Under fusion reactor conditions, large quantities of irradiation defects and transmutation gases are produced per unit time by neutrons, resulting in accelerated degradation of structural candidate ferritic (F) and ferritic/martensitic (F/M) steels. Due to the lack of a suitable fusion neutron testing facility, we must rely on high-dose-rate ion-beam experiments and present-day crude modeling estimates. Of particular interest is the possibility of synergistic (positive feedback) effects on materials properties due to the simultaneous action of He, H, and displacement damage (dpa) during operation. In this paper we discuss the state-of-the-art in terms of the experimental understanding of synergistic effects and carry out simulations of triple-species irradiation under ion-beam conditions using first-of-its-kind modeling techniques. Although, state-of-the-art modeling and simulation is not sufficiently well developed to shed light on the experimental uncertainties, we are able to conclude that it is not clear whether synergistic effects, the evidence of which is still not conclusive, will ultimately play a critical role in material performance under fusion energy conditions. We review here some of the evidence for the synergistic effects of hydrogen in the presence of helium and displacement damage, and also include some recent data from our research. While the experimental results to date suggest possible mechanisms for the observed synergistic effects, it is only with more advanced modeling that we can hope to understand the details underlying the experimental observations. By employing modeling and simulation we propose an interaction model that is qualitatively consistent with experimental observations of dpa/He/H irradiation behavior. Our modeling, the results of which should be helpful to researchers going forward, points to gaps and voids in the current understanding of triple ion-beam irradiation effects (displacement damage produced simultaneously with helium and hydrogen implantation) and the synergistic effects of hydrogen.

Growth faltering among children during the first five years of life is a common problem among low and middle-income countries. The purpose of this study was to determine the effect of a nutrient-rich, food-based supplement given to Vietnamese rural women prior to and/or during pregnancy on the growth of their infants during first 24 months of life and to identify maternal and newborn factors associated with the infant's growth. This prospective cohort study included 236 infants born to mothers who had received nutritional advice or a food supplement from pre-conception to term or from mid-gestation to term as part of a prior randomized controlled trial. Infant anthropometry and feeding information were monitored monthly and the infant weight for age Z-score (WAZ), length for age Z-score (LAZ), and weight for length Z-score (WLZ) were assessed at 6, 12, 18, and 24 months of age using mixed-effects regression modeling. Compared to the non-supplemented mothers, infants born to mothers receiving food supplementation from mid-gestation to term had significantly higher WLZ only at 18 months (p = 0.03) and did not differ in other outcomes. Supplementation from pre-conception to term did not affect infant growth at any time point during the first 24 months. In the entire study cohort, maternal height and gestational weight gain were positively associated with the infant's WAZ and LAZ from 6 to 24 months of age. Programs designed to improve gestational weight gain among women performing demanding physical work throughout a reproductive cycle may improve postnatal infant growth. Trial registration: Registered Clinical Trials.Gov: NCT01235767.

Background: Sustainability-the routinization and institutionalization of processes that improve the quality of healthcare-is difficult to achieve and not often studied. Objective: To evaluate the sustainability of increased rates of HIV testing after implementation of a multi-component intervention in two Veterans Health Administration healthcare systems. Design: Quasi-experimental implementation study in which the effect of transferring responsibility to conduct the provider education component of the intervention from research to operational staff was assessed. Patients: Persons receiving healthcare between 2005 and 2006 (intervention year) and 2006 and 2007 (sustainability year). Measurements: Monthly HIV testing rate, stratified by frequency of clinic visits. Results: The monthly adjusted testing rate increased from 2% at baseline to 6% at the end intervention year and then declined reaching 4% at the end of the sustainability year. However, the stratified, visit-specific testing rate for persons newly exposed to the intervention (i.e., having their first through third visits during the study period) increased throughout the intervention and sustainability years. Increases in the proportion of visits by patients who remained untested despite multiple, prior exposures to the intervention accounted for the aggregate attenuation of testing during the sustainability year. Overall, the percentage of patients who received an HIV test in the sustainability year was 11.6%, in the intervention year 11.1%, and in the pre-intervention year 5.0% Conclusions: Provider education combined with informatics and organizational support had a sustainable effect on HIV testing rates. The effect was most pronounced during patients' early contacts with the healthcare system. © 2009 Society of General Internal Medicine..

Nutrient interventions initiated after conception tend to have modest effects on maternal nutritional status and pregnancy outcomes. Thus, we compared the association between micronutrient intakes and the trajectories of their biomarkers before and during pregnancy. Data from a randomized trial of the effect of a nutrient-rich, food-based supplement given to 317 Vietnamese women prior to or during pregnancy on birth outcomes were used to assess nutrient intakes with biomarker trajectories of zinc, iron, folate, cobalamin, and vitamin A using linear mixed regression models. The circulating plasma or serum trajectories of all five micronutrients were associated to their baseline levels (p < 0.0001). Plasma zinc trajectories were also related to farm work (p = 0.024). Cobalamin and vitamin A trajectories were associated with gestational weight gain (p = 0.003 and p = -0.037, respectively). In this population of rural Vietnamese women, nutrient intakes during pregnancy did not affect biomarker trajectories. The primary determinant of each nutrient biomarker trajectory was its respective baseline level prior to conception.

Obtaining a nutrient-rich diet during pregnancy is a challenge for pregnant women living in low-income countries. This randomized, controlled trial was designed to determine if a freshly prepared food supplement from local animal-source foods and dark-green leafy vegetables given prior to and/or during pregnancy improved birth outcomes in rural Vietnamese women. Primiparous women, 18 to 30 years of age, who participated in the study were assigned to one of three groups: PC-T women received the supplement from pre-conception to term, MG-T women received the supplement from mid-gestation to term, and the RPC women received routine prenatal care. Supplement intake was observed and quantified. Infant anthropometry was measured at birth and/or within seven days of delivery. The effect of the intervention on maternal and birth outcomes was determined using linear regression modeling. Of the 460 women enrolled in the study, 317 women completed the study. Those not completing the study had either moved from the area, did not conceive within 12 months of study enrollment, or miscarried. The food-based supplement increased protein, iron, zinc, folate, vitamin A and B12 intakes in the PC-T and the MG-T groups. However, it failed to alter infant anthropometric measurements at birth. In the entire cohort, maternal gestational weight gain was greater in women with a low pre-pregnancy BMI (<18.5) and in women with a higher educational attainment. Working as a farmer reduced gestational weight gain but it did not affect birth weight or length. In summary, a nutrient-rich, food-based supplement given to rural Vietnamese women from pre-conception to term or mid-gestation to term did not affect maternal or infant outcomes. The low weight gains, possibly due to demanding farm work done throughout the reproductive cycle, may have obviated any effects of the low energy, nutrient-rich food supplement on birth outcomes. Trial registration : Registered Clinical Trials.gov: NCT01235767.

Background

We evaluated combined targeting with cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, and bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody, in squamous cell carcinoma of the head and neck (SCCHN).

Patients and methods

The combination was studied in human endothelial cells and head and neck and lung cancer xenograft model systems. Patients with recurrent or metastatic SCCHN were treated with weekly cetuximab and bevacizumab, 15 mg/kg on day 1 given intravenously every 21 days, until disease progression. Analysis of tumor biomarkers and related serum cytokines was performed.

Results

Cetuximab plus bevacizumab enhanced growth inhibition both in vitro and in vivo, and resulted in potent reduction in tumor vascularization. In the clinical trial, 46 eligible patients were enrolled. The objective response rate was 16% and the disease control rate 73%. The median progression-free survival and overall survival were 2.8 and 7.5 months, respectively. Grade 3-4 adverse events were expected and occurred in less than 10% of patients. transforming growth factor alpha, placenta-derived growth factor, EGFR, VEGFR2 increased and VEGF decreased after treatment but did not correlate with treatment efficacy.

Conclusions

Cetuximab and bevacizumab are supported by preclinical observations and are well tolerated and active in previously treated patients with SCCHN.

Background

In infants, distinct nasopharyngeal bacterial microbiotas differentially associate with the incidence and severity of acute respiratory tract infection and childhood asthma development.

Objective

We hypothesized that distinct nasal airway microbiota structures also exist in children with asthma and relate to clinical outcomes.

Methods

Nasal secretion samples (n = 3122) collected after randomization during the fall season from children with asthma (6-17 years, n = 413) enrolled in a trial of omalizumab (anti-IgE) underwent 16S rRNA profiling. Statistical analyses with exacerbation as the primary outcome and rhinovirus infection and respiratory illnesses as secondary outcomes were performed. Using A549 epithelial cells, we assessed nasal isolates of Moraxella, Staphylococcus, and Corynebacterium species for their capacity to induce epithelial damage and inflammatory responses.

Results

Six nasal airway microbiota assemblages, each dominated by Moraxella, Staphylococcus, Corynebacterium, Streptococcus, Alloiococcus, or Haemophilus species, were observed. Moraxella and Staphylococcus species-dominated microbiotas were most frequently detected and exhibited temporal stability. Nasal microbiotas dominated by Moraxella species were associated with increased exacerbation risk and eosinophil activation. Staphylococcus or Corynebacterium species-dominated microbiotas were associated with reduced respiratory illness and exacerbation events, whereas Streptococcus species-dominated assemblages increased the risk of rhinovirus infection. Nasal microbiota composition remained relatively stable despite viral infection or exacerbation; only a few taxa belonging to the dominant genera exhibited relative abundance fluctuations during these events. In vitro, Moraxella catarrhalis induced significantly greater epithelial damage and inflammatory cytokine expression (IL-33 and IL-8) compared with other dominant nasal bacterial isolates tested.

Conclusion

Distinct nasal airway microbiotas of children with asthma relate to the likelihood of exacerbation, rhinovirus infection, and respiratory illnesses during the fall season.