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S Kaplan

Publications and source records attributed to S Kaplan.

At least 91 records · Page 5Linked to original sources

A decision theory perspective on the disposal of high-level radioactive waste.

In this paper the problem of high-level nuclear waste disposal is viewed as a five-stage, cascaded decision problem. The first four of these decisions having essentially been made, the work of recent years has been focused on the fifth stage, which concerns specifics of the repository design. The probabilistic performance assessment (PPA) work is viewed as the outcome prediction for this stage, and the site characterization work as the information gathering option. This brief examination of the proposed Yucca Mountain repository through a decision analysis framework resulted in three conclusions: (1) A decision theory approach to the process of selecting and characterizing Yucca Mountain would enhance public understanding of the issues and solutions to high-level waste management; (2) engineered systems are an attractive alternative to offset uncertainties in the containment capability of the natural setting and should receive greater emphasis in the design of the repository; and (3) a strategy of "waste management" should be adopted, as opposed to "waste disposal," as it allows for incremental confirmation and confidence building of a permanent solution to the high-level waste problem.

Bayes Theorem↗

Multiple chromosomes in bacteria. The yin and yang of trp gene localization in Rhodobacter sphaeroides 2.4.1.

The existence of multiple chromosomes in bacteria has been known for some time. Yet the extent of functional solidarity between different chromosomes remains unknown. To examine this question, we have surveyed the well-described genes of the tryptophan biosynthetic pathway in the multichromosomal photosynthetic eubacterium Rhodobacter sphaeroides 2.4.1. The genome of this organism was mutagenized using Tn5, and strains that were auxotrophic for tryptophan (Trp(-)) were isolated. Pulsed-field gel mapping indicated that Tn5 insertions in both the large (3 Mb CI) and the small (0.9 Mb CII) chromosomes created a Trp(-) phenotype. Sequencing the DNA flanking the sites of the Tn5 insertions indicated that the genes trpE-yibQ-trpGDC were at a locus on CI, while genes trpF-aroR-trpB were at locus on CII. Unexpectedly, trpA was not found downstream of trpB. Instead, it was placed on the CI physical map at a locus 1.23 Mb away from trpE-yibQ-trpGDC. To relate the context of the R. sphaeroides trp genes to those of other bacteria, the DNA regions surrounding the trp genes on both chromosomes were sequenced. Of particular significance was the finding that rpsA1, which encodes ribosomal protein S1, and cmkA, which encodes cytidylate monophosphate kinase, were on CII. These genes are considered essential for translation and chromosome replication, respectively. Southern blotting suggested that the trp genes and rpsA1 exist in single copy within the genome. To date, this topological organization of the trp "operon" is unique within a bacterial genome. When taken with the finding that CII encodes essential housekeeping functions, the overall impression is one of close regulatory and functional integration between these chromosomes.

Chromosome Mapping↗

Genomic complexity among strains of the facultative photoheterotrophic bacterium Rhodobacter sphaeroides.

Pulsed-field gel electrophoresis following the use of rare cutting restriction endonucleases together with Southern hybridization, using markers distributed on chromosomes I and II of Rhodobacter sphaeroides 2.4.1, has been used to examine approximately 25 strains of R. sphaeroides in an effort to assess the occurrence of genome complexity in these strains. The results suggest that genome complexity is widespread and is accompanied by substantial genomic heterogeneity.

Cloning, Molecular↗

Alcohol availability and homicide in New Orleans: conceptual considerations for small area analysis of the effect of alcohol outlet density.

OBJECTIVE: To determine the geographic relation between homicide rate and two competing measures of exposure to alcohol outlets, alcohol outlets per square mile and alcohol outlets per person. METHOD: Homicides occurring in 1994 and 1995 and on-sale and off-sale alcohol outlets with active 1995 licenses were geocoded by address for aggregation at the census tract level. Ecologic analysis of the 155 urban residential census tracts in New Orleans was conducted with controls for potential sociodemographic confounders (% black, % adults unemployed, % unmarried households, and ratio males 15-24/males 35-44). RESULTS: After logarithmic transformation of all study variables, sociodemographic confounders alone accounted for 58% (R2 = .58) of the variance of homicide rates. Adding off-sale alcohol outlet density to the models, measured (beta +/- SE) either as outlets per square mile (beta = .211 +/- .062) or outlets per person (beta = .244 +/- .063), yielded strong geographic relations with homicide and increased the amount of variance explained (R2 = .62). A 10% higher off-sale outlet density accounted for a 2.4% higher homicide rate. CONCLUSIONS: Both off-sale alcohol outlets per square mile and off-sale outlets per person demonstrate strong geographic associations with homicide rates among urban residential census tracts in New Orleans. These findings suggest that communities faced with high rates of assaultive violence might consider policy interventions that address alcohol outlet related factors.

Adolescent↗

Cardiac complications in children with human immunodeficiency virus infection. Pediatric Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection (P2C2 HIV) Study Group, National Heart, Lung, and Blood Institute.

OBJECTIVE: Although numerous cardiac abnormalities have been reported in HIV-infected children, precise estimates of the incidence of cardiac disease in these children are not well-known. The objective of this report is to describe the 2-year cumulative incidence of cardiac abnormalities in HIV-infected children. METHODOLOGY DESIGN: Prospective cohort (Group I) and inception cohort (Group II) study design. SETTING: A volunteer sample from 10 university and public hospitals. PARTICIPANTS: Group I consisted of 205 HIV vertically infected children enrolled at a median age of 22 months. This group was comprised of infants and children already known to be HIV-infected at the time of enrollment in the study. Most of the children were African-American or Hispanic and 89% had symptomatic HIV infection at enrollment. The second group included 611 neonates born to HIV-infected mothers, enrolled during fetal life or before 28 days of age (Group II). In contrast to the older Group I children, all the Group II children were enrolled before their HIV status was ascertained. INTERVENTIONS: According to the study protocol, children underwent a series of cardiac evaluations including two-dimensional echocardiogram and Doppler studies of cardiac function every 4 to 6 months. They also had a 12- or 15-lead surface electrocardiogram (ECG), 24-hour ambulatory ECG monitoring, and a chest radiograph every 12 months. OUTCOME MEASURES: Main outcome measures were the cumulative incidence of an initial episode of left ventricular (LV) dysfunction, cardiac enlargement, and congestive heart failure (CHF). Because cardiac abnormalities tended to cluster in the same patients, we also determined the number of children who had cardiac impairment which we defined as having either left ventricular fractional shortening (LV FS) </=25% after 6 months of age, CHF, or treatment with cardiac medications. RESULTS: CARDIAC ABNORMALITIES: In Group I children (older cohort), the prevalence of decreased LV function (FS </=25%) was 5.7% and the 2-year cumulative incidence (excluding prevalent cases) was 15.3%. The prevalence of echocardiographic LV enlargement (LV end-diastolic dimension z score >2) at the time of the first echocardiogram was 8. 3%. The cumulative incidence of LV end-diastolic enlargement was 11. 7% after 2 years. The cumulative incidence of CHF and/or the use of cardiac medications was 10.0% in Group I children. There were 14 prevalent cases of cardiac impairment (LV FS </=25% after 6 months of age, CHF, or treatment with cardiac medications) in Group I. After excluding these prevalent cases, the 2-year cumulative incidence of cardiac impairment was 19.1% among Group I children and 80.9% remained free of cardiac impairment after 2 years of follow-up. Within Group II (neonatal cohort), the 2-year cumulative incidence of decreased LV FS was 10.7% in the HIV-infected children compared with 3.1% in the HIV-uninfected children. LV dilatation was also more common in Group II infected versus uninfected children (8.7% vs 2.1%). The cumulative incidence of CHF and/or the use of cardiac medications was 8.8% in Group II infected versus 0.5% in uninfected subjects. The 1- and 2-year cumulative incidence rates of cardiac impairment for Group II infected children were 10.1% and 12.8%, respectively, with 87.2% free of cardiac impairment after the first 2 years of life. MORTALITY: In the Group I cohort, the 2-year cumulative death rate from all causes was 16.9% [95% CI: 11.7%-22. 1%]. The 1- and 2-year mortality rates after the diagnosis of CHF (Kaplan-Meier estimates) were 69% and 100%, respectively. In the Group II cohort, the 2-year cumulative death rate from all causes was 16.3% [95% CI: 8.8%-23.9%] in the HIV-infected children compared with no deaths among the 463 uninfected Group II children. Two of the 4 Group II children with CHF died during the 2-year observation period and 1 more died within 2 years of the diagnosis of CHF. The 2-year mortality rate after the

Adolescent↗

AppA, a redox regulator of photosystem formation in Rhodobacter sphaeroides 2.4.1, is a flavoprotein. Identification of a novel fad binding domain.

The AppA protein is required for increased photosystem gene expression upon transition of the facultatively photoheterotrophic bacterium Rhodobacter sphaeroides 2.4.1 from aerobic to anaerobic photosynthetic conditions. AppA shows no obvious similarity to proteins with established function. Genetic evidence suggests that its effect is exerted through modulation of the activity of the repressor PpsR, which controls expression of multiple photosystem genes. To gain insight into the nature of AppA involvement in redox-dependent photosystem gene expression, the appA gene was overexpressed in Escherichia coli. AppA was produced as insoluble inclusion bodies. The purified inclusion bodies were found to contain FAD. By overexpressing various deletion derivatives, we were able to localize the region of AppA sufficient for FAD binding to approximately 120 amino-terminal residues. To assess the role of FAD binding in AppA function, we constructed an AppA derivative lacking the entire FAD binding domain. Surprisingly, this derivative complemented the AppA null mutant undergoing transition from aerobic to anaerobic photosynthetic growth conditions almost to the same extent as the full-length AppA protein. When the sequence of the amino-terminal portion of AppA was examined, it was shown not to contain any known flavin binding motifs. However, two open reading frames of unknown function, showing significant similarity to the amino terminus of AppA, were identified, i.e. Synechocystis sp. Srl1694 and E. coli F403. The latter gene was amplified and overexpressed in E. coli, and the partially purified F403 protein was found to contain FAD as a cofactor. We have therefore concluded that the amino terminus of AppA represents a novel FAD binding domain present in a small group of bacterial proteins. The binding of FAD by AppA may be the first clue as to how this regulatory protein is involved in redox-regulated reactions.

Amino Acid Sequence↗

Prevalence of congenital cardiovascular malformations in children of human immunodeficiency virus-infected women: the prospective P2C2 HIV Multicenter Study. P2C2 HIV Study Group, National Heart, Lung, and Blood Institute, Bethesda, Maryland.

OBJECTIVES: The purpose of the study was to assess the effects of maternal HIV-1 (human immunodeficiency virus) infection and vertically transmitted HIV-1 infection on the prevalence of congenital cardiovascular malformations in children. BACKGROUND: In the United States, an estimated 7000 children are born to HIV-infected women annually. Previous limited reports have suggested an increase in the prevalence of congenital cardiovascular malformations in vertically transmitted HIV-infected children. METHODS: In a prospective longitudinal multicenter study, diagnostic echocardiograms were performed at 4-6-month intervals on two cohorts of children exposed to maternal HIV-1 infection: 1) a Neonatal Cohort of 90 HIV-infected, 449 HIV-uninfected and 19 HIV-indeterminate children; and 2) an Older HIV-Infected Cohort of 201 children with vertically transmitted HIV-1 infection recruited after 28 days of age. RESULTS: In the Neonatal Cohort, 36 lesions were seen in 36 patients, yielding an overall congenital cardiovascular malformation prevalence of 6.5% (36/558), with a 8.9% (8/90) prevalence in HIV-infected children and a 5.6% (25/449) prevalence in HIV-uninfected children. Two children (2/558, 0.4%) had cyanotic lesions. In the Older HIV-Infected Cohort, there was a congenital cardiovascular malformation prevalence of 7.5% (15/201). The distribution of lesions did not differ significantly between the groups. CONCLUSIONS: There was no statistically significant difference in congenital cardiovascular malformation prevalence in HIV-infected versus HIV-uninfected children born to HIV-infected women. With the use of early screening echocardiography, rates of congenital cardiovascular malformations in both the HIV-infected and HIV-uninfected children were five- to ten-fold higher than rates reported in population-based epidemiologic studies but not higher than in normal populations similarly screened. Potentially important subclinical congenital cardiovascular malformations were detected.

Cohort Studies↗

Spontaneous skin ulceration and defective T cell function in CD18 null mice.

A null mutation was prepared in the mouse for CD18, the beta2 subunit of leukocyte integrins. Homozygous CD18 null mice develop chronic dermatitis with extensive facial and submandibular erosions. The phenotype includes elevated neutrophil counts, increased immunoglobulin levels, lymphadenopathy, splenomegaly, and abundant plasma cells in skin, lymph nodes, gut, and kidney. Very few neutrophils were found in spontaneously occurring skin lesions or with an induced toxic dermatitis. Intravital microscopy in CD18 null mice revealed a lack of firm neutrophil attachment to venules in the cremaster muscle in response to N-formyl- methionyl-leucyl-phenylalanine. A severe defect in T cell proliferation was found in the CD18 null mice when T cell receptors were stimulated either by staphylococcal enterotoxin A or by major histocompatibility complex alloantigens demonstrating a greater role of CD11/CD18 integrins in T cell responses than previously documented. The null mice are useful for delineating the functions of CD18 in vivo.

Animals↗

Left ventricular structure and function in children infected with human immunodeficiency virus: the prospective P2C2 HIV Multicenter Study. Pediatric Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection (P2C2 HIV) Study Group.

BACKGROUND: The frequency of, course of, and factors associated with cardiovascular abnormalities in pediatric HIV are incompletely understood. METHODS AND RESULTS: A baseline echocardiogram (median age, 2.1 years) and 2 years of follow-up every 4 months were obtained as part of a prospective study on 196 vertically HIV-infected children. Age- or body surface area-adjusted z scores were calculated by use of data from normal control subjects. Although 88% had symptomatic HIV infection, only 2 had CHF at enrollment, with a 2-year cumulative incidence of 4.7% (95% CI, 1.5% to 7.9%). All mean cardiac measurements were abnormal at baseline (decreased left ventricular fractional shortening [LV FS] and contractility and increased heart rate and LV dimension, mass, and wall stresses). Most of the abnormal baseline cardiac measurements correlated with depressed CD4 cell count z scores and the presence of HIV encephalopathy. Heart rate and LV mass showed significantly progressive abnormalities, whereas FS and contractility tended to decline. No association was seen between longitudinal changes in FS and CD4 cell count z score. Children who developed encephalopathy during follow-up had depressed initial FS, and FS continued to decline during follow-up. CONCLUSIONS: Subclinical cardiac abnormalities in HIV-infected children are common, persistent, and often progressive. Dilated cardiomyopathy (depressed contractility and dilatation) and inappropriate LV hypertrophy (elevated LV mass in the setting of decreased height and weight) were noted. Depressed LV function correlated with immune dysfunction at baseline but not longitudinally, suggesting that the CD4 cell count may not be a useful surrogate marker of HIV-associated LV dysfunction. However, the development of encephalopathy may signal a decline in FS.

AIDS Dementia Complex↗

Postmortem blood tests for HIV, HBV, and HCV in a body donation program.

A retrospective analysis of the results of blood tests conducted on body donors received by the Anatomical Gift Registry of the Medical College of Wisconsin (MCW) was performed. Over the 5-year period from April 1992 through March 1997 a total of 785 body donors were tested for Human Immunodeficiency Virus (HIV) and Hepatitis B and C Viruses (HBV and HCV). Eighteen of the 785 donors (2.3%) tested positive for one of these infectious agents. Two donors were positive for HIV, six were positive for HBV and ten were positive for HCV. The death certificates and files of those donors who tested positive were reviewed and the results are presented here. Blood testing prior to the use of the body donors is an effective and reasonable way of identifying the presence of these infectious agents, thus reducing the risk to those who work with cadavers. The cost for the testing at MCW is about $60 per donor.

Aged↗

Fiberoptic endoscopic evaluation of swallowing with sensory testing (FEESST) in healthy controls.

The purpose of this study was to introduce a new method of bedside assessment of both the motor and sensory components of swallowing called fiberoptic endoscopic evaluation of swallowing with sensory testing (FEESST). This approach combines the established bedside endoscopic swallowing evaluation with a more recently described technique that allows objective determination of laryngopharyngeal (LP) sensory discrimination thresholds by delivering air pulse stimuli to the mucosa innervated by the superior laryngeal nerve via a flexible endoscope. A prospective study was conducted of FEESST in 20 healthy control subjects, mean age of 34 +/- 11 years. LP sensory thresholds were defined as either normal (< 4.0 mmHg air pulse pressure [APP]), moderate deficit (4.0-6.0 mmHg APP), or severe deficits (> 6.0 mmHg APP). Subsequent to LP sensory testing, food of varying consistencies, mixed with green food coloring, was given and attention was paid to spillage, laryngeal penetration, pharyngeal residue, aspiration, and reflux. Therapeutic maneuvers such as postural changes and airway protection techniques were performed on each subject to determine if the assessed swallowing parameters were affected by maneuvers. All patients completed the study; all had normal LP sensory discrimination thresholds (2.9 +/- 0.7 mmHg APP). There were no instances of spillage, laryngeal penetration, or aspiration. Two of 20 subjects had pharyngeal residue and 2 of 20 had reflux. Institution of therapeutic maneuvers resulted in a predictable change in the endoscopic view of the laryngopharyngeal anatomy. FEESST provides comprehensive, objective sensory and motor information about deglutition in the bedside setting and might have implications for the bedside diagnosis and management of patients with dysphagia.

Adult↗

Apparent blood stream origin of endothelial and smooth muscle cells in the neointima of long, impervious carotid-femoral grafts in the dog.

The purpose of this study was to determine whether endothelial and smooth muscle cells originating from the blood stream contribute to the endothelialization of impervious, small-caliber, long Dacron grafts used as extraanatomical bypasses in dogs. We implanted silicone-rubber-coated, permanently impervious grafts 64 to 77 cm long and 6 mm in diameter, made of externally supported knitted Dacron as unilateral carotid-femoral bypasses with distal femoral arteriovenous fistulae in 10 dogs for 3 months; sides were alternated between cases. Subjects received 162 mg/day of aspirin, and its effectiveness on platelet aggregation (PA) was evaluated and expressed as a PA score. Graft healing was studied by stereomicroscopy with silver nitrate staining, by light microscopy with hematoxylin-eosin and immunocytochemical staining for endothelial and smooth muscle cells, and by scanning and transmission electron microscopy. Five grafts were patent for 3 months and could be included in the healing study; the five occluded grafts thrombosed within 14 days. Although there was no transinterstitial tissue ingrowth from perigraft tissues into the impervious Dacron grafts, scattered islands of endothelial cells were conclusively demonstrated on graft flow surfaces 3 months after implantation. Average endothelial-like cell coverage of the flow surfaces was 15.6% +/- 3.8%, and alpha-actin-positive smooth muscle cells and microvessels were found beneath some of the endothelial islands. These findings suggest that blood stream-derived endothelial and smooth muscle cells play a role in the healing of the inner wall of Dacron grafts in the dog.

Animals↗

Cervical aortic arch with aneurysm formation.

Cervical aortic arch is a very rare anomaly presented as a pulsatile mass on the neck and usually with symptoms of dysphagia, cough and hoarseness. Rarer than the cervical aortic arch, is the aneurysm formation and, despite the equal sex distribution of cervical aortic arch, aneurysm formation always occurs in young females with only nine cases reported. We report herein a 24-year-old woman, diagnosed as cervical aortic arch with aneurysm formation due to basophilic degeneration, treated successfully with surgical intervention. To our knowledge no similar case has been reported.

Adult↗

Posttraumatic stress disorder and family functioning in adolescent cancer.

Twenty three adolescents with a history of cancer, 27 physically abused adolescents, and 23 healthy, nonabused adolescents were administered structured posttraumatic stress disorder (PTSD) interviews and self-report questionnaires regarding family functioning. Thirty five percent of adolescent cancer subjects met criteria for lifetime PTSD as compared to only 7% of the abused adolescents: 17% of the cancer subjects and 11% of the abuse subjects met criteria for current PTSD. Adolescents with cancer viewed their mothers and fathers as significantly more caring and more protective than the comparison and abused adolescents. Cancer subjects who met criteria for lifetime PTSD saw their families as significantly more chaotic than those who did not have PTSD. Eighty three percent of cancer subjects who had lifetime PTSD also had mothers who had PTSD.

Adolescent↗

Tidal volume perception in a C1-C2 tetraplegic subject is blocked by airway anesthesia.

We administered lidocaine aerosol intratracheal anesthesia to a ventilator-dependent, tracheostomized C1-C2 tetraplegic subject to determine its effect on her ability to detect small changes in tidal volume. A psychophysical test of volume detection was given before and immediately after a 20 percent lidocaine aerosol was delivered through the subject's cuffed tracheostomy tube. On each of three occasions, she reliably (p < .001) detected changes in tidal volume during a control period; on two of these occasions she could not detect the same volume after inhaling the anesthetic. On one occasion the anesthetic had no effect on volume perception, possibly because copious airway secretions interfered with lidocaine uptake. Subject-blinded control tests with saline aerosol inhalation did not affect detection. We concluded that this subject's tidal volume perception depended on mechanoreceptors in the lungs and thoracic airways and that local anesthetic interrupted these sensory signals when airway secretions were not excessive.

Adult↗

A methodological note on the selection of friends as controls.

A number of issues inherent in the selection of friends as controls in case-control studies are illustrated in the light of a recent dietary study, based on hospital and friend controls. Preselection of certain characteristics of the controls by the interviewee is almost unavoidable. The choice of controls to be used in a case-control study must reflect the nature and type of hypothesis which is being tested. Advantages and drawbacks of potential control groups must be weighted against each other.

Adult↗

Plasma nitrite and nitrate concentrations and multiple organ failure in pediatric sepsis.

OBJECTIVE: To determine whether plasma nitrite and nitrate concentrations are associated with the development of sepsis-induced multiple organ failure. DESIGN: Prospective study. SETTING: University children's hospital. PATIENTS: Fifty-three consecutive children meeting criteria for sepsis and not receiving exogenous sources of nitric oxide. INTERVENTIONS: Plasma nitrite and nitrate concentrations were measured, and the number of organs failing was scored using an organ failure index on the first 3 days of sepsis. MEASUREMENTS AND MAIN RESULTS: Children with three or more organs failing on day 3 of sepsis had higher plasma nitrite and nitrate concentrations than children who had resolution of failure of three or more organs by day 3 of sepsis (days 2 and 3) and children who never had three organs failing in the first 3 days of sepsis (days 1, 2, and 3). Children who developed sequential pulmonary/hepatic/renal organ failure had significantly higher plasma nitrite and nitrate concentrations (days 1, 2, and 3). Nonsurvivors had significantly higher plasma nitrite and nitrate concentrations (days 2 and 3) than survivors. Plasma nitrite and nitrate concentrations on day 1 predicted the development of persistent failure of three of more organs and sequential multiple organ failure but not mortality. CONCLUSION: Increased plasma nitrite and nitrate concentrations are associated with the development of multiple organ failure in pediatric sepsis.

Adolescent↗