Analysis and Insights from a Dynamical Model of Nuclear Plant Safety Risk

In this paper, we expand upon previously reported results of a dynamical systems model for the impact of plant processes and programmatic performance on nuclear plant safety risk. We utilize both analytical techniques and numerical simulations typical of the analysis of nonlinear dynamical systems to obtain insights important for effective risk management. This includes use of bifurcation diagrams to show that period doubling bifurcations and regions of chaotic dynamics can occur. We also investigate the impact of risk mitigating functions (equipment reliability and loss prevention) on plant safety risk and demonstrate that these functions are capable of improving risk to levels that are better than those that are represented in a traditional risk assessment. Next, we analyze the system response to the presence of external noise and obtain some conclusions with respect to the allocation of resources to ensure that safety is maintained at optimal levels. In particular, we demonstrate that the model supports the importance of management and regulator attention to plants that have demonstrated poor performance by providing an external stimulus to obtain desired improvements. Equally important, the model suggests that excessive intervention, by either plant management or regulatory authorities, can have a deleterious impact on safety for plants that are operating with very effective programs and processes. Finally, we propose a modification to the model that accounts for the impact of plant risk culture on process performance and plant safety risk. We then use numerical simulations to demonstrate the important safety benefits of a strong risk culture.Nonlinear Dynamical Systems, Process Model, Risk Management

An unsymmetric ligand framework for noncoupled homo- and heterobimetallic complexes

We introduce a new unsymmetric ligand, PDIpCy (PDI = pyridyldiimine; Cy = cyclam), that offers two distinct, noncoupled coordination sites. A series of homo- and heterobimetallic complexes, [Zn2(PDIpCy)(THF)(OTf)4] (1; THF = tetrahydrofuran and OTf = triflate), [Ni2(PDIpCy)(THF)(OTf)2](OTf)2 (2), and [NiZn(PDIpCy)(THF)(OTf)4] (3), are described. The one-electron-reduced compounds, [Zn2(PDIpCy)(OTF)3] (4), [Ni2(PDIpCy)(OTf)](OTf)2 (5), and [NiZn(PDIpCy)(OTf)3] (6), were isolated, and their electronic structures were characterized. The reduced compounds are charge-separated species, with electron storage at either the PDI ligand (4) or at the PDI-bound metal ion (5 and 6)

Small-quantity lipid-based nutrient supplements, regardless of their zinc content, increase growth and reduce the prevalence of stunting and wasting in young Burkinabe children : a cluster-randomized trial

Small-quantity lipid-based nutrient supplements (SQ-LNS) are promising home fortification products, but the optimal zinc level needed to improve growth and reduce morbidity is uncertain. We aimed to assess the impact of providing SQ-LNS with varied amounts of zinc, along with illness treatment, on zinc-related outcomes compared with standard care. In a placebo-controlled, cluster-randomized trial, 34 communities were stratified to intervention (IC) or nonintervention cohorts (NIC). 2435 eligible IC children were randomly assigned to one of four groups: 1) SQ-LNS without zinc, placebo tablet; 2) SQ-LNS containing 5mg zinc, placebo tablet; 3) SQ-LNS containing 10mg zinc, placebo tablet; or 4) SQ-LNS without zinc and 5mg zinc tablet from 9-18 months of age. During weekly morbidity surveillance, oral rehydration salts were provided for reported diarrhea and antimalarial therapy for confirmed malaria. Children in NIC (n = 785) did not receive SQ-LNS, tablets, illness surveillance or treatment. At 9 and 18 months, length, weight and hemoglobin were measured in all children. Reported adherence was 97 +/- 6% for SQ-LNS and tablets. Mean baseline hemoglobin was 89 +/- 15g/L. At 18 months, change in hemoglobin was greater in IC than NIC (+8 vs -1g/L, p<0.0001), but 79.1% of IC were still anemic (vs. 91.1% in NIC). Final plasma zinc concentration did not differ by group. During the 9-month observation period, the incidence of diarrhea was 1.10 +/- 1.03 and of malaria 0.54 +/- 0.50 episodes per 100 child-days, and did not differ by group. Length at 18 months was significantly greater in IC compared to NIC (77.7 +/- 3.0 vs. 76.9 +/- 3.4cm; p<0.001) and stunting prevalence was significantly lower in IC (29.3%) than NIC (39.3%; p<0.0001), but did not differ by intervention group within IC. Wasting prevalence was also significantly lower in IC (8.7%) than in NIC (13.5%; p = 0.0003). Providing SQ-LNS daily with or without zinc, along with malaria and diarrhea treatment, significantly increased growth and reduced stunting, wasting and anemia prevalence in young children

Non-Coding RNA Sequencing of Equine Endometrium During Maternal Recognition of Pregnancy.

Maternal recognition of pregnancy (MRP) in the mare is not well defined. In a non-pregnant mare, prostaglandin F2α (PGF) is released on day 14 post-ovulation (PO) to cause luteal regression, resulting in loss of progesterone production. Equine MRP occurs prior to day 14 to halt PGF production. Studies have failed to identify a gene candidate for MRP, so attention has turned to small, non-coding RNAs. The objective of this study was to evaluate small RNA (&lt;200 nucleotides) content in endometrium during MRP. Mares were used in a cross-over design with each having a pregnant and non-mated cycle. Each mare was randomly assigned to collection day 11 or 13 PO (n = 3/day) and endometrial biopsies were obtained. Total RNA was isolated and sequencing libraries were prepared using a small RNA library preparation kit and sequenced on a HiSeq 2000. EquCab3 was used as the reference genome and DESeq2 was used for statistical analysis. On day 11, 419 ncRNAs, representing miRNA, snRNA, snoRNA, scaRNA, and vaultRNA, were different between pregnancy statuses, but none on day 13. Equine endometrial ncRNAs with unknown structure and function were also identified. This study is the first to describe ncRNA transcriptome in equine endometrium. Identifying targets of these ncRNAs could lead to determining MRP

Differing growth responses to nutritional supplements in neighboring health districts of Burkina Faso are likely due to benefits of small-quantity lipid-based nutrient supplements (LNS)

Background : Of two community-based trials among young children in neighboring health districts of Burkina Faso, one found that small-quantity lipid-based nutrient supplements (LNS) increased child growth compared with a non-intervention control group, but zinc supplementation did not in the second study. Objectives : We explored whether the disparate growth outcomes were associated with differences in intervention components, household demographic variables, and/or children's morbidity. Methods : Children in the LNS study received 20g LNS daily containing different amounts of zinc (LNS). Children in the zinc supplementation study received different zinc supplementation regimens (Z-Suppl). Children in both studies were visited weekly for morbidity surveillance. Free malaria and diarrhea treatment was provided by the field worker in the LNS study, and by a village-based community-health worker in the zinc study. Anthropometric assessments were repeated every 13-16 weeks. For the present analyses, study intervals of the two studies were matched by child age and month of enrollment. The changes in length-for-age z-score (LAZ) per interval were compared between LNS and Z-Suppl groups using mixed model ANOVA or ANCOVA. Covariates were added to the model in blocks, and adjusted differences between group means were estimated. Results : Mean ages at enrollment of LNS (n = 1716) and Z-Suppl (n = 1720) were 9.4 +/- 0.4 and 10.1 +/- 2.7 months, respectively. The age-adjusted change in mean LAZ per interval declined less with LNS (-0.07 +/- 0.44) versus Z-Suppl (-0.21 +/- 0.43; p<0.0001). There was a significant group by interval interaction with the greatest difference found in 9-12 month old children (p<0.0001). Adjusting for demographic characteristics and morbidity did not reduce the observed differences by type of intervention, even though the morbidity burden was greater in the LNS group. Conclusions : Greater average physical growth in children who received LNS could not be explained by known cross-trial differences in baseline characteristics or morbidity burden, implying that the observed difference in growth response was partly due to LNS

Sitting and Supine Esophageal Pressures in Overweight and Obese Subjects Authors

Esophageal pressure can be used to approximate pleural pressure and might be clinically useful, particularly in the obese e.g to guide mechanical ventilator settings in critical illness. However, mediastinal artifact (the difference between true pleural pressure and esophageal pressure) may limit acceptance of the measurement, and reproducibility of esophageal pressure measurements remains unknown. Therefore, we aimed to assess the effect of body posture on esophageal pressure in a cohort of obese but healthy subjects, some of whom had multiple measurements, to address the clinical robustness of esophageal manometry. Twenty-five overweight and obese subjects (BMI>25kg/m2) and 11 control lean subjects (BMI<25kg/m2) underwent esophageal manometry with pressures measured seated and supine. Twenty overweight and obese subjects had measurements repeated after ~1-2 weeks. Anthropometric data and sitting and supine spirometry were recorded. The average end-expiratory esophageal pressures sitting and supine were greater in the overweight and obese group than the lean group (sitting −0.1±2.1 vs. −3.3±1.2cmH2O, supine 9.3±3.3 vs. 6.9±2.8cmH2O, respectively). The mean differences between repeated measurements were small (−0.3 ± 1.7cmH2O sitting and −0.1 ± 1.5cmH2O supine). Esophageal pressures correlated with a number of anthropometric and spirometric variables. In conclusion, esophageal pressures are slightly greater in overweight and obese subjects than lean subjects; but changes with position are similar in both groups. These data indicate that mediastinal weight and postural effects on esophageal pressure are within a clinically acceptable range, and suggest that esophageal manometry can be used to inform clinical decision making across wide range of body types

High Aldehyde Dehydrogenase Activity Identifies a Subset of Human Mesenchymal Stromal Cells with Vascular Regenerative Potential

During culture expansion, multipotent mesenchymal stromal cells (MSCs) differentially express aldehyde dehydrogenase (ALDH), an intracellular detoxification enzyme that protects long-lived cells against oxidative stress. Thus, MSC selection based on ALDH-activity may be used to reduce heterogeneity and distinguish MSC subsets with improved regenerative potency. After expansion of human bone marrow-derived MSCs, cell progeny was purified based on low versus high ALDH-activity (ALDHhi) by fluorescence-activated cell sorting, and each subset was compared for multipotent stromal and provascular regenerative functions. Both ALDHl° and ALDHhi MSC subsets demonstrated similar expression of stromal cell (\u3e95% CD73+, CD90+, CD105+) and pericyte (\u3e95% CD146+) surface markers and showed multipotent differentiation into bone, cartilage, and adipose cells in vitro. Conditioned media (CDM) generated by ALDHhi MSCs demonstrated a potent proliferative and prosurvival effect on human microvascular endothelial cells (HMVECs) under serum-free conditions and augmented HMVEC tube-forming capacity in growth factor-reduced matrices. After subcutaneous transplantation within directed in vivo angiogenesis assay implants into immunodeficient mice, ALDHhi MSC or CDM produced by ALDHhi MSC significantly augmented murine vascular cell recruitment and perfused vessel infiltration compared with ALDHl° MSC. Although both subsets demonstrated strikingly similar mRNA expression patterns, quantitative proteomic analyses performed on subset-specific CDM revealed the ALDHhi MSC subset uniquely secreted multiple proangiogenic cytokines (vascular endothelial growth factor beta, platelet derived growth factor alpha, and angiogenin) and actively produced multiple factors with chemoattractant (transforming growth factor-β, C-X-C motif chemokine ligand 1, 2, and 3 (GRO), C-C motif chemokine ligand 5 (RANTES), monocyte chemotactic protein 1 (MCP-1), interleukin [IL]-6, IL-8) and matrix-modifying functions (tissue inhibitor of metalloprotinase 1 & 2 (TIMP1/2)). Collectively, MSCs selected for ALDHhi demonstrated enhanced proangiogenic secretory functions and represent a purified MSC subset amenable for vascular regenerative applications. Stem Cells 2017;35:1542–1553

Expanded Hematopoietic Progenitor Cells Reselected for High Aldehyde Dehydrogenase Activity Demonstrate Islet Regenerative Functions

Human umbilical cord blood (UCB) hematopoietic progenitor cells (HPC) purified for high aldehyde dehydrogenase activity (ALDHhi) stimulate islet regeneration after transplantation into mice with streptozotocin-induced β cell deletion. However, ALDHhi cells represent a rare progenitor subset and widespread use of UCB ALDHhi cells to stimulate islet regeneration will require progenitor cell expansion without loss of islet regenerative functions. Here we demonstrate that prospectively purified UCB ALDHhi cells expand efficiently under serum-free, xeno-free conditions with minimal growth factor supplementation. Consistent with the concept that ALDH-activity is decreased as progenitor cells differentiate, kinetic analyses over 9 days revealed the frequency of ALDHhi cells diminished as culture time progressed such that total ALDHhi cell number was maximal (increased 3-fold) at day 6. Subsequently, day 6 expanded cells (bulk cells) were sorted after culture to reselect differentiated progeny with low ALDH-activity (ALDHlo subset) from less differentiated progeny with high ALDH-activity (ALDHhi subset). The ALDHhi subset retained primitive cell surface marker coexpression (32.0% ± 7.0% CD34+/CD38- cells, 37.0% ± 6.9% CD34+/CD133+ cells), and demonstrated increased hematopoietic colony forming cell function compared with the ALDHlo subset. Notably, bulk cells or ALDHlo cells did not possess the functional capacity to lower hyperglycemia after transplantation into streptozotocin-treated NOD/SCID mice. However, transplantation of the repurified ALDHhi subset significantly reduced hyperglycemia, improved glucose tolerance, and increased islet-associated cell proliferation and capillary formation. Thus, expansion and delivery of reselected UCB cells that retain high ALDH-activity after short-term culture represents an improved strategy for the development of cellular therapies to enhance islet regeneration in situ