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Much research indicates that exposure to early life adversity (ELA) predicts chronic inflammatory activity, increasing one’s risk of developing diseases of aging later in life. Despite its costs, researchers have proposed that chronic inflammation may be favored in this context because it would help promote immunological vigilance in environments with an elevated risk of infection and injury. Although intuitively appealing, the assumption that exaggerated inflammatory activity predicts favorable immunological outcomes among those exposed to ELA has not been tested. Here, we seek to address this gap, examining the links between exposure to ELA, inflammation, and immune function. Consistent with others’ work, results revealed that those from low socioeconomic status (SES) childhood environments exhibited exaggerated unstimulated inflammatory activity relative to what was observed among those from higher SES childhood environments. Further, results revealed that – although levels of inflammation predicted the magnitude of immunological responses in those from higher SES backgrounds – for those who grew up in low SES environments, higher levels of inflammation were unrelated to the magnitude of immunological responses. Results suggest that exaggerated inflammatory activity in the context of ELA may not predict improved ability to manage acute immunological threats.
Registry-based trials have emerged as a potentially cost-saving study methodology. Early estimates of cost savings, however, conflated the benefits associated with registry utilisation and those associated with other aspects of pragmatic trial designs, which might not all be as broadly applicable. In this study, we sought to build a practical tool that investigators could use across disciplines to estimate the ranges of potential cost differences associated with implementing registry-based trials versus standard clinical trials.
We built simulation Markov models to compare unique costs associated with data acquisition, cleaning, and linkage under a registry-based trial design versus a standard clinical trial. We conducted one-way, two-way, and probabilistic sensitivity analyses, varying study characteristics over broad ranges, to determine thresholds at which investigators might optimally select each trial design.
Registry-based trials were more cost effective than standard clinical trials 98.6% of the time. Data-related cost savings ranged from $4300 to $600,000 with variation in study characteristics. Cost differences were most reactive to the number of patients in a study, the number of data elements per patient available in a registry, and the speed with which research coordinators could manually abstract data. Registry incorporation resulted in cost savings when as few as 3768 independent data elements were available and when manual data abstraction took as little as 3.4 seconds per data field.
Registries offer important resources for investigators. When available, their broad incorporation may help the scientific community reduce the costs of clinical investigation. We offer here a practical tool for investigators to assess potential costs savings.
The Single Ventricle Reconstruction Trial randomised neonates with hypoplastic left heart syndrome to a shunt strategy but otherwise retained standard of care. We aimed to describe centre-level practice variation at Fontan completion.
Centre-level data are reported as median or median frequency across all centres and range of medians or frequencies across centres. Classification and regression tree analysis assessed the association of centre-level factors with length of stay and percentage of patients with prolonged pleural effusion (>7 days).
The median Fontan age (14 centres, 320 patients) was 3.1 years (range from 1.7 to 3.9), and the weight-for-age z-score was −0.56 (−1.35 + 0.44). Extra-cardiac Fontans were performed in 79% (4–100%) of patients at the 13 centres performing this procedure; lateral tunnels were performed in 32% (3–100%) at the 11 centres performing it. Deep hypothermic circulatory arrest (nine centres) ranged from 6 to 100%. Major complications occurred in 17% (7–33%). The length of stay was 9.5 days (9–12); 15% (6–33%) had prolonged pleural effusion. Centres with fewer patients (<6%) with prolonged pleural effusion and fewer (<41%) complications had a shorter length of stay (<10 days; sensitivity 1.0; specificity 0.71; area under the curve 0.96). Avoiding deep hypothermic circulatory arrest and higher weight-for-age z-score were associated with a lower percentage of patients with prolonged effusions (<9.5%; sensitivity 1.0; specificity = 0.86; area under the curve 0.98).
Fontan perioperative practices varied widely among study centres. Strategies to decrease the duration of pleural effusion and minimise complications may decrease the length of stay. Further research regarding deep hypothermic circulatory arrest is needed to understand its association with prolonged pleural effusion.
Involved fatherhood is crucial for the development of healthy, well-functioning families. In this chapter, we review empirical research from around the world on (a) the effects of involved fatherhood on the well-being of children, women, and families, (b) the predictors of and barriers to paternal involvement, and (c) how family-supportive public and employer-based policy can better support fathers so they can succeed both at the workplace and in their families. We conclude with suggestions for further research, public policy, and business practice.
Pepper & Nettle's theory of the behavioral constellation of deprivation (BCD) would benefit from teasing apart the conceptually distinct – although related – constructs of predictability and control. Our commentary draws from prior research conducted in the learning domain to demonstrate that predictability moderates the effects of control and independently exerts a powerful influence on outcomes relevant to the BCD.
In the United States alone, ∼14,000 children are hospitalised annually with acute heart failure. The science and art of caring for these patients continues to evolve. The International Pediatric Heart Failure Summit of Johns Hopkins All Children’s Heart Institute was held on February 4 and 5, 2015. The 2015 International Pediatric Heart Failure Summit of Johns Hopkins All Children’s Heart Institute was funded through the Andrews/Daicoff Cardiovascular Program Endowment, a philanthropic collaboration between All Children’s Hospital and the Morsani College of Medicine at the University of South Florida (USF). Sponsored by All Children’s Hospital Andrews/Daicoff Cardiovascular Program, the International Pediatric Heart Failure Summit assembled leaders in clinical and scientific disciplines related to paediatric heart failure and created a multi-disciplinary “think-tank”. The purpose of this manuscript is to summarise the lessons from the 2015 International Pediatric Heart Failure Summit of Johns Hopkins All Children’s Heart Institute, to describe the “state of the art” of the treatment of paediatric cardiac failure, and to discuss future directions for research in the domain of paediatric cardiac failure.
Travel, stump speeches, and pressing-the-flesh make up a large part of any presidential electoral campaign. Obviously, candidates feel that their appearances are important, as they make hundreds of appearances between Labor Day and Election Day. But are they right? Well over 100 million people cast ballots in November, but only the tiniest fraction of voters meets or catches a glimpse of either of the candidates. Do candidate appearances and contact sway voters in some way? In this article, we use changes in weekly state tracking polls to determine the impact of candidate appearances in battleground and non-battleground states. Using polling data from the 2000, 2004, and 2008 elections, we find that campaign appearances can change a candidate's polling percentages, and that the impact varies by candidate and location (battleground state, safe Democratic state, or safe Republican state). We also find that the selection of a vice-presidential candidate is important, because of this candidate's ability to campaign effectively.
There is considerable interest in the relationship between milk
polymorphism and cheesemaking properties of milk (e.g. Jakob & Puhan,
1995; Jakob, 1993). For example, the B variant of κ-casein
is associated with firmer
cheese curds, shorter renneting times, a smaller average micelle size,
casein and κ-casein concentrations and lower whey protein
concentrations (Jakob, 1994; Horne et al. 1995).
Experimental measurements of material effects induced by the passage of sharp shock fronts require techniques which provide high temporal resolution and high spatial resolution. Since typical shock velocities are a few microns per nanosecond, sub-nanosecond probing requires sub-micron spatial resolution. In our experiments, the required temporal resolution is furnished using picosecond laser generated shock waves and picosecond spectroscopy. The spatial resolution is furnished by engineering nanometer scale structures into our shock target arrays. In one technique, absorption transients in the spectrum of a thin layer of molecules, termed an optical nanogauge, are investigated. Shock-induced molecular energy transfer processes are observed in condensed matter for the first time. In a second technique, sub-micron particles of an energetic material are shocked and probed using ps coherent Raman spectroscopy. This probing technique permits the instantaneous measurement of the temperature, pressure and composition of an energetic material under dynamic shock loading.
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