Harmonizing longitudinal and survival data using a joint-modeling framework: An efficient approach to assessing social interventions

Objective: This article is an exposition of the joint-modeling approach to testing intervention effects through the harmonization of longitudinal and timeto- event data. We demonstrate the advantages of the joint-modeling approach over the classical approach of separately analyzing these types of outcome data. Method: We used a subset of 150 participants from the Illinois Birth through Three Title IV-E Waiver intervention study, which collected longitudinal Devereux Early Childhood Assessment for Infants and Toddlers (DECA-I/T) scores and time-to-permanence data for up to 3 years. We ran and contrasted three competing models: Cox proportional hazard, linear mixed-effects, and joint modeling. Results: If analyzed separately, the DECA-I/T scores are highly nonsignificantly related to time to permanence (p 5:929). However, when analyzed jointly, the significance level drops 88 percentage points, from.929 to.105. Because of its efficiency in addressing information loss when longitudinal and survival data are incorporated together, the joint model properly accounts for outcome-dependent missingness. Conclusion: This article highlights the utility of joint modeling in randomized longitudinal intervention studies by demonstrating its ability to preserve information from both longitudinal and time-to-event data, produce unbiased estimates, and retain higher statistical power than the traditional approach

NMR investigations of the interaction between the azo-dye sunset yellow and Fluorophenol

The interaction of small molecules with larger noncovalent assemblies is important across a wide range of disciplines. Here, we apply two complementary NMR spectroscopic methods to investigate the interaction of various fluorophenol isomers with sunset yellow. This latter molecule is known to form noncovalent aggregates in isotropic solution, and form liquid crystals at high concentrations. We utilize the unique fluorine-19 nucleus of the fluorophenol as a reporter of the interactions via changes in both the observed chemical shift and diffusion coefficients. The data are interpreted in terms of the indefinite self-association model and simple modifications for the incorporation of a second species into an assembly. A change in association mode is tentatively assigned whereby the fluorophenol binds end-on with the sunset yellow aggregates at low concentration and inserts into the stacks at higher concentrations

Functional Magnetic Resonance Imaging in Conscious Animals: A New Tool in Behavioural Neuroscience Research

Functional magnetic resonance imaging (fMRI) is a unique window to the brain, enabling scientists to follow changes in brain activity in response to hormones, ageing, environment, drugs of abuse and other stimuli. In this review, we present a general background to fMRI and the different imaging modalities that can be used in fMRI studies. Included are examples of the application of fMRI in behavioural neuroscience research, along with discussion of the advantages and disadvantages of this technology

The Influence of Moderate Hypercapnia on Neural Activity in the Anesthetized Nonhuman Primate

Hypercapnia is often used as vasodilatory challenge in clinical applications and basic research. In functional magnetic resonance imaging (fMRI), elevated CO2 is applied to derive stimulus-induced changes in the cerebral rate of oxygen consumption (CMRO2) by measuring cerebral blood flow and blood-oxygenation-level–dependent (BOLD) signal. Such methods, however, assume that hypercapnia has no direct effect on CMRO2. In this study, we used combined intracortical recordings and fMRI in the visual cortex of anesthetized macaque monkeys to show that spontaneous neuronal activity is in fact significantly reduced by moderate hypercapnia. As expected, measurement of cerebral blood volume using an exogenous contrast agent and of BOLD signal showed that both are increased during hypercapnia. In contrast to this, spontaneous fluctuations of local field potentials in the beta and gamma frequency range as well as multiunit activity are reduced by ∼15% during inhalation of 6% CO2 (pCO2 = 56 mmHg). A strong tendency toward a reduction of neuronal activity was also found at CO2 inhalation of 3% (pCO2 = 45 mmHg). This suggests that CMRO2 might be reduced during hypercapnia and caution must be exercised when hypercapnia is applied to calibrate the BOLD signal

Epidemiology of intra-abdominal infection and sepsis in critically ill patients: “AbSeS”, a multinational observational cohort study and ESICM Trials Group Project

Purpose: To describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock). Methods: We performed a multicenter (n = 309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis. Results: The cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation. Conclusion: This multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection

Advances, Challenges and Opportunities in 3D CMOS Sequential Integration

3D sequential integration enables the full use of the third dimension thanks to its high alignment performance. In this paper, we address the major challenges of 3D sequential integration: in particular, the control of molecular bonding allows us to obtain pristine quality top active layer. With the help of Solid Phase Epitaxy, we can match the performance of top FET, processed at low temperature (600°C), with the bottom FET devices. Finally, the development of a stable salicide enables to retain bottom performance after top FET processing. Overcoming these major technological issues offers a wide range of applications