Initial Active Interrogation Experiments at The University of Michigan Linear Accelerator Laboratory

To support the mission of the Countering Weapons of Mass Destruction Office of the Department of Homeland Security, the Detection for Nuclear Nonproliferation group is researching active interrogation techniques and the development of new detection algorithms for fast neutron spectroscopy. The Countering Weapons of Mass Destruction Officehas loaned us a Varian M9 linear accelerator (linac), helium-3 detectors, boron-coated straw detectors, and perfluorocarbondetectors as part of this research, providing a variety of tools to conduct our experiments.In the summer of 2018, a thorough licensing process concluded, and preliminary experiments commenced. Later in the year, the facility was approved to possess and irradiate depleted uranium, which enabledus to conduct active interrogation experiments.In the fall of 2018, we conducted our first active interrogation measurements using the linac facility. The measurements used the linac to irradiate depleted uranium,lead, and tungsten targets to induce photonuclear reactions to emit fast neutrons. The neutrons were then detected using a simple helium-3 detector. Simulations were developed using MCNPX-PoliMi and MCNP 6.1 to validate the measured results. The simulations showed close agreement for depleted uranium but indicated that additional investigation is required for the lead and tungsten data. The facility will be indispensable as the researchprogressesbyproviding a mixed-radiation field consisting of fast neutrons and photons, which is similar to the radiation environment encountered in active interrogation scenarios.Additionally, the facility is involved inresearch related toradiation damage, dosimetry, and radiation-oncology.Future activities will involve characterization of photonuclear properties of various materials, and collaborations with other university researchers

Multiplicity counting using organic scintillators to distinguish neutron sources: An advanced teaching laboratory

In this advanced instructional laboratory, students explore complex detection systems and nondestructive assay techniques used in the field of nuclear physics. After setting up and calibrating a neutron detection system, students carry out timing and energy deposition analyses of radiation signals. Through the timing of prompt fission neutron signals, multiplicity counting is used to carry out a special nuclear material (SNM) nondestructive assay. Our experimental setup is comprised of eight trans-stilbene organic scintillation detectors in a well-counter configuration, and measurements are taken on a spontaneous fission source as well as two ({\alpha},n) sources. By comparing each source's measured multiplicity distribution, the resulting measurements of the ({\alpha},n) sources can be distinguished from that of the spontaneous fission source. Such comparisons prevent the spoofing, i.e., intentional imitation, of a fission source by an ({\alpha},n) neutron source. This instructional laboratory is designed for nuclear engineering and physics students interested in organic scintillators, neutron sources, and nonproliferation radiation measurement techniques.Comment: 29 pages, 17 figures, pre-proof accepted to AJP, AJP number AJP22-AR-01524R2 (DOI: 10.1119/5.0139531

Surface-reconstructed Icosahedral Structures for Lead Clusters

We describe a new family of icosahedral structures for lead clusters. In general, structures in this family contain a Mackay icosahedral core with a reconstructed two-shell outer-layer. This family includes the anti-Mackay icosahedra, which have have a Mackay icosahedral core but with most of the surface atoms in hexagonal close-packed positions. Using a many-body glue potential for lead, we identify two icosahedral structures in this family which have the lowest energies of any known structure in the size range from 900 to 15000 lead atoms. We show that these structures are stabilized by a feature of the many-body glue part of the interatomic potential.Comment: 9 pages, 8 figure

Submillimeter-resolution radiography of shielded structures with laser-accelerated electron beams

We investigate the use of energetic electron beams for high-resolution radiography of flaws embedded in thick solid objects. A bright, monoenergetic electron beam (with energy \u3e100 MeV) was generated by the process of laser-wakefield acceleration through the interaction of 50-TW, 30-fs laser pulses with a supersonic helium jet. The high energy, low divergence, and small source size of these beams make them ideal for high-resolution radiographic studies of cracks or voids embedded in dense materials that are placed at a large distance from the source. We report radiographic imaging of steel with submillimeter resolution

Antiprogestins reduce epigenetic field cancerization in breast tissue of young healthy women

Background: Breast cancer is a leading cause of death in premenopausal women. Progesterone drives expansion of luminal progenitor cells, leading to the development of poor-prognostic breast cancers. However, it is not known if antagonising progesterone can prevent breast cancers in humans. We suggest that targeting progesterone signalling could be a means of reducing features which are known to promote breast cancer formation. Methods: In healthy premenopausal women with and without a BRCA mutation we studied (i) estrogen and progesterone levels in saliva over an entire menstrual cycle (n = 20); (ii) cancer-free normal breast-tissue from a control population who had no family or personal history of breast cancer and equivalently from BRCA1/2 mutation carriers (n = 28); triple negative breast cancer (TNBC) biopsies and healthy breast tissue taken from sites surrounding the TNBC in the same individuals (n = 14); and biopsies of ER+ve/PR+ve stage T1–T2 cancers and healthy breast tissue taken from sites surrounding the cancer in the same individuals (n = 31); and (iii) DNA methylation and DNA mutations in normal breast tissue (before and after treatment) from clinical trials that assessed the potential preventative effects of vitamins and antiprogestins (mifepristone and ulipristal acetate; n = 44). Results: Daily levels of progesterone were higher throughout the menstrual cycle of BRCA1/2 mutation carriers, raising the prospect of targeting progesterone signalling as a means of cancer risk reduction in this population. Furthermore, breast field cancerization DNA methylation signatures reflective of (i) the mitotic age of normal breast epithelium and (ii) the proportion of luminal progenitor cells were increased in breast cancers, indicating that luminal progenitor cells with elevated replicative age are more prone to malignant transformation. The progesterone receptor antagonist mifepristone reduced both the mitotic age and the proportion of luminal progenitor cells in normal breast tissue of all control women and in 64% of BRCA1/2 mutation carriers. These findings were validated by an alternate progesterone receptor antagonist, ulipristal acetate, which yielded similar results. Importantly, mifepristone reduced both the TP53 mutation frequency as well as the number of TP53 mutations in mitotic-age-responders. Conclusions: These data support the potential usage of antiprogestins for primary prevention of poor-prognostic breast cancers

Neoliberalism is not a theory of everything: a Bourdieuian analysis of illusio in educational research

 Despite the frequency with which the concept of neoliberalism is employed within academic literature, its complex and multifaceted nature makes it difficult to define and describe. Indeed, data reported in this article suggest that there is a tendency in educational research to make extensive use of the word ‘neoliberalism’ (or its variants neoliberal, neo-liberal and neo-liberalism) as a catch-all for something negative but without offering a definition or explanation. The article highlights a number of key risks associated with this approach and draws on the Bourdieuian concept of illusio to suggest the possibility that when as educational researchers we use the word ‘neoliberalism’ in this way, rather than interrupting the implementation of neoliberal policies and practices, we may, in fact, be further entrenching the neoliberal doxa. That is to say, we are both playing the neoliberal game and inadvertently demonstrating our belief that it is a game worth being played. In so doing, this article seeks to extend understandings of what illusio means within the context of educational research

Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): Survival results from an adaptive, multiarm, multistage, platform randomised controlled trial

BACKGROUND Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone. METHODS Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m(2)) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544). FINDINGS 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60-71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23-184). Median follow-up was 43 months (IQR 30-60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC + ZA (HR 0·94, 95% CI 0·79-1·11; p=0·450), 81 months (41 to not reached) for SOC + Doc (0·78, 0·66-0·93; p=0·006), and 76 months (39 to not reached) for SOC + ZA + Doc (0·82, 0·69-0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3-5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC + ZA, 288 (52%) receiving SOC + Doc, and 269 (52%) receiving SOC + ZA + Doc. INTERPRETATION Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy. FUNDING Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network, Swiss Group for Clinical Cancer Research