Indexing dynamic collective constructs using computer-aided text analysis: Construct validity evidence and illustrations featuring team processes.

Organizational processes have been widely recognized as both multilevel and dynamic, yet traditional methods of measurements limit our ability to model and understand such phenomena. Featuring a popular model of team processes advanced by Marks et al. (2001), we illustrate a method to use individuals' communications as construct valid unobtrusive measures of collective constructs occurring over time. Thus, the purpose of this investigation is to develop computer-aided text analysis (CATA) techniques that can score members' communications into valid team process measures. We apply a deductive content validity-based method to construct CATA dictionaries for Marks et al.'s dimensions. We then demonstrate their convergent validity with subject matter experts' (SMEs) hand-coded team communications and different SMEs' behaviorally anchored rating scales based on video recordings of team interactions, using multitrait-multimethod analyses in two samples. Using a third sample of paramedics performing a high-fidelity mass casualty incident exercise, we further demonstrate the convergent validity of the CATA and SME scorings of communications. We then model the relationships among processes across episodes using all three samples. Next, we test criterion-related validity using a longitudinal dual-discontinuous change growth modeling design featuring the paramedic CATA-scored team processes as related to a dynamic performance criterion. Finally, we integrate behavioral data from wearable sensor badges to illustrate how CATA can be scored at the individual level and then leveraged to model dynamic networks of team interactions. Implications, limitations, directions for the future research, and guidelines for the application of these techniques to other collective constructs are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Identifying patients' support needs following critical illness: a scoping review of the qualitative literature.

BACKGROUND: Intensive care survivors suffer chronic and potentially life-changing physical, psychosocial and cognitive sequelae, and supporting recovery is an international priority. As survivors' transition from the intensive care unit to home, their support needs develop and change. METHODS: In this scoping review, we categorised patients' support needs using House's Social Support Needs framework (informational, emotional, instrumental, appraisal) and mapped these against the Timing it Right framework reflecting the patient's transition from intensive care (event/diagnosis) to ward (stabilisation/preparation) and discharge home (implementation/adaptation). We searched electronic databases from 2000 to 2017 for qualitative research studies reporting adult critical care survivors' experiences of care. Two reviewers independently screened, extracted and coded data. Data were analysed using a thematic framework approach. RESULTS: From 3035 references, we included 32 studies involving 702 patients. Studies were conducted in UK and Europe (n = 17, 53%), Canada and the USA (n = 6, 19%), Australasia (n = 6, 19%), Hong Kong (n = 1, 3%), Jordan (n = 1, 3%) and multi-country (n = 1, 3%). Across the recovery trajectory, informational, emotional, instrumental, appraisal and spiritual support needs were evident, and the nature and intensity of need differed when mapped against the Timing it Right framework. Informational needs changed from needing basic facts about admission, to detail about progress and treatments and coping with long-term sequelae. The nature of emotional needs changed from needing to cope with confusion, anxiety and comfort, to a need for security and family presence, coping with flashbacks, and needing counselling and community support. Early instrumental needs ranged from managing sleep, fatigue, pain and needing nursing care and transitioned to needing physical and cognitive ability support, strength training and personal hygiene; and at home, regaining independence, strength and return to work. Appraisal needs related to obtaining feedback on progress, and after discharge, needing reassurance from others who had been through the ICU experience. CONCLUSIONS: This review is the first to identify the change in social support needs among intensive care survivors as they transition from intensive care to the home environment. An understanding of needs at different transition periods would help inform health service provision and support for survivors.

Helping fluid teams work: A research agenda for effective team adaptation in healthcare.

Although membership changes within teams are a common practice, research into this phenomenon is relatively nascent (Summers et al.; Acad Manag J 55:314-338, 2012). The small literature base, however, does provide insight into skills required for effective adaptation. The purpose of this effort is to provide a brief research synopsis, leading to research hypotheses about medical team training. By generalizing previous scientific findings regarding skills required for effective membership adaptation in different kinds of teams, we posit mechanisms whereby teamwork training might also support adaptation among medical teams (Burke et al.; Qual & Saf Health Care 13:i96-i104, 2004 and Salas et al.; Theor Issues Ergon Sci 8:381-394, 2007). We provide an overview of the membership change literature. Drawing upon literature from both within and outside of the medical domain, we suggest a framework and research propositions to aid in research efforts designed to determine the best content for helping to create adaptable medical teams through team training efforts. For effective adaptation, we suggest ad hoc teams should be trained on generalizable teamwork skills, to share just "enough" and the "right" information, to engage in shared leadership, and to shift from explicit to implicit coordination. Our overarching goal was to present what is known from the general research literature on successful team adaptation to membership changes, and to propose a research agenda to evaluate whether findings generalize to member changes in medical teams.

Responsiveness of the frontal EMG for monitoring the sedation state of critically ill patients.

BACKGROUND: Excessive sedation is associated with adverse patient outcomes during critical illness, and a validated monitoring technology could improve care. We developed a novel method, the responsiveness index (RI) of the frontal EMG. We compared RI data with Ramsay clinical sedation assessments in general and cardiac intensive care unit (ICU) patients. METHODS: We developed the algorithm by iterative analysis of detailed observational data in 30 medical-surgical ICU patients and described its performance in this cohort and 15 patients recovering from scheduled cardiac surgery. Continuous EMG data were collected via frontal electrodes and RI data compared with modified Ramsay sedation state assessments recorded regularly by a blinded trained observer. RI performance was compared with Entropy™ across Ramsay categories to assess validity. RESULTS: RI correlated well with the Ramsay category, especially for the cardiac surgery cohort (general ICU patients ρ=0.55; cardiac surgery patients ρ=0.85, both P<0.0001). Discrimination across all Ramsay categories was reasonable in the general ICU patient cohort [P(K)=0.74 (sem 0.02)] and excellent in the cardiac surgery cohort [P(K)=0.92 (0.02)]. Discrimination between 'lighter' vs 'deeper' (Ramsay 1-3 vs 4-6) was good for general ICU patients [P(K)=0.80 (0.02)] and excellent for cardiac surgery patients [P(K)=0.96 (0.02)]. Performance was significantly better than Entropy™. Examination of individual cases suggested good face validity. CONCLUSIONS: RI of the frontal EMG has promise as a continuous sedation state monitor in critically ill patients. Further investigation to determine its utility in ICU decision-making is warranted.

The rs4774 CIITA missense variant is associated with risk of systemic lupus erythematosus.

The major histocompatibility complex (MHC) class II transactivator gene (CIITA) encodes an important transcription factor required for human leukocyte antigens (HLA) class II MHC-restricted antigen presentation. MHC genes, including the HLA class II DRB1*03:01 allele, are strongly associated with systemic lupus erythematosus (SLE). Recently the rs4774 CIITA missense variant (+1632G/C) was reported to be associated with susceptibility to multiple sclerosis. In the current study, we investigated CIITA, DRB1*03:01 and risk of SLE using a multi-stage analysis. In stage 1, 9 CIITA variants were tested in 658 cases and 1363 controls (N=2021). In stage 2, rs4774 was tested in 684 cases and 2938 controls (N=3622). We also performed a meta-analysis of the pooled 1342 cases and 4301 controls (N=5643). In stage 1, rs4774(*)C was associated with SLE (odds ratio (OR)=1.24, 95% confidence interval (95% CI)=1.07-1.44, P=4.2 × 10(-3)). Similar results were observed in stage 2 (OR=1.16, 95% CI=1.02-1.33, P=8.5 × 10(-3)) and the meta-analysis of the combined data set (OR=1.20, 95% CI=1.09-1.33, P(meta)=2.5 × 10(-4)). In all three analyses, the strongest evidence for association between rs4774(*)C and SLE was present in individuals who carried at least one copy of DRB1*03:01 (P(meta)=1.9 × 10(-3)). Results support a role for CIITA in SLE, which appears to be stronger in the presence of DRB1*03:01.

CIITA is not associated with risk of developing rheumatoid arthritis.

The major histocompatibility complex (MHC) class II transactivator gene (CIITA) encodes an important transcription factor regulating genes required for human leukocyte antigen (HLA) class II MHC-restricted antigen presentation. MHC genes, particularly HLA class II, are strongly associated with risk of developing rheumatoid arthritis (RA). Given the strong biological relationship between CIITA and HLA class II genes, a comprehensive investigation of CIITA variation in RA was conducted. This study tested 31 CIITA single-nucleotide polymorphisms in 2542 RA cases and 3690 controls (N=6232). All individuals were of European ancestry, as determined by ancestry informative genetic markers. No evidence for association between CIITA variation and RA was observed after a correction for multiple testing was applied. This is the largest study to fully characterize common genetic variation in CIITA, including an assessment of haplotypes. Results exclude even a modest role for common CIITA polymorphisms in susceptibility to RA.

Do simple ventilation and gas exchange measurements predict early successful weaning from respiratory support in unselected general intensive care patients?

BACKGROUND: The value of respiratory variables as weaning predictors in the intensive care unit (ICU) is controversial. We evaluated the ability of tidal volume (Vt(exp)), respiratory rate (f), minute volume (MV(exp)), rapid shallow breathing index (f/Vt), inspired-expired oxygen concentration difference [(I-E)O(2)], and end-tidal carbon dioxide concentration (Pe'(co(2))) at the end of a weaning trial to predict early weaning outcomes. METHODS: Seventy-three patients who required >24 h of mechanical ventilation were studied. A controlled pressure support weaning trial was undertaken until 5 cm H(2)O continuous positive airway pressure or predefined criteria were reached. The ability of data from the last 5 min of the trial to predict whether a predefined endpoint indicating discontinuation of ventilator support within the next 24 h was evaluated. RESULTS: Pre-test probability for achieving the outcome was 44% in the cohort (n=32). Non-achievers were older, had higher APACHE II and organ failure scores before the trial, and higher baseline arterial H(+) concentrations. The Vt, MV, f, and f/Vt had no predictive power using a range of cut-off values or from receiver operating characteristic (ROC) analysis. The [I-E]O(2) and Pe'(co(2)) had weak discriminatory power [area under the ROC curve: [I-E]O(2) 0.64 (P=0.03); Pe'(co(2)) 0.63 (P=0.05)]. Using best cut-off values for [I-E]O(2) of 5.6% and Pe'(co(2)) of 5.1 kPa, positive and negative likelihood ratios were 2 and 0.5, respectively, which only changed the pre- to post-test probability by about 20%. CONCLUSIONS: In unselected ICU patients, respiratory variables predict early weaning from mechanical ventilation poorly.

A candidate gene study of CLEC16A does not provide evidence of association with risk for anti-CCP-positive rheumatoid arthritis.

CLEC16A, a putative immunoreceptor, was recently established as a susceptibility locus for type I diabetes and multiple sclerosis. Subsequently, associations between CLEC16A and rheumatoid arthritis (RA), Addison's disease and Crohn's disease have been reported. A large comprehensive and independent investigation of CLEC16A variation in RA was pursued. This study tested 251 CLEC16A single-nucleotide polymorphisms in 2542 RA cases (85% anti-cyclic citrullinated peptide (anti-CCP) positive) and 2210 controls (N=4752). All individuals were of European ancestry, as determined by ancestry informative genetic markers. No evidence for significant association between CLEC16A variation and RA was observed. This is the first study to fully characterize common genetic variation in CLEC16A including assessment of haplotypes and gender-specific effects. The previously reported association between RA and rs6498169 was not replicated. Results show that CLEC16A does not have a prominent function in susceptibility to anti-CCP-positive RA.

Supervised machine learning and logistic regression identifies novel epistatic risk factors with PTPN22 for rheumatoid arthritis.

Investigating genetic interactions (epistasis) has proven difficult despite the recent advances of both laboratory methods and statistical developments. With no 'best' statistical approach available, combining several analytical methods may be optimal for detecting epistatic interactions. Using a multi-stage analysis that incorporated supervised machine learning and methods of association testing, we investigated epistatic interactions with a well-established genetic factor (PTPN22 1858T) in a complex autoimmune disease (rheumatoid arthritis (RA)). Our analysis consisted of four principal stages: Stage I (data reduction)-identifying candidate chromosomal regions in 292 affected sibling pairs, by predicting PTPN22 concordance using multipoint identity-by-descent probabilities and a supervised machine learning algorithm (Random Forests); Stage II (extension analysis)-testing detailed genetic data within candidate chromosomal regions for epistasis with PTPN22 1858T in 677 cases and 750 controls using logistic regression; Stage III (replication analysis)-confirmation of epistatic interactions in 947 cases and 1756 controls; Stage IV (combined analysis)-a pooled analysis including all 1624 RA cases and 2506 control subjects for final estimates of effect size. A total of seven replicating epistatic interactions were identified. SNP variants within CDH13, MYO3A, CEP72 and near WFDC1 showed significant evidence for interaction with PTPN22, affecting susceptibility to RA.

Analysis of maternal-offspring HLA compatibility, parent-of-origin and non-inherited maternal effects for the classical HLA loci in type 1 diabetes.

AIM: Type 1 diabetes (T1D) is a complex trait for which variation in the classical human leucocyte antigen (HLA) loci within the Major Histocompatibility Complex (MHC) significantly influences disease risk. To date, HLA class II DR-DQ genes confer the strongest known genetic effect in T1D. HLA loci may also influence T1D through additional inherited or non-inherited effects. Evidence for the role of increased maternal-offspring HLA compatibility, and both parent-of-origin (POO) and non-inherited maternal HLA (NIMA) effects in autoimmune disease has been previously established. The current study tested hypotheses that classical HLA loci influence T1D through these mechanisms, in addition to genetic transmission of particular risk alleles. METHODS: The Type 1 Diabetes Genetics Consortium (T1DGC) cohort was of European descent and consisted of 2271 affected sib-pair families (total n = 11 023 individuals). Class I genes HLA-A, Cw and B, and class II genes HLA-DRB1, DQA1, DQB1, DPA1 and DPB1 were studied. The pedigree disequilibrium test was used to examine transmission of HLA alleles to individuals with T1D. Conditional logistic regression was used to model compatibility relationships between mother-offspring and father-offspring for all HLA loci. POO and NIMA effects were investigated by comparing frequencies of maternal and paternal transmitted and non-transmitted HLA alleles for each locus. Analyses were also stratified by gender of T1D-affected offspring. RESULTS: Strong associations were observed for all classical HLA loci except for DPA1, as expected. Compatibility differences between mother-offspring and father-offspring were not observed for any HLA loci. Furthermore, POO and NIMA HLA effects influencing T1D were not present. CONCLUSIONS: Maternal-offspring HLA compatibility, POO and NIMA effects for eight classical HLA loci were investigated. Results suggest that these HLA-related effects are unlikely to play a major role in the development of T1D.

Genetic variation in nitric oxide synthase 2A (NOS2A) and risk for multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system with a strong genetic component. Variation in the major histocompatibility complex on chromosome 6p21, specifically the HLA-DRB1*15 haplotype, is the strongest genetic factor for MS, yet it is estimated to account for only a portion of risk for the disease. Previous evidence has implicated the nitric oxide synthase gene (NOS2A) encoding inducible NOS on chromosome 17q11 as a potential MS susceptibility gene. To determine whether variation in the NOS2A gene contributes to MS risk, we investigated a total of 50 polymorphisms within or flanking the locus for evidence of association using a comprehensive analytical strategy. A total of 6265 members from 1858 well-characterized MS families were utilized. No evidence for overtransmission of any individual single-nucleotide polymorphism allele or haplotype to the MS-affected individuals was observed. Furthermore, different transmission rates were not observed in either DRB1*15-positive or DRB1*15-negative family subgroups, or when extreme clinical outcomes characterizing disease progression were examined. The very largest study of NOS2A variation in MS, to date, excludes even a modest role for this locus in susceptibility.

Men transmit MS more often to their children vs women: the Carter effect.

OBJECTIVE: Multiple sclerosis (MS) is approximately twice as common among women as men. If men have greater physiologic resistance to MS, they might theoretically require stronger genetic predisposition than women to overcome this resistance. In this circumstance, men would be expected to transmit the disease more often to their children, a phenomenon known as the Carter effect. The authors evaluated whether the Carter effect is present in MS. METHODS: The authors studied 441 children (45 with definite MS) of an affected father or mother (197 families of interest) from 3598 individuals in 206 multiplex pedigrees. The authors compared transmission of MS from affected men with transmission from affected women. RESULTS: Fathers with MS transmitted the disease to their children more often (transmitted: 18, not transmitted: 99) than mothers with MS (transmitted: 27, not transmitted: 296) (p = 0.032; OR: 1.99, 95% CI: 1.05, 3.77). Adjusting for both the sex of the affected child and multiple transmissions from a single affected parent, the sex of the affected parent remained as an independent risk factor for transmission of MS to children, fathers transmitting more often than mothers (p = 0.036; OR: 2.21, 95% CI: 1.05, 4.63). CONCLUSIONS: The authors have demonstrated the Carter effect in multiple sclerosis (MS). These observations may be explained by greater genetic loading in men that leads to relative excess paternal vs maternal transmission. Linkage analysis in genetic studies of MS may be more informative if patrilineal transmission were given additional weighting.

APOE epsilon variation in multiple sclerosis susceptibility and disease severity: some answers.

BACKGROUND: Previous studies have examined the role of APOE variation in multiple sclerosis (MS), but have lacked the statistical power to detect modest genetic influences on risk and disease severity. The meta- and pooled analyses presented here utilize the largest collection, to date, of MS cases, controls, and families genotyped for the APOE epsilon polymorphism. METHODS: Studies of MS and APOE were identified by searches of PubMed, Biosis, Web of Science, Cochrane Review, and Embase. When possible, authors were contacted for individual genotype data. Meta-analyses of MS case-control data and family-based analyses were performed to assess the association of APOE epsilon genotype with disease risk. Pooled analyses of MS cases were also performed to assess the influence of APOE epsilon genotype on disease severity. RESULTS: A total of 22 studies (3,299 MS cases and 2,532 controls) were available for meta-analysis. No effect of epsilon2 or epsilon4 status on MS risk was observed (summary OR 1.14, 95% CI 0.96-1.34 and OR 0.89, 95% CI 0.78-1.01). Results obtained from analyses of APOE genotypes in 1,279 MS families were also negative (p = 0.61). Finally, results from pooled analyses of 4,048 MS cases also argue strongly that APOE epsilon status does not distinguish a relapsing-remitting from primary progressive disease course, or influence disease severity, as measured by the Expanded Disability Status Scale and disease duration. CONCLUSION: Overall, these findings do not support a role for APOE in multiple sclerosis, and underscore the importance of using large sample sizes to detect modest genetic effects, particularly in studies of genotype-phenotype relationships.

Risk of fracture among women who lose bone density during treatment with alendronate. The Fracture Intervention Trial.

It is commonly believed that the response to treatment in patients on alendronate is proportional to the increase in bone mineral density (BMD), and that those who lose BMD during treatment might not respond to treatment. In the Fracture Intervention Trial 6,459 women were randomly assigned to treatment with alendronate or placebo; BMD was measured annually, and new spine fractures were assessed by lateral spine films, taken at baseline and end of follow-up. Among subjects who took at least 70% of the study drug (5,220 women), we compared reductions in risk of spine fractures at end of follow-up (3 or 4 years) within various levels of change in total hip and spine BMD after 1 and 2 years of treatment, after adjustment for differences in characteristics between the treatment and control groups. Women "losing" BMD at the lumbar spine (0% to 4%) while on alendronate had a reduction of 60% in vertebral fracture risk [OR = 0.40 (0.16, 0.99)] compared to their counterparts in the placebo group. The few women that lost more than 4% did not have a significant benefit [OR = 0.15 (0.02, 1.29)]. Those who "gained" BMD (0% to 4%) during treatment had a reduction in risk of 51% [OR = 0.49 (0.30, 0.78)]. Similarly, women who "lost" total hip BMD (0% to 4%) during the first year on alendronate had a 53% decreased risk of vertebral fracture compared to their controls taking placebo [OR = 0.47 (0.27, 0.81)], whereas those "gaining" BMD (0% to 4%) had a comparable risk reduction [OR = 0.49 (0.34, 0.71)]. This was not observed for the few women who lost more than 4% [OR = 0.61 (0.11, 3.45)]. Patients who lost BMD at both the hip and spine were not protected by alendronate. Among patients who adhere to treatment with alendronate, even those who lose BMD benefit from a substantial reduction in risk of vertebral fracture. So, the reduction in bone turnover induced by alendronate might be more important than BMD changes. The few women who lose the most BMD (more than 4% per year) might not benefit from the treatment.

Multiple mechanisms for oxygen-induced regulation of the Clara cell secretory protein gene.

The Clara cell secretory protein (CCSP) imparts a protective effect to the lung during oxidant injury. However, exposure to supplemental oxygen, a common therapeutic modality for lung disease, represses the expression of CCSP in the adult mouse lung. We investigated the mechanisms of hyperoxia-induced repression of the mouse CCSP promoter. Deletion experiments in vivo and in vitro indicated that the hyperoxia-responsive elements are localized to the proximal -166 bp of the CCSP promoter. Electrophoretic mobility shift and supershift analyses demonstrated increased binding of c-Jun at the activator protein-1 site, increased binding of CCAAT/enhancer binding protein (C/EBP) beta at the C/EBP sites, and decreased binding at the Nkx2.1 sites. Western analyses revealed that hyperoxia exposure induced an increase in the expression of the C/EBPbeta isoform liver-inhibiting protein (LIP) and an increase in cytoplasmic Nkx2.1. Cotransfection of LIP or c-Jun expression plasmids decreased the transcriptional activity of the proximal -166-bp CCSP promoter. These observations suggest that hyperoxia-induced repression of the CCSP gene is mediated, at least in part, at the level of transcription and that multiple mechanisms mediate this repression. Moreover, these novel observations may provide insights for generation of therapeutic interventions for the amelioration of oxidant-induced lung injury.

Transcriptional regulation of CCSP by interferon-gamma in vitro and in vivo.

Interferon gamma (IFN-gamma), a potent cytokine inducing a wide range of immunologic activities, is increased in the airway secondary to viral infection or during an inflammatory response. This increase in IFN-gamma concentration may alter the expression of specific airway epithelial cell genes that regulate adaptation of airway inflammatory responses. One protein induced by IFN-gamma is Clara cell secretory protein (CCSP), which may contribute to the attenuation of airway inflammation. This study was done to investigate the molecular mechanism by which IFN-gamma stimulates the expression of the CCSP gene in mouse transformed Clara cells and transgenic mice. Deletion mapping and linker-scanning mutations demonstrated that IFN-gamma-induced expression of CCSP was regulated, in part, at the level of transcription. In vitro and in vivo studies verified that the minimal IFN-gamma-responsive segment was localized to the proximal 166 bp of the 5'-flanking region. Additionally, IFN-gamma-induced expression of CCSP was mediated indirectly through an interferon regulatory factor-1-mediated increase in hepatocyte nuclear factor-3beta.

Clara cell secretory protein oxidation and expression in premature infants who develop bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects prematurely born infants and appears to evolve in part from early inflammatory responses in the lung. The inflammatory responses have been associated with protein and lipid oxidation in tracheal aspirate fluids. The present study was designed to test the hypothesis that in the first week of life specific oxidations and/ or altered expressions of proteins would be observed in tracheal aspirate fluids in infants who would subsequently develop BPD. We obtained tracheal aspirate fluids on Days of life 1, 3, and 6 from infants born at < or = 29 wk gestation, incubated the fluids with 2,4-dinitrophenylhyrazine (DNPH), separated the proteins electrophoretically, and assessed DNPH reactivity by immunonblots. DNPH reactivity of a protein that was identified as Clara cell secretory protein (CCSP) was observed more consistently in tracheal aspirate fluids from infants who later developed BPD than from infants who did not develop BPD. Tracheal aspirate fluid levels of immunoreactive CCSP were also lower on Day of life 1 in infants who developed BPD than in those who did not develop BPD. Increased CCSP oxidation and decreased immunoreactive CCSP expression in infants who subsequently developed BPD suggest that Clara cell function and CCSP expression may be critical for normal bronchoalveolar fluid homeostasis and that maintaining CCSP expression and function may be useful goals for targeted therapies for inhibition of the development of BPD.

Detection of microorganisms in the tracheal aspirates of preterm infants by polymerase chain reaction: association of adenovirus infection with bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is recognized as an important cause of morbidity and mortality in preterm infants. Because the role of congenital infections in BPD has been debated, the purpose of this study was to test the hypothesis that detection of infectious agents in tracheal aspirate samples was associated with the development of BPD. Tracheal aspirate samples were obtained within the 1st week of life and screened by polymerase chain reaction for adenovirus, cytomegalovirus, parvovirus, enteroviruses, Ureaplasma urealyticum, Mycoplasma hominis, Mycoplasma pneumoniae, and Chlamydia species. BPD was defined as persistent oxygen dependence at 28 d of age and 36 wk postconceptional age (PCA). Infants that expired before these time points were excluded from statistical analysis. Out of 89 infants studied, at 28 d of life, 13 had expired, 45 had BPD, and 31 had no BPD (controls). At 36 wk PCA, 15 infants expired, 39 still had BPD, and 35 did not. A significant increase in the frequency of adenovirus genome was identified in BPD patients compared with controls, both at 28 d of life (12/45 = 27% versus 1/31 = 3%: p< or =0.01) and at 36 wk PCA (10/39 = 29% versus 2/35 = 6%: p = 0.01). Other microorganisms were rarely detected and not associated with the development of BPD. This is the first study reporting the frequency of detection of adenovirus DNA in tracheal aspirate samples obtained during the 1st week of life from infants with BPD and suggests that prenatal acquisition may be important in the development of BPD.

Physiological regulation of uteroglobin/CCSP expression.

Uteroglobin/CCSP is expressed specifically in the Clara cells. This allows the gene to be used as a marker to identify the elements regulating the physiologic and cell-specific expression of this gene. The regulation of UG/CCSP by IFN-gamma was shown to be at the level of the proximal promoter by the upregulation of HNF3 beta. This has allowed the determination of the factors responsible for the expression of UG/CCSP.