Small‐Scale Mechanical Testing of Nuclear Structural Materials

Material property changes due to harsh reactor environment conditions, such as neutron irradiation and high temperature, may limit the performance and the safe operating envelopes of all reactor types. Quantitative information on the material properties changes is needed to support ongoing life extension/ life management efforts of the existing global reactor fleet, as well as for design and development of future advanced reactor concepts. Testing of larger radioactive test specimens is challenging and expensive, as it requires their handling and testing in shielded facilities. Testing smaller sized specimens has an advantage in terms of their reduced activity that allows for safer handling and cost effective testing processes. Please click Additional Files below to see the full abstract

Efficacy and Tolerability of Adjunctive Intravenous Sodium Nitroprusside Treatment for Outpatients With Schizophrenia: A Randomized Clinical Trial

Importance: Antipsychotic medications for the treatment of schizophrenia have limitations, and new treatments are needed. A prior pilot investigation suggested that adjunctive sodium nitroprusside (SNP) administered intravenously had rapid efficacy in the treatment of patients with schizophrenia. Objective: To determine the efficacy and tolerability of intravenous SNP infused at a rate of 0.5 mug/kg/min for 4 hours in patients with schizophrenia with some degree of treatment resistance. Design, Setting, and Participants: Multicenter, randomized, double-blind acute treatment study using a sequential parallel comparison design conducted in two 2-week phases at 4 academic medical centers beginning May 20, 2015, and ending March 31, 2017. Participants were adults 18 to 65 years of age with a diagnosis of schizophrenia as confirmed by the Structured Clinical Interview for DSM-IV, taking antipsychotic medication for at least 8 weeks, and had at least 1 failed trial of an antipsychotic medication within the past year. A total of 90 participants consented, 60 participants enrolled, and 52 participants were included in the analyses. A modified intent-to-treat analysis was used. Interventions: Participants were randomized in a 1:1:1 ratio to 1 of 3 treatment sequences: SNP and SNP, placebo and SNP, and placebo and placebo. The SNP and SNP group received SNP in phase 1 and SNP in phase 2 for the purpose of blinding, but the data from phase 2 were not included in the results. The placebo and SNP group received placebo in phase 1 and SNP in phase 2. If there was no response to placebo in phase 1, data from phase 2 were included in the analyses. The placebo and placebo group received placebo in both phases; if there was no response to placebo in phase 1, data from phase 2 were included in the analyses. Main Outcomes and Measures: Effectiveness of SNP compared with placebo in improving Positive and Negative Syndrome Scale (PANSS) total, positive, and negative scores across each 2-week phase. Results: Fifty-two participants (12 women and 40 men) were included in the study. In the SNP and SNP group, the mean (SD) age was 47.1 (10.5) years. In the placebo and SNP group, the mean (SD) age was 45.9 (12.3) years. In the placebo and placebo group, the mean (SD) age was 40.4 (11.0) years. There were no significant differences between the SNP and placebo groups at baseline or in change from baseline for PANSS-total (weighted beta = -1.04; z = -0.59; P = .57), PANSS-positive (weighted beta = -0.62; z = -0.93; P = .35), or PANSS-negative (weighted beta = -0.12; z = -0.19; P = .85) scores. No significant differences in safety or tolerability measures were identified. Conclusions and Relevance: Although intravenous SNP is well tolerated, it was not an efficacious adjunctive treatment of positive or negative symptoms of psychosis among outpatients with schizophrenia with prior history of treatment resistance. Trial Registration: ClinicalTrials.gov identifier: NCT02164981

Monkey Steering Responses Reveal Rapid Visual-Motor Feedback

The neural mechanisms underlying primate locomotion are largely unknown. While behavioral and theoretical work has provided a number of ideas of how navigation is controlled, progress will require direct physiolgical tests of the underlying mechanisms. In turn, this will require development of appropriate animal models. We trained three monkeys to track a moving visual target in a simple virtual environment, using a joystick to control their direction. The monkeys learned to quickly and accurately turn to the target, and their steering behavior was quite stereotyped and reliable. Monkeys typically responded to abrupt steps of target direction with a biphasic steering movement, exhibiting modest but transient overshoot. Response latencies averaged approximately 300 ms, and monkeys were typically back on target after about 1 s. We also exploited the variability of responses about the mean to explore the time-course of correlation between target direction and steering response. This analysis revealed a broad peak of correlation spanning approximately 400 ms in the recent past, during which steering errors provoke a compensatory response. This suggests a continuous, visual-motor loop controls steering behavior, even during the epoch surrounding transient inputs. Many results from the human literature also suggest that steering is controlled by such a closed loop. The similarity of our results to those in humans suggests the monkey is a very good animal model for human visually guided steering

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Quantitative Survey - Pre/Post/Long-termPost

Quantitative Survey - Pre/Post/Long-termPost The survey was administered with the same questions at all three time points

Inference by Exclusion in Lion-Tailed Macaques (Macaca silenus), a Hamadryas Baboon (Papio hamadryas), Capuchins (Sapajus apella), and Squirrel Monkeys (Saimiri sciureus)

Previous research has suggested that several primate species may be capable of reasoning by exclusion based on the finding that they can locate a hidden object when given information about where the object is not. The present research replicated and extended the literature by testing 2 Old World monkey species, lion-tailed macaques (Macaca silenus) and a hamadryas baboon (Papio hamadryas), and 2 New World species, capuchin monkeys (Sapajus apella) and squirrel monkeys (Saimiri sciureus). The New World monkeys were tested on the traditional 2-way object choice task, and all 4 species were also tested on a more complex 3-way object choice task. In addition, the squirrel monkeys were tested on a 2-way object choice task with auditory information. The results showed that, whereas the Old World species were able to infer by exclusion on the 3-object task, some of the capuchin monkeys had difficulty on each of the 2- and 3-cup tasks. All but 1 of the squirrel monkeys failed to infer successfully, and their strategies appeared to differ between the visual and auditory versions of the task. Taken together, this research suggests that the ability to succeed on this inference task may be present throughout Old World monkey species, but is fragile in the New World species tested thus far