid species, western lowland gorillas (Gorilla gorilla gorilla), that occur sympatrically in the Loango National Park in Gabon. In both events, the chimpanzees significantly outnumbered the gorillas and victims were infant gorillas. We discuss these observations in light of the two most widely accepted theoretical explanations for interspecific lethal violence, predation and competition, and combinations of the two-intraguild predation and interspecific killing. Given these events meet conditions proposed to trigger coalitional killing of neighbours in chimpanzees, we also discuss them in light of chimpanzees’ intraspecific interactions and territorial nature. Our findings may spur further research into the complexity of interspecies interactions. In addition, they may aid in combining field data from extant models with the Pliocene hominid fossil record to better understand behavioural adaptations and interspecific killing in the hominin lineage

Automated Recognition of Grooming Behavior in Wild Chimpanzees

Video recording is a widely used tool for studying animal behavior, especially in fields such as primatology. Primatologists rely on video data to analyze and research topics such as social grooming to uncover subtle mechanisms behind complex social behavior and structures. Insights into these social behaviors may provide us with a better understanding of our closest living relatives, but also new theories and insights into our own behavior. However, analyzing this type of data using manual annotation is currently a time-consuming task. Here we present an end-to-end pipeline to track chimpanzee (Pan troglodytes) poses using DeepLabCut (DLC) which then serves as input to a support vector machine. This classifier was trained to detect role transitions within grooming interactions. We replicate a recent study showing that DLC has usability value for chimpanzee data collected in natural environments. Our combined method of tracking and classification is remarkably successful in detecting the presence of grooming, indicating the directionality and a change in turn with an accuracy above 86% on unseen videos. We can identify particular pose features used in the classification of grooming, which will contribute to the exploration of turn-taking dynamics on a scale that would otherwise be difficult to attain with traditional methods. Finally, our pipeline can in principle be applied to recognize a variety of other socially interactive behaviors that are largely recognizable by (joint) postural states

Application of insects to wounds of self and others in chimpanzees in the wild

Medical practices characterize human societies and have been suggested to originate from observing the behavior of other animals. Mascaro and colleagues report that chimpanzees apply insects to their own and the open wounds of other conspecifics, thereby adding to the current debate on self-medicative and prosocial behaviours in nonhuman animals

The peril of acceptance: American Jewry assimilation trends 60 years after the Holocaust

Jews have always been aware of persecutions and historically have clung together as a community to pass their culture from one generation to the next. In contemporary America, however, Jews rarely experience prejudice due to their religious identity. Rather, Jews are so fully integrated into American life that they have intermarried, the associated stigma in secular America so imperceptible. But now that American Jews finally enjoy a quality of life defined by acceptance and equality, many have chosen to move away from the religion they are at last free to practice.The Holocaust still a recent memory, some Jews fear that this assimilation presents a threat greater than the violent annihilations of the camps. It is extermination by choice. America's acceptance has caused Jews, in these early years of the 21 st century, to wonder why they should preserve Judaism and Jewish culture. If assimilation is the ultimate approval, why should they resist it? What of Jewish culture must survive? The answers to these questions, as the following profiles of three children of Holocaust survivors attest, arise viscerally; the answers are personal, even primal, each a unique expression attempting to define what it means to be a Jew.Thesis (M.A.)--University of Southern California, 2008.School code: 0208

Differences in access and patient outcomes across antiretroviral treatment clinics in the Free State province: A prospective cohort study

Objective. To assess differences in access to antiretroviral treatment (ART) and patient outcomes across public sector treatment facilities in the Free State province, South Africa. Design. Prospective cohort study with retrospective database linkage. We analysed data on patients enrolled in the treatment programme across 36 facilities between May 2004 and December 2007, and assessed percentage initiating ART and percentage dead at 1 year after enrolment. Multivariable logistic regression was used to estimate associations of facility-level and patient-level characteristics with both mortality and treatment status. Results. Of 44 866 patients enrolled, 15 219 initiated treatment within 1 year; 8 778 died within 1 year, 7 286 before accessing ART. Outcomes at 1 year varied greatly across facilities and more variability was explained by facility-level factors than by patient-level factors. The odds of starting treatment within 1 year improved over calendar time. Patients enrolled in facilities with treatment initiation available on site had higher odds of starting treatment and lower odds of death at 1 year compared with those enrolled in facilities that did not offer treatment initiation. Patients were less likely to start treatment if they were male, severely immunosuppressed (CD4 count ≤50 cells/μl), or underweight (<50 kg). Men were also more likely to die in the first year after enrolment. Conclusions. Although increasing numbers of patients started ART between 2004 and 2007, many patients died before accessing ART. Patient outcomes could be improved by decentralisation of treatment services, fast-tracking the most immunodeficient patients and improving access, especially for men

Modelling the effect of different core sizes and magnetic interactions inside magnetic nanoparticles on hyperthermia performance

We present experimental intrinsic loss power (ILP) values, measured at an excitation frequency of 1 MHz and at relatively low field amplitudes of 3.4–9.9 kA/m, as a function of the mean core diameter, for selected magnetic nanoparticles (MNPs). The mean core sizes ranged from ca. 8 nm to 31 nm. Transmission electron microscopy indicated that those with smaller core sizes (less than ca. 22 nm) were single-core MNPs, while those with larger core sizes (ca. 29 nm to 31 nm) were multi-core MNPs. The ILP data showed a peak at core sizes of ca. 20 nm. We show here that this behaviour correlates well with the predicted ILP values obtained using either a non-interacting Debye model, or via dynamic Monte-Carlo simulations, the latter including core-core magnetic interactions for the multi-core particles. This alignment of the models is a consequence of the low field amplitudes used. We also present interesting results showing that the core-core interactions affect the ILP value differently depending on the mean core size