The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of prostate carcinoma.

Prostate cancer is the most commonly diagnosed malignancy and second leading cause of cancer death among men in the United States. In recent years, several new agents, including cancer immunotherapies, have been approved or are currently being investigated in late-stage clinical trials for the management of advanced prostate cancer. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel, including physicians, nurses, and patient advocates, to develop consensus recommendations for the clinical application of immunotherapy for prostate cancer patients. To do so, a systematic literature search was performed to identify high-impact papers from 2006 until 2014 and was further supplemented with literature provided by the panel. Results from the consensus panel voting and discussion as well as the literature review were used to rate supporting evidence and generate recommendations for the use of immunotherapy in prostate cancer patients. Sipuleucel-T, an autologous dendritic cell vaccine, is the first and currently only immunotherapeutic agent approved for the clinical management of metastatic castrate resistant prostate cancer (mCRPC). The consensus panel utilized this model to discuss immunotherapy in the treatment of prostate cancer, issues related to patient selection, monitoring of patients during and post treatment, and sequence/combination with other anti-cancer treatments. Potential immunotherapies emerging from late-stage clinical trials are also discussed. As immunotherapy evolves as a therapeutic option for the treatment of prostate cancer, these recommendations will be updated accordingly

Modelling Harvester-Forwarder System Performance in a Selection Harvest

A harvester - forwarder system was studied in a selection harvest operation conducted in an interior forest stand composed of Douglas fir (Pseudotsuga menziesii), Ponderosa pine (Pinus ponderosa), and Grand fir (Abies grandis). A time-study analysis was used to develop models for predicting individual machine productivity over time for both the harvester and forwarder involved in the study. Analysis indicates that harvester productivity (13.85 m3 per SMH) closely matched forwarder production (14.10 m3 per SMH) during the study. Further analysis yielded models that can be used to predict system productivity across the range of stand values observed during the study. The results suggest that system productivity is balanced when operating in stands averaging 15 to 25 cm DBH. In stands of larger or smaller average diameter, productivity for the system becomes unbalanced and affects machine operation, particularly the forwarder. Further research is suggested to improve the developed predictor models and allow for prediction of system performance over a broad range of stand and site conditions

The observation of long-range three-body Coloumb effects in the decay of 16Ne

The interaction of an $E/A$=57.6-MeV $^{17}$Ne beam with a Be target was used to populate levels in $^{16}$Ne following neutron knockout reactions. The decay of $^{16}$Ne states into the three-body $^{14}$O+$p$+$p$ continuum was observed in the High Resolution Array (HiRA). For the first time for a 2p emitter, correlations between the momenta of the three decay products were measured with sufficient resolution and statistics to allow for an unambiguous demonstration of their dependence on the long-range nature of the Coulomb interaction. Contrary to previous experiments, the intrinsic decay width of the $^{16}$Ne ground state was found to be narrow ($\Gamma<60$~keV), consistent with theoretical estimates.Comment: 6 pages, 5 figure

Genomic-Bioinformatic Analysis of Transcripts Enriched in the Third-Stage Larva of the Parasitic Nematode Ascaris suum

Differential transcription in Ascaris suum was investigated using a genomic-bioinformatic approach. A cDNA archive enriched for molecules in the infective third-stage larva (L3) of A. suum was constructed by suppressive-subtractive hybridization (SSH), and a subset of cDNAs from 3075 clones subjected to microarray analysis using cDNA probes derived from RNA from different developmental stages of A. suum. The cDNAs (n = 498) shown by microarray analysis to be enriched in the L3 were sequenced and subjected to bioinformatic analyses using a semi-automated pipeline (ESTExplorer). Using gene ontology (GO), 235 of these molecules were assigned to ‘biological process’ (n = 68), ‘cellular component’ (n = 50), or ‘molecular function’ (n = 117). Of the 91 clusters assembled, 56 molecules (61.5%) had homologues/orthologues in the free-living nematodes Caenorhabditis elegans and C. briggsae and/or other organisms, whereas 35 (38.5%) had no significant similarity to any sequences available in current gene databases. Transcripts encoding protein kinases, protein phosphatases (and their precursors), and enolases were abundantly represented in the L3 of A. suum, as were molecules involved in cellular processes, such as ubiquitination and proteasome function, gene transcription, protein–protein interactions, and function. In silico analyses inferred the C. elegans orthologues/homologues (n = 50) to be involved in apoptosis and insulin signaling (2%), ATP synthesis (2%), carbon metabolism (6%), fatty acid biosynthesis (2%), gap junction (2%), glucose metabolism (6%), or porphyrin metabolism (2%), although 34 (68%) of them could not be mapped to a specific metabolic pathway. Small numbers of these 50 molecules were predicted to be secreted (10%), anchored (2%), and/or transmembrane (12%) proteins. Functionally, 17 (34%) of them were predicted to be associated with (non-wild-type) RNAi phenotypes in C. elegans, the majority being embryonic lethality (Emb) (13 types; 58.8%), larval arrest (Lva) (23.5%) and larval lethality (Lvl) (47%). A genetic interaction network was predicted for these 17 C. elegans orthologues, revealing highly significant interactions for nine molecules associated with embryonic and larval development (66.9%), information storage and processing (5.1%), cellular processing and signaling (15.2%), metabolism (6.1%), and unknown function (6.7%). The potential roles of these molecules in development are discussed in relation to the known roles of their homologues/orthologues in C. elegans and some other nematodes. The results of the present study provide a basis for future functional genomic studies to elucidate molecular aspects governing larval developmental processes in A. suum and/or the transition to parasitism

DNA vaccination for prostate cancer: key concepts and considerations

While locally confined prostate cancer is associated with a low five year mortality rate, advanced or metastatic disease remains a major challenge for healthcare professionals to treat and is usually terminal. As such, there is a need for the development of new, efficacious therapies for prostate cancer. Immunotherapy represents a promising approach where the host’s immune system is harnessed to mount an anti-tumour effect, and the licensing of the first prostate cancer specific immunotherapy in 2010 has opened the door for other immunotherapies to gain regulatory approval. Among these strategies DNA vaccines are an attractive option in terms of their ability to elicit a highly specific, potent and wide-sweeping immune response. Several DNA vaccines have been tested for prostate cancer and while they have demonstrated a good safety profile they have faced problems with low efficacy and immunogenicity compared to other immunotherapeutic approaches. This review focuses on the positive aspects of DNA vaccines for prostate cancer that have been assessed in preclinical and clinical trials thus far and examines the key considerations that must be employed to improve the efficacy and immunogenicity of these vaccines

Structure of C 14 and B 14 from the C 14,15 (d, He 3) B 13,14 reactions

We have studied the C14,15(d,He3)B13,14 proton-removing reactions in inverse kinematics. The (d,He3) reaction probes the proton occupation of the target ground state, and also provides spectroscopic information about the final states in B13,14. The experiments were performed using C14,15 beams from the ATLAS accelerator at Argonne National Laboratory. The reaction products were analyzed with the HELIOS device. Angular distributions were obtained for transitions from both reactions. The C14-beam data reveal transitions to excited states in B13 that suggest configurations with protons outside the π(0p3/2) orbital, and some possibility of proton cross-shell 0p-1s0d excitations, in the C14 ground state. The C15-beam data confirm the existence of a broad 2- excited state in B14. The experimental data are compared to the results of shell-model calculations

Ground-state properties of H 5 from the He 6 (d, He 3) H 5 reaction

We have studied the ground state of the unbound, very neutron-rich isotope of hydrogen H5, using the He6(d,He3)H5 reaction in inverse kinematics at a bombarding energy of E(He6)=55A MeV. The present results suggest a ground-state resonance energy ER=2.4±0.3 MeV above the H3+2n threshold, with an intrinsic width of Γ=5.3±0.4 MeV in the H5 system. Both the resonance energy and width are higher than those reported in some, but not all previous studies of H5. The previously unreported He6(d,t)Heg.s.5 reaction is observed in the same measurement, providing a check on the understanding of the response of the apparatus. The data are compared to expectations from direct two-neutron and dineutron decay. The possibility of excited states of H5 populated in this reaction is discussed using different calculations of the He6→H5+p spectroscopic overlaps from shell-model and ab initio nuclear-structure calculations

Strong Evidence for \u3csup\u3e9\u3c/sup\u3eN and the Limits of Existence of Atomic Nuclei

The boundaries of the chart of nuclides contain exotic isotopes that possess extreme proton-to-neutron asymmetries. Here we report on strong evidence of 9N, one of the most exotic proton-rich isotopes where more than one half of its constitute nucleons are unbound. With seven protons and two neutrons, this extremely proton-rich system would represent the first-known example of a ground-state five-proton emitter. The invariant-mass spectrum of its decay products can be fit with two peaks whose energies are consistent with the theoretical predictions of an open-quantum-system approach; however, we cannot rule out the possibility that only a single resonancelike peak is present in the spectrum