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Abstract Introduction Human milk oligosaccharides (HMOs) are important components of human milk having diverse functions in the development of infants. Randomized controlled trials (RCTs) have demonstrated that infant formulas with the HMOs 2′-fucosyllactose (2′FL) and lacto-N-neotetraose (LNnT) are safe, well-tolerated, and support normal growth. This study aimed to generate real-world evidence (RWE) on growth and gastrointestinal (GI) tolerance in infants consuming a formula with 1 g/L 2′FL and 0.5 g/L LNnT, including a mixed feeding group not studied before in RCTs. Participants and methods This 8-week open-label prospective multicenter study was conducted in Germany and Austria, and included groups of healthy, exclusively breastfed infants (BF), exclusively formula-fed infants (FF) who received the HMO-formula, and infants mixed fed with both HMO formula and human milk (MF). Co-primary outcomes were anthropometry and gastrointestinal tolerance via validated Infant Gastrointestinal Symptom Questionnaire (IGSQ). Secondary outcomes included formula satisfaction and adverse events (AEs). Results One-hundred six infants completed the study (46 FF, 22 MF, and 38 BF). Mean anthropometric z-scores were comparable between groups and generally within ± 0.5 of WHO medians at week 8. IGSQ composite scores demonstrated good GI tolerance in all groups with no significant group differences at week 4 or 8. IGSQ composite scores in FF improved during the course of the study and parents provided high satisfaction ratings for the HMO-formula. Four potentially product-related AEs were reported in FF (no in MF). Conclusions In this RWE study examining an infant formula with HMOs, growth and GI tolerance outcomes were confirming the good tolerance and safety of this early feeding option previously reported in RCTs.

Abstract Background Glycoprotein-96, a non-polymorphic heat-shock protein, associates with intracellular peptides. Autologous tumor-derived heat shock protein-peptide complex 96 (HSPPC-96) can elicit potent tumor-specific T cell responses and protective immunity in animal models. We sought to investigate the feasibility, safety, and antitumor activity of HSPPC-96 vaccines prepared from tumor specimens of patients with metastatic melanoma. Methods Patients with a Karnofsky Performance Status >70% and stage III or stage IV melanoma had to have a metastasis >3 cm in diameter resectable as part of routine clinical management. HSPPC-96 tumor-derived vaccines were prepared in one of three dose levels (2.5, 25, or 100 μg/dose) and administered as an intradermal injection weekly for 4 consecutive weeks. In vivo induction of immunity was evaluated using delayed-type hypersensitivity (DTH) to HSPPC-96, irradiated tumor, and dinitrochlorobenzene (DNCB). The γ-interferon (IFNγ) ELISPOT assay was used to measure induction of a peripheral blood mononuclear cell response against autologous tumor cells at baseline and at the beginning of weeks 3, 4, and 8. Results Among 36 patients enrolled, 72% had stage IV melanoma and 83% had received prior systemic therapy. The smallest tumor specimen from which HSPPC-96 was prepared weighed 2 g. Twelve patients (including 9 with stage IV and indicator lesions) had a negative DNCB skin test result at baseline. All 36 patients were treated and evaluable for toxicity and response. There were no serious toxicities. There were no observed DTH responses to HSPPC-96 or to autologous tumor cells before or during treatment. The IFNγ-producing cell count rose modestly in 5 of 26 patients and returned to baseline by week 8, with no discernible association with HSPPC-96 dosing or clinical parameters. There were no objective responses among 16 patients with stage IV disease and indicator lesions. Among 20 patients treated in the adjuvant setting, 11 with stage IV melanoma at baseline had a progression-free and overall survival of 45% and 82%, respectively, with a median follow-up of 10 years. Conclusion Treatment with autologous tumor-derived HSPPC-96 was feasible and safe at all doses tested. Observed immunological effects and antitumor activity were modest, precluding selection of a biologically active dose. Nevertheless, the 25-μg dose level was shown to be practical for further study.

The Abstract is incorrect in PubMed. The corrected Abstract is provided here.

Cell-free (cf) DNA in the plasma of cancer patients offers an easily obtainable source of biologic material for mutation analysis. Plasma samples from 157 patients with advanced cancers who progressed on systemic therapy were tested for 21 mutations in BRAF, EGFR, KRAS, and PIK3CA using the BEAMing method and results were compared to mutation analysis of archival tumor tissue from a CLIA-certified laboratory obtained as standard of care from diagnostic or therapeutic procedures. Results were concordant for archival tissue and plasma cfDNA in 91% cases for BRAF mutations (kappa = 0.75, 95% confidence interval [CI] 0.63 - 0.88), in 99% cases for EGFR mutations (kappa = 0.90, 95% CI 0.71- 1.00), in 83% cases for KRAS mutations (kappa = 0.67, 95% CI 0.54 - 0.80) and in 91% cases for PIK3CA mutations (kappa = 0.65, 95% CI 0.46 - 0.85). Patients (n = 41) with > 1% of KRAS mutant cfDNA had a shorter median survival compared to 20 patients with 1% of mutant cfDNA (BRAF, EGFR, KRAS, or PIK3CA) had a shorter median survival compared to 33 patients with

The Large Underground Xenon (LUX) experiment is a dual-phase xenon time-projection chamber operating at the Sanford Underground Research Facility (Lead, South Dakota). The LUX cryostat was filled for the first time in the underground laboratory in February 2013. We report results of the first WIMP search data set, taken during the period from April to August 2013, presenting the analysis of 85.3 live days of data with a fiducial volume of 118 kg. A profile-likelihood analysis technique shows our data to be consistent with the background-only hypothesis, allowing 90% confidence limits to be set on spin-independent WIMP-nucleon elastic scattering with a minimum upper limit on the cross section of 7.6 × 10(-46) cm(2) at a WIMP mass of 33 GeV/c(2). We find that the LUX data are in disagreement with low-mass WIMP signal interpretations of the results from several recent direct detection experiments.

Peptide vaccination against tumor-associated antigens remains one of the most common methods of immunization in cancer vaccine clinical trials. Although peptide vaccination has been reported to increase circulating antigen-specific T-cells, they have had limited clinical efficacy and there is a necessity to increase their capacity to generate strong antitumor responses. We sought to improve the clinical efficacy of peptide-based vaccines in cancer immunotherapy of metastatic melanoma using a LHRH agonist (leuprolide) as adjuvant. Seventy HLA-A*0201 stage IIb-IV melanoma patients were vaccinated with class I HLA-A*0201-restricted gp100209-2M peptide and stratified for HLA-DP4 restriction. HLA-DP4 patients were also vaccinated with class II HLA-DP4-restricted MAGE-3243-258 peptide. Patients from both groups were randomized to receive 2 doses of leuprolide or not. Here we report the increase in PBMC TREC levels at week 24 after peptide vaccination, which was independent of the leuprolide treatment. This change was mirrored by a small increase in the TREC-enriched CD8CD45RAROCD27CD103, but not the TREC-enriched CD4CD45RAROCD31 T-cell population. Serum concentration of 2 important factors for thymopoiesis was measured: insulin growth factor 1 (IGF-1) levels were not changed, whereas a moderate increase in IL-7 levels was noted in the sera of all patients 6 weeks after vaccination. Increased expression of CD127 (IL-7 receptor-α) at week 24, compared with baseline, was only seen in the CD8CD45RAROCD27CD103 T-cell population. Our results suggest that leuprolide has no effect on thymic output when used as peptide vaccine adjuvant, but IFA-based peptide vaccination may unexpectedly affect the thymus by increasing thymic output of new T cells.

The Large Underground Xenon (LUX) collaboration has designed and constructed a dual-phase xenon detector, in order to conduct a search for Weakly Interacting Massive Particles (WIMPs), a leading dark matter candidate. The goal of the LUX detector is to clearly detect (or exclude) WIMPS with a spin independent cross-section per nucleon of 2×10-46cm2, equivalent to ∼1event/100kg/month in the inner 100-kg fiducial volume (FV) of the 370-kg detector. The overall background goals are set to have

Geant4 has been used throughout the nuclear and high-energy physics community to simulate energy depositions in various detectors and materials. These simulations have mostly been run with a source beam outside the detector. In the case of low-background physics, however, a primary concern is the effect on the detector from radioactivity inherent in the detector parts themselves. From this standpoint, there is no single source or beam, but rather a collection of sources with potentially complicated spatial extent. LUXSim is a simulation framework used by the LUX collaboration that takes a component-centric approach to event generation and recording. A new set of classes allows for multiple radioactive sources to be set within any number of components at run time, with the entire collection of sources handled within a single simulation run. Various levels of information can also be recorded from the individual components, with these record levels also being set at run time. This flexibility in both source generation and information recording is possible without the need to recompile, reducing the complexity of code management and the proliferation of versions. Within the code itself, casting geometry objects within this new set of classes rather than as the default Geant4 classes automatically extends this flexibility to every individual component. No additional work is required on the part of the developer, reducing development time and increasing confidence in the results. We describe the guiding principles behind LUXSim, detail some of its unique classes and methods, and give examples of usage. © 2012 Elsevier B.V. All rights reserved.

LUX is a two-phase (liquid/gas) xenon time projection chamber designed to detect nuclear recoils from interactions with dark matter particles. Signals from the LUX detector are processed by custom-built analog electronics which provide properly shaped signals for the trigger and data acquisition (DAQ) systems. The DAQ is composed of commercial digitizers with firmware customized for the LUX experiment. Data acquisition systems in rare-event searches must accommodate high rate and large dynamic range during precision calibrations involving radioactive sources, while also delivering low threshold for maximum sensitivity. The LUX DAQ meets these challenges using real-time baseline suppression that allows for a maximum event acquisition rate in excess of 1.5 kHz with virtually no deadtime. This paper describes the LUX DAQ and the novel acquisition techniques employed in the LUX experiment. © 2011 Elsevier B.V. All rights reserved.

We report on the screening of samples of titanium metal for theirradio-purity. The screening process described in this work led to the selectionof materials used in the construction of the cryostats for the LargeUnderground Xenon (LUX) dark matter experiment. Our measurements establishtitanium as a highly desirable material for low background experimentssearching for rare events. The sample with the lowest total long-lived activitywas measured to contain

© Proceedings of the 2011 Meeting of the Division of Particles and Fields of the American Physical Society, DPF 2011. All rights reserved. The LZ program consists of two stages of direct dark matter searches using liquid Xe detectors. The first stage will be a 1.5-3 tonne detector, while the last stage will be a 20 tonne detector. Both devices will benefit tremendously from research and development performed for the LUX experiment, a 350 kg liquid Xe dark matter detector currently operating at the Sanford Underground Laboratory. In particular, the technology used for cryogenics and electrical feedthroughs, circulation and purification, low-background materials and shielding techniques, electronics, calibrations, and automated control and recovery systems are all directly scalable from LUX to the LZ detectors. Extensive searches for potential background sources have been performed, with an emphasis on previously undiscovered background sources that may have a significant impact on tonne-scale detectors. The LZ detectors will probe spin-independent interaction cross sections as low as 5 × 10-49 cm2 for 100 GeV WIMPs, which represents the ultimate limit for dark matter detection with liquid xenon technology.

The Large Underground Xenon (LUX) dark matter search experiment is currently being deployed at the Homestake Laboratory in South Dakota. We will highlight the main elements of design which make the experiment a very strong competitor in the field of direct detection, as well as an easily scalable concept. We will also present its potential reach for supersymmetric dark matter detection, within various timeframes ranging from 1 year to 5 years or more. © 2010 American Institute of Physics.

The Large Underground Xenon (LUX) dark matter search experiment is currently being deployed at the Homestake Laboratory in South Dakota. We will highlight the main elements of design which make the experiment a very strong competitor in the field of direct detection, as well as an easily scalable concept. We will also present its potential reach for supersymmetric dark matter detection, within various timeframes ranging from 1 year to 5 years or more. © 2010 American Institute of Physics.