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Serological tests play an important role in the fight against Coronavirus Disease 2019 (COVID-19), including monitoring the dynamic immune response after vaccination, identifying past infection and determining community infection rate. Conventional methods for serological testing, such as enzyme-linked immunosorbent assays and chemiluminescence immunoassays, provide reliable and sensitive antibody detection but require sophisticated laboratory infrastructure and/or lengthy assay time. Conversely, lateral flow immunoassays are suitable for rapid point-of-care tests but have limited sensitivity. Here, we describe the development of a rapid and sensitive magnetofluidic immuno-PCR platform that can address the current gap in point-of-care serological testing for COVID-19. Our magnetofluidic immuno-PCR platform automates a magnetic bead-based, single-binding, and one-wash immuno-PCR assay in a palm-sized magnetofluidic device and delivers results in ∼30 min. In the device, a programmable magnetic arm attracts and transports magnetically-captured antibodies through assay reagents pre-loaded in a companion plastic cartridge, and a miniaturized thermocycler and a fluorescence detector perform immuno-PCR to detect the antibodies. We evaluated our magnetofluidic immuno-PCR with 108 clinical serum/plasma samples and achieved 93.8% (45/48) sensitivity and 98.3% (59/60) specificity, demonstrating its potential as a rapid and sensitive point-of-care serological test for COVID-19.

BackgroundSustained molecular detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in the upper respiratory tract (URT) in mild to moderate coronavirus disease 2019 (COVID-19) is common. We sought to identify host and immune determinants of prolonged SARS-CoV-2 RNA detection.MethodsNinety-five symptomatic outpatients self-collected midturbinate nasal, oropharyngeal (OP), and gingival crevicular fluid (oral fluid) samples at home and in a research clinic a median of 6 times over 1–3 months. Samples were tested for viral RNA, virus culture, and SARS-CoV-2 and other human coronavirus antibodies, and associations were estimated using Cox proportional hazards models.ResultsViral RNA clearance, as measured by SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR), in 507 URT samples occurred a median (interquartile range) 33.5 (17–63.5) days post–symptom onset. Sixteen nasal-OP samples collected 2–11 days post–symptom onset were virus culture positive out of 183 RT-PCR-positive samples tested. All participants but 1 with positive virus culture were negative for concomitant oral fluid anti-SARS-CoV-2 antibodies. The mean time to first antibody detection in oral fluid was 8–13 days post–symptom onset. A longer time to first detection of oral fluid anti-SARS-CoV-2 S antibodies (adjusted hazard ratio [aHR], 0.96; 95% CI, 0.92–0.99; P = .020) and body mass index (BMI) ≥25 kg/m2 (aHR, 0.37; 95% CI, 0.18–0.78; P = .009) were independently associated with a longer time to SARS-CoV-2 viral RNA clearance. Fever as 1 of first 3 COVID-19 symptoms correlated with shorter time to viral RNA clearance (aHR, 2.06; 95% CI, 1.02–4.18; P = .044).ConclusionsWe demonstrate that delayed rise of oral fluid SARS-CoV-2-specific antibodies, elevated BMI, and absence of early fever are independently associated with delayed URT viral RNA clearance.

We evaluated the durability of IgG responses specific to SARS-CoV-2 nucleocapsid (N), receptor binding domain (RBD), and spike (S) antigens in saliva up to 8 months after RT-PCR-confirmed COVID-19 using a multiplex salivary assay. We estimated a half-life of 64 days (d) (95% CI: 49, 80 d) for N, 100 d for RBD (95% CI: 58, 141 d), and 148 d (95% CI: 62, 238 d) for S IgG responses in saliva, consistent with half-life estimates previously reported in blood. Saliva can serve as an alternative to blood to monitor humoral immune responses on a large scale following SARS-CoV-2 infection and vaccination for surveillance and assessment of population immunity.

BackgroundOutpatient COVID-19 has been insufficiently characterized.ObjectiveTo determine the progression of disease and subsequent determinants of hospitalization.DesignA prospective outpatient cohort.SettingOutpatients were recruited by phone between April 21 to June 23, 2020 after receiving outpatient or emergency department testing within a large health network in Maryland, USA.ParticipantsOutpatient adults with positive RT-PCR results for SARS-CoV-2.MeasurementsSymptoms, portable pulse oximeter oxygen saturation (SaO2), heart rate, and temperature were collected by participants on days 0, 3, 7, 14, 21, and 28 after enrollment. Baseline demographics, comorbid conditions were evaluated for risk of subsequent hospitalization using negative binomial, logistic, and random effects logistic regression.ResultsAmong 118 SARS-CoV-2 infected outpatients, the median age was 56.0 years (IQR, 50.0 to 63.0) and 50 (42.4%) were male. Among those reporting active symptoms, the most common symptoms during the first week since symptom onset included weakness/fatigue (67.3%), cough (58.0%), headache (43.8%), and sore throat (34.8%). Participants returned to their usual health a median of 20 days (IQR, 13 to 38) from the symptom onset, and only 65.5% of respondents were at their usual health during the fourth week of illness. Over 28 days, 10.9% presented to the emergency department and 7.6% required hospitalization. Individuals at the same duration of illness had a 6.1 times increased adjusted odds of subsequent hospitalization per every percent decrease in home SaO2(95% confidence interval [CI]: 1.41 to 31.23, p=0.02).LimitationsSeverity and duration of illness may differ in a younger population.ConclusionSymptoms often persisted but uncommonly progressed to hospitalization. Home SaO2might be an important adjunctive tool to identify progression of COVID-19.RegistrationClinicaltrials.gov NCT number:NCT04496466Funding SourceThe Sherrilyn and Ken Fisher Center for Environmental Infectious Diseases Discovery Program and the Johns Hopkins University School of Medicine

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic that has infected over 36 million and killed over 1 million people. Informed implementation of government public health policies depends on accurate data on SARS-CoV-2 immunity at a population scale. We hypothesized that detection of SARS-CoV-2 salivary antibodies could serve as a noninvasive alternative to serological testing for monitoring of SARS-CoV-2 infection and seropositivity at a population scale., Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic that has infected over 36 million and killed over 1 million people. Informed implementation of government public health policies depends on accurate data on SARS-CoV-2 immunity at a population scale. We hypothesized that detection of SARS-CoV-2 salivary antibodies could serve as a noninvasive alternative to serological testing for monitoring of SARS-CoV-2 infection and seropositivity at a population scale. We developed a multiplex SARS-CoV-2 antibody immunoassay based on Luminex technology that comprised 12 CoV antigens, mostly derived from SARS-CoV-2 nucleocapsid (N) and spike (S). Saliva and sera collected from confirmed coronavirus disease 2019 (COVID-19) cases and from the pre-COVID-19 era were tested for IgG, IgA, and IgM to the antigen panel. Matched saliva and serum IgG responses (n = 28) were significantly correlated. The salivary anti-N IgG response resulted in the highest sensitivity (100%), exhibiting a positive response in 24/24 reverse transcription-PCR (RT-PCR)-confirmed COVID-19 cases sampled at >14 days post-symptom onset (DPSO), whereas the salivary anti-receptor binding domain (RBD) IgG response yielded 100% specificity. Temporal kinetics of IgG in saliva were consistent with those observed in blood and indicated that most individuals seroconvert at around 10 DPSO. Algorithms employing a combination of the IgG responses to N and S antigens result in high diagnostic accuracy (100%) by as early as 10 DPSO. These results support the use of saliva-based antibody testing as a noninvasive and scalable alternative to blood-based antibody testing.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic control will require widespread access to accurate diagnostics. Salivary sampling circumvents swab supply chain bottlenecks, is amenable to self-collection, and is less likely to create an aerosol during collection compared with the nasopharyngeal swab. Methods We compared real-time reverse-transcription polymerase chain reaction Abbott m2000 results from matched salivary oral fluid (gingival crevicular fluid collected in an Oracol device) and nasal-oropharyngeal (OP) self-collected specimens in viral transport media from a nonhospitalized, ambulatory cohort of coronavirus disease 2019 (COVID-19) patients at multiple time points. These 2 sentences should be at the beginning of the results. Results There were 171 matched specimen pairs. Compared with nasal-OP swabs, 41.6% of the oral fluid samples were positive. Adding spit to the oral fluid percent collection device increased the percent positive agreement from 37.2% (16 of 43) to 44.6% (29 of 65). The positive percent agreement was highest in the first 5 days after symptoms and decreased thereafter. All of the infectious nasal-OP samples (culture positive on VeroE6 TMPRSS2 cells) had a matched SARS-CoV-2 positive oral fluid sample. Conclusions In this study of nonhospitalized SARS-CoV-2-infected persons, we demonstrate lower diagnostic sensitivity of self-collected oral fluid compared with nasal-OP specimens, a difference that was especially prominent more than 5 days from symptom onset. These data do not justify the routine use of oral fluid collection for diagnosis of SARS-CoV-2 despite the greater ease of collection. It also underscores the importance of considering the method of saliva specimen collection and the time from symptom onset especially in outpatient populations.

Many properties of layered materials change as they are thinned from their bulk forms down to single layers, with examples including indirect-to-direct band gap transition in 2H semiconducting transition metal dichalcogenides as well as thickness-dependent changes in the valence band structure in post-transition metal monochalcogenides and black phosphorus. Here, we use angle-resolved photoemission spectroscopy to study the electronic band structure of monolayer ReSe$_{2}$, a semiconductor with a distorted 1T structure and in-plane anisotropy. By changing the polarization of incoming photons, we demonstrate that for ReSe$_{2}$, in contrast to the 2H materials, the out-of-plane transition metal $d_{z^{2}}$ and chalcogen $p_{z}$ orbitals do not contribute significantly to the top of the valence band which explains the reported weak changes in the electronic structure of this compound as a function of layer number. We estimate a band gap of 1.7 eV in pristine ReSe$_{2}$ using scanning tunneling spectroscopy and explore the implications on the gap following surface-doping with potassium. A lower bound of 1.4 eV is estimated for the gap in the fully doped case, suggesting that doping-dependent many-body effects significantly affect the electronic properties of ReSe$_{2}$. Our results, supported by density functional theory calculations, provide insight into the mechanisms behind polarization-dependent optical properties of rhenium dichalcogenides and highlight their place amongst two-dimensional crystals., Comment: 37 pages (including Supporting Information), 7 figures in the main text

A problem of electromagnetic wave scattering from cylindrical posts of arbitrary cross section located in waveguide junction is presented. The method of analysis is based on the direct field matching technique. Multimode scattering matrices of every section of waveguide junction are calculated and cascading procedure is utilized to investigate the whole structure. The results are verified by comparing them with those obtained from the mode matching method analysis as well as commercial software calculations.

In this paper a machine learning algorithm was applied to analyze the integrated data responses of magnetic multi-sensor matrix transducer. In order to proceed the algorithm, a large database was prepared considering measurement as well as simulation results. A finite element method was utilized to conduct a numerical calculation and provide transducers response signals for the various configurations of defects. The deep artificial neural network was used for implementation of machine learning algorithm and then the model was verified.

Background Actinic keratoses (AK) are pre-malignant cutaneous lesions caused by prolonged exposure to ultraviolet radiation. As AKs lesions are generally accepted to be the initial lesions in a disease continuum that progresses to squamous cell carcinoma (SCC), AK lesions have to be treated. They are also the second most common reason for visits to the dermatologist. Several treatments are available but their efficacy still needs to be improved. The UV-B-induced KA lesion mouse model is used in preclinical studies to assess the efficacy of novel molecules, even though it is often more representative of advanced AK or SCC. Objectives Here we report on a translational study, comparing the various stages of AK development in humans and in the UV-B irradiated mouse model, as well as the optimization of photograph acquisition of AK lesions on mouse skin. Methods Human and mouse skin lesions were analysed by histology and immunohistochemistry. Mouse lesions were also assessed using a digital dermatoscope. Results An histological and phenotypic analysis, including p53, Ki67 and CD3 expression detection, performed on human and mouse AK lesions, shows that overall AK modelling in mice is relevant in the clinical situation. Some differences are observed, such as disorganization of keratinocytes of the basal layer and a number of atypical nuclei which are more numerous in human AK, whereas much more pronounced acanthosis is observed in skin lesion in mice. Thanks to this translational study, we are able to select appropriate experimental conditions for establishing either early or advanced stage AK or an SCC model. Furthermore, we optimized photograph acquisition of AK lesions on mouse skin by using a digital dermatoscope which is also used in clinics and allows reproducible photograph acquisition for further reliable assessment of mouse lesions. Use of this camera is illustrated through a pharmacological study assessing the activity of CARAC®. Conclusion These data demonstrate that this mouse model of UV-B-induced skin lesions is predictive for the identification of novel therapeutic treatments for both early and advanced stages of the disease.

Vinflunine is a new Vinca alkaloid uniquely fluorinated, by the use of superacid chemistry, in a little exploited region of the catharanthine moiety. In vitro investigations have confirmed the mitotic-arresting and tubulin-interacting properties of vinflunine shared by other Vinca alkaloids. However, differences in terms of the inhibitory effects of vinflunine on microtubules dynamics and its tubulin binding affinities have been identified which appear to distinguish it from the other Vinca alkaloids. Vinflunine induced smaller spirals with a shorter relaxation time, effects, which might be associated with reduced neurotoxicity. Studies investigating the in vitro cytotoxicity of vinflunine in combination therapy have revealed a high level of synergy when vinflunine was combined with either cisplatin, mitomycin C, doxorubicin or 5-fluorouracil. Furthermore, although vinflunine appears to participate in P-glycoprotein-mediated drug resistance mechanisms, it has proved only a weak substrate for this protein and a far less potent inducer of resistance than vinorelbine. Vinflunine was identified in preclinical studies as having marked antitumour activity in vivo against a large panel of experimental tumour models, with tumour regressions being recorded in human renal and small cell lung cancer tumour xenografts. Overall its level of activity was superior to that of vinorelbine in many of the experimental models used. Interestingly, an in vivo study using a well vascularised adenocarcinoma of the colon has suggested that vinflunine mediates its antitumour activity at least in part via an antivascular mechanism, even at sub-cytotoxic doses. Therefore, these data provide a favourable preclinical profile for vinflunine, supporting its promising candidacy for clinical development. Phase I evaluations of vinflunine have been completed in Europe and phase II clinical trials are now ongoing.

Clostridium sordellii is a gram-positive anaerobic bacillus. Review of the English literature reveals only five reported cases of fatal postpartum gynaecologic infections due to Clostridium sordellii , all presenting three to six days after delivery. We report a case of fatal Clostridium sordellii endometritis presenting II days after vaginal delivery of twins.

Introduction The potency of the combination of primary chondrocytes with multipotent cells to support cartilage tissue regeneration, without the need for cell culture, was first evidenced in 2001. INSTRUCT (CellCoTec B.V., Netherlands) is a patented technology that combines freshly isolated autologous chondrocytes and mono-nucleated cells from bone marrow with a porous scaffold in a single surgical procedure. Objectives The objective of the INSTRUCT study was to assess the safety and efficacy of a cell mixture of non-expanded chondrocytes and bone marrow cells seeded on a co-polymer scaffold for the treatment of symptomatic cartilage defects of the knee. Methods Forty patients were enrolled at 6 European sites in a prospective, open-label, single-arm clinical trial. Patients were to be aged 18–55 years, with a Modified Outerbridge grade III or IV focal cartilage defect on the femoral condyle. Mal-alignment, ligament laxity and osteoarthritis (KL grade III or IV) were exclusion criteria. Safety and efficacy endpoints (clinical improvement: KOOS, IKDC, Pain VAS and structural repair: MRIs and histology) were evaluated at baseline, 3, 6, 12, 18 and 24 months. A macroscopic evaluation of the repair tissue was performed during the second-look arthroscopy using the ICRS cartilage repair assessment score. Results A total of 40 patients were enrolled and treated. Ninety percent of patients (36/40) completed the 2-year follow-up. Patients were predominantly male patients (72%), the mean age was 35 years, the mean BMI was 26. Lesions were mostly Modified Outerbridge grade IV (70%) lesions of traumatic origin (60%) with a mean size of 2.1 cm 2 . The results showed a clinically and statistically significant ( P P P Conclusions The results from the INSTRUCT study show that the treatment of cartilage lesions with a combination of primary chondrocytes and bone marrow cells results in articular cartilage tissue repair associated with a sustained and significant clinical improvement and a safety profile in line with existing treatment options. This first clinical experience suggests that this single-surgery solution is a viable treatment option for patients with full-thickness cartilage defects of the knee.

Vinflunine, or 20',20'-difluoro-3',4'-dihydrovinorelbine, is a novel Vinca alkaloid obtained by hemisynthesis using superacidic chemistry. The most impressive structural modification of this vinorelbine derivative was the selective introduction of two fluorine atoms at the 20' position, a part of the molecule previously inaccessible by classic chemistry. The antitumor activity of vinflunine was evaluated against a range of transplantable murine and human tumors. Vinflunine exhibited marked activity against murine P388 leukemia grafted i.v. when given i.p. in single or multiple doses according to various schedules or in single i.v. or p.o. doses. Increases in life span achieved with vinflunine, as assessed by T/C ratios, ranged from 200% to 457% and proved markedly superior to those of 129-186% obtained with the other Vinca alkaloids tested. Against s.c.-implanted B16 melanoma, multiple i.p. administration of vinflunine proved active in terms of both survival prolongation and tumor growth inhibition, with optimal T/C values and relative areas under the tumor growth curves (rAUC) being 24% and 36%, respectively. The extent of this activity was superior to that noted for vinorelbine under the same experimental conditions. Growth inhibition of human tumor xenografts LX-1 (lung) and MX-1 (breast) was also observed following four weekly i.p. injections of vinflunine as reflected by optimal T/C values of 23% and 26%, respectively, and significant differences in the rAUCs noted for treated versus control animals. It was also noticeable that vinflunine induced considerably more prolonged inhibitory effects on tumor growth than did vinorelbine. These results demonstrate that vinflunine is well tolerated and is definitively active against a range of experimental animal tumor models. Vinflunine activity has been documented in terms of both survival prolongation and tumor growth inhibition, with definite superiority over vinorelbine being shown in each tumor model evaluated.

To review a series of critically ill obstetric patients admitted to a general intensive care unit in a Canadian centre, to assess the spectrum of diseases, interventions required and outcome.A retrospective chart review was performed of obstetric patients admitted to the intensive care unit of an academic hospital with a high-risk obstetric service, during a five-year period. Data obtained included the admission diagnosis, ICU course and outcome. Daily APACHE II and TISS scores were recorded.Sixty-five obstetric patients, representing 0.26% of deliveries in this hospital, were admitted to the ICU during the study period. All had received prenatal care. Admission diagnoses included obstetric (71%) and non-obstetric (29%) complications. The mean APACHE II score was 6.8 +/- 4.2 and mean TISS score was 24 +/- 8.1. Twenty-seven patients (42%) required mechanical ventilation. No maternal mortality occurred and the perinatal mortality rate was 11%.A small proportion of obstetric patients develop complications requiring ICU admission. The outcome in this study was excellent, in contrast to that reported in other published studies with similar ICU admission rates. The universal availability of prenatal care may be an important factor in the outcome of this group of patients. The lack of a specific severity of illness scoring system for the pregnant patient makes comparison of case series difficult.

We propose a theory of optical absorption in monolayer graphene-hexagonal boron nitride (hBN) heterostructures. In highly oriented heterostructures, the hBN underlay produces a long-range moir\'e superlattice potential for the graphene electrons which modifies the selection rules for absorption of incoming photons in the infrared to visible frequency range. The details of the absorption spectrum modification depend on the relative strength of the various symmetry-allowed couplings between the graphene electrons and the hBN, and the resulting nature of the reconstructed band structure., Comment: 8 pages, 3 figures

The main advantages of gasless laparoscopy arise from the use of conventional laparotomy instruments (clamps, scissors and needle pushers). The operative time, for example, for hysterectomy procedures decreases to about 60% of the time taken hysterectomy for using conventional gas techniques. During cauterization, smoke escapes immediately through the open trocars and may even be suctioned using a conventional suction tube. As far as the nursing team is concerned, the equipment is familiar as they use the same instruments and the same sutures as in laparotomy. High respiration pressure, caused by the elevated abdominal pressure, as well as hypercapnia, are avoided. Therefore this procedure may also be performed on higher risk patients. The advantages for the patients are the shorter operative time, pain reduction and fewer complications, while retaining all the benefits of minimally invasive surgery.

Computational fluid dynamics solutions of the full Navier-Stokes equations have been used to numerically simulate the reacting in-bore flowfield for the ram accelerator projectile propulsion system. In this system a projectile and obturator are injected at supersonic velocity into a stationary tube filled with a pressurized mixture of hydrocarbon, oxidizer, and inert gases. Flow stagnation on the obturator initiates combustion of the mixture, before it is discarded. A system of shock waves on the projectile, in conjunction with viscous heating, sustains combustion. The resulting energy release, which travels with the projectile, also generates high pressures that impart thrust to the projectile. Numerical simulation utilizing finite rate chemical kinetics have been used to investigate this flowfield. Numerical results are used to visualize the flowfield, predict the effects of variation in system parameters, and predict projectile in-bore velocity.

Avascular necrosis of the proximal femur still remains the major complication of the treatment for developmental dislocation of the hip. In a three part study I reviewed this problem. Part I analyzed incidence, causes, and risk factors of avascular necrosis. In 105 children with 113 hips who developed avascular necrosis out of 636 consecutive patients with 823 hips treated nonoperatively for developmental dislocation of the hip in the years 1972-1976 the risk factors of avascular necrosis were determined. A method of treatment in most cases was Frejka pillow. Conventional radiographs obtained in AP views during the course of treatment and follow-up were analyzed. Avascular necrosis was found in 14 percent of the hips, classified as mild (49%), moderate (14%), and severe (37%). The differences between mild and severe cases were significant as regards age at the onset of treatment (p 0.006); with higher average age in mild forms, and degree of dislocation (p 0.01) with higher values in severe forms. The older the child was at the onset of treatment, the greater the risk of necrosis, notably if treatment was begun after 6 months of age. However, the incidence of the more severe cases was higher in the group up to 6 month of age. In general, avascular necrosis was more likely to occur in cases with high degree of initial dislocation and the differences between groups with low and high degree of dislocation were significant. In the group with highest initial dislocation the number of both mild and severe forms was high. Part II evaluated the growth and remodeling of the hip joint with avascular necrosis after nonoperative treatment of developmental dislocation on the basis of conventional radiography. An attempt was also made to determine the correlation between the severity of necrosis as seen in conventional radiography and the clinical and radiographic appearance of the hip after completion of growth. Finally the prognostic value of conventional radiography in prediction of deformities of the proximal femur due to necrosis was estimated. 68 patients with 98 involved hips treated exclusively nonoperatively for developmental dislocation of the hip in whom avascular necrosis developed were selected for the study. The average age at the time when the final radiograph was made was 25 (18-36) years and the average follow-up period was 23 (18-35) years. 16 patients (27 hips) were examined twice after completion of growth with the time interval of 10 years, the second examination being at an average age of 30 (26-36) years. In this group also progress of signs and symptoms of degenerative changes in clinical and radiographic examination was noted. To achieve sufficient data necessary to establish indications for further operative treatment in 2 patients also CT examinations with three-dimensional surface reconstruction were performed after physeal closure. Physical examinations were performed in all patients after completion of growth. Radiographs made before the onset of treatment for developmental dislocation of the hip, during treatment, at the child's age of 4-6 years, all obtained until the cessation of growth, and at final assessment, were studied. By physical evaluation 77 hips were rated as excellent or good, being pain free or with only occasional mild pain after walking long distances, with a good range of hip motion and negative Trendelenburg sign. The reasons for 21 fair or poor clinical end-results were pain, mostly with activity, and limp due to pain and abductor weakness. By radiographic evaluation in this group there were 50 hips rated as excellent or good, and 48 hips rated as fair or poor. In 29 hips excellent or good clinical findings at final review contrasted with fair or poor radiographic scores. In no case fair or poor clinical end-result coexisted with excellent radiographic ones. In the group examined twice after completion of growth with the time interval of 10 years no difference in clinical score was found in

PURPOSE: A human Dukes B colonic adenocarcinoma was grafted onto 40 nude mice. The mice were divided into four groups, one control and three representing experimental conditions. Animals in the three experimental groups received either adriamycin (ADR), 5-fluorouracil (5-FU), or camptothecin (CPT) over a 25-day period beginning 34 days after grafting. Control animals received saline on an identical schedule. Animals were killed 105 days after grafting. METHODS: The effect of therapy was assessed by three techniques: 1) tumor size was periodically measured during the life of the animals, 2) modifications of APC, Ki-ras, and p53 genes were studied by polymerase chain reaction, dotblot analysis, restriction analysis, and DNA sequencing, and 3) image cytometry of Feulgen-stained material was used to characterize 15 parameters describing morphometric, densitometric, and textural features of tumor nuclei. RESULTS: When compared with controls, tumor growth (size) was maximumly suppressed by treatment with CPT (P

To improve spatial resolution in in vivo bioluminescence imaging, a photon scattering correction, image restoration method was tested. The chosen algorithm was tested on in vivo bioluminescent images acquired on three representative tumor models: subcutaneous, pulmonary, and disseminated peritoneal. Tumor size was chosen as a quantitative criterion, such that the tumor reference measurements (determined photographically or by computed tomography) were compared to those derived from bioluminescent images, before and after restoration. This technique allowed a significant reduction to be achieved in the relative error between reference measurements and dimensions derived from bioluminescent images. In addition, improved delineation of the tumor foci was achieved. The restoration method allows spatial resolution in bioluminescence imaging to be improved, with interesting perspectives in terms of staging and quantitation in experimental oncology.

Our experience with high flow CAVH (1-2 L/hr) and intermittent hemodialysis in our combined medical-surgical tertiary care intensive care unit was reviewed. During a 16 month period, 12 patients received CAVH and 23 patients received hemodialysis (3-7 days/week). Mean CAVH treatment duration was 5.5 days (0.5-18 days). Hemodialysis patients received a mean of 4.3 treatments (1-16). CAVH patients had a mean age of 44.5 +/- 16.4 years (19-68), whereas the hemodialysis patients had a mean age of 60.9 +/- 14 years (34-82) (p = 0.004). Mean admission APACHE II score was 21.3 (11-29) for the CAVH group and 25.5 (10-39) for the hemodialysis group (p = NS). Peak ICU APACHE II score did not differ between groups (CAVH 26.2 [11-37], HD 28 [10-40]; p = NS). There were 4 deaths in the CAVH group (25%) and 19 deaths in the HD group (82%) (p = 0.006: chi-squared test). Although age was significantly different between groups, APACHE II scores were similar. Mortality rate was significantly higher in the hemodialysis group. This supports the hypothesis that CAVH may be the renal replacement therapy of choice in the ICU.

The Combustion Light Gas Gun, or CLGG, has been investigated for over ten years. During this time, the research has shown that the technology provides a minimum of 30% more muzzle energy than advanced solid propellent guns which translates to significant advantages in range and/or throw weight. For the Navy Barrage round fired from a 155mm bore CLGG, the predicted range is up to 200 nm, sufficient to provide effective amphibious and in-shore fire support without endangering capital assets. In addition, the CLGG provides: * The ability to "manufacture" propellant as needed on board ship * The ability to remotely discharge propellant in damage control situations * The ability to automatically adjust the propellant charge as needed. This year's work built on last year's effort by continuing to address remaining issues associated with successful system demonstration such as cryogenic propellant handling, multi-shot demonstration, modeling, and proof of principal at 155mm scale.

Epithelial ovarian cancer is the fourth cause of death among cancer-bearing women, frequently associated with carboplatin resistance, underlining the need of more efficient and targeted therapies. F14512 is a novel concept of drug vectorization that we propose here to investigate in ovarian cancer models. F14512 is an epipodophyllotoxin-core linked to a spermine chain, which enters selectively tumor cells via the polyamine transport system (PTS), currently in clinical phase II evaluation in AML. We compared the effects of F14512 versus etoposide against OVCAR-3, IGROV-1, SKOV-3, A2780S and A2780R cancer cell lines. Using the F17073 PTS fluorescent probe, we determined the PTS activity of these cells and of 18 clinical samples. As results, F14512 displayed strong anti-proliferative and pro-apoptotic activities in carboplatin-resistant models, being increased in cell lines with high levels of PTS. Consistently, at a dose of 1.25 mg/kg, F14512 significantly inhibited tumor growth in cisplatin-resistant SKOV-3 xenograft model. Interestingly, ex vivo analysis indicated that 15 patients sample out of 18 presented a higher F17073 fluorescent probe incorporation into CD326-positive tumor cells as compared to normal cells, even in the case of 2 platinum-refractory patients. Therefore, F14512 is a targeted drug with a potent anti-tumor efficacy regardless the status of cisplatin resistance. The high PTS activity detected in fresh clinical samples highlights the potential of F14512 as a new therapy for PTS-positive and platinum resistant ovarian cancer patients. Citation Format: Benoît Thibault, Gregoire Zorza, Samuel Meignan, Nicolas Guilbaud, Christian Bailly, Jean-Pierre Delord, Bettina Couderc, Anna Kruczynski, Pierre Ferre, Jean-Philippe Annereau. Translational study of F14512, a novel vectorised epipodophyllotoxin, which demonstrates a marked activity on ovarian cancer models from patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2428. doi:10.1158/1538-7445.AM2015-2428

In recent years, efforts have been made to improve the selectivity of anti-cancer agents via the targeting of cancer-specific proteins or signalization pathways. Novel anticancer drugs inhibiting defined kinases, the proteasome, and selected growth factor receptors for examples have been developed with success for a few cancer types. But in parallel to these novel "soft" drugs, conventional "hard" cytotoxic molecules targeting DNA, topoisomerases or tubuline remain extensively used to treat solid tumors. This letter evokes the utility and limitations of the two drug categories and comments on new directions of the antitumor pharmacology taken to improve the efficacy of cancer chemotherapy and the development of new molecules.

Leiomyomatosis peritonealis disseminata (LPD) is a rare benign disease characterised by the presence of multiple intraabdominal nodules, consisting of benign smooth muscle. LPD has only been found in women, predominantly in their late reproductive age. There is a very high association with excess exogenous and endogenous female gonadal steroids, specifically oestrogen and progesterone. Since it is grossly indistinguishable from diffuse carcinomatosis of the peritoneum, several unnecessary radical procedures have resulted. We describe the 44th documented case and the first case of minimal invasive surgery in a 42-year-old women with peritoneal leiomyoma on the right pelvic wall and uterine subserous and submucous leiomyoma.

Despite recent advances in the therapy of metastatic melanoma, patients have a poor prognosis and die from their disease, with a 5-year survival rate of less than 20%. Metastatic melanoma remains mainly chemoresistant, therefore novel therapeutic strategies to overcome primary or acquired resistance are required. In order to more reliably predict clinical activity of novel compounds in melanoma patients, we have established a series of patient-derived tumor xenograft models (PDTX). Surgically resected tumors samples were obtained from patients with metastatic melanoma before or after treatment. Twenty-three samples from 9 patients and representative of various stages of disease progression were implanted onto immunocompromised NSG mice. A high take rate of 56% (13/23 samples) was observed, corresponding to the samples from 8/9 patients. Tumor take was independent of tumor size, histologic parameters and B-RAF status. The first tumor generation (graft) harbouring the patient-derived sample (G1), as well as the subsequent generations were characterized for each PDTX. The pattern of expression of the melanoma differentiation markers S100, melanosome, tyrosinase and melan-A were maintained over the serial transplantations. These models also closely recapitulated the heterogeneity of patient tumors in terms of cell morphology over the first generations (G1-G5), but this heterogeneity tended to decrease with the number of generations. One of these primary PDTXs, MEL-11 exhibited metastatic spread in axillary lymph nodes. Furthermore 2 other primary melanoma PDTXs, MEL-1 and MEL-3, established from primary refractory patient metastatic melanoma retained complete resistance to temozolomide and vemurafenib, the two reference drugs for melanoma. The MEL-3 model was selected to assess the anti-melanoma activity of F-RK-4, a novel multi-kinases inhibitor (including inhibition of mutated B-RAF). Multiple i.p. administrations of F-RK-4 resulted in a significant antitumor activity, as reflected by a tumor growth inhibition of 50%. Overall these results suggest that these patient-derived melanoma xenografts represent a useful preclinical tool to identify novel anti-melanoma therapeutics. Citation Format: Bruno Gomes, Céline ROBICHON, Arnaud Pillon, Jean-Philippe Annereau, Sandrine Pourtau, Jean-Christophe Blanchet, Aline Stennevin, Karim Bedjeguelal, Philippe Rochaix, Ignacio Garrido-Stowhas, Laurence Lamant, Nicolas Meyer, Nicolas Guilbaud, Christian Bailly, Anna Kruczynski. Patient-derived tumor models of resistant metastatic melanoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1219. doi:10.1158/1538-7445.AM2014-1219

Transplantable animal tumors have been associated with the discovery of most clinically active anticancer agents. They are still useful today in conducting detailed evaluations of new candidate anticancer drugs. Three protocols relating to transplantable experimental tumors are described in this unit. Included are the intravenously-implanted murine P388 leukemia, the subcutaneously-implanted murine B16 melanoma and two examples of subcutaneously-implanted human tumor xenografts, the LX-1 (lung) and MX-1 (breast) tumors.

F 11782 is a novel inhibitor of topoisomerases I and II, with an original mechanism of action (Perrin et al, 2000). This study, aimed to define its anticancer efficacy against a series of murine and human tumour models, has provided evidence of major antitumour activity for F 11782. This was demonstrated as a high level of activity against the P388 leukaemia, as reflected by increased survival of 143–457%, when administered i.p., p.o. or i.v. as single or multiple doses, and proved consistently superior to etoposide or camptothecin tested concurrently. Single or multiple i.p. doses of F 11782 also proved highly active against the s.c. grafted B16 melanoma, significantly increasing survival (P < 0.001) and inhibiting tumour growth (T/C of 0.3%), again superior to etoposide tested concurrently. Furthermore, F 11782 inhibited the number of pulmonary metastatic foci of the B16F10 melanoma by 99%. In human tumour xenograft studies, multiple i.p. doses of F 11782 resulted in major inhibitory activity against MX-1 (breast) tumours (T/C of 0.1%), as well as causing definite tumour regressions, whereas none resulted from similar experimental treatments with etoposide. Significant activity was also recorded with F 11782 against the relatively refractory LX-1 (lung) xenografts, with an optimal T/C value of 19%. It was notable that the antitumour activity of F 11782 was consistently demonstrated over a wide range of 2–6 dose levels, providing evidence of its good overall tolerance. In conclusion, these results emphasize the preclinical interest of this novel molecule and support its further preclinical development. © 2000 Cancer Research Campaign http://www.bjcancer.com

The antitumour activity of vinflunine, 20',20'-dichloro-3',4'-dihydrovinorelbine, a fluorinated Vinca alkaloid obtained by reaction in superacid media, was evaluated in comparison with vinorelbine against a series of subcutaneously-implanted human tumour xenografts. The tumours studied were established from bladder (BXF1299), pancreas (PAXF546), kidney (RXF944LX), colon (DLD-1, HT-29, TC37), central nervous system (SF-295), small cell lung (NCI-H69) and prostate (PC-3). Vinflunine or vinorelbine was administered as four weekly intraperitoneal treatments, within dose ranges of 5-80 or 0.63-10 mg/kg/injection, respectively. The overall antitumour activity of vinflunine was superior to that of vinorelbine. Vinflunine showed high activity against RXF944LX and NCI-H69 xenografts and moderate activity against PAXF546, PC-3 and TC37 tumours, achieving an overall response of 64%. This contrasts with a 27% response with vinorelbine, which proved only moderately active against RXF944LX and TC37 xenografts. These results confirm and extend our previous report of the broad spectrum of in vivo antitumour activity of vinflunine and reinforce its potential as a valuable addition to current chemotherapeutic agents.

This paper summarizes continuing efforts in 120-mm scale towards reducing ram accelerator length and complexity by eliminating or reducing components such as vent sections which were previously considered required for proper ram operation. In addition, simultaneous efforts to increase projectile acceleration by increasing combustion pressures is detailed. As might be expected, igniting proper ram acceleration combustion (starting) under these conditions has been shown to be difficult, requiring a better understanding of the complex physics in early ram combustion start-up. Companion Computational Fluid Dynamics efforts have provided some of this insight and led to partial successes.

Some applications for ram acceleration require high projectile accelerations or energy increases within constrained tube lengths. This may be accomplished through increased combustion pressure, increased propellant chemical energy, and/or optimized projectile geometry. Taken together these items serve to enhance overall ram accelerator performance. In addition, reduction of overall accelerator length can be accomplished by reducing accelerator entrance velocity requirements and by eliminating unnecessary components such as vent sections. This paper summarizes these effects and presents continuing large caliber experimental efforts towards developing "high performance" ram accelerators.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC F14512 is a novel polyamine-vectorized topoisomerase II inhibitor currently in phase 1/2 clinical trial in acute myeloid leukemia (AML). Since ABCB1 (also called P-glycoprotein or MDR1) has been reported to be expressed at high levels in patients with resistant leukaemia cells, and constitutes a pejorative marker of therapy, we decided to investigate whether F14512 could be exported by ABCB1 or other ABC transporters susceptible to confer drug resistance to chemotherapy, such as MRP1. In addition, we established a F14512-resistant cell line to study the mechanism of resistance to the drug. With membrane preparation enriched in functional MDR1, we found that [F14512][1] was unable to stimulate the ATPase activity of this transporter. Using a cellular assay over expressing MDR1 transporter by recombinant transfection of MDCKII cells, [F14512][1] was detectable, but the intracellular level was unchanged regardless of the MDR1 status or in presence of MDR1 competitors. Consistently, iterative selection of a [F14512][1]-resistant A-549 cell line with 36 cycles of [F14512][1] at cytotoxic doses (0.5 EC50) over 9 months, led to only moderate shift of resistance (9 fold). In the resulting selected A-549 subclones, MDR1, MRP1 and ABCG2 were detectable at the basal level. The ability of [F14512][1] to bypass MDR1 was finally assessed in a vinorelbine-resistant P388 model overexpressing high level of functional ABCB1 as indicated with the positive rhodamine export assay and cross resistance to MDR1 substrate. Moreover, [F14512][1] displays strong antileukemic activity in MDR1-positive P388 cells in vitro and additional in vivo measurements are in progress. In conclusion, the data concur to show that the antitumor activity of the targeted cytotoxic agent [F14512][1] is not impacted by the MDR1 status of cancer cells. MDR1 clearly does not affect the potency of [F14512][1] and this characteristic augurs well for the ongoing development of the drug in AML patients. Citation Format: Jean Philippe Annereau, Viviane Brel, William Riquet, Laurent Creancier, Isabelle Vandenberghe, Emmanuel Fournier, Celine Robichon, Aline Stennevin, Vanessa Offrete, Laurence Lacastaigneratte, Bruno Gomes, Anna Kruczynski, Christian Bailly, Nicolas Guilbaud. F14512, a novel vectorized topoiserase II inhibitor, bypasses MDR1 mediated resistance. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 988. doi:10.1158/1538-7445.AM2013-988 [1]: /lookup/external-ref?link_type=GEN&access_num=F14512&atom=%2Fcanres%2F73%2F8_Supplement%2F988.atom

Thirty patients with unruptured ectopic pregnancy (4-10 weeks' gestation) were treated locally with methotrexate (MTX) under sonographic guidance. The transvaginal puncture was performed under analgesic sedation using an automatic puncturing device. Local MTX therapy was successful in 25 patients (83.3%). Eighteen of these patients had received a single MTX instillation with a total dose of 10 mg, 7 patients had received a second instillation with 10 mg because of plateauing hCG levels after the first instillation. In 5 patients MTX therapy was unsuccessful. Surgical intervention was necessary within 4 h to 15 days after MTX treatment, due to severe tubal bleeding (n = 1) or the development of an increasing peritubal hematoma (n = 4). Patients with an outer trophoblast diameteror = 1.5 cm could be treated successfully in all cases (25/25). In patients with hCG values5,000 mIU/ml the success rate was 70% (7/10) and in patients with demonstration of cardiac activity of the embryo 63% (5/8). The fluid aspirated from the ectopic cavity showed an average hCG concentration that was 53 times higher than in the serum. The decline in hCG to values below 10 mIU/ml ranged between 7 and 75 days (mean 28 days). The hysterosalpingography performed 4-6 months after MTX therapy showed tubal patency on both sides in 85.7% of the patients examined. In the meantime 4 of these patients gave birth to healthy children.

36 children (61 hips) who had nonoperative treatment of developmental hip dislocation with the Frejka pillow and developed avascular necrosis were followed-up for an average of 20 (17-26) years. The radiographic pattern of necrosis was classified into 5 types. At final follow-up after completion of growth, the radiographic outcome was excellent in 11 hips, good in 21, fair in 19, and poor in 10 hips. There was a close correlation between the pattern of necrosis and the outcome: all the poor results were observed in cases with changes also involving the metaphysis.

New antileukemic agents are urgently needed to achieve improvement of the survival of patients suffering from Acute Myelogenous Leukemia (AML). F14512 combines an epipodophyllotoxin core with a spermine moiety that targets cells with a high demand for polyamines such as cancer cells. F14512 exhibits a high level of in vivo anti-tumor activity in a series of experimental murine and human solid tumor models and has entered into clinical phase one. In this study, we investigated the in vivo antileukemic activity of F14512 against cell line or primary human AML models and evaluated its potential in combination with the reference antileukemic agent, AraC. HL60 cells or AML cells collected from different patients were engrafted onto NSG mice. Using flow cytometry and q-PCR analysis, we demonstrated that multiple administrations of F14512 for 3 weeks resulted in an extensive reduction of AML cell number in the bone marrow and blood of treated mice. We also showed in vitro and in vivo synergistic activity of F14512 in combination with AraC in HL-60 and primary AML models when both compounds were used at suboptimal doses. The mechanisms triggering primary leukemic cell death were investigated and our results indicated that senescence could be involved. Collectively, these results demonstrate that F14512 exhibits a marked in vivo antileukemic activity, supporting the Phase I clinical trials of this novel promising drug candidate. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2747. doi:1538-7445.AM2012-2747

A technique to visualize transient and steady combustion phenomena in ram accelerators using sacrificial transparent acrylic chambers is demonstrated. This technique allows the normal operating environment of ram accelerators to be very closely approximated. Using this technique, details of the environment during the transient starting phase as the projectile enters the accelerator and the obtrurator is discarded are seen for the first time. In addition, steady or running combustion around the projectile after the obtrurator has been shed is captured. These flow visualizations are shown to be useful in validating computational fluid dynamics codes and in providing guidance in reducing projectile unstarts while increasing initial accelerator performance.

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Targeted anticancer therapies represent an increasing subject of interest in order to improve tumor cell selectivity. Extensive study suggests that the Polyamine Transport System (PTS) is an energy-dependent machinery generally hyper-activated in cancer cells with a high demand for polyamines. This system can be viewed as a suitable molecular target to deliver selectively polyamine-based molecules into cancer cells. We exploited this strategy to target a potent cytotoxic agent to PTS-positive tumor cells with [F14512][1], a novel polyamine-epipodophyllotoxin conjugate that exhibits a high in vivo anti-tumor activity in a series of experimental murine and human tumors. [F14512][1] has recently entered into clinical development. This preclinical study was undertaken to investigate its potential in combination chemotherapy therapies. The in vitro cytotoxicity of [F14512][1] against the A549 human non-small cell lung cancer cell line was investigated following simultaneous incubation with a variety of cytotoxic/cytostatic drugs. When using median effect analysis, [F14512][1] in combination with 5-fluorouracil, camptothecin, gemcitabine or mitoxantrone showed synergistic cytotoxicity. Additive effects were demonstrated when [F14512][1] was combined with bortezomib, doxorubicin or SAHA while antagonistic anti-proliferative effects were observed only with co-incubation of [F14512][1] and etoposide, vinorelbine or paclitaxel. Combinations inducing synergistic anti-proliferative activities were also investigated against the HL-60 human acute myeloid leukemia cell line, confirming the synergy with gemcitabine. Cellular effects of [F14512][1] are characterized by a DNA damage induction, a cell cycle blockage in G2 phase and a cell death induction. Such characteristics were investigated in A549 cells treated with this combination in order to propose mechanistic explanation of this synergy. In vivo, [F14512][1] combined with irinotecan, gemcitabine, mitoxantrone or doxorubicin showed a gain of anti-tumor activity against P388 murine leukemia grafted intravenously. As an example, the administration of sub-optimal doses of [F14512][1] (0.63 mg/kg, q1d4 schedule) and mitoxantrone (1.25 mg/kg, single dose) alone resulted in an increased life span of only 29% compared to untreated mice, while combined treatments improved survival of tumor bearing mice with an increase life span of 57%. Moreover, [F14512][1] combined with doxorubicin displayed an increased antitumor activity against MX-1 human breast cancer in nude mice.F14512 appears to be a promising candidate for combination chemotherapy, especially with DNA-damaging agents and antimetabolites. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3518. doi:10.1158/1538-7445.AM2011-3518 [1]: /lookup/external-ref?link_type=GEN&access_num=F14512&atom=%2Fcanres%2F71%2F8_Supplement%2F3518.atom

Im Rahmen eines Informations-Systems fur die Gynakologie und Geburtshilfe, welches die Daten einer gynakologisch-geburtshilflichen Abteilung organisieren kann, entstand das OP-Buch. Es ist ein Subsystem eines auf graphisch-visueller Interkommunikation mit dem Anwender basierenden Computer-Systems. Der Aufbau des Systems ist in Form einer visuellen Schnittstelle (Abb. 1) zum Benutzer realisiert, welches das Einarbeiten in das System sehr einfach und ohne Computerkenntnisse erlaubt.

Despite advances in the therapy of acute myeloid leukemia (AML), the majority of patients die from their disease. Therefore, the lack of effective therapy mandates the development of novel compounds to improve the outcome of patients with relapsed and refractory leukemias. F14512 is a potent spermine-epipodophyllotoxin conjugate exploiting the polyamine transport system for tumor cell delivery. In this study, we report the in vivo antitumor activity of F14512 against experimental models of AML cell lines and of patient AML samples. F14512 markedly reduced the growth of HL-60 and U937 cell lines in an in vivo xenotransplantation model, resulting in a highly significant increase of survival of leukemia-bearing mice. Etoposide evaluated concurrently demonstrated only moderate in vivo activity against these models. F14512 induced in vivo apoptosis of HL-60 cells, as shown by caspase-3 activation and PARP cleavage. In an effort to mimic the human disease, we injected approximately 106 AML cells collected from a patient into NOD/SCID mice and allowed them to establish as xenografts for 8 weeks. Subsequent treatment with F14512 was carried out for 2 or 3 weeks followed by the analysis at the end of treatment and 1 week after the end of treatment. Two human AML samples were analyzed. Multiple i.v. administrations of F14512 at 0.32 mg/kg, induced an extensive reduction of the number of leukemic cells in mouse bone marrow and blood (97–99%), assessed by flow cytometry analysis, quantitative RT-PCR and histology. To identify leukemic cells expressing an active polyamine transport system, we developed a functional method based on the measurement of the cellular uptake of a nitrobenzoxadiazole fluorescent probe (F96982) combining the same spermine moiety as F14512. The level of fluorescence emitted by the probe F96982 was high in HL-60 cells as well in the 2 patient AML samples that proved to be sensitive to F14512 in vivo. Collectively, these results demonstrated that F14512 exhibits a marked in vivo antileukemic activity, supporting its clinical development. Phase I clinical trials in onco-hematology are now initiated with this novel promising drug candidate. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B186.

Ram acceleration is an emerging propulsion technology which appears capable of producing very high velocities with significant masses. Work at the University of Washington has demonstrated velocities in excess of 2.6 km/s in 38-mm caliber, while theory predicts velocities in excess of 10 km/s may be obtainable, Following a brief introduction to the theory of ram acceleration, advantages and disadvantages of the technology for large caliber hypervelocity applications are examined. An empirical performance analysis of a scaled-up ram accelerator (120-mm) is presented and compared to a theoretical analysis of conventional solid propulsion. A theoretical and experimental program ongoing at the Ballistic Research Laboratory to explore scaling the technology to 120-mm is then described.