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A man in his mid-50s presented with palpitations, chest pain and syncope. After initial workup for a non-ST elevation myocardial infarction, a CT scan revealed metastatic melanoma. The malignancy was infiltrating his right ventricle, resulting in recurrent ventricular tachycardia. Although initially hard to manage, his arrhythmias were eventually controlled with medication. Unfortunately, despite an initial response to immunotherapy, he died six months after diagnosis.Cardiac metastases are rare, but melanoma has a high predication for metastasising to the heart and a small number of cases of such metastases causing ventricular arrhythmias have previously been reported. This case shows the importance of concurrent investigations when patients report multiple, seemingly unrelated symptoms as a unifying diagnosis may be uncovered.

Introduction Tumor quantity while receiving cancer therapy is the sum of simultaneous regression of treatment‐sensitive and growth of treatment‐resistant fractions at constant rates. Exponential rate constants for tumor regression/decay (d) and growth (g) can be estimated. Previous studies established g as a biomarker for overall survival; g increases after treatment cessation, can estimate doubling times, and can assess treatment effectiveness in small cohorts by benchmarking to large reference data sets. Using this approach, we analyzed data from the clinical trial CLARINET, evaluating lanreotide depot/autogel 120 mg/4 weeks (LAN) for treatment of neuroendocrine tumors (NETs). Methods and Materials Computed tomography imaging data from 97 LAN‐ and 101 placebo‐treated patients from CLARINET were analyzed to estimate g and d. Results Data from 92% of LAN‐ and 94% of placebo‐treated patients could be fit to one of the equations to derive g and d (p < .001 in most data sets). LAN‐treated patients demonstrated significantly slower g than placebo recipients (p = .00315), a difference of 389 days in doubling times. No significant difference was observed in d. Over periods of LAN administration up to 700 days, g did not change appreciably. Simulated analysis with g as the endpoint showed a sample size of 48 sufficient to detect a difference in median g with 80% power. Conclusion Although treatment of NETs with LAN can affect tumor shrinkage, LAN primarily slows tumor growth rather than accelerates tumor regression. Evidence of LAN efficacy across tumors was identified. The growth‐retarding effect achieved with LAN was sustained for a prolonged period of time. Implications for Practice The only curative treatment for neuroendocrine tumors (NETs) is surgical resection; however, because of frequent late diagnosis, this is often impossible. Because of this, treatment of NETs is challenging and often aims to reduce tumor burden and delay progression. A novel method of analysis was used to examine data from the CLARINET trial, confirming lanreotide depot/autogel is effective at slowing tumor growth and extending progression‐free survival. By providing the expected rate and doubling time of tumor growth early in the course of treatment, this method of analysis has the potential to guide physicians in their management of patients with NETs., Treatment of neuroendocrine tumors is challenging, mainly aiming to reduce tumor burden and delay disease progression. This article reports on the kinetics of tumor growth using a novel method of analysis and data from the CLARINET study.

Background Handheld devices can automatically give an estimate of refraction. The established method for refraction comparison using spherical equivalent (M) and J0, J45 vector transformations by Bland–Altman analysis is too complex for non-eye doctors involved with vision screening and remote vision clinics. Therefore, a simpler comparison technique was developed. Methods Based on the spectacle limit to resolve grade A 1 logMAR, B 3 logMAR and C 6 logMAR blur, J0, J45, and M are combined into the Alaska Blind Child Discovery (ABCD) composite ellipsoid GRADE system. Pediatric eye patients had confirmatory examination after dry refraction with three portable autorefractors: Plusoptix, 2WIN and Retinomax. The refractions were then compared using both Bland–Altman and ABCD composite. Performance to detect AAPOS amblyopia risk factors was also assessed. Results A total of 202 children, mean age seven years, 28% high spectacle need and 43% AAPOS 2013 amblyopia risk factors showed high correlation with cycloplegic refraction (intraclass correlation 0.49 to 0.90) for sphere, J0 and J45 spectacle components. Plusoptix had more (10%) inconclusives due to patients out-of-range. The Retinomax was unable to screen some younger children and was less reliable for sphere but gave more precise astigmatism estimates. The proportion of autorefractions expected to give GRADE A/B high-need patients acuity improvement to 20/40 would be 41% for Plusoptix, 39% for 2WIN and 65% for Retinomax. Sensitivity/specificity for amblyopia risk factor detection was 80%/83% for Plusoptix, 72%/88% for 2WIN and 84%/73% for Retinomax. Conclusion The simplified spectacle comparison resembled Bland–Altman and could assist lay vision screeners and non-eye doctors attempting remote spectacle donation worldwide., Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/buIzzVgabtU

Previous studies in humans and in animals have shown dramatic effects of cocaine on measures of brain function that persist into abstinence. The purpose of this study was to examine the neurobiological consequences of abstinence from cocaine, using a model that removes the potential confound of cocaine cues. Adult male rhesus monkeys self-administered cocaine (0.3 mg/kg/injection; N = 8) during daily sessions or served as food-reinforcement controls (N = 4). Two times per week, monkeys were placed in a neutral environment and presented with a cartoon video for ~30 min, sometimes pre- and sometimes post-operant session, but no reinforcement was presented during the video. After ~100 sessions and when the cocaine groups had self-administered 900 mg/kg cocaine, the final experimental condition was a terminal 2-[

Crop disease management depends on efficient and adequate pesticide distribution to reduce pest population. Instrument-based methods to evaluate the spatial distribution of pesticides are available, but they are not field-compatible because of instrument size, cost, and extensive sample preparation. The current gold standard of water-sensitive papers is field-compatible; however, these papers often produce false positives due to reaction with water from sources other than the pesticide mixture. Thus, we developed a novel method in which a fluorescent dye is sprayed over a crop with circles of filter paper (samplers) attached to the leaves. After collection, a lightbox is used to take pictures of the samplers, and an algorithm analyzes each image for percent coverage to visualize the pesticide distribution within the crop. Our method produces results quickly and inexpensively compared to current methods and can be applied to any crop to inform best pesticide application strategies.

Background: Octreotide has been used for decades in the United States (US) and Europe to treat patients with advanced neuroendocrine tumors (NETs). Lanreotide was approved in 2014 to improve progressionfree survival (PFS) in patients with unresectable, well- or moderately-differentiated, locally advanced or metastatic gastroenteropancreatic NETs. Therefore, clinicians and patients may consider sequencing therapy from octreotide to lanreotide. However, current real-world outcomes data on patients who have made this transition is limited. Methods: We conducted a multicenter, noninterventional, retrospective medical record review of patients with locally advanced or metastatic gastroenteropancreatic NETs (NCT03112694). Included patients had been treated with long-acting octreotide monotherapy for ≥90 days before transitioning to lanreotide monotherapy and continued on lanreotide for ≥90 days. Abstractors entered patient demographic and clinical data into a customized, web-based case report form. We assessed clinically defined PFS and other tumorrelated outcomes while patients were treated with lanreotide. Outcomes were analyzed according to level of response at the time of transition from octreotide to lanreotide: progressive disease, nonprogressive disease, or unknown. Statistical analyses were descriptive. Clinically defined PFS and duration of treatment with lanreotide were estimated using the Kaplan-Meier method. Results: Data were abstracted for 91 patients with gastroenteropancreatic NETs who received long-acting octreotide followed by lanreotide at six US based sites. At initial diagnosis, 71.4% of patients had stage IV disease. Small intestine (63.7%) and pancreas (14.3%) were the most common primary tumor sites. Mean [standard deviation (SD)] duration of follow-up from diagnosis was 70.6 (41.3) months. Patients received long-acting octreotide for a mean (SD) of 38.4 (32.8) months. When patients transitioned to lanreotide, 57.1% had nonprogressive disease on octreotide, 30.8% had progressive disease, and the remainder had unknown disease status. The most common reasons for switching from octreotide to lanreotide were progressive disease (22.0%), formulary change (15.4%), and patient preference (9.9%). Patients received lanreotide for a median (95% CI) duration of 24.7 (16.7–59.9) months. At the end of follow-up, 74% of patients remained on lanreotide monotherapy. Progression occurred in 24.2% of patients during lanreotide treatment. Overall median (95% CI) clinician-defined PFS following the transition to lanreotide was estimated to be 23.7 months [20.2 months–NE (not estimable)]. Patients with nonprogressive disease when they transitioned to lanreotide experienced a median clinician-defined PFS of 24.7 (17.0–NE) months. Among patients reported to have progressive disease when they transitioned to lanreotide, median (95% CI) clinician-defined PFS was estimated to be 15.2 (11.4–NE) months. There were no material differences in adverse events recorded during the long-acting octreotide and lanreotide treatment periods. Conclusions: Our study suggests that lanreotide monotherapy is well tolerated and may contribute to stabilization of disease in a subset of patients with locally advanced or metastatic gastroenteropancreatic NETs previously treated with long-acting octreotide.

The field of biometric face recognition blends methods from computer science, engineering and statistics, however statistical reasoning has been applied predominantly in the design of recognition algorithms. A new opportunity for the application of statistical methods is driven by growing interest in biometric performance evaluation. Methods for performance evaluation seek to identify, compare and interpret how characteristics of subjects, the environment and images are associated with the performance of recognition algorithms. Some central topics in face recognition are reviewed for background and several examples of recognition algorithms are given. One approach to the evaluation problem is then illustrated with a generalized linear mixed model analysis of the Good, Bad, and Ugly Face Challenge, a pre-eminent face recognition dataset used to test state-of-the-art still-image face recognition algorithms. Findings include that (i) between-subject variation is the dominant source of verification heterogeneity when algorithm performance is good, and (ii) many covariate effects on verification performance are 'universal' across easy, medium and hard verification tasks. Although the design and evaluation of face recognition algorithms draw upon some familiar statistical ideas in multivariate statistics, dimension reduction, classification, clustering, binary response data, generalized linear models and random effects, the field also presents some unique features and challenges. Opportunities abound for innovative statistical work in this new field.

A brain-computer interface (BCI) offers movement-free control of a computer application and is achieved by reading and translating the cortical activity of the brain into semantic control signals. Motion-onset visual evoked potentials (mVEP) are neural potentials employed in BCIs and occur when motion-related stimuli are attended visually. mVEP dynamics are correlated with the position and timing of the moving stimuli. To investigate the feasibility of utilizing the mVEP paradigm with video games of various graphical complexities including those of commercial quality, we conducted three studies over four separate sessions comparing the performance of classifying five mVEP responses with variations in graphical complexity and style, in-game distractions, and display parameters surrounding mVEP stimuli. To investigate the feasibility of utilizing contemporary presentation modalities in neurogaming, one of the studies compared mVEP classification performance when stimuli were presented using the oculus rift virtual reality headset. Results from 31 independent subjects were analyzed offline. The results show classification performances ranging up to 90% with variations in conditions in graphical complexity having limited effect on mVEP performance; thus, demonstrating the feasibility of using the mVEP paradigm within BCI-based neurogaming.

e16174Background: Somatostatin analogs (SSA), such as OCT and LAN, are used to treat GEP-NETs. LAN is effective for carcinoid syndrome (CS) control in both SSA-experienced and -naive patients (pts)...

e24329Background: Tumor size following cancer-related therapy is the result of regression of the treatment-sensitive fraction and growth of the treatment-resistant fraction, occurring simultaneousl...

Copyright © 2009 by the American Thoracic Society. Rationale: An effective new tuberculosis (TB) vaccine regimen must be safe in individuals with latent TB infection (LTBI) and is a priority for global health care. Objectives: To evaluate the safety and immunogenicity of a leading new TB vaccine, recombinant Modified Vaccinia Ankara expressing Antigen 85A (MVA85A) in individuals with LTBI. Methods: An open-label, phase I trial of MVA85A was performed in 12 subjects with LTBI recruited from TB contact clinics in Oxford and London or by poster advertisements in Oxford hospitals. Patients were assessed clinically and had blood samples drawn for immunological analysis over a 52-week period after vaccination with MVA85A. Thoracic computed tomography scans were performed at baseline and at 10 weeks after vaccination. Safety of MVA85A was assessed by clinical, radiological, and inflammatory markers. The immunogenicity of MVA85A was assessed by IFNγ and IL-2 ELISpot assays and FACS. Measurements and Main Results: MVA85A was safe in subjects with LTBI, with comparable adverse events to previous trials of MVA85A. There were no clinically significant changes in inflammatory markers or thoracic computed tomography scans after vaccination. MVA85A induced a strong antigen-specific IFN-γ and IL-2 response that was durable for 52 weeks. The magnitude of IFN-γ response was comparable to previous trials of MVA85A in bacillus Calmette-Guérin–vaccinated individuals. Antigen 85A–specific polyfunctional CD4+ T cells were detectable prior to vaccination with statistically significant increases in cell numbers after vaccination. Conclusions: MVA85A is safe and highly immunogenic in individuals with LTBI. These results will facilitate further trials in TB-endemic areas. Oxford Biomedical Research Centre, Wellcome Trust, and AFTBVAC.

The Cameron project has developed a language called single assignment C (SA-C), and a compiler for mapping image-based applications written in SA-C to field programmable gate arrays (FPGAs). The paper tests this technology by implementing several applications in SA-C and compiling them to an Annapolis Microsystems (AMS) WildStar board with a Xilinx XV2000E FPGA. The performance of these applications on the FPGA is compared to the performance of the same applications written in assembly code or C for an 800 MHz Pentium III. (Although no comparison across processors is perfect, these chips were the first of their respective classes fabricated at 0.18 microns, and are therefore of comparable ages.) We find that applications written in SA-C and compiled to FPGAs are between 8 and 800 times faster than the equivalent program run on the Pentium III.

RC systems typically consist of an array of configurable computing elements. The computational granularity of these elements ranges from simple gates - as abstracted by FPGA lookup tables - to complete arithmetic-logic units with or without registers. A rich programmable interconnect completes the array. RC system developer manually partitions an application into two segments: a hardware component in a hardware description language such as VHDL or Verilog that will execute as a circuit on the FPGA and a software component that will execute as a program on the host. Single-assignment C is a C language variant designed to create an automated compilation path from an algorithmic programming language to an FPGA-based reconfigurable computing system.

Objectives Control of the tuberculosis (TB) epidemic is a global health priority and one that is likely to be achieved only through vaccination. The critical overlap with the HIV epidemic requires any effective TB vaccine regimen to be safe in individuals who are infected with HIV. The objectives of this clinical trial were to evaluate the safety and immunogenicity of a leading candidate TB vaccine, MVA85A, in healthy, HIV-infected adults. Design This was an open-label Phase I trial, performed in 20 healthy HIV-infected, antiretroviral-naïve subjects. Two different doses of MVA85A were each evaluated as a single immunisation in 10 subjects, with 24 weeks of follow-up. The safety of MVA85A was assessed by clinical and laboratory markers, including regular CD4 counts and HIV RNA load measurements. Vaccine immunogenicity was assessed by ex vivo interferon γ (IFN-γ) ELISpot assays and flow-cytometric analysis. Results MVA85A was safe in subjects with HIV infection, with an adverse-event profile comparable with historical data from previous trials in HIV-uninfected subjects. There were no clinically significant vaccine-related changes in CD4 count or HIV RNA load in any subjects, and no evidence from qPCR analyses to indicate that MVA85A vaccination leads to widespread preferential infection of vaccine-induced CD4 T cell populations. Both doses of MVA85A induced an antigen-specific IFN-γ response that was durable for 24 weeks, although of a lesser magnitude compared with historical data from HIV-uninfected subjects. The functional quality of the vaccine-induced T cell response in HIV-infected subjects was remarkably comparable with that observed in healthy HIV-uninfected controls, but less durable. Conclusion MVA85A is safe and immunogenic in healthy adults infected with HIV. Further safety and efficacy evaluation of this candidate vaccine in TB- and HIV-endemic areas is merited., Article summary Article focus HIV infection increases susceptibility to TB, and globally, TB is the cause of death in up to half of AIDS deaths. There is an urgent need for a safe and effective TB vaccine in HIV-infected people. Key messages MVA85A, a leading candidate TB vaccine, is safe and well tolerated in HIV-infected people and does not induce changes in either CD4 count or HIV RNA load. MVA85A is immunogenic in HIV-infected people, and induces a similar immune profile to that seen in HIV-uninfected people, but the immunogenicity is less durable in HIV-infected people. Strengths and limitations of this study This is a Phase I study with 20 subjects, and further studies are needed in TB endemic countries in this important target population.

© 2011 Griffiths et al. Vaccination with Bacille Calmette-Gue´ rin (BCG) has traditionally been used for protection against disease caused by the bacterium Mycobacterium tuberculosis (M.tb). The efficacy of BCG, especially against pulmonary tuberculosis (TB) is variable. The best protection is conferred in temperate climates and there is close to zero protection in many tropical areas with a high prevalence of both tuberculous and non-tuberculous mycobacterial species. Although interferon (IFN)-c is known to be important in protection against TB disease, data is emerging on a possible role for interleukin (IL)-17 as a key cytokine in both murine and bovine TB vaccine studies, as well as in humans. Modified Vaccinia virus Ankara expressing Antigen 85A (MVA85A) is a novel TB vaccine designed to enhance responses induced by BCG. Antigen-specific IFN-c production has already been shown to peak one week post-MVA85A vaccination, and an inverse relationship between IL-17-producing cells and regulatory T cells expressing the ectonucleosidease CD39, which metabolises pro-inflammatory extracellular ATP has previously been described. This paper explores this relationship and finds that consumption of extracellular ATP by peripheral blood mononuclear cells from MVA85A-vaccinated subjects drops two weeks post-vaccination, corresponding to a drop in the percentage of a regulatory T cell subset expressing the ectonucleosidase CD39. Also at this time point, we report a peak in co-production of IL-17 and IFN-c by CD4+ T cells. These results suggest a relationship between extracellular ATP and effector responses and unveil a possible pathway that could be targeted during vaccine design. KLG’s Wellcome Trust studentship

The establishment of an aerosol challenge model in nonhuman primates (NHPs) for the testing of vaccines against Mycobacterium tuberculosis would assist the global effort to optimize novel vaccination strategies. The endpoints used in preclinical challenge studies to identify measures of disease burden need to be accurate and sensitive enough to distinguish subtle differences and benefits afforded by different tuberculosis (TB) vaccine regimens when group sizes are inevitably small. This study sought to assess clinical and nonclinical endpoints as potentially sensitive measures of disease burden in a challenge study with rhesus macaques by using a new protocol of aerosol administration of M. tuberculosis . Immunological and clinical readouts were assessed for utility in vaccine evaluation studies. This is the first example of TB vaccine evaluation with rhesus macaques where long-term survival was one of the primary endpoints. However, we found that in NHP vaccine efficacy studies with maximum group sizes of six animals, survival did not provide a valuable endpoint. Two approaches used in human clinical trials for the evaluation of the gamma interferon (IFN-γ) response to vaccination (enzyme-linked immunospot [ELISpot] assay and enzyme-linked immunosorbent assay [ELISA]) were included in this study. The IFN-γ profiles induced following vaccination were found not to correlate with protection, nor did the level of purified protein derivative (PPD)-specific proliferation. The only readout to reliably distinguish vaccinated and unvaccinated NHPs was the determination of lung lesion burden using magnetic resonance (MR) imaging combined with stereology at the end of the study. Therefore, the currently proposed key markers were not shown to correlate with protection, and only imaging offered a potentially reliable correlate.

Background: The vaccine efficacy reported following Mycobacterium bovis Bacillus Calmette Guerin (BCG) administration to UK adolescents is 77% and defining the cellular immune response in this group can inform us as to the nature of effective immunity against tuberculosis. The aim of this study was to identify which cytokines and lymphocyte populations characterise the peripheral blood cellular immune response following BCG vaccination. Results: Diluted blood from before and after vaccination was stimulated with Mycobacterium tuberculosis purified protein derivative for 6 days, after which soluble biomarkers in supernatants were assayed by multiplex bead array. Ten out of twenty biomarkers measured were significantly increased (p < 0.0025) 1 month after BCG vaccination when compared to paired samples (n = 12) taken prior to vaccination (IFNγ, TNFα, IL-1α, IL-2, IL-6, IL-10, IL-17, GM-CSF, MIP1α, IP-10). All of these remained detectable by multiplex bead array in samples taken 12 months after BCG vaccination of a partially overlapping adolescent group (n = 12). Intracellular cytokine staining after 24 hour Mycobacterium tuberculosis purified protein derivative stimulation of PBMC samples from the 12 month group revealed that IFNγ expression was detectable in CD4 and CD8 T-cells and natural killer cells. Polyfunctional flow cytometry analysis demonstrated that cells expressing IFNγ alone formed the majority in each subpopulation of cells. Only in CD4 T-cells and NK cells were there a notable proportion of responding cells of a different phenotype and these were single positive, TNFα producers. No significant expression of the cytokines IL-2, IL-17 or IL-10 was seen in any population of cells. Conclusions: The broad array of biomarker responses detected by multiplex bead array suggests that BCG vaccination is capable, in this setting, of inducing a complex immune phenotype. Although polyfunctional T-cells have been proposed to play a role in protective immunity, they were not present in vaccinated adolescents who, based on earlier epidemiological studies, should have developed protection against pulmonary tuberculosis. This may be due to the later sampling time point available for testing or on the kinetics of the assays used.

The theory of illumination subspaces is well developed and has been tested extensively on the Yale Face Database B (YDB) and CMU-PIE (PIE) data sets. This paper shows that if face recognition under varying illumination is cast as a problem of matching sets of images to sets of images, then the minimal principal angle between subspaces is sufficient to perfectly separate matching pairs of image sets from nonmatching pairs of image sets sampled from YDB and PIE. This is true even for subspaces estimated from as few as six images and when one of the subspaces is estimated from as few as three images if the second subspace is estimated from a larger set (10 or more). This suggests that variation under illumination may be thought of as useful discriminating information rather than unwanted noise.

Interferon gamma (IFNgamma) is a critical component of the pro-inflammatory immune response that provides protection against Mycobacterium tuberculosis. In the absence of an immunological correlate of protection, antigen-specific production of IFNgamma is a commonly used marker of a protective immune response. To facilitate the evaluation of tuberculosis candidate vaccines three different IFNgamma detection methods were compared. The cultured whole blood ELISA, ex vivo IFNgamma ELISpot and whole blood ex vivo intracellular cytokine staining (ICS) assays were performed head-to-head during a Phase I clinical trial using the candidate vaccine MVA85A. Whilst all three assays detected significant increases in IFNgamma production immediately following vaccination, distinctions between the assays were apparent. Higher baseline IFNgamma responses were detected using the cultured whole blood ELISA, whereas the ex vivo ELISpot assay was the most sensitive in detecting long-term (52 weeks) post-vaccination responses. The whole blood ex vivo ICS assay provided novel information by dissecting the IFNgamma response into responding CD4, CD8 and gamma/delta T cell subsets. Future tuberculosis vaccine trials and immunology studies should ideally include a combination of ex vivo and cultured assays to ensure a thorough and multifaceted evaluation of the immune response is achieved.

This paper summarizes a study carried out on data from the Face Recognition Vendor Test 2006 (FRVT 2006). The finding of greatest practical importance is the discovery of a strong connection between a relatively simple measure of image quality and performance of state-of-the-art vendor algorithms in FRVT 2006. The image quality measure quantifies edge density and likely relates to focus. This effect is part of a larger four-way interaction observed between edge density, face size and whether images are acquired indoors our outdoors. This finding illustrates the broader potential for statistical modeling of empirical data to play an important role in finding and codifying biometric quality measures.

An image-set based face recognition algorithm is proposed that exploits the full geometrical interpretation of Canonical Correlation Analysis (CCA). CCA maximizes the correlation between two linear subspaces associated with image-sets, where an image-set is assumed to contain multiple images of a person's face. When these linear subspaces are viewed as points on a Grassmann manifold, then geodesic distance on the manifold becomes the natural way to compare image-sets. The proposed method is tested on the ORL data set where it achieves a rank one identification rate of 98.75%. The proposed method is also tested on a subset of the Face Recognition Grand Challenge Experiment 4 data. Specifically, 82 probe and 230 gallery subjects with 32 images per probe and gallery image-set. Our algorithm achieves a rank one identification rate of 87% and a verification rate of 81% at a false accept rate of 1/1;000. These results on FRGC are significantly better than the well-known image-set matching algorithm, Mutual Subspace Method (MSM), which does not use geodesic distance. Another important finding is that cohort normalization boosts verification performance by 50% when used in conjunction with image-set matching. These results suggest that excellent levels of face recognition performance are possible when using image-sets, geodesic distance and cohort normalization. Finally, the proposed approach is generic in the sense that no training is required.

In the search for effective vaccines against intracellular pathogens such as HIV, tuberculosis and malaria, recombinant viral vectors are increasingly being used to boost previously primed T cell responses. Published data have shown prime-boost vaccination with BCG-MVA85A (modified vaccinia virus Ankara expressing antigen 85A) to be highly immunogenic in humans as measured by ex vivo IFN-gamma ELISPOT. Here, we used polychromatic flow cytometry to investigate the phenotypic and functional profile of these vaccine-induced Mycobacterium tuberculosis (M.tb) antigen 85A-specific responses in greater detail. Promisingly, antigen 85A-specific CD4(+) T cells were found to be highly polyfunctional, producing IFN-gamma, TNF-alpha, IL-2 and MIP-1beta. Surface staining showed the responding CD4(+) T cells to be relatively immature (CD45RO(+) CD27(int)CD57(-)); this observation was supported by the robust proliferative responses observed following antigenic stimulation. Furthermore, these phenotypic and functional properties were independent of clonotypic composition and epitope specificity, which was maintained through the different phases of the vaccine-induced immune response. Overall, these data strongly support the use of MVA85A in humans as a boosting agent to expand polyfunctional M.tb-specific CD4(+) T cells capable of significant secondary responses.

OBJECTIVES: To investigate the safety and immunogenicity of boosting BCG with modified vaccinia Ankara expressing antigen 85A (MVA85A), shortly after BCG vaccination, and to compare this first with the immunogenicity of BCG vaccination alone and second with a previous clinical trial where MVA85A was administered more than 10 years after BCG vaccination. DESIGN: There are two clinical trials reported here: a Phase I observational trial with MVA85A; and a Phase IV observational trial with BCG. These clinical trials were all conducted in the UK in healthy, HIV negative, BCG naïve adults. Subjects were vaccinated with BCG alone; or BCG and then subsequently boosted with MVA85A four weeks later (short interval). The outcome measures, safety and immunogenicity, were monitored for six months. The immunogenicity results from this short interval BCG prime-MVA85A boost trial were compared first with the BCG alone trial and second with a previous clinical trial where MVA85A vaccination was administered many years after vaccination with BCG. RESULTS: MVA85A was safe and highly immunogenic when administered to subjects who had recently received BCG vaccination. When the short interval trial data presented here were compared with the previous long interval trial data, there were no significant differences in the magnitude of immune responses generated when MVA85A was administered shortly after, or many years after BCG vaccination. CONCLUSIONS: The clinical trial data presented here provides further evidence of the ability of MVA85A to boost BCG primed immune responses. This boosting potential is not influenced by the time interval between prior BCG vaccination and boosting with MVA85A. These findings have important implications for the design of efficacy trials with MVA85A. Boosting BCG induced anti-mycobacterial immunity in either infancy or adolescence are both potential applications for this vaccine, given the immunological data presented here. TRIAL REGISTRATION: ClinicalTrials.gov NCT00427453 (short boosting interval), NCT00427830 (long boosting interval), NCT00480714 (BCG alone).

Subject covariate data were collected on 1, 072 pairs of FERET images for analysis in a human face verification experiment. The subject data included information about facial hair, bangs, eyes, gender, and age. The verification experiment was replicated at seven different false alarm rates ranging from 1/10, 000 to 1/100. A generalized linear mixed model (GLMM) was fit to the binary outcomes indicating correct verification. Statistically significant main effects for bangs, eyes, gender, and age were found. The effect of the log false positive rate on verification success was found to interact significantly with bangs, gender, and age. These results have important implications for future evaluation of biometrics, and the GLMM methodology used here is shown to be effective and informative for this sort of data.

Henry Schneiderman at Carnegie Mellon University developed a face detection algorithm based upon a semi-naive Bayesian classifier and 5/3 linear phase wavelets. This paper explores the relative value of these wavelet features compared to simpler pixel and edge features. Experiments suggest edge features are superior for highly controlled lighting, while pixel features are better and more stable for uncontrolled lighting. Tests use the Notre Dame face data collected in Fall 2003 and Spring 2004 and use over 400, 000 face and non-face test image chips.

The FERET evaluation compared recognition rates for different semi-automated and automated face recognition algorithms. We extend FERET by considering when differences in recognition rates are statistically distinguishable subject to changes in test imagery. Nearest Neighbor classifiers using principal component and linear discriminant subspaces are compared using different choices of distance metric. Probability distributions for algorithm recognition rates and pairwise differences in recognition rates are determined using a permutation methodology. The principal component subspace with Mahalanobis distance is the best combination; using L2 is second best. Choice of distance measure for the linear discriminant subspace matters little, and performance is always worse than the principal components classifier using either Mahalanobis or L1 distance. We make the source code for the algorithms, scoring procedures and Monte Carlo study available in the hopes others will extend this comparison to newer algorithms.

Recognition difficulty is statistically linked to 11 subject covariate factors such as age and gender for three face recognition algorithms: principle components analysis, an interpersonal image difference classifier, and an elastic bunch graph matching algorithm. The covariates assess race, gender, age, glasses use, facial hair, bangs, mouth state, complexion, state of eyes, makeup use, and facial expression. We use two statistical models. First, an ANOVA relates covariates to normalized similarity scores. Second, logistic regression relates subject covariates to probability of rank one recognition. These models have strong explanatory power as measured by R/sup 2/ and deviance reduction, while providing complementary and corroborative results. Some factors, like changes to the eye status, affect all algorithms similarly. Other factors, such as race, affect different algorithms differently. Tabular and graphical summaries of results provide a wealth of empirical evidence. Plausible explanations of many results can be motivated from knowledge of the algorithms. Other results are surprising and suggest a need for further study.

Projection pursuit is concerned with finding interesting low-dimensional subspace of multivariate data. In this paper we proposed a genetic optimization approach to find the globally optimal orthogonal subspace given training data and user defined criterion on what subspaces are interesting. We then applied this approach to human face recognition. Suppose face recognition is done by simple correlation, a subspace is obtained using our approach that achieve the lowest error rate of face recognition given FERET data set as training set. As Yambor [W.S. Yambor, et al., 2000] showed in experiments that PCA subspace is a pretty good subspace for correlation-based face recognition, we compared the performance of the sub-space we obtained with that of PCA subspace. Experiment result showed this subspace outperformed PCA subspace.

The Cameron project has developed a language and compiler for mapping image-based applications to field programmable gate arrays (FPGAs). The paper tests this technology on several applications and finds that FPGAs are between 8 and 800 times faster than comparable Pentiums for image based tasks.

The history of the image understanding environment (IUE) project, a five-year program to develop a common software environment for the development of algorithms and application systems, is reviewed. An overview of some of the data structures that are currently evolving as a specification for the IUE is provided. The ultimate goal of the project is to provide the basic data structures and algorithms that are required to carry state-of-the-art research in image understanding. >

Background Data suggest that chemotherapy regimens administered to NSCLC patients in the metastatic setting is not typically associated with febrile neutropenia rates of 20% or greater, therefore, use of WBCGF in this setting should be minimal. National guidelines recommend reduction of chemotherapy dosing in these patients. Our objective was to evaluate the current US Oncology Network utilization of WBCGF in the metastatic setting to determine current practice and associated costs in this palliative chemotherapy setting. Methods We retrospectively identified metastatic NSCLC patients between 7/2006 and 6/2011 using the US Oncology Network EHR database (iKnowMed™). Secondary diagnoses and clinical trials were excluded. Chemotherapy and WBCGF utilization was determined by the number of patients assigned to a 1st or 2nd+ (and beyond) line of therapy (LOT) during the study period. Results During this timeframe, 10,374 patients (female: 44%; median age 67) diagnosed with metastatic NSCLC were identified. Of these, 3284 patients received WBCGF with chemotherapy; where, 2825 patients (33%) were administered 1st LOT and 459 patients (27%) were administered 2nd+ LOT. When reviewing the chemotherapy regimens assigned (regardless of WBCGF administration), the most commonly utilized regimens were: Carboplatin + Paclitaxel +/- Bevacizumab, Pemetrexed containing regimens, Docetaxel containing regimens, Gemcitabine containing regimens, and Vinorelbine. The average estimated cost for these chemotherapy regimens (Medicare Allowable 1Q2012) is $2589/cycle; the average estimated cost of WBCGF usage in the metastatic setting was $1889/dose (Medicare Allowable 1Q2012). Conclusion The American Society of Clinical Oncology has recently identified two opportunities to reduce the cost of care without adversely affecting outcomes (i.e., ineffective chemotherapy at the end of life; the use of WBCGF in palliative chemotherapy where dose reduction is an option). These intersect in this study of NSCLC. These data indicate there is an opportunity to address 40% of the drug costs of NSCLC by the judicious use of protocols using dose reduction as a strategy. Disclosure J.R. Hoverman: I am a medical director for Innovent Oncology. R. Beveridge: I am EVP, Medical Director for McKesson Specialty Health. All other authors have declared no conflicts of interest.

Color is a powerful cue for determining the pose of 3D objects viewed by a single camera. We present a method based on hue histograms for locating multiple objects with respect to a fixed camera. The algorithm is tested on controlled blocks-world scenes and an indoor office scene. On these examples, a pose refinement algorithm performs better when guided by color than when guided by more traditional edge information.