Missionland, a multinational co-operation program to construct and share a generic mission simulation environment

A simulation environment is a virtual representation of the real-world natural and cultural environment. Such an environment contains dynamic elements, for example weather, time of day and moving vehicles, as well as static elements, for example vegetation, buildings and infrastructure. When performing distributed (joint) simulations a number of problems exist concerning the selection and use of a simulation environment. These problems can either be caused by the different requirements of the participating users or by different technical capabilities. As training via distributed mission simulation has the potential to enhance force readiness and operational effectiveness in coalition operations, these problems with the environment representation should be solved. Normally, this can be done by correlating existing environment databases, but that is costly, both in effort and in money, and the end-result will always be hampered by technical incompatibilities. It also does not address security and political limitations. Therefore it is preferable to create a generic and geo-unspecific simulation environment, Missionland

Effective Use of Simulation Means in Collective Mission Simulation

Mission training and rehearsal are vital to successful operations. Advances in modeling and simulation (M&S) technology now allow for Collective Mission Simulation (CMS). The Royal Netherlands Armed Forces have exploited CMS through participation in a number of virtual exercises. The potential of collective mission simulation has been recognized and the requirement for a CMS capability was formalized. Such a capability is characterized by effective realism, interoperable systems across domains, and seamless information flow. Within the next few years the Royal Netherlands Armed Forces want to establish a validated, reusable, interoperable mission simulation environment that will support the distributed simulation of tactical and operational missions at varying degrees of security classification

Statistical analysis of kerf mark measurements in bone

Saw marks on bone have been routinely reported in dismemberment cases. When saw blade teeth contact bone and the bone is not completely sawed into two parts, bone fragments are removed forming a channel or kerf. Therefore, kerf width can approximate the thickness of the saw blade. The purpose of this study is to evaluate 100 saw kerf widths in bone produced by ten saw types to determine if a saw can be eliminated based on the kerf width. Five measurements were taken from each of the 100 saw kerfs to establish an average thickness for each kerf mark. Ten cuts were made on 10 sections of bovine bone, five with human-powered saws and five with mechanical-powered saws. The cuts were examined with a stereoscopic microscope utilizing digital camera measuring software. Two statistical cumulative logistic regression models were used to analyze the saw kerf data collected. In order to estimate the prediction error, repeated stratified cross-validation was applied in analyzing the kerf mark data. Based on the two statistical models used, 70–90% of the saws could be eliminated based on kerf width

Radioimmunotherapy of human head and neck squamous cell carcinoma xenografts with 131I-labelled monoclonal antibody E48 IgG.

Monoclonal antibody (MAb) E48 reacts with a 22 kD antigen exclusively expressed in squamous and transitional epithelia and their neoplastic counterparts. Radiolabelled with 99mTc, MAb E48 is capable of targeting metastatic and recurrent disease in patients with head and neck cancer. In this study, the capacity of 131I-labelled MAb E48 to eradicate xenografts of human squamous cell carcinoma of the head and neck (HNSCC) in nude mice was examined. Experimental groups received a single i.v. bolus injection of 400 microCi MAb E48 IgG (number of mice (n = 6, number of tumours (t) = 9) or 800 microCi MAb E48 IgG (n) = 5,t = 7), whereas control groups received either diluent (n = 3,t = 5), unlabelled MAb E48 IgG (n = 4,t = 5) or 800 microCi 131I-labelled isotype-matched control MAb (n = 6,t = 9). A 4.1-fold increase in the median tumour volume doubling time and regression of two out of ten tumours (20%) was observed in mice treated with 400 microCi. In mice treated with 800 microCi. In mice treated with 800 microCi, two out of seven tumours (29%) showed complete remission without regrowth during follow-up (greater than 3 months). Median tumour volume doubling time in the remaining five tumours was increased 7.8-fold. No antitumour effects were observed in mice injected with diluent, unlabelled MAb E48 or 131I-labelled control MAb. In the same xenograft model, chemotherapy with doxorubicin, 5-fluorouracil, cisplatin, bleomycin, methotrexate or 2',2'-difluorodeoxycytidine yielded a less profound effect on tumour volume doubling time. Increases in tumour volume doubling time with these chemotherapeutic agents were 4, 2.2, 2.1, 1.7, 0, and 2.6 respectively. Moreover, no cures were observed with any of these chemotherapeutic agents. From the tissue distribution of 800 microCi MAb E48, the absorbed cumulative radiation doses of tumour and various organs were calculated using the trapezoid integration method for the area under the curve. To tumour xenografts, 12,170 cGy was delivered, blood received 2,984 cGy, whereas in every other tissue the accumulated dose was less than 6% of the dose delivered to tumour. These data, describing the first radiolabelled MAb with therapeutic efficacy against HNSCC, suggest radioimmunotherapy with MAb E48 to be a potential therapeutic modality for the treatment of head and neck cancer

On the functions counting walks with small steps in the quarter plane

Models of spatially homogeneous walks in the quarter plane ${\bf Z}_+^{2}$ with steps taken from a subset $\mathcal{S}$ of the set of jumps to the eight nearest neighbors are considered. The generating function $(x,y,z)\mapsto Q(x,y;z)$ of the numbers $q(i,j;n)$ of such walks starting at the origin and ending at $(i,j) \in {\bf Z}_+^{2}$ after $n$ steps is studied. For all non-singular models of walks, the functions $x \mapsto Q(x,0;z)$ and $y\mapsto Q(0,y;z)$ are continued as multi-valued functions on ${\bf C}$ having infinitely many meromorphic branches, of which the set of poles is identified. The nature of these functions is derived from this result: namely, for all the 51 walks which admit a certain infinite group of birational transformations of ${\bf C}^2$, the interval $]0,1/|\mathcal{S}|[$ of variation of $z$ splits into two dense subsets such that the functions $x \mapsto Q(x,0;z)$ and $y\mapsto Q(0,y;z)$ are shown to be holonomic for any $z$ from the one of them and non-holonomic for any $z$ from the other. This entails the non-holonomy of $(x,y,z)\mapsto Q(x,y;z)$, and therefore proves a conjecture of Bousquet-M\'elou and Mishna.Comment: 40 pages, 17 figure

Superior localisation and imaging of radiolabelled monoclonal antibody E48 F(ab')2 fragment in xenografts of human squamous cell carcinoma of the head and neck and of the vulva as compared to monoclonal antibody E48 IgG.

Monoclonal antibody (MAb) E48 and its F(ab')2 fragment, radiolabelled with 131I, were tested for tumour localisation and imaging in nude mice bearing a squamous cell carcinoma xenograft line derived from a head and neck carcinoma (HNX-HN) or from a vulva carcinoma (VX-A431). MAb IgG or F(ab')2 fragments were injected in parallel and at day 1, 2, 3 and 6 or 7, mice were either scanned with a gamma camera or dissected for determination of isotope biodistribution. In HNX-HN bearing mice, E48 IgG as well as F(ab')2 showed highly specific localisation in tumour tissue. The mean tumour uptake (n = 4) expressed as the percentage of the injected dose per gram of tumour tissue (percentage ID/g) of IgG was 11.9% at day 1 and increased to 14.6% at day 6 whereas percentage ID/g of F(ab')2 was 7.2% at day 1 and decreased during subsequent days. Tumour to blood ratios (T/B) at day 1 were 1.2 for IgG and 13.6 for F(ab')2 and reached a maximum at day 6 with values of 6.4 and 54.2 respectively. In VX-A431 bearing mice, only E48 F(ab')2 showed preferential localisation in tumour tissue. At day 1, Percentage ID/g of IgG was 3.7 and T/B was 0.3, while percentage ID/g of F(ab')2 was 2.4 and T/B was 3.2. Percentage ID/g decreased after day 1 while T/B increased. In these experiments no preferential localisation of either isotype matched 125I-labelled control IgG or F(ab')2 was observed. In F(ab')2 injected HNX-HN bearing mice as well as VX-A431 bearing mice, tumours could be visualised at day 1 and 2 without any appreciable background activity. With MAb IgG this was also possible in HNX-HN bearing mice (but not in VX-A431 bearing mice) but only at day 3 and 6. These findings suggest that the superior tumour to non-tumour ratios render the E48 F(ab')2 fragment more qualified for specific targeting of radioisotopes to tumour xenografts in this experimental setting

Visualization of Coronary Wall Atherosclerosis in Asymptomatic Subjects and Patients with Coronary Artery Disease Using Magnetic Resonance Imaging

Background: Magnetic resonance imaging (MRI) is sensitive to early atherosclerotic changes such as positive remodeling in patients with coronary artery disease (CAD). We assessed prevalence, quality, and extent of coronary atherosclerosis in a group of healthy subjects compared to patients with confirmed CAD. Methodology: Twenty-two patients with confirmed CAD (15M, 7F, mean age 60.4±10.4 years) and 26 healthy subjects without history of CAD (11M, 15F, mean age 56.1±4.4 years) underwent MRI of the right coronary artery (RCA) and vessel wall (MR-CVW) on a clinical 1.5T MR-scanner. Wall thickness measurements of both groups were compared. Principal Findings: Stenoses of the RCA (both < and ≥50% on CAG) were present in all patients. In 21/22 patients, stenoses detected at MRI corresponded to stenoses detected with conventional angiography. In 19/26 asymptomatic subjects, there was visible luminal narrowing in the MR luminography images. Fourteen of these subjects demonstrated corresponding increase in vessel wall thickness. In 4/26 asymptomatic subjects, vessel wall thickening without luminal narrowing was present. Maximum and mean wall thicknesses in patients were significantly higher (2.16 vs 1.92 mm, and 1.38 vs 1.22 mm, both p<0.05). Conclusions: In this cohort of middle-aged individuals, both patients with stable angina and angiographically proven coronary artery disease, as well as age-matched asymptomatic subjects. exhibited coronary vessel wall thickening detectable with MR coronary vessel wall imaging. Maximum and mean wall thicknesses were significantly higher in patients. The vast majority of asymptomatic subjects had either positive remodeling without luminal narrowing, or non-significant stenosis. Trial registration ClinicalTrials.gov NCT00456950

Double aortic arch with double aneuploidy—rare anomaly in combined Down and Klinefelter syndrome

A 14-month-old boy with double aneuploidy and a double aortic arch suffered from frequently recurrent severe feeding and respiratory problems. Chromosomal analysis showed a 48,XXY + 21 karyotype: a double aneuploidy of Down syndrome (DS) and Klinefelter syndrome (KS). Only four cases of double aneuploidy (DS + KS) associated with congenital heart defects have been published of which none had a double aortic arch. Our case report should draw attention to the possibility of a double aortic arch in patients with severe feeding and respiratory problems and a double aneuploidy