Physiologically based modelling of nanoparticle biodistribution and biokinetics

To predict the toxicity of nanoparticles (1-100 nm), it is crucial to understand their biokinetics i.e. how they are taken up, distributed, dissolved and removed from the body. Such information can be gained from biodistribution studies in animals. However, to make predictions for other types of nanoparticles, exposure conditions and species, including humans, extrapolations from such studies are required. Use of models, such as physiologically based pharmacokinetic (PBPK) models, makes extrapolations feasible, given that the models are sufficiently validated. In this thesis, a conceptual nanospecific PBPK model for intravenous administration to rats was developed and applied to different types of inert nanoparticles using experimental data from recent scientific publications (Papers I and II). The model represents systemic distribution and serves as a foundation for expansion to other species and other exposure routes (inhalation, dermal, oral). The PBPK simulations suggest that the model is able to describe the biokinetics of different types of inert nanoparticles given intravenously despite large differences in properties and exposure conditions. Our model is the first to include separate compartments for phagocytic cells and saturable phagocytosis. The simulations show that (1) phagocytosis needs to be incorporated in nano PBPK models, (2) the dose has a clear impact on biokinetics, but (3) further refinements are needed to better reflect processes such as agglomeration, corona formation and dissolution. The model was slightly modified to describe the biodistribution and biokinetics of nanoceria of different sizes and administered via other routes (Paper III). While the model could well predict the biokinetics after intravenous dosing, the predictions of inhalation, instillation and ingestion data were poor. The poor agreement may be partly due to low absorption via these routes, resulting in low nanoceria levels in tissues and organs, often close to or below the detection limit, in tissues. However, low absorption is hardly the only explanation, as the experimentally observed concentration time courses of nanoceria in tissues suggest that the biokinetics depend not only on the nanoparticle properties (size, coating) but also on the exposure conditions (dose, exposure route). The PBPK model was further developed to account for the complexity of inhalation exposure to nanoparticles (Paper IV). The modified model includes regional particle deposition in the respiratory tract, mucociliary clearance and phagocytosis in the lungs, olfactory uptake, and transport into the systemic circulation by alveolar wall translocation. The PBPK model described the biodistribution well and again suggested phagocytosis to be very important. The PBPK simulations were performed assuming that the nanoparticles are inert, i.e. do not dissolve or degrade in the body. However, when modelling the experimental data it seemed that the biokinetics might be better explained by introducing dissolution in the PBPK model. A related problem is that most experimental studies of metal nanoparticles use elemental analysis such as inductively coupled plasma mass spectrometry (ICP-MS). Such analyses do not discriminate between different forms of metal and therefore obscures the biokinetics. To test if gold nanoparticles dissolve in biological media, we developed an in vitro method to characterize dissolution of gold nanoparticles in contact with cell medium, macrophages and lipopolysaccharide (LPS)-triggered macrophages, simulating a disease state (Paper V). We demonstrated that gold nanoparticles are dissolved by cell medium and macrophages and even more so by LPS-triggered macrophages. The dissolution rate was higher for 5 nm than for 50 nm gold particles

Objektiv rörelseanalys för mätning av hälta hos kliniskt halta kor

Hälta hos mjölkkor medför lidande för korna och ekonomiska förluster för djurhållaren. En automatiserad metod för hältdetektion som går att använda i stallmiljö skulle kunna leda till tidigare upptäckt av hälta och minska de negativa konsekvenserna. Ett i praktiken välfungerande system för automatiserad hältövervakning finns inte idag och för utveckling av en sådan metod behöver rörelsemönstret hos halta och friska kor förstås bättre. Syftet med denna studie var att undersöka om huvudets och sacrums vertikala rörelse i skritt kan användas för att objektivt avgöra om en ko är halt eller inte. Därför mättes kliniskt halta kor med accelerometerbaserade systemet EquiMoves före och efter behandling av hälta och det vertikala rörelsemönstret analyserades. Slutsatsen dras att systemet tillåter upptäckt av bakbenshälta genom att mäta sacrums rörelse, även om ett fåtal kor omfattas av mätningarna. Ytterligare studier behövs för att utvärdera tillämparheten samt vidare analys av rörelsevariabler för frambenhälta.Lameness in dairy cows is related to pain for the cows and economical losses for the farmer. An automated method for lameness detection that could be used in a stable could lead to earlier detection of disease, and reduce the negative consequences of the same. Such a method does not exist today, and to develop such a method the motion pattern for lame and healthy cows needs to be understood. The aim of this study was to investigate if the vertical displacement of the head and sacrum during walk can be used to objectively discern whether or not a cow is lame. Therefore, clinically lame cows were measured with the accelerometer-based system EquiMoves before and after treatment of lameness and the vertical motion was analyzed. To conclude, the system allows hindlimb lameness to be detected, even if only a few cows are measured. Additional studies are required to evaluate the applicability for front leg lameness

A Bayesian approach for estimating length-weight relationships in fishes

A Bayesian hierarchical approach is presented for the estimation of length-weight relationships (LWR) in fishes. In particular, estimates are provided for the LWR parameters a and b in general as well as by body shape. These priors and existing LWR studies were used to derive species-specific LWR parameters. In the cases of data-poor species, the analysis includes LWR studies of closely related species with the same body shape. This approach yielded LWR parameter estimates with measures of uncertainty for practically all known 32 000 species of fishes. Provided is a 3 large LWR data set extracted from www.fishbase.org, the source code of the respective analyses, and ready-to-use tools for practitioners. This is presented as an example of a self-learning online database where the addition of new studies improves the species-specific parameter estimates, and where these parameter estimates inform the analysis of new data

Book Review: Fragile Giants: A Natural History of the Loess Hills

The Loess Hills, which are a special feature of the eastern bank of the Missouri River in Iowa and northern Missouri, have been cited by Dean Roosa, Iowa\u27s State Ecologist, as a world treasure and ... our best-kept secret. These Hills are mounds of finely ground soil, glacial flour, deposited by dust storms after the glaciers receded 31 to 12 thousand years ago. Loess is rather widely distributed in Iowa, but the extensive deposits (often over 200 feet deep) on and against the eastern wall of the valley left a rolling, wave-like, terrain which on erosion leaves vertical banks of compacted soil. Cornelia Mutel of the University of Iowa has compiled a comprehensive introduction to this unique Iowa treasure. The characteristic features of the Hills and their flora and fauna are illustrated with drawings and photographs (5 maps, 77 figures, and 8 colored photographs)

Mode of delivery : does it affect contact with the newborn child, future reproduction and health-related quality of life five years after the birth of the first child?

Background: major changes have occurred in Swedish maternity care since the early 20th century and is now characterized by an increased medicalisation. The incidence of caesarean section and instrumental vaginal births has risen substantially in Sweden the last decades, which means that fewer women give birth spontaneously. Both caesarean section and instrumental vaginal births are associated with adverse physical as well as physiological consequences for both mother and child. The overall aim of this thesis was to explore and describe the impact of mode of delivery and other aspects related to the birth of the first child. Methods: three of studies were conducted using a prospective cohort design and one using a qualitative approach. A total of 551 healthy first-time mothers where enrolled in the cohort and divided into five different delivery groups; vaginal delivery, instrumental vaginal birth, caesarean section on maternal request, caesarean section on obstetrical indication and emergency caesarean section. A plurality of self-reported questionnaires were administrated at five different time points; in late pregnancy, two days, three and nine months post partum as well as five years after inclusion in the cohort. One of the questionnaires answered by 510 mothers was analyzed in paper I. Follow-up studies were carried out five years after the first birth using questionnaires and were based on answers from 355 (Paper III) respectively 249 (Paper IV) women. Paper II was performed with semi-structured individual interviews with 12 primiparae women requesting a caesarean section in the absence of a medical indication. The women were interviewed between gestational week 26 and 36 weeks. Results: the contact with the child and the relation to the partner was rated as positive on all occasions and there were no significant differences between the groups. Mothers with a vaginal delivery experienced breastfeeding less stressful than the mothers with a caesarean section. Three and nine months after delivery the mothers with a caesarean delivery on request reported more breastfeeding problems. Women requesting a caesarean section in their first pregnancy described a belief of always knowing that they would not give birth vaginally. A caesarean section was considered as a more controlled and safe way of giving birth. This was described as ‘deeply rooted emotions’ and reflected that this group of women’s emotions towards birth goes beyond fear of childbirth. No differences were observed regarding mode of delivery, factors related to birth and having a second child. Nor was there an association between postnatal depression, fear of childbirth, a negative birth experience and self-estimated contact towards the child and subsequent reproduction. Planning a second child at nine months postpartum was most important in determining to have a second child. The overall health-related quality of life (HRQoL) was perceived to be good five years after the first birth. Suboptimal scores were obtained for the variables sleeping problems, emotional well-being negative effect and sexual functioning. Women having a vaginal birth, an instrumental vaginal delivery or women who underwent caesarean section on maternal request at birth of their first child were more likely to report better perceived HRQoL than women who had undergone an emergency caesarean section or caesarean section due to medical indication. Conclusions and clinical implications: this thesis provides insights on how mode of delivery and aspects related to birth have different importance to women, depending on the context. Mode of delivery did matter in some respects, and in others it had no meaning. Taking these results into account may assist women and health professionals to better understand how childbirth and mode of delivery may be significant for women from various perspectives

Use of Gill Nets in Studying Fish Populations, Clear Lake, Iowa

Gill nets are among the most effective gear for collecting many species of lake fishes. In scientific investigations we usually use gill nets with several sizes of mesh to sample fish of various sizes. The standard experimental gill net usually consists of 25-foot lengths of the following stretch measure mesh sizes: 1.5, 2, 2.5, 3, and 4 inches. These nets will catch, with little size selection, walleyes and suckers from 6 to 23 inches, and yellow perch, yellow bass, white \u27bass, and bullheads from 4.5 inches to their maximum sizes

The American School of Wildlife, McGregor, Iowa 1919-1941

46. The American School The American School of Wildlife Protection was established at McGregor in August, 1919, and continued every summer until 1941. The school grew out of a summer meeting of the Iowa Conservation Association in 1918. This Association and the McGregor Citizens Association set up a five-day session in 1919. The 1920 session lasted one week and all later sessions were two weeks in length. Faculty was drawn from Iowa State College, the State University of Iowa, colleges of the Midwest, and state and federal conservation agencies. Major fields covered were Indian lore, botany, geology, forestry, entomology, and ornithology. No textbooks were used, no examinations required, and no credit given. Desire for a national park for the Midwest and intensified interest in conservation following World War I were factors in the establishment of the Wildlife School. It was the first of its kind in the United States and set a pattern which was followed in other parts of the country, notably Colorado

Integration of cost-risk assessment of denial of service within an intelligent maintenance system

As organisations become richer in data the function of asset management will have to increasingly use intelligent systems to control condition monitoring systems and organise maintenance. In the future the UK rail industry is anticipating having to optimize capacity by running trains closer to each other. In this situation maintenance becomes extremely problematic as within such a high-performance network a relatively minor fault will impact more trains and passengers; such denial of service causes reputational damage for the industry and causes fines to be levied against the infrastructure owner, Network Rail. Intelligent systems used to control condition monitoring systems will need to optimize for several factors; optimization for minimizing denial of service will be one such factor. With schedules anticipated to be increasingly complicated detailed estimation methods will be extremely difficult to implement. Cost prediction of maintenance activities tend to be expert driven and require extensive details, making automation of such an activity difficult. Therefore a stochastic process will be needed to approach the problem of predicting the denial of service arising from any required maintenance. Good uncertainty modelling will help to increase the confidence of estimates. This paper seeks to detail the challenges that the UK Railway industry face with regards to cost modelling of maintenance activities and outline an example of a suitable cost model for quantifying cost uncertainty. The proposed uncertainty quantification is based on historical cost data and interpretation of its statistical distributions. These estimates are then integrated in a cost model to obtain accurate uncertainty measurements of outputs through Monte-Carlo simulation methods. An additional criteria of the model was that it be suitable for integration into an existing prototype integrated intelligent maintenance system. It is anticipated that applying an integrated maintenance management system will apply significant downward pressure on maintenance budgets and reduce denial of service. Accurate cost estimation is therefore of great importance if anticipated cost efficiencies are to be achieved. While the rail industry has been the focus of this work, other industries have been considered and it is anticipated that the approach will be applicable to many other organisations across several asset management intensive industrie