ABSTRACT
OBJECTIVE: This study evaluated pulse oximetry screening (POS) for critical congenital heart disease (CCHD) in planned out of hospital births with special attention to births in Plain communities (Amish, Mennonite and similar). STUDY DESIGN: Wisconsin out of hospital births in 2013 and 2014 were evaluated. Care providers were supplied with and trained in the use of pulse oximeters for CCHD screening. State records were reviewed to identify deaths and hospital admissions due to CCHD in this population. RESULTS: Detailed information on POS was available in 1616 planned out of hospital births. Seven hundred and ninety-nine were from the Plain community. In total, 1584 babies (98%) passed their POS, 16 infants (1%) failed and 16 (1%) were not screened. Five infants from the Plain community had CCHD and three were detected by POS. CONCLUSION: POS for CCHD can be successfully implemented outside the hospital setting and plays a particularly important role in communities with high rates of CCHD and where formal prenatal screening is uncommon.
Subject(s)
Heart Defects, Congenital/diagnosis , Home Childbirth/statistics & numerical data , Neonatal Screening/methods , Oximetry , Amish , Heart Defects, Congenital/blood , Heart Defects, Congenital/epidemiology , Humans , Incidence , Infant, Newborn , Wisconsin/epidemiologyABSTRACT
OBJECTIVE: Pulse oximetry screening (POS) is an effective tool to detect critical congenital heart disease (CCHD) in asymptomatic term infants, but its value in the neonatal intensive care unit (NICU) requires further clarification. STUDY DESIGN: A retrospective review of 1005 babies without previously diagnosed CCHD admitted to a level III NICU was performed to assess the risk for missed CCHD and performance of POS. RESULT: Of the 1005 NICU patients, 812 had documented POS and none failed POS. In 812 patients, 547 had delayed POS because of the use of supplemental oxygen. In 259/812 patients, POS was delayed until the baby was >2 weeks old. CCHD was excluded by echocardiography, irrespective of POS, in 287/1005 patients. CONCLUSION: POS can be performed in the NICU with minimal adverse effects. However, in many NICU patients CCHD is confirmed or excluded before POS, and POS will frequently be performed after CCHD would have been expected to become symptomatic.
Subject(s)
Heart Defects, Congenital/diagnosis , Intensive Care Units, Neonatal , Length of Stay/statistics & numerical data , Neonatal Screening/methods , Oximetry , Echocardiography , Female , Gestational Age , Humans , Infant , Infant, Newborn , Male , Retrospective Studies , WisconsinABSTRACT
Inadvertent mammalian tissue exposures to low doses of ionizing radiation (IR) after radiation accidents, remediation of radioactive-contaminated areas, space travel or a dirty bomb represent an interesting trauma to an organism. Possible low-dose IR-induced bystander effects could impact our evaluation of human health effects, as cells within tissue are not equally damaged after doses of IR ≤10 cGy. To understand tissue responses after low IR doses, we generated a reporter system using the human clusterin promoter fused to firefly luciferase (hCLUp-Luc). Secretory clusterin (sCLU), an extracellular molecular chaperone, induced by low doses of cytotoxic agents, clears cell debris. Low-dose IR (≥2 cGy) exposure induced hCLUp-Luc activity with peak levels at 96 h, consistent with endogenous sCLU levels. As doses increased (≥1 Gy), sCLU induction amplitudes increased and time-to-peak response decreased. sCLU expression was stimulated by insulin-like growth factor-1, but suppressed by p53. Responses in transgenic hCLUp-Luc reporter mice after low IR doses showed that specific tissues (that is, colon, spleen, mammary, thymus and bone marrow) of female mice induced hCLUp-Luc activity more than male mice after whole body (≥10 cGy) irradiation. Tissue-specific, non-linear dose- and time-responses of hCLUp-Luc and endogenous sCLU levels were noted. Colon maintained homeostatic balance after 10 cGy. Bone marrow responded with delayed, but prolonged and elevated expression. Intraperitoneal administration of α-transforming growth factor (TGF)ß1 (1D11), but not control (13C4) antibodies, immediately following IR exposure abrogated CLU induction responses. Induction in vivo also correlated with Smad signaling by activated TGFß1 after IR. Mechanistically, media with elevated sCLU levels suppressed signaling, blocked apoptosis and increased survival of TGFß1-exposed tumor or normal cells. Thus, sCLU is a pro-survival bystander factor that abrogates TGFß1 signaling and most likely promotes wound healing.
Subject(s)
Clusterin/genetics , Gamma Rays , Insulin-Like Growth Factor I/genetics , Transforming Growth Factor beta1/genetics , Tumor Suppressor Protein p53/genetics , Whole-Body Irradiation , Animals , Apoptosis/genetics , Bone Marrow/metabolism , Bone Marrow/radiation effects , Cell Line, Tumor , Clusterin/metabolism , Colon/metabolism , Colon/radiation effects , Epithelial Cells/metabolism , Epithelial Cells/pathology , Epithelial Cells/radiation effects , Female , HCT116 Cells , Humans , Insulin-Like Growth Factor I/metabolism , MCF-7 Cells , Male , Mice , Mice, Transgenic , Molecular Chaperones/genetics , Molecular Chaperones/metabolism , Promoter Regions, Genetic , Signal Transduction/radiation effects , Smad Proteins/genetics , Smad Proteins/metabolism , Transforming Growth Factor beta1/metabolism , Tumor Suppressor Protein p53/metabolismABSTRACT
Secretory clusterin (sCLU) is a stress-induced, pro-survival glycoprotein elevated in early-stage cancers, in particular in APC/Min-defective colon cancers. sCLU is upregulated after exposure to various cytotoxic agents, including ionizing radiation (IR), leading to a survival advantage. We found that stimulation of insulin-like growth factor-1 (IGF-1) and IGF-1R protein kinase signaling was required for sCLU induction after IR exposure. Here, we show that activation of Ataxia telangiectasia-mutated kinase (ATM) by endogenous or exogenous forms of DNA damage was required to relieve basal repression of IGF-1 transcription by the p53/NF-YA complex, leading to sCLU expression. Although p53 levels were stabilized and elevated after DNA damage, dissociation of NF-YA, and thereby p53, from the IGF-1 promoter resulted in IGF-1 induction, indicating that NF-YA was rate limiting. Cells with elevated endogenous DNA damage (deficient in H2AX, MDC1, NBS1, mTR or hMLH1) or cells exposed to DNA-damaging agents had elevated IGF-1 expression, resulting in activation of IGF-1R signaling and sCLU induction. In contrast, ATM-deficient cells were unable to induce sCLU after DNA damage. Our results integrate DNA damage resulting from genetic instability, IR, or chemotherapeutic agents, to ATM activation and abrogation of p53/NF-YA-mediated IGF-1 transcriptional repression, that induces IGF-1-sCLU expression. Elucidation of this pathway should uncover new mechanisms for cancer progression and reveal new targets for drug development to overcome resistance to therapy.
Subject(s)
Cell Cycle Proteins/metabolism , Clusterin/genetics , DNA Damage , DNA-Binding Proteins/metabolism , Gene Expression Regulation, Neoplastic , Genomic Instability , Insulin-Like Growth Factor I/genetics , Neoplasms/genetics , Protein Serine-Threonine Kinases/metabolism , Tumor Suppressor Proteins/metabolism , Ataxia Telangiectasia Mutated Proteins , CCAAT-Binding Factor/metabolism , Cell Cycle Proteins/genetics , Cell Line , DNA-Binding Proteins/genetics , Humans , Neoplasms/pathology , Promoter Regions, Genetic , Protein Serine-Threonine Kinases/genetics , Transcription, Genetic , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Proteins/geneticsABSTRACT
This study examined the effects of the daily Reading Center in a preschool classroom on 16 children over a school year. Objective variables, related to the Center and derived from the interface between the concepts of developmentally appropriate practice and emergent literacy, were measured. The Center was found to be developmentally appropriate since it was child-centered in terms of the interaction with children, adults and materials, voluntary participation, child-selected words and individualized instruction based on a pretest for 20 beginning reading skills (i.e., emergent literacy). Concurrently, the Center had features of a teacher-centered activity with the implementation of a rather specific instructional procedure. The experimental children showed marked gains in their acquisition of the 20 beginning reading skills while their matched controls, in other classrooms, who did not have the Reading Center experience, showed a slight increase. The advantages are discussed of a detailed behavior analysis on related independent, dependent, and accompanying measures for a thorough understanding of the results.
Subject(s)
Language Development , Reading , Schools, Nursery , Child, Preschool , Female , Humans , Male , Verbal Learning , VocabularySubject(s)
Reading , Teaching/methods , Child, Preschool , Generalization, Psychological , Humans , Learning , Memory , Pattern Recognition, Visual , PhoneticsABSTRACT
The use of primes, contingent attention, and training sessions to assess a child's engagement and skill in six large motor activities was examined using a combination reversal and multiple-baseline design. Assessment was based on four levels: proximity to equipment, touching equipment, unskilled participation, and skilled participation. Before training, priming (suggestion to the child) was more effective than contingent attention for increasing the subject's engagement (but not skill) in five activities and for increasing skilled participation in one activity. Training of four activities in the natural environment effectively increased the subject's skill level in five activities. Thus, training appeared to generalize to one of these five activities in this setting and also to skillfully executed stair climbing in an adjoining setting. After training, primes and contingent attention were sufficient to maintain both the subject's skill level and engagement in all activities. Postchecks in the same setting the following semester with different teachers revealed only slight increases in participation, as compared to previous baselines, but all participation was at the skilled level. Social interaction, which was not experimentally manipulated, did not systematically vary in relation to changes in experimental conditions.
ABSTRACT
Differential reinforcement of other behavior (DRO) and noncontingent reinforcement were compared as control procedures during the modification of a 3-yr-old preschooler's compliance. The recorded reinforcer was teacher proximity (within 3 ft (0.9) of the subject for at least 5 sec) which was often accompanied by positive verbal comments that varied in content across experimental conditions. The verabal content during contingent reinforcement might have been: "Thank you for picking up the blocks"; during non-contingent reinforcement: "You're wearing a pretty dress"; and during DRO: "I don't blame you for not picking up because it isn't any fun". Contingent reinforcement increased compliance in all manipulation conditions. Noncontingent reinforcement decreased compliance during two reversal conditions. However, the behavior was variable and did not decrease to the low levels reached during the two DRO reversals.
Subject(s)
Behavior Therapy , Child Behavior , Cooperative Behavior , Reinforcement, Psychology , Child, Preschool , Female , Humans , Reinforcement Schedule , Reinforcement, Verbal , Schools, Nursery , Spatial Behavior , Teaching , Verbal BehaviorABSTRACT
The blockbuilding behavior of three preschool girls was analyzed in terms of the forms manifest in any completed block construction, and found to contain few different forms in baseline sessions. Social reinforcement, given contingent on the production of any form not previously constructed within the current session (i.e., every first appearance of any form within a session was reinforced but no subsequent appearances of that form within that session were), increased the number of different forms built per sessions. Social reinforcement, given for all second and later appearances within the session, decreased the number of different forms built per session. Furthermore, it was found that new forms (forms never seen before in the child's total prior sequence of blockbuilding sessions) emerged at higher rates during periods of reinforcement of different forms (first appearances) than during periods of baseline or reinforcement of same forms (second and later appearances).