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We present a broad study of linear, clustered, noble gas puffs irradiated with the frequency doubled (527 nm) Titan laser at Lawrence Livermore National Laboratory. Pure Ar, Kr, and Xe clustered gas puffs, as well as two mixed-gas puffs consisting of KrAr and XeKrAr gases, make up the targets. Characterization experiments to determine gas-puff density show that varying the experimental parameter gas-delay timing (the delay between gas puff initialization and laser-gas-puff interaction) provides a simple control over the gas-puff density. X-ray emission (>1.4 keV) is studied as a function of gas composition, density, and delay timing. Xe gas puffs produce the strongest peak radiation in the several keV spectral region. The emitted radiation was found to be anisotropic, with smaller X-ray flux observed in the direction perpendicular to both laser beam propagation and polarization directions. The degree of anisotropy is independent of gas target type but increases with photon energy. X-ray spectroscopic measurements estimate plasma parameters and highlight their difference with previous studies. Electron beams with energy in excess of 72 keV are present in the noble gas-puff plasmas and results indicate that Ar plays a key role in their production. A drastic increase in harder X-ray emissions (X-ray flash effect) and multi-MeV electron-beam generation from Xe gas-puff plasma occurred when the laser beam was focused on the front edge of the linear gas puff.
The Developmental Origins of Disease hypothesis has spurred increased interest in how prenatal exposures affect lifelong health, while mechanisms such as epigenetics may explain the multigenerational influences on health. Such factors are not well captured within conventional epidemiologic study designs. We explored the feasibility of collecting information on the offspring and grand-offspring of participants in a long-running study.
The Bogalusa Heart Study is a study, begun in 1973, of life-course cardiovascular health in a semirural population (65% white and 35% black).
Female participants who had previously provided information on their pregnancies were contacted to obtain contact information for their daughters aged 12 and older. Daughters were then contacted to obtain reproductive histories, and invited for a clinic or lab visit to measure cardiovascular risk factors.
Two hundred seventy-four daughters of 208 mothers were recruited; 81% (223) had a full clinic visit and 19% (51) a phone interview only. Forty-five percent of the daughters were black, and 55% white. Mean and median age at interview was 27, with 15% under the age of 18. The strongest predictors of participation were black race, recent maternal participation in the parent study, and living in or near Bogalusa. Simple correlations for cardiovascular risk factors across generations were between r = 0.19 (systolic blood pressure) and r = 0.39 (BMI, LDL).
It is feasible to contact the children of study participants even when participants are adults, and initial information on the grandchildren can also be determined in this manner.
This article, part of a historical study of childbirth in the Sahel, draws upon oral interviews, ethnographic materials, and studies of midwifery to explore placenta burial in Niger. In the region the placenta is often referred to as the “traveling companion” that ushers the new human from one world to the next. Only through proper respect toward the placenta by means of careful burial can a woman’s future fertility be protected. The importance of protecting a woman’s future reproductive capacity accounts for both the centrality of this ritual to childbirth and for the appeal of the ritual expertise of elderly “traditional birth attendants” despite access to bio-medically trained midwives. Protecting a vulnerable parturient mother from the envy of those (such as co-wives) who might “tie up” her womb is an integral part of the process of childbirth. Appropriate placenta burial orchestrated by a woman’s therapy management group makes good on the cyclical intergenerational entrustment through which ancestors and descendants endure in a cycle linking birth and death, planting, and burial. “Traditional” rituals bear marks of major shifts in the agricultural economy, rapid urbanization, and ongoing adoption and reinterpretation of Islam. Multi-generational interviews reveal that across a broad range of ethnicities, status groups, and educational profiles, women in Niger share a concern for proper placenta burial. This approach to preserving women’s reproductive health and fertility is shared by adjacent neighbors, generations, and ethnicities.
Hydrilla is an invasive aquatic plant that has rapidly spread through many inland water bodies across the globe by outcompeting native aquatic plants. The negative impacts of hydrilla invasion have become a concern for water resource management authorities, power companies, and environmental scientists. The early detection of hydrilla infestation is very important to reduce the costs associated with control and removal efforts of this invasive species. Therefore, in this study, we aimed to develop a tool for rapid, frequent, and large-scale monitoring and predicting spatial extent of hydrilla habitat. This was achieved by integrating in situ and Landsat 8 Operational Land Imager satellite data for Lake J. Strom Thurmond, the largest US Army Corps of Engineers lake east of the Mississippi River, located on the border of Georgia and South Carolina border. The predictive model for presence of hydrilla incorporated radiometric and physical measurements, including remote-sensing reflectance, Secchi disk depth (SDD), light-attenuation coefficient (Kd), maximum depth of colonization (Zc), and percentage of light available through the water column (PLW). The model-predicted ideal habitat for hydrilla featured high SDD, Zc, and PLW values, low values of Kd. Monthly analyses based on satellite images showed that hydrilla starts growing in April, reaches peak coverage around October, begins retreating in the following months, and disappears in February. Analysis of physical and meteorological factors (i.e., water temperature, surface runoff, net inflow, precipitation) revealed that these parameters are closely associated with hydrilla extent. Management agencies can use these results not only to plan removal efforts but also to evaluate and adapt their current mitigation efforts.
Cardiac surgery-associated acute kidney injury is common. In order to improve our understanding of acute kidney injury, we formed the multi-centre Neonatal and Pediatric Heart and Renal Outcomes Network. Our main goals are to describe neonatal kidney injury epidemiology, evaluate variability in diagnosis and management, identify risk factors, investigate the impact of fluid overload, and explore associations with outcomes.
The Neonatal and Pediatric Heart and Renal Outcomes Network collaborative includes representatives from paediatric cardiac critical care, cardiology, nephrology, and cardiac surgery. The collaborative sites and infrastructure are part of the Pediatric Cardiac Critical Care Consortium. An acute kidney injury module was developed and merged into the existing infrastructure. A total of twenty-two participating centres provided data on 100–150 consecutive neonates who underwent cardiac surgery within the first 30 post-natal days. Additional acute kidney injury variables were abstracted by chart review and merged with the corresponding record in the quality improvement database. Exclusion criteria included >1 operation in the 7-day study period, pre-operative renal replacement therapy, pre-operative serum creatinine >1.5 mg/dl, and need for extracorporeal support in the operating room or within 24 hours after the index operation.
A total of 2240 neonatal patients were enrolled across 22 centres. The incidence of acute kidney injury was 54% (stage 1 = 31%, stage 2 = 13%, and stage 3 = 9%).
Neonatal and Pediatric Heart and Renal Outcomes Network represents the largest multi-centre study of neonatal kidney injury. This new network will enhance our understanding of kidney injury and its complications.
Chemical analysis of geological materials such as nickel ores has been accomplished by atomic absorption (1,3) x-ray fluorescence (11,14) and conventional wet methods (10). Procedures utilizing these techniques are capable of producing excellent results but are often difficult and time consuming.
Minerals often present serious problems in chemical analysis by wet methods. X-ray analysis can therefore offer the analyst considerable savings in time providing the obstacles which exist are understood and minimized or eliminated. The most serious problems to solve are absorption and enhancement effects, mineralogical differences among samples, sample preparation, and particle size effects which often influence the intensities of the analytical lines. In addition, the element of interest may be of low concentration in a variable and unknown matrix.
A procedure using tube excited energy dispersive x-ray fluorescence analysis with interelement corrections has been developed for multielement analysis of major and trace elements and ash content of coal, coke, and fly ash. The procedure uses pressed pellets and an exponential correction for interelement effects. The average deviations ranged from about 0.0003% for V at an average concentration of about .003% to 0.1% for S at an average concentration of 4%. About 25 elements were measured and 100 second minimum detectable concentrations ranged from about one part per million for elements near arsenic to about one tenth of one percent for sodium.
A rapid multielement analysis procedure for cement and ceramic type materials has been developed which uses pelletized powders and an exponential correction to the observed x-ray intensities. Only the more significant interactions are considered in an iterative process requiring a minimum of standards. The interaction coefficients are determined by a nonlinear multiple least squares fit of the standards. Average deviations obtained for the analysis of light elements in cement ranged from a low of 0.006% for K2O to a high of 0.13% absolute for SiO2.
This study argues that rights discourse influences heterosexual public opinion in Washington State. We tested this through a survey experiment conducted in the 2011 Washington Poll. We broke interviewees into three groups, with each group exposed to a different frame: a pro–lesbian and gay equal rights frame, an anti–lesbian and gay special rights frame, and a control or no frame. Immediately following the treatment, we asked interviewees if they agreed with a pro–lesbian and gay policy: changing state antidiscrimination law to encompass those who identify as lesbian and gay. Overall, this study concludes that a special rights frame dampens support among some while an equal rights frame has no effect. Respondents who indicated that they were against same-sex marriage even more strongly opposed altering antidiscrimination policy to include sexual orientation when confronted with an equal rights frame than when confronted with the special rights frame or no frame at all.
There are no estimates of the heritability of phenotypic udder traits in suckler sheep, which produce meat lambs, and whether these are associated with resilience to mastitis. Mastitis is a common disease which damages the mammary gland and reduces productivity. The aims of this study were to investigate the feasibility of collecting udder phenotypes, their heritability and their association with mastitis in suckler ewes. Udder and teat conformation, teat lesions, intramammary masses (IMM) and litter size were recorded from 10 Texel flocks in Great Britain between 2012 and 2014; 968 records were collected. Pedigree data were obtained from an online pedigree recording system. Univariate quantitative genetic parameters were estimated using animal and sire models. Linear mixed models were used to analyse continuous traits and generalised linear mixed models were used to analyse binary traits. Continuous traits had higher heritabilities than binary with teat placement and teat length heritability (h2) highest at 0.35 (SD 0.04) and 0.42 (SD 0.04), respectively. Udder width, drop and separation heritabilities were lower and varied with udder volume. The heritabilities of IMM and teat lesions (sire model) were 0.18 (SD 0.12) and 0.17 (SD 0.11), respectively. All heritabilities were sufficiently high to be in a selection programme to increase resilience to mastitis in the population of Texel sheep. Further studies are required to investigate genetic relationships between traits and to determine whether udder traits predict IMM, and the potential benefits from including traits in a selection programme to increase resilience to chronic mastitis.
Because rationalism and logocentrism have no eternal political essences, … they can be put to different political uses in different historical contexts. This is not to say that epistemological claims (or literary styles, or any other symbolic structures) are ideology-free and impervious to ideological analysis, only that the relation between the epistemological claim or other symbolic structure and the interests it serves is a contextual one that can change as the historical context changes.
Oscar Kenshur, “(Avoidable) Snares and Avoidable Muddles”
Better indicators of prognosis are needed to personalise post-traumatic stress disorder (PTSD) treatments.
We aimed to evaluate early symptom reduction as a predictor of better outcome and examine predictors of early response.
Patients with PTSD (N = 134) received sertraline or prolonged exposure in a randomised trial. Early response was defined as 20% PTSD symptom reduction by session two and good end-state functioning defined as non-clinical levels of PTSD, depression and anxiety.
Early response rates were similar in prolonged exposure and sertraline (40 and 42%), but in sertraline only, early responders were four times more likely to achieve good end-state functioning at post-treatment (Number Needed to Treat = 1.8, 95% CI 1.28–3.00) and final follow-up (Number Needed to Treat = 3.1, 95% CI 1.68–16.71). Better outcome expectations of sertraline also predicted higher likelihood of early response.
Higher expectancy of sertraline coupled with early response may produce a cascade-like effect for optimal conditions for long-term symptom reduction. Therefore, assessing expectations and providing clear treatment rationales may optimise sertraline effects.
40% of people with dementia have disturbed sleep but there are currently no known effective treatments. Studies of sleep hygiene and light therapy have not been powered to indicate feasibility and acceptability and have shown 40–50% retention. We tested the feasibility and acceptability of a six-session manualized evidence-based non-pharmacological therapy; Dementia RElAted Manual for Sleep; STrAtegies for RelaTives (DREAMS-START) for sleep disturbance in people with dementia.
We conducted a parallel, two-armed, single-blind randomized trial and randomized 2:1 to intervention: Treatment as Usual. Eligible participants had dementia and sleep disturbances (scoring ≥4 on one Sleep Disorders Inventory item) and a family carer and were recruited from two London memory services and Join Dementia Research. Participants wore an actiwatch for two weeks pre-randomization. Trained, clinically supervised psychology graduates delivered DREAMS-START to carers randomized to intervention; covering Understanding sleep and dementia; Making a plan (incorporating actiwatch information, light exposure using a light box); Daytime activity and routine; Difficult night-time behaviors; Taking care of your own (carer's) sleep; and What works? Strategies for the future. Carers kept their manual, light box, and relaxation recordings post-intervention. Outcome assessment was masked to allocation. The co-primary outcomes were feasibility (≥50% eligible people consenting to the study) and acceptability (≥75% of intervention group attending ≥4 intervention sessions).
In total, 63out of 95 (66%; 95% CI: 56–76%) eligible referrals consented between 04/08/2016 and 24/03/2017; 62 (65%; 95% CI: 55–75%) were randomized, and 37 out of 42 (88%; 95% CI: 75–96%) adhered to the intervention.
DREAM-START for sleep disorders in dementia is feasible and acceptable.
Major depressive disorder (MDD) is a highly heterogeneous condition in terms of symptom presentation and, likely, underlying pathophysiology. Accordingly, it is possible that only certain individuals with MDD are well-suited to antidepressants. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes of depression, such as neuroticism, anhedonia, and cognitive control deficits.
Within an 8-week multisite trial of sertraline v. placebo for depressed adults (n = 216), we examined whether the combination of machine learning with a Personalized Advantage Index (PAI) can generate individualized treatment recommendations on the basis of endophenotype profiles coupled with clinical and demographic characteristics.
Five pre-treatment variables moderated treatment response. Higher depression severity and neuroticism, older age, less impairment in cognitive control, and being employed were each associated with better outcomes to sertraline than placebo. Across 1000 iterations of a 10-fold cross-validation, the PAI model predicted that 31% of the sample would exhibit a clinically meaningful advantage [post-treatment Hamilton Rating Scale for Depression (HRSD) difference ⩾3] with sertraline relative to placebo. Although there were no overall outcome differences between treatment groups (d = 0.15), those identified as optimally suited to sertraline at pre-treatment had better week 8 HRSD scores if randomized to sertraline (10.7) than placebo (14.7) (d = 0.58).
A subset of MDD patients optimally suited to sertraline can be identified on the basis of pre-treatment characteristics. This model must be tested prospectively before it can be used to inform treatment selection. However, findings demonstrate the potential to improve individual outcomes through algorithm-guided treatment recommendations.
Dietary fatty acid (FA) composition may influence metabolism, possibly affecting weight management. The purpose of this study was to compare the effects of a 5-d diet rich in PUFA v. MUFA. A total of fifteen normal-weight men participated in a randomised cross-over design with two feeding trials (3 d lead-in diet, pre-diet visit, 5-d PUFA- or MUFA-rich diet, post-diet visit). The 5-d diets (50 % fat) were rich in either PUFA (25 % of energy) or MUFA (25 % of energy). At pre- and post-diet visits, subjects consumed breakfast and lunch test meals, rich in the FA for that 5-d diet. Indirect calorimetry was used for 4 h after each meal. There were no treatment differences in fasting metabolism acutely or after the 5-d diet. For acute meal responses before diet, RER was higher for PUFA v. MUFA (0·86 (sem 0·01) v. 0·84 (sem 0·01), P<0·05), whereas diet-induced thermogenesis (DIT) was lower for PUFA v. MUFA (18·91 (SEM 1·46) v. 21·46 (SEM 1·34) kJ, P<0·05). After the 5-d diets, the change in RER was different for PUFA v. MUFA (−0·02 (sem 0·01) v. 0·00 (sem 0·01), P<0·05). Similarly, the change in fat oxidation was greater for PUFA v. MUFA (0·18 (sem 0·07) v. 0·04 (sem 0·06) g, P<0·05). In conclusion, acutely, a MUFA-rich meal results in lower RER and greater DIT. However, after a 5-d high-fat diet, the change in metabolic responses was greater in the PUFA diet, showing the metabolic adaptability of a PUFA-rich diet.
The depletion of neutral helium atoms has been studied in an unmagnetised spherical plasma created by DC discharge in a multidipole confinement field. Knowing the neutral density profile is critical to predicting the equilibrium flow of such plasmas. A model of the emissivity due to electron-impact excitation of neutral atoms in the plasma has been derived and used to fit radiance measurements of several neutral transitions to extract the radial profile of neutral density for plasmas of varying temperature and density. We report a depletion of the core neutral density varying between negligible levels to 80 % of the edge neutral density depending on the input power and fuelling. The corresponding ionisation fraction varies between 30–80 % in the plasma core. A simple neutral diffusion model is sufficient to describe the shape of neutral density profile implied by the radiance measurements. We have used the measurements to include a drag force due to neutral charge-exchange collisions in simulations of driven plasma flow. The simulation predicts a better fit to Mach probe flow measurements when this neutral drag is accounted for. This work shows that accounting for a realistic neutral profile is important to predict the plasma flow geometry and its magnetohydrodynamics (MHD) stability.
OBJECTIVES/SPECIFIC AIMS: This study aims to assess the safety, feasibility, clinical benefits and pharmacodynamics of adding allopurinol to standard maintenance therapy that includes 6-mecaptopurine (6-MP) in pediatric patients with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma. Our goal is to investigate if allopurinol improves hepatotoxicity and GI toxicity, if it safely decreases acute neutrophil count (ANC), if it reduces the 6-MP dose required during chemotherapy, and if it works through our hypothesized mechanism by lowering the levels of the toxic metabolite, 6-methylmecaptopurine (6-MMP) and by raising the levels of the active metabolite, 6-thioguanine (6-TGN). METHODS/STUDY POPULATION: This is a single arm, nonblinded pilot study of patients under age 30 years who were being treated in the maintenance phase of therapy for ALL or lymphoblastic lymphoma, and had adverse effects such as high 6-MMP:6-TGN ratio, high ANC, and high liver enzymes. Patients enrolled were started with allopurinol in addition to ongoing oral chemotherapy. Data from beginning maintenance to end of chemotherapy was collected in the electronic medical record, EPIC for the 13 patients enrolled at Johns Hopkins, and data analysis was conducted using STATA and Excel. RESULTS/ANTICIPATED RESULTS: Initial data analysis reveals that the required dose of 6-MP after addition of allopurinol to the chemotherapy regimen was significantly lower compared with that before the addition of allopurinol in 11 out of the 12 patients assessed (p<0.05). Among the 10 patients that were assessed for 6MMP:6TG ratio, all had lower average 6MMP:6TGN ratios after allopurinol compared to before allopurinol; the percentage of weeks that goal 6MMP:6TGN ratio (<40) were maintained were statistically significant in 6 patients (p<0.05) and close to significance in 2 other patients (p=0.057). The percentage of weeks that patients maintained alanine aminotransferase levels below 120 was significantly greater after addition of allopurinol compared to before the addition of allopurinol in 9 out of 13 patients assessed, suggesting that allopurinol may be associated with reduced hepatotoxicity. Further data analysis is ongoing to assess the percentage of weeks that patients maintained goal total bilirubin, direct bilirubin, and ANC, as well as average number of admissions for infections and average number of therapy holds after allopurinol addition compared to before allopurinol addition. DISCUSSION/SIGNIFICANCE OF IMPACT: Allopurinol is associated with reduction in required 6-MP dose, decrease in the percentage of weeks that patients have hepatotoxicity, and reduction in the ratio of toxic metabolite to active anti-leukemic metabolite in several patients. We hope that the results of this study can be used for further research and for guiding clinical practice since there are no established guidelines in pediatric oncology regarding addressing side effects of oral chemotherapy using 6-MP. If allopurinol indeed is safe and effective, adding it to the standard chemotherapy regimen can lead to better tolerance and compliance to oral maintenance chemotherapy, and hopefully improved outcomes for children with ALL and lymphoblastic leukemia.
Approximately 32,000 infants are born with CHDs each year in the United States of America. Of every 1000 live births, 2.3 require surgical or transcatheter intervention in the first year of life. There are few more stressful times for parents than when their neonate receives a diagnosis of complex CHD requiring surgery. The stress of caring for these infants is often unrelenting and may last for weeks, months, and often years, placing parents at risk for developing post-traumatic stress disorder, as well as a drastic decrease in quality of life. Anxiety often peaks in the days and weeks after discharge from the hospital as families no longer have immediate access to nursing and medical staff. The purpose of this paper is to describe the methods of a randomised controlled trial that was designed to determine whether REACH would favourably affect parental and infant outcomes by decreasing parental stress, improve parental quality of life, increase infant stability, and decrease resource utilisation in infants with complex CHD.
Prisoner's Dilemma (PD) games have become a well-established paradigm for studying the mechanisms by which cooperative behavior may evolve in societies consisting of selfish individuals. Recent research has focused on the effect of spatial and connectivity structure in promoting the emergence of cooperation in scenarios where individuals play games with their neighbors, using simple “memoryless” rules to decide their choice of strategy in repeated games. While heterogeneity and structural features such as clustering have been seen to lead to reasonable levels of cooperation in very restricted settings, no conditions on network structure have been established, which robustly ensure the emergence of cooperation in a manner that is not overly sensitive to parameters such as network size, average degree, or the initial proportion of cooperating individuals. Here, we consider a natural random network model, with parameters that allow us to vary the level of “community” structure in the network, as well as the number of high degree hub nodes. We investigate the effect of varying these structural features and show that, for appropriate choices of these parameters, cooperative behavior does now emerge in a truly robust fashion and to a previously unprecedented degree. The implication is that cooperation (as modelled here by PD games) can become the social norm in societal structures divided into smaller communities, and in which hub nodes provide the majority of inter-community connections.
Arachidonic acid (ARA) and DHA, supplied primarily from the mother, are required for early development of the central nervous system. Thus, variations in maternal ARA or DHA status may modify neurocognitive development. We investigated the relationship between maternal ARA and DHA status in early (11·7 weeks) or late (34·5 weeks) pregnancy on neurocognitive function at the age of 4 years or 6–7 years in 724 mother–child pairs from the Southampton Women’s Survey cohort. Plasma phosphatidylcholine fatty acid composition was measured in early and late pregnancy. ARA concentration in early pregnancy predicted 13 % of the variation in ARA concentration in late pregnancy (β=0·36, P<0·001). DHA concentration in early pregnancy predicted 21 % of the variation in DHA concentration in late pregnancy (β=0·46, P<0·001). Children’s cognitive function at the age of 4 years was assessed by the Wechsler Preschool and Primary Scale of Intelligence and at the age of 6–7 years by the Wechsler Abbreviated Scale of Intelligence. Executive function at the age of 6–7 years was assessed using elements of the Cambridge Neuropsychological Test Automated Battery. Neither DHA nor ARA concentrations in early or late pregnancy were associated significantly with neurocognitive function in children at the age of 4 years or the age of 6–7 years. These findings suggest that ARA and DHA status during pregnancy in the range found in this cohort are unlikely to have major influences on neurocognitive function in healthy children.