The Detection of Unsteady Flow Separation with Bioinspired Hair-Cell Sensors

Biologists hypothesize that thousands of micro-scale hairs found on bat wings function as a network of air-flow sensors as part of a biological feedback flow control loop. In this work, we investigate hair-cell sensors as a means of detecting flow features in an unsteady separating flow over a cylinder. Individual hair-cell sensors were modeled using an Euler-Bernoulli beam equation forced by the fluid flow. When multiple sensor simulations are combined into an array of hair-cells, the response is shown to detect the onset and span of flow reversal, the upstream movement of the point of zero wall shear-stress, and the formation and growth of eddies near the wall of a cylinder. A linear algebraic hair-cell model, written as a function of the flow velocity, is also derived and shown to capture the same features as the hair-cell array simulatio

Clinical and hemodynamic follow-up of left ventricular to aortic conduits in patients with aortic stenosis

To assess the long-term results of left ventricular outflow tract reconstruction utilizing an apical left ventricular to aortic valved (porcine) conduit the clinical and hemodynamic data were reviewed from 24 patients who had placement of an apico-aortic conduit. Eighteen of the patients are asymptomatic and taking no cardiac medications. Three patients were reoperated on, one patient 1.5 years after his original operation for subacute bacterial endocarditis and two patients 3 to 4 years after their original operation for severe conduit valve insufficiency. None of the patients is taking anticoagulants and no thromboembolic events have occurred. Postoperative catheterization has been performed 1 to 1.5 years (mean 1.2) after repair in 15 of 21 patients. The rest left ventricular outflow tract gradient has decreased from 102.5 ± 20 mm Hg preoperatively to 14.8 ± 9.9 mm Hg postoperatively (probability [p] < 0.001). Some degree of conduit obstruction was demonstrated by catheter passage in 11 of the 15 patients. In these 11 patients, the obstruction occurred at three distant sites: at the egress of the left ventricle in 9, at the porcine valve in 5 and at the aortic to conduit junction in 1. Isometric exercise in five and supine bicycle exercise in six patients increased the left ventricular outflow tract gradient by 2.5 ± 1.1 and 20.8 ± 11.8 mm Hg, respectively, despite an increase in cardiac index of 1 ± 0.3 and 3.7 ± 0.4 liters/min per m2, respectively. The data suggest that a left ventricular to aortic conduit is an effective form of therapy for severe left ventricular outflow tract obstruction

Can Genetics Predict Response to Complex Behavioral Interventions? Evidence from a Genetic Analysis of the Fast Track Randomized Control Trial.

Early interventions are a preferred method for addressing behavioral problems in high-risk children, but often have only modest effects. Identifying sources of variation in intervention effects can suggest means to improve efficiency. One potential source of such variation is the genome. We conducted a genetic analysis of the Fast Track randomized control trial, a 10-year-long intervention to prevent high-risk kindergarteners from developing adult externalizing problems including substance abuse and antisocial behavior. We tested whether variants of the glucocorticoid receptor gene NR3C1 were associated with differences in response to the Fast Track intervention. We found that in European-American children, a variant of NR3C1 identified by the single-nucleotide polymorphism rs10482672 was associated with increased risk for externalizing psychopathology in control group children and decreased risk for externalizing psychopathology in intervention group children. Variation in NR3C1 measured in this study was not associated with differential intervention response in African-American children. We discuss implications for efforts to prevent externalizing problems in high-risk children and for public policy in the genomic era

Developmental mediation of genetic variation in response to the Fast Track Prevention Program

We conducted a developmental analysis of genetic moderation of the effect of the Fast Track intervention on adult externalizing psychopathology. The Fast Track intervention enrolled 891 children at high risk to develop externalizing behavior problems when they were in kindergarten. Half of the enrolled children were randomly assigned to receive 10 years of treatment, with a range of services and resources provided to the children and their families, and the other half to usual care (controls). We previously showed that the effect of the Fast Track intervention on participants\u27 risk of externalizing psychopathology at age 25 years was moderated by a variant in the glucocorticoid receptor gene. Children who carried copies of the A allele of the single nucleotide polymorphism rs10482672 had the highest risk of externalizing psychopathology if they were in the control arm of the trial and the lowest risk of externalizing psychopathology if they were in the treatment arm. In this study, we test a developmental hypothesis about the origins of this for better and for worse Gene × Intervention interaction (G × I): that the observed G × I effect on adult psychopathology is mediated by the proximal impact of intervention on childhood externalizing problems and adolescent substance use and delinquency. We analyzed longitudinal data tracking the 270 European American children in the Fast Track randomized control trial with available genetic information (129 intervention children, 141 control group peers, 69% male) from kindergarten through age 25 years. Results show that the same pattern of for better and for worse susceptibility to intervention observed at the age 25 follow-up was evident already during childhood. At the elementary school follow-ups and at the middle/high school follow-ups, rs10482672 predicted better adjustment among children receiving the Fast Track intervention and worse adjustment among children in the control condition. In turn, these proximal G × I effects early in development mediated the ultimate G × I effect on externalizing psychopathology at age 25 years. We discuss the contribution of these findings to the growing literature on genetic susceptibility to environmental intervention

Developmental mediation of genetic variation in response to the Fast Track Prevention Program

We conducted a developmental analysis of genetic moderation of the effect of the Fast Track intervention on adult externalizing psychopathology. The Fast Track intervention enrolled 891 children at high risk to develop externalizing behavior problems when they were in kindergarten. Half of the enrolled children were randomly assigned to receive 10 years of treatment, with a range of services and resources provided to the children and their families, and the other half to usual care (controls). We previously showed that the effect of the Fast Track intervention on participants\u27 risk of externalizing psychopathology at age 25 years was moderated by a variant in the glucocorticoid receptor gene. Children who carried copies of the A allele of the single nucleotide polymorphism rs10482672 had the highest risk of externalizing psychopathology if they were in the control arm of the trial and the lowest risk of externalizing psychopathology if they were in the treatment arm. In this study, we test a developmental hypothesis about the origins of this for better and for worse Gene × Intervention interaction (G × I): that the observed G × I effect on adult psychopathology is mediated by the proximal impact of intervention on childhood externalizing problems and adolescent substance use and delinquency. We analyzed longitudinal data tracking the 270 European American children in the Fast Track randomized control trial with available genetic information (129 intervention children, 141 control group peers, 69% male) from kindergarten through age 25 years. Results show that the same pattern of for better and for worse susceptibility to intervention observed at the age 25 follow-up was evident already during childhood. At the elementary school follow-ups and at the middle/high school follow-ups, rs10482672 predicted better adjustment among children receiving the Fast Track intervention and worse adjustment among children in the control condition. In turn, these proximal G × I effects early in development mediated the ultimate G × I effect on externalizing psychopathology at age 25 years. We discuss the contribution of these findings to the growing literature on genetic susceptibility to environmental intervention

Can Genetics Predict Response to Complex Behavioral Interventions? Evidence from a Genetic Analysis of the Fast Track Randomized Control Trial

Early interventions are a preferred method for addressing behavioral problems in high-risk children, but often have only modest effects. Identifying sources of variation in intervention effects can suggest means to improve efficiency. One potential source of such variation is the genome. We conducted a genetic analysis of the Fast Track randomized control trial, a 10-year-long intervention to prevent high-risk kindergarteners from developing adult externalizing problems including substance abuse and antisocial behavior. We tested whether variants of the glucocorticoid receptor gene NR3C1 were associated with differences in response to the Fast Track intervention. We found that in European-American children, a variant of NR3C1 identified by the single-nucleotide polymorphism rs10482672 was associated with increased risk for externalizing psychopathology in control group children and decreased risk for externalizing psychopathology in intervention group children. Variation in NR3C1 measured in this study was not associated with differential intervention response in African-American children. We discuss implications for efforts to prevent externalizing problems in high-risk children and for public policy in the genomic era

Poliomyelitis in Intraspinally Inoculated Poliovirus Receptor Transgenic Mice

AbstractMice transgenic with the human poliovirus receptor gene develop clinical signs and neuropathology similar to those of human poliomyelitis when neurovirulent polioviruses are inoculated into the central nervous system (CNS). Factors contributing to disease severity and the frequencies of paralysis and mortality include the poliovirus strain, dose, and gender of the mouse inoculated. The more neurovirulent the virus, as defined by monkey challenge results, the higher the rate of paralysis, mortality, and severity of disease. Also, the time to disease onset is shorter for more neurovirulent viruses. Male mice are more susceptible to polioviruses than females. TGM-PRG-3 mice have a 10-fold higher transgene copy number and produce 3-fold more receptor RNA and protein levels in the CNS than TGM-PRG-1 mice. CNS inoculations with type III polioviruses differing in relative neurovirulence show that these mouse lines are similar in disease frequency and severity, demonstrating that differences in receptor gene dosage and concomitant receptor abundance do not affect susceptibility to infection. However, there is a difference in the rate of accumulation of clinical signs. The time to onset of disease is shorter for TGM-PRG-3 than TGM-PRG-1 mice. Thus, receptor dosage affects the rate of appearance of poliomyelitis in these mice

Transposition of the great arteries, right aortic arch, coarctation, and isolation of the left subclavian artery: Report of surgical therapy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24449/1/0000723.pd

Aortic aneurysms after subclavian angioplasty repair of coarctation of the aorta

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27336/1/0000361.pd

A Discrete Subpopulation of Dendritic Cells Transports Apoptotic Intestinal Epithelial Cells to T Cell Areas of Mesenteric Lymph Nodes

This study identifies a dendritic cell (DC) subset that constitutively transports apoptotic intestinal epithelial cell remnants to T cell areas of mesenteric lymph nodes in vivo. Rat intestinal lymph contains two DC populations. Both populations have typical DC morphology, are major histocompatibility complex class IIhi, and express OX62, CD11c, and B7. CD4+/OX41+ DCs are strong antigen-presenting cells (APCs). CD4−/OX41− DCs are weak APCs and contain cytoplasmic apoptotic DNA, epithelial cell–restricted cytokeratins, and nonspecific esterase (NSE)+ inclusions, not seen in OX41+ DCs. Identical patterns of NSE electrophoretic variants exist in CD4−/OX41− DCs, intestinal epithelial cells, and mesenteric node DCs but not in other DC populations, macrophages, or tissues. Terminal deoxynucleotidyl transferase–mediated dUTP-biotin nick-end labeling (TUNEL)-positive DCs and strongly NSE+ DCs are present in intestinal lamina propria. Peyer's patches and mesenteric but not other lymph nodes contain many strongly NSE+ DCs in interfollicular and T cell areas. Similar DCs are seen in the ileum and in T cell areas of mesenteric nodes in gnotobiotic rats. These results show that a distinct DC subset constitutively endocytoses and transports apoptotic cells to T cell areas and suggest a role for these DCs in inducing and maintaining peripheral self-tolerance