Updated NGNP Fuel Acquisition Strategy

A Next Generation Nuclear Plant (NGNP) fuel acquisition strategy was first established in 2007. In that report, a detailed technical assessment of potential fuel vendors for the first core of NGNP was conducted by an independent group of international experts based on input from the three major reactor vendor teams. Part of the assessment included an evaluation of the credibility of each option, along with a cost and schedule to implement each strategy compared with the schedule and throughput needs of the NGNP project. While credible options were identified based on the conditions in place at the time, many changes in the assumptions underlying the strategy and in externalities that have occurred in the interim requiring that the options be re-evaluated. This document presents an update to that strategy based on current capabilities for fuel fabrication as well as fuel performance and qualification testing worldwide. In light of the recent Pebble Bed Modular Reactor (PBMR) project closure, the Advanced Gas Reactor (AGR) fuel development and qualification program needs to support both pebble and prismatic options under the NGNP project. A number of assumptions were established that formed a context for the evaluation. Of these, the most important are: • Based on logistics associated with the on-going engineering design activities, vendor teams would start preliminary design in October 2012 and complete in May 2014. A decision on reactor type will be made following preliminary design, with the decision process assumed to be completed in January 2015. Thus, no fuel decision (pebble or prismatic) will be made in the near term. • Activities necessary for both pebble and prismatic fuel qualification will be conducted in parallel until a fuel form selection is made. As such, process development, fuel fabrication, irradiation, and testing for pebble and prismatic options should not negatively influence each other during the period prior to a decision on reactor type. • Additional funding will be made available beginning in fiscal year (FY) 2012 to support pebble bed fuel fabrication process development and fuel testing while maintaining the prismatic fuel schedule. Options for fuel fabrication for prismatic and pebble bed were evaluated based on the credibility of each option, along with a cost and schedule to implement each strategy. The sole prismatic option is Babcock and Wilcox (B&W) producing uranium oxycarbide (UCO) tristructural-isotropic (TRISO) fuel particles in compacts. This option finishes in the middle of 2022 . Options for the pebble bed are Nuclear Fuel Industries (NFI) in Japan producing uranium dioxide (UO2) TRISO fuel particles, and/or B&W producing UCO or UO2 TRISO fuel particles. All pebble options finish in mid to late 2022

Variation in levels of acceptance, developmental success, and abortion of Halyomorpha halys eggs by native North American parasitoids

Using native North American parasitoid species (Hymenoptera: Scelionidae) that often unsuccessfully attack the eggs of the invasive brown marmorated stink bug Halyomorpha halys (Hemiptera: Pentatomidae), we assessed variation in traits that may determine the parasitoids’ ability to adapt to the invasive host by either exploiting or avoiding H. halys eggs (acceptance, developmental success). We also assessed variation in the parasitoids’ ability to induce H. halys host egg abortion, which may contribute to biological control of H. halys in invaded areas. The first set of experiments evaluated intra- and interspecific variation using standardized laboratory tests with iso-female lines of Telenomus podisi and Trissolcus euschisti that included matching of detailed behavioural observations of acceptance with developmental outcomes. In a second set of experiments, we assessed how variation in developmental ability and abortion induction may affect levels of biological control by indigenous parasitoid species. We examined a broader sample of parasitoids that emerged from field collections of egg masses of an indigenous north American stink bug Podisus maculiventris in a region newly invaded by H. halys. Results from the first set of experiments showed high levels of acceptance of H. halys eggs among iso-female lines of parasitoids, but offspring development success was almost zero. H. halys egg abortion due to unsuccessful parasitism was often very low and varied among iso-female lines only for T. podisi. In the second set of experiments we never observed increases in abortion levels of Halyomorpha halys eggs above natural levels, even for the two species (T. euschisti and T. podisi) that were observed to oviposit in and abort H. halys eggs in the first set of experiments. We conclude that while there may be some variation in behavioural and physiological parameters mediating acceptance and abortion of H. halys eggs by native North American egg parasitoids, there does not appear to be significant variation in developmental success. Moreover, current biological control impact of H. halys eggs via host egg abortion is likely very low

Programmable bio-nanochip-based cytologic testing of oral potentially malignant disorders in Fanconi anemia

Fanconi anemia (FA) is caused by mutations of DNA repair genes. The risk of oral squamous cell carcinoma (OSCC) among FA patients is 800-folds higher than in the general population. Early detection of OSCC, preferably at it precursor stage, is critical in FA patients to improve their survival. In an ongoing clinical trial, we are evaluating the effectiveness of the programmable bio-nanochip (p-BNC)-based oral cytology test in diagnosing oral potentially malignant disorders (OPMD) in non-FA patients. We used this test to compare cytomorphometric and molecular biomarkers in OSCC cell lines derived from FA and non-FA patients to brush biopsy samples of a FA patient with OPMD and normal mucosa of healthy volunteers. Our data showed that expression patterns of molecular biomarkers were not notably different between sporadic and FA-OSCC cell lines. The p-BNC assay revealed significant differences in cytometric parameters and biomarker MCM2 expression between cytobrush samples of the FA patient and cytobrush samples of normal oral mucosa obtained from healthy volunteers. Microscopic examination of the FA patient's OPMD confirmed the presence of dysplasia. Our pilot data suggests that the p-BNC brush biopsy test recognized dysplastic oral epithelial cells in a brush biopsy sample of a FA patient

HPV types 16/18 L1 E6 and E7 proteins seropositivity and cervical cancer risk in HIV-positive and HIV-negative black South African women

BACKGROUND: In populations with high rates of human immunodeficiency virus (HIV)-coinfection, the nature of the relationship between human papillomavirus (HPV)-16 and -18 (L1, E6 and E7) antibodies and cervical cancer is still uncertain. We measured the association between seropositivity to HPV (L1, E6 and E7) proteins and cervical cancer among black South African women with and without HIV co-infection. METHODS: We used questionnaire data and serum collected from consecutively recruited patients with a newly diagnosed cancer from the Johannesburg Cancer Study from 1346 cervical cancer cases and 2532 controls (diagnosed with other non-infection related cancers). Seropositivity to HPV proteins was measured using a multiplex serological assay based on recombinant glutathione S-transferase (GST) fusion proteins. We measured associations between their presence and cervical cancer using unconditional logistic regression models and evaluated the sensitivity and specificity of these HPV biomarkers. RESULTS: Among controls, HIV-negative women from rural areas compared to urban had significantly higher HPV seroprevalence, HPV16 E7 (8.6% vs 3.7%) and HPV18 E7 (7.9% vs 2.0%). HPV16 E6 and E7 antibodies were positively associated with cervical cancer in HIV-positive (Adjusted Odds Ratio (AOR) = 33; 95% CI 10-107) and HIV-negative women (AOR = 97; 95% CI 46-203). In HIV-positive women, HPV E6/E7 antibodies had low sensitivity (43.0%) and high specificity (90.6%) for cervical cancer detection. In HIV-negative women, HPV E6/E7 antibodies sensitivity was 70.6% and specificity was 89.7%. CONCLUSIONS: Our data show that HPV (L1, especially E6 and E7) antibody positivity is associated with cervical cancer in both HIV-positive and HIV-negative women. Nonetheless, being HIV-positive plays an important role in the development of cervical cancer

Ranking lifestyle risk factors for cervical cancer among black women : A case-control study from Johannesburg, South Africa

BACKGROUND: Aside from human papillomavirus (HPV), the role of other risk factors in cervical cancer such as age, education, parity, sexual partners, smoking and human immunodeficiency virus (HIV) have been described but never ranked in order of priority. We evaluated the contribution of several known lifestyle co-risk factors for cervical cancer among black South African women. METHODS: We used participant data from the Johannesburg Cancer Study, a case-control study of women recruited mainly at Charlotte Maxeke Johannesburg Academic Hospital between 1995 and 2016. A total of 3,450 women in the study had invasive cervical cancers, 95% of which were squamous cell carcinoma. Controls were 5,709 women with cancers unrelated to exposures of interest. Unconditional logistic regression models were used to calculate adjusted odds ratios (ORadj) and 95% confidence intervals (CI). We ranked these risk factors by their population attributable fractions (PAF), which take the local prevalence of exposure among the cases and risk into account. RESULTS: Cervical cancer in decreasing order of priority was associated with (1) being HIV positive (ORadj = 2.83, 95% CI = 2.53-3.14, PAF = 17.6%), (2) lower educational attainment (ORadj = 1.60, 95% CI = 1.44-1.77, PAF = 16.2%), (3) higher parity (3+ children vs 2-1 children (ORadj = 1.25, 95% CI = 1.07-1.46, PAF = 12.6%), (4) hormonal contraceptive use (ORadj = 1.48, 95% CI = 1.24-1.77, PAF = 8.9%), (5) heavy alcohol consumption (ORadj = 1.44, 95% CI = 1.15-1.81, PAF = 5.6%), (6) current smoking (ORadj = 1.64, 95% CI = 1.41-1.91, PAF = 5.1%), and (7) rural residence (ORadj = 1.60, 95% CI = 1.44-1.77, PAF = 4.4%). CONCLUNSION: This rank order of risks could be used to target educational messaging and appropriate interventions for cervical cancer prevention in South African women

Usefulness of high-risk HPV early oncoprotein (E6 and E7) serological markers in the detection of cervical cancer : A systematic review and meta-analysis

Abstract We reviewed the literature on the importance of selected anti-high-risk human papillomavirus (HR-HPV) antibodies (namely, 16/18 and early oncoproteins E6 and E7) as potential serological markers for early detection of individuals at high risk of cervical cancer. We searched for studies in PubMed and Embase databases published from 2010 to 2020 on antibodies against HR-HPV E6 and E7 early proteins and cervical cancer. Pooled sensitivity and specificity for HPV16 and HPV18 antibodies were calculated using a bivariate hierarchical random-effects model. A total of 69 articles were identified; we included three studies with 1550 participants. For the three HPV16/18 E6 and E7 antibody tests, enzyme-linked immunosorbent assay-based assays had a sensitivity of 18+ (95CI]: 15–21) and a specificity of 9695 92–98), for slot-blot, sensitivity was 28.995 23.3–35.1) and specificity was 7295 66.6–77.0) for detecting CIN2+, and for multiplex HPV serology assay based on a glutathione S-transferase, sensitivity was 1695 8.45–28.6) and specificity was 9895 97–99) for detecting invasive cervical cancer. HR-HPV16/18 E6 and E7 serological markers showed high specificity, but sensitivity was suboptimal for the detection of cervical cancer in either population screening settings or as point-of-care screening tests

Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial

BackgroundAnterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability.MethodsWe did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367.FindingsBetween Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications.InterpretationSurgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management