Which spring is the best? Comparison of methods for virtual stenting.

This paper presents a methodology for modeling the deployment of implantable devices used in minimally invasive vascular interventions. Motivated by the clinical need to perform preinterventional rehearsals of a stent deployment, we have developed methods enabling virtual device placement inside arteries, under the constraint of real-time application. This requirement of rapid execution narrowed down the search for a suitable method to the concept of a dynamic mesh. Inspired by the idea of a mesh of springs, we have found a novel way to apply it to stent modeling. The experiments conducted in this paper investigate properties of the stent models based on three different spring types: lineal, semitorsional, and torsional springs. Furthermore, this paper compares the results of various deployment scenarios for two different classes of devices: a stent graft and a flow diverter. The presented results can be of a high-potential clinical value, enabling the predictive evaluation of the outcome of a stent deployment treatment

Towards Predicting Patient-Specific Flow-Diverter Treatment Outcomes for Bifurcation Aneurysms: From Implantation Rehearsal to Virtual Angiograms

Despite accounting for the majority of all cerebral aneurysm cases, bifurcation aneurysms present many challenges to standard endovascular treatment techniques. This study examines the treatment of bifurcation aneurysms endovascularly with flow-diverting stents and presents an integrative computational modeling suite allowing for rehearsing all aspects of the treatment. Six bifurcation aneurysms are virtually treated with 70% porosity flow-diverters. Substantial reduction (>50%) in aneurysm inflow due to device deployment is predicted in addition to reductions in peak and average aneurysm wall shear stress to values considered physiologically normal. The subsequent impact of flow-diverter deployment on daughter vessels that are jailed by the device is investigated further, with a number of simulations conducted with increased outlet pressure conditions at jailed vessels. Increased outlet pressures at jailed daughter vessels are found to have little effect on device-induced aneurysm inflow reduction, but large variation (13-86%) is seen in the resulting reduction in daughter vessel flow rate. Finally, we propose a potentially powerful approach for validation of such models, by introducing an angiographic contrast model, with contrast transport modeled both before and after virtual treatment. Virtual angiograms and contrast residence curves are created, which offer unique clinical relevance and the potential for future in vivo verification of simulated results

Comparison and calibration of a real-time virtual stenting algorithm using Finite Element Analysis and Genetic Algorithms

In this paper, we perform a comparative analysis between two computational methods for virtual stent deployment: a novel fast virtual stenting method, which is based on a spring–mass model, is compared with detailed finite element analysis in a sequence of in silico experiments. Given the results of the initial comparison, we present a way to optimise the fast method by calibrating a set of parameters with the help of a genetic algorithm, which utilises the outcomes of the finite element analysis as a learning reference. As a result of the calibration phase, we were able to substantially reduce the force measure discrepancy between the two methods and validate the fast stenting method by assessing the differences in the final device configurations

Информационные технологии в управлении интеллектуальным капиталом организации

The report examines how organization can use information technologies for management of intellectual capital

Etablierung der homöopathischen Mastitistherapie in einem biologisch-dynamisch wirtschaftenden Milcherzeugerbetrieb unter Berücksichtigung ökologischer, epidemiologischer und ökonomischer Gesichtspunkte.

6 Summary The dairy cow mastitis as a disease with an immense economic impact is widely spread in organic as well as in conventional farms. Due to the lack of alternatives to antibiotic treatment, most therapeutical measures are based on antibiotics even in organic farms and against common regulations. In contrary to these procedures the EU regulations (Council Regulation EC 1804/99)as well as the consumer’s anticipation demand the possibly lowest levels of residual charges of dairy products and environment. A two and a half year study in a bio-dyn dairy herd in Brandenburg (Germany) with 300 dairy cows suffering from udder health problems was conducted to evaluate if clinical mastitis in dairy cows is to control successfully with homeopathic remedies to minimize antibiotic treatment. To assess the efficacy of the homeopathic treatment the investigations are made using a double blind placebo controlled study design (RCCT). Using a predetermined treatment protocol and a certain diagnostic pattern to match right remedies in the sense of the homeopathic remedy pictures, the intention of the chosen treatment schedule was to provide a very transparent concept which can be used also by unexperienced veterinarians. For treatment of acute mastitis the following remedies were used: Phytolacca D6, Bryonia D6 , Echinacea D6 and Belladonna D6. Aconitum D6 was added in case of fever at the beginning of disease. Cases of chronical and subclinical mastitis were treated by Echinacea D6, Phytolacca D6 and Hepar sulfuris D8. In the first part of the study nearly all mastitis cases were treated only with homeopathics avoiding antibiotics strictly. The unsatisfying results in this part lead to a modification in the second part in which in case of certain infections (S.aureus, Sc.spp.) a limited use of antibiotics was admitted. Furthermore, selected udders with subclinical and chronical infections with these kind of bacteria were dried off antibiotically. Simultaneously the farmer was engaged to intensify the efforts to optimize preventive and environmental measures in the herd. In the second part of the study 126 cows (148 quarters) suffered from clinical mastitis (Verum: n=60; Placebo: n=66). The cure rates were nearly identical. In the whole population the clinical cure rate (CCR) immediately after treatment was 95%, 7 to 8 weeks after treatment 65%. The 107 clinically affected quarters which were infected by pathogenic bacteria showed a bacteriological cure rate (BCR) of 55% each and a complete bacterio-cytological cure rate (BCCR) of 35% and 40% after 4-5 weeks and 7-8 weeks after treatment, respectively. During the observation time of 8 weeks a total of 12 cows in each of the treatment groups produced a homologous recurrent infection. 6 cows in the verum group and 4 cows in the placebo group developed a new infection in one of the other quarters. The treatment results seems to be satisfying while the enhanced but still not optimized environmental conditions in the herd are possibly responsible for the high amount of new infections and recurrences. Looking at the results of the study at all, the use of antibiotics could be decreased by 75% due to the therapy management (in spite of the change of it because of unsatisfying results) in combination with preventive measures. Additionally the herd udder health could be increased. So the mean herd somatic cell count decreased by 75.000 somatic cells/ml to 165.000 somatic cells/ml. Furthermore, the milk yield increased by 250 kg to 6.500 kg/cow/year. The count of infections with S. aureus in the herd decreased dramatically. The decreasing input of antibiotics in mastitis therapy in the project farm lead to a decrease of 36.000 kg antibiotically loaded milk compared to a hypothetic conventional mastitis management. Furthermore, the omission of withdrawal times after homeopathic treatment resulted in a benefit of additional production milk of 25.000 kg. The antibiotics minimizing therapy concept of the second part of this investigation which could be evaluated under practice conditions can be recommended for other farms too if simultaneous herd prevention measures can be assured by the farm manager to ensure good preconditions for the convalescence of the cows. The cure rates after placebo are unexpected high. Due to these results it is profoundly debatable whether the strategies of conventional therapy of bovine mastitis are suitable to ensure herd udder health. It should be evaluated which part of the cure rate is amounted by self cure and which other factors have an effect on the healing. The nearly identical cure rates in both treatment groups do not allow the proof of homeopathic efficacy at all. Indeed, comparing the bacteriologically caused mastitis cases (107 quarters), there is a significantly higher cure rate in the verum group (p < 0.05)

Virtual flow-diverter treatment planning: The effect of device placement on bifurcation aneurysm haemodynamics

Bifurcation aneurysms account for a large fraction of cerebral aneurysms and often present morphologies that render traditional endovascular treatments, such as coiling, challenging and problematic. Flow-diverter stents offer a potentially elegant treatment option for such aneurysms, but clinical use of these devices remains controversial. Specifically, the deployment of a flow-diverter device in a bifurcation entails jailing one or more potentially vital vessels with a low-porosity mesh designed to restrict the flow. When multiple device placement configurations exist, the most appropriate clinical decision becomes increasingly opaque. In this study, three bifurcation aneurysm geometries were virtually treated by flow-diverter device. Each aneurysm was selected to offer two possible device deployment positions. Flow-diverters similar to commercially available designs were deployed with a fast-deployment algorithm before transient and steady state computational fluid dynamics simulations were performed. Reductions in aneurysm inflow, mean wall shear stress and maximum wall shear stress, all factors often linked with aneurysm treatment outcome, were compared for different device configurations in each aneurysm. In each of the three aneurysms modelled, a particular preferential device placement was shown to offer superior performance with the greatest reduction in the flow metrics considered. In all the three aneurysm geometries, substantial variations in inflow reduction (up to 25.3%), mean wall shear stress reduction (up to 14.6%) and maximum wall shear stress reduction (up to 12.1%) were seen, which were all attributed to device placement alone. Optimal device placement was found to be non-trivial and highly aneurysm specific; in only one-third of the simulated geometries, the best overall performance was achieved by deploying a device in the daughter vessel with the highest flow rate. Good correspondence was seen between transient results and steady state computations that offered a significant reduction in simulation run time. If accurate steady state computations are combined with the fast-deployment algorithm used, the modest run time and corresponding hardware make a virtual treatment pipeline in the clinical setting a meaningful possibility

Global assessment of nitrogen deposition effects on terrestrial plant diversity : a synthesis

Atmospheric nitrogen (N) deposition is it recognized threat to plant diversity ill temperate and northern parts of Europe and North America. This paper assesses evidence from field experiments for N deposition effects and thresholds for terrestrial plant diversity protection across a latitudinal range of main categories of ecosystems. from arctic and boreal systems to tropical forests. Current thinking on the mechanisms of N deposition effects on plant diversity, the global distribution of G200 ecoregions, and current and future (2030) estimates of atmospheric N-deposition rates are then used to identify the risks to plant diversity in all major ecosystem types now and in the future. This synthesis paper clearly shows that N accumulation is the main driver of changes to species composition across the whole range of different ecosystem types by driving the competitive interactions that lead to composition change and/or making conditions unfavorable for some species. Other effects such its direct toxicity of nitrogen gases and aerosols long-term negative effects of increased ammonium and ammonia availability, soil-mediated effects of acidification, and secondary stress and disturbance are more ecosystem, and site-specific and often play a supporting role. N deposition effects in mediterranean ecosystems have now been identified, leading to a first estimate of an effect threshold. Importantly, ecosystems thought of as not N limited, such as tropical and subtropical systems, may be more vulnerable in the regeneration phase. in situations where heterogeneity in N availability is reduced by atmospheric N deposition, on sandy soils, or in montane areas. Critical loads are effect thresholds for N deposition. and the critical load concept has helped European governments make progress toward reducing N loads on sensitive ecosystems. More needs to be done in Europe and North America. especially for the more sensitive ecosystem types. including several ecosystems of high conservation importance. The results of this assessment Show that the Vulnerable regions outside Europe and North America which have not received enough attention are ecoregions in eastern and Southern Asia (China, India), an important part of the mediterranean ecoregion (California, southern Europe). and in the coming decades several subtropical and tropical parts of Latin America and Africa. Reductions in plant diversity by increased atmospheric N deposition may be more widespread than first thought, and more targeted Studies are required in low background areas, especially in the G200 ecoregions

Free fatty acids link metabolism and regulation of the insulin-sensitizing fibroblast growth factor-21

OBJECTIVE—Fibroblast growth factor (FGF)-21 improves insulin sensitivity and lipid metabolism in obese or diabetic animal models, while human studies revealed increased FGF-21 levels in obesity and type 2 diabetes. Given that FGF-21 has been suggested to be a peroxisome proliferator–activator receptor (PPAR) –dependent regulator of fasting metabolism, we hypothesized that free fatty acids (FFAs), natural agonists of PPAR, might modify FGF-21 levels. RESEARCH DESIGN AND METHODS—The effect of fatty acids on FGF-21 was investigated in vitro in HepG2 cells. Within a randomized controlled trial, the effects of elevated FFAs were studied in 21 healthy subjects (13 women and 8 men). Within a clinical trial including 17 individuals, the effect of insulin was analyzed using an hyperinsulinemic-euglycemic clamp and the effect of PPAR activation was studied subsequently in a rosiglitazone treatment trial over 8 weeks. RESULTS—Oleate and linoleate increased FGF-21 expression and secretion in a PPAR-dependent fashion, as demonstrated by small-interfering RNA–induced PPAR knockdown, while palmitate had no effect. In vivo, lipid infusion induced an increase of circulating FGF-21 in humans, and a strong correlation between the change in FGF-21 levels and the change in FFAs was observed. An artificial hyperinsulinemia, which was induced to delineate the potential interaction between elevated FFAs and hyperinsulinemia, revealed that hyperinsulinemia also increased FGF-21 levels in vivo, while rosiglitazone treatment had no effect. CONCLUSIONS—The results presented here offer a mechanism explaining the induction of the metabolic regulator FGF-21 in the fasting situation but also in type 2 diabetes and obesity

Renal function is independently associated with circulating betatrophin

OBJECTIVE: Betatrophin has been identified as a marker linking liver with beta cell function and lipid metabolism in murine models. Until now, the regulation of circulating betatrophin in humans is not entirely clear. We here analyzed the relation of betatrophin levels to phenotypes of the metabolic syndrome and speculated that renal function might influence circulating betatrophin levels and explain age-dependent changes of betatrophin. SUBJECTS: We analyzed blood samples from 535 individuals participating in the Metabolic Syndrome Berlin Potsdam study. RESULTS: In a crude analysis we found a positive correlation between betatrophin levels and HbA1c (r = 0.24; p < 0.001), fasting glucose (r = 0.20; p < 0.001) and triglycerides (r = 0.12; p = 0.007). Furthermore betatrophin was positively correlated with age (r = 0.47; p <0.001), systolic blood pressure (r = 0.17; p < 0.001), intima media thickness (r = 0.26; p < 0.001) and negatively correlated with CKD-EPI eGFR (r = -0.33; p < 0.001) as an estimate of renal function. Notably, eGFR remained highly associated with betatrophin after adjustment for age, waist circumference, gender, HbA1c and lipid parameters in a multivariate linear regression model ({beta} = -0.197, p< 0.001). CONCLUSIONS: Our data suggest that circulating levels of betatrophin depend on age, gender, waist circumference, total/HDL cholesterol ratio and renal function. Especially the association to eGFR highlights the importance for future studies to address renal function as possible influence on betatrophin regulation and consider eGFR as potential confounder when analyzing the role of betatrophin in humans

Palliative treatment of uncontrollable hypercalcemia due to parathyrotoxicosis: denosumab as rescue therapy

Parathyroid carcinoma is a rare disease leading to severe hypercalcemia due to hyperparathyroidism. Surgery is the primary treatment option. A more progressive form of the disease is characterized by parathyrotoxicosis, and subsequent hypercalcemia is the most common cause of death. We report a case presenting with severe hypercalcemia due to parathyrotoxicosis from parathyroid carcinoma treated for the first time using the monoclonal antibody denosumab as a rescue therapy and present long-term follow-up data. The 71-year-old patient presented with severe hypercalcemia due to metastatic parathyroid carcinoma. Despite undergoing treatment with bisphosphonates, cinacalcet hydrochloride, and forced diuresis, the patient's condition deteriorated rapidly due to resistant hypercalcemia. Surgery performed because of spinal metastasis and forced diuresis lowered calcium levels, albeit they remained in the hypercalcemic range and significantly increased when forced diuresis was stopped. Considering a palliative situation to overcome hypercalcemia, we decided to administer denosumab, a monoclonal antibody that binds to the receptor activator of nuclear factor-kappa B ligand. After a single subcutaneous administration of 60 mg denosumab, calcium levels normalized within one day. Subsequent denosumab injections led to permanent control of serum calcium for more than 2 years despite rising parathyroid hormone levels and repeated surgeries. Together with recent cases in the literature supporting our observation, we believe that denosumab is relevant for future trials and represents an effective tool to control hypercalcemia in patients with advanced stages of parathyroid cancer