Tumor size and prognosis in aggressively treated osteosarcoma

PURPOSE: The aim of this retrospective analysis was to investigate the prognostic significance and optimal measures of tumor size in osteosarcoma treated with intensive neoadjuvant chemotherapy. PATIENTS AND METHODS: Initial anterior-posterior (AP) and lateral x-ray films of 128 patients treated within the trials Cooperative Osteosarcoma Study (COSS)-80, -82, and -86, were evaluated for the following three tumor diameters: length, width, and depth. Metastasis-free survival (MFS) analyses were performed in univariate and multivariate models with one, two, and three dimensions of the tumor as absolute or relative measures (tumor length, referred to bone length, plane and volume to body-surface area). RESULTS: Univariate analyses of MFS showed a high prognostic significance of all absolute measures. Relative measures, at best, showed a comparable predictive value. Cox regression analysis indicated the high prognostic significance of absolute tumor volume (ATV; P < .0001) and histologic response (P < .0001). None of 19 patients with an ATV < or = 70 cm3 and only four of 53 with an ATV < or = 150 cm3 relapsed, while in patients with an ATV more than 150 cm3, the relapse rate remained 40% to 60%, irrespective of further increase in volume. CONCLUSION: Initial tumor size is an important and easily obtainable prognostic factor in osteosarcoma and may serve as a basis for risk-adapted therapy. It is best represented by the absolute three-dimensional measure ATV. There is a cut-off point regarding the incidence of metastases at a tumor volume of approximately 150 cm3 as calculated from two-plane x-ray films.     

(S)-Reutericyclin: Susceptibility Testing and In Vivo Effect on Murine Fecal Microbiome and Volatile Organic Compounds

We aimed to assess the in vitro antimicrobial activity and the in vivo effect on the murine fecal microbiome and volatile organic compound (VOC) profile of (S)-reutericyclin. The antimicrobial activity of (S)-reutericyclin was tested against Clostridium difficile, Listeria monocytogenes, Escherichia coli, Enterococcus faecium, Staphylococcus aureus, Staphylococcus (S.) epidermidis, Streptococcus agalactiae, Pseudomonas aeruginosa and Propionibacterium acnes. Reutericyclin or water were gavage fed to male BALBc mice for 7 weeks. Thereafter stool samples underwent 16S based microbiome analysis and VOC analysis by gas chromatography mass spectrometry (GC-MS). (S)-reutericyclin inhibited growth of S. epidermidis only. Oral (S)-reutericyclin treatment caused a trend towards reduced alpha diversity. Beta diversity was significantly influenced by reutericyclin. Linear discriminant analysis Effect Size (LEfSe) analysis showed an increase of Streptococcus and Muribaculum as well as a decrease of butyrate producing Ruminoclostridium, Roseburia and Eubacterium in the reutericyclin group. VOC analysis revealed significant increases of pentane and heptane and decreases of 2,3-butanedione and 2-heptanone in reutericyclin animals. The antimicrobial activity of (S)-reutericyclin differs from reports of (R)-reutericyclin with inhibitory effects on a multitude of Gram-positive bacteria reported in the literature. In vivo (S)-reutericyclin treatment led to a microbiome shift towards dysbiosis and distinct alterations of the fecal VOC profile.     

Patterns of Iridoid Glycoside Production and Induction in Plantago lanceolata and the Importance of Plant Age

Induction of allelochemicals is one way that plants efficiently deploy defenses against herbivory. In two separate experiments we investigated the time course of this inductive response and the importance of the timing of herbivory for Plantago lanceolata (Plantaginaceae). We found a localized induced response of catalpol and the ratio of catalpol to total iridoid glycosides in damaged leaves that was evident at d 6 after caterpillars of the specialist Junonia coenia were put onto the plants. On the whole plant level, we detected small, but significant changes in the iridoid glycoside metabolism of P. lanceolata on several different days following herbivory. We also found considerable change in the amounts of allelochemicals produced during P. lanceolata's ontogeny. This ontogenetic effect might help to explain some of the reasons why induction may be difficult to detect in P. lanceolata. We also investigated the importance of the timing of herbivory on P. lanceolata's inductive response, but neither herbivory after 5 wk of growth nor after 6 or 7 wk of growth induced an increase in aucubin or catalpol.     

Visual Analytics for Exploring Local Impact of Air Traffic

The environmental and noise impact of airports often causes extensive political discussion which in some cases even lead to transnational tensions. Analyzing local approach and departure patterns around an airport is difficult since it depends on a variety of complex variables like weather, local and general regulations and many more. Yet, understanding these movements and the expected amount of flights during arrival and departure is of great interest to both casual and expert users, as planes have a higher impact on the areas beneath during these phases. We present a Visual Analytics framework that enables users to develop an understanding of local flight behavior through visual exploration of historical data and interactive manipulation of prediction models with direct feedback, as well as a classification quality visualization using a random noise metaphor. We showcase our approach using real world data from the Zurich International Airport region, where aircraft noise has led to an ongoing conflict between Germany and Switzerland. The use cases, findings and expert feedback demonstrate how our approach helps in understanding the situation and to substantiate the otherwise often subjective discourse on the topic.     

Evaluation of Reorientation Techniques and Distractors for Walking in Large Virtual Environments

Vir tual Environments (VEs) that use a real-walking locomotion interface have typically been restricted in size to the area of the tracked lab space. Techniques proposed to lift this size constraint, enabling real walking in VEs that are larger than the tracked lab space, all require reorientation techniques (ROTs) in the worst-case situation—when a user is close to walking out of the tracked space. We propose a new ROT using visual and audial distractors—objects in the VE that the user focuses on while the VE rotates—and compare our method to current ROTs through three user studies. ROTs using distractors were preferred and ranked more natural by users. Our findings also suggest that improving visual realism and adding sound increased a user's feeling of presence. Users were also less aware of the rotating VE when ROTs with distractors were used.     

Absolute calibration of photostimulable image plate detectors used as (0.5-20 MeV) high-energy proton detectors

In this paper, the absolute calibration of photostimulable image plates (IPs) used as proton detectors is presented. The calibration is performed in a wide range of proton energies (0.5-20 MeV) by exposing simultaneously the IP and calibrated detectors (radiochromic films and solid state detector CR39) to a source of broadband laser-accelerated protons, which are spectrally resolved. The final result is a calibration curve that enables retrieving the proton number from the IP signal.     

Prosthetic valve endocarditis: superiority of surgical valve replacement versus medical therapy only

The objective of our study was to assess the long-term outcome of patients with prosthetic valve endocarditis. We used a multicenter, prospective, observational study design. Six university teaching hospitals with high volume cardiothoracic surgery participated. Seventy-four patients with prosthetic valve endocarditis as defined by explicit, objective criteria were selected for participation. All patients were followed up prospectively for 1 year. Thirty-one percent and 69% had development of endocarditis within 60 days of valve insertion ("early") and after 60 days ("late"), respectively. The most common causes were Staphylococcus epidermidis (40%), Staphylococcus aureus (20%), streptococcal species (18%), and aerobic gram-negative bacilli (11%). Physical signs of endocarditis (new or changing murmur, stigmata, emboli) were seen in 58%. At 6 months and 12 months, mortality was 46% and 47%, respectively. Surgical replacement of the infected valve led to significantly lower mortality (23%) as compared with medical therapy alone (56%), as assessed by both univariate and multivariate analyses (p < 0.05). Improved outcome was seen for the surgical group even when controlling for severity of illness at time of diagnosis. From these findings we conclude that accurate assessment of outcome in prosthetic valve endocarditis requires long-term follow-up of at least 6 months following diagnosis. Surgical therapy warrants greater scrutiny; evaluation in controlled clinical trials is appropriate.     

Influence of craniofacial surgery on the social attitudes toward the malformed and their handling in different cultures and at different times: a contribution to social world history

A historic overview including the European, American, Asian, and African continents is given on attitudes toward and the handling of humans with congenital malformations in ancient cultures and on pertinent customs in some prehistoric peoples. Figures of early works of art showing malformed individuals are presented testifying to this worldwide and timeless problem of humankind. In parallel, analogous patient photographs from our hospital before and after reconstructive surgery are shown. Philosophies of ancient Greece, rome, and China on the subject of malformed infants essentially did not differ from the known attitudes of the less developed tribes in Europe and pre-Columbian America, although the means of elimination of unwanted offspring were rather passive (exposure) than active (manual killing). A radical change in attitudes and practices occurred with the spread of the Christian religion and its political installment in Europe. The care for the underprivileged including the malformed ones was considered a Christian duty to be performed with compassion and love. In our century, the clocks have been and apparently are turned back again. Atheistic and Darwinian influences, political atheism, and the belief in "higher ethics" issued by "superman" have led to a relapse into barbarism, also within the medical system. We, as craniofacial surgeons, are privileged to have the means to turn the clocks forward again by rehabilitating the physically most underprivileged: those with conspicuous craniofacial malformations. The necessary techniques exist and are applied, as the figures of patients from our hospital demonstrate, but the will and the emotional strength for their consequent application require more than our hands.     

Overcoming Anode Instability in Solid-State Batteries through Control of the Lithium Metal Microstructure

Enabling the lithium metal anode (LMA) in solid-state batteries (SSBs) is the key to developing high energy density battery technologies. However, maintaining a stable electrode–electrolyte interface presents a critical challenge to high cycling rate and prolonged cycle life. One such issue is the interfacial pore formation in LMA during stripping. To overcome this, either higher stack pressure or binary lithium alloy anodes are used. Herein, it is shown that fine-grained (d = 20 µm) polycrystalline LMA can avoid pore formation by exploiting the microstructural dependence of the creep rates. In a symmetric cell set-up, i.e., LiǀLi_6.25Al_0.25La₃Zr₂O₁₂(LLZO)ǀLi, fine-grained LMA achieves > 11.0 mAh cm⁻² compared to ≈ 3.6 mAh cm⁻² for coarse-grained LMA (d = 295 µm) at 0.1 mA cm⁻² and at moderate stress of 2.0 MPa. Smaller diffusion lengths (≈ 20 µm) and higher diffusivity pathway along dislocations (D_d ≈ 10⁻⁷ cm² s⁻¹), generated during cell fabrication, result in enhanced viscoplastic deformation in fine-grained polycrystalline LMA. The electrochemical performances corroborate well with estimated creep rates. Thus, microstructural control of LMA can significantly reduce the required stack pressure during stripping. These results are particularly relevant for “anode-free” SSBs wherein both the microstructure and the mechanical state of the lithium are critical parameters.     

Nodes on ropes: a comprehensive data and control flow for steering ensemble simulations

Flood disasters are the most common natural risk and tremendous efforts are spent to improve their simulation and management. However, simulation-based investigation of actions that can be taken in case of flood emergencies is rarely done. This is in part due to the lack of a comprehensive framework which integrates and facilitates these efforts. In this paper, we tackle several problems which are related to steering a flood simulation. One issue is related to uncertainty. We need to account for uncertain knowledge about the environment, such as levee-breach locations. Furthermore, the steering process has to reveal how these uncertainties in the boundary conditions affect the confidence in the simulation outcome. Another important problem is that the simulation setup is often hidden in a black-box. We expose system internals and show that simulation steering can be comprehensible at the same time. This is important because the domain expert needs to be able to modify the simulation setup in order to include local knowledge and experience. In the proposed solution, users steer parameter studies through the World Lines interface to account for input uncertainties. The transport of steering information to the underlying data-flow components is handled by a novel meta-flow. The meta-flow is an extension to a standard data-flow network, comprising additional nodes and ropes to abstract parameter control. The meta-flow has a visual representation to inform the user about which control operations happen. Finally, we present the idea to use the data-flow diagram itself for visualizing steering information and simulation results. We discuss a case-study in collaboration with a domain expert who proposes different actions to protect a virtual city from imminent flooding. The key to choosing the best response strategy is the ability to compare different regions of the parameter space while retaining an understanding of what is happening inside the data-flow system.