bluuebunny/crossref_metadata_2025 huggingface dataset:
Polyphyletic Origin of Pyrrolizidine Alkaloids within the Asteraceae. Evidence from Differential Tissue Expression of Homospermidine Synthase
Authors: Anke Sven , Niemüller Daniel , Moll Stefanie , Hänsch Robert , Ober Dietrich
Published: December 2004

The evolution of pathways within plant secondary metabolism has been studied by using the pyrrolizidine alkaloids (PAs) as a model system. PAs are constitutively produced by plants as a defense against herbivores. The occurrence of PAs is restricted to certain unrelated families within the angiosperms. Homospermidine synthase (HSS), the first specific enzyme in the biosynthesis of the necine base moiety of PAs, was originally recruited from deoxyhypusine synthase, an enzyme involved in the posttranslational activation of the eukaryotic initiation factor 5A. Recently, this gene recruitment has been shown to have occurred several times independently within the angiosperms and even twice within the Asteraceae. Here, we demonstrate that, within these two PA-producing tribes of the Asteraceae, namely Senecioneae and Eupatorieae, HSS is expressed differently despite catalyzing the same step in PA biosynthesis. Within Eupatorium cannabinum, HSS is expressed uniformly in all cells of the root cortex parenchyma, but not within the endodermis and exodermis. Within Senecio vernalis, HSS expression has been previously identified in groups of specialized cells of the endodermis and the adjacent root cortex parenchyma. This expression pattern was confirmed for Senecio jacobaea as well. Furthermore, the expression of HSS in E. cannabinum is dependent on the development of the plant, suggesting a close linkage to plant growth.
Functional Analysis of Methylthioribose Kinase Genes in Plants
Authors: Sauter Margret , Cornell Kenneth A. , Beszteri Sára , Rzewuski Guillaume
Published: December 2004

Through a biochemical and a genetic approach, we have identified several plant genes encoding methylthioribose (MTR) kinase, an enzyme involved in recycling of methionine through the methylthioadenosine (MTA) cycle. OsMTK1, an MTR kinase from rice (Oryza sativa), is 48.6 kD in size and shows cooperative kinetics with a Vmax of 4.9 pmol/min and a K0.5 of 16.8 μm. MTR kinase genes are the first genes to be identified from the MTA cycle in plants. Insertional mutagenesis of the unique AtMTK gene in Arabidopsis (Arabidopsis thaliana) resulted in an inability of plants to grow on MTA as a supplemental sulfur source. MTK knock-out plants were not impaired in growth under standard conditions, indicating that the MTA cycle is a nonessential metabolic pathway in Arabidopsis when sulfur levels are replete. In rice, OsMTK genes were strongly up-regulated in shoots and roots when plants were exposed to sulfur starvation. Gene expression was largely unaffected by lack of nitrogen or iron in the nutrient solution, indicating that OsMTK regulation was linked specifically to sulfur metabolism.
The uncertainty of valuation
Authors: French Nick , Gabrielli Laura
Published: December 2004

Valuation is often said to be “an art not a science” but this relates to the techniques employed to calculate value not to the underlying concept itself. Valuation is the process of estimating price in the market place. Yet, such an estimation will be affected by uncertainties. These input uncertainties will translate into an uncertainty with the output figure, the valuation. The degree of the uncertainties will vary according to the level of market activity; the more active a market, the more credence will be given to the input information. In the UK at the moment the Royal Institution of Chartered Surveyors (RICS) is considering ways in which the uncertainty of the valuation can be conveyed to the use of the valuation, but as yet no definitive view has been taken apart from a single Guidance Note (GN5). One of the major problems is that valuation models (in the UK) are based on comparable information and rely on single inputs. They are not probability‐based, yet uncertainty is probability driven. This paper discusses the issues underlying uncertainty in valuations and suggests a probability‐based model (using Crystal Ball) to address the shortcomings of the current model.
Different risk measures: different portfolio compositions?
Authors: Byrne Peter , Lee Stephen
Published: December 2004

Traditionally, the measure of risk used in portfolio optimisation models is the variance. However, alternative measures of risk have many theoretical and practical advantages and it is peculiar therefore that they are not used more frequently. This may be because of the difficulty in deciding which measure of risk is best and any attempt to compare different risk measures may be a futile exercise until a common risk measure can be identified. To overcome this, another approach is considered, comparing the portfolio holdings produced by different risk measures, rather than the risk return trade‐off. In this way we can see whether the risk measures used produce asset allocations that are essentially the same or very different. The results indicate that the portfolio compositions produced by different risk measures vary quite markedly from measure to measure. These findings have a practical consequence for the investor or fund manager because they suggest that the choice of model depends very much on the individual's attitude to risk rather than any theoretical and/or practical advantages of one model over another.
The level of direct property in Hong Kong property company performance
Authors: Newell Graeme , Kwong Wing Chau , Siu Kei Wong
Published: December 2004

Hong Kong is one of the most dynamic property markets in the world, and now provides the economic gateway to China. Using style analysis, the level of direct property in Hong Kong property company performance is shown to be approximately 15 per cent over 1984‐2000, with the level of direct property increasing to approximately 25 per cent in recent years. The level of direct property in Hong Kong property company performance is significantly below that seen for the USA, Europe and Australia. This highlights a number of key strategic property investment issues over 1984‐2000, relating to the level of direct property in Hong Kong property company performance. Also assesses the level of direct property at the individual property company level, as well as the property company sector level, further emphasising the strategic role of Hong Kong property companies in an investment portfolio. This research complements the previous research by Brown and Chau on excess returns in the Hong Kong property market, as well as highlighting the issues and role of both direct and indirect property for inclusion in diversified investment portfolios; these being key areas of Gerald Brown's extensive property research agenda.
The valuation of specialised property
Authors: French Nick
Published: December 2004

Provides a brief overview of the methods that used in real estate valuation with a particular emphasis on the valuation of specialised property. Proposes that the underlying requirement is to estimate market value and that the role of the valuer is to choose the method that is the best model to achieve this objective. Concludes that a valuer must work with the recognised techniques and, in the case of specialised property, these are methods that go back to analysing value from first principles by identifying the value of the property to the business.
The Mentality of Crows: Convergent Evolution of Intelligence in Corvids and Apes
Authors: Emery Nathan J. , Clayton Nicola S.
Published: December 2004

Discussions of the evolution of intelligence have focused on monkeys and apes because of their close evolutionary relationship to humans. Other large-brained social animals, such as corvids, also understand their physical and social worlds. Here we review recent studies of tool manufacture, mental time travel, and social cognition in corvids, and suggest that complex cognition depends on a “tool kit” consisting of causal reasoning, flexibility, imagination, and prospection. Because corvids and apes share these cognitive tools, we argue that complex cognitive abilities evolved multiple times in distantly related species with vastly different brain structures in order to solve similar socioecological problems.
Organic Aerosol Growth Mechanisms and Their Climate-Forcing Implications
Authors: Maria Steven F. , Russell Lynn M. , Gilles Mary K. , Myneni Satish C. B.
Published: December 2004

Surface- and volume-limited chemical reactions on and in atmospheric aerosol particles cause growth while changing organic composition by 13 to 24% per day. Many of these particles contain carbonaceous components from mineral dust and combustion emissions in Africa, Asia, and North America and reveal reaction rates that are three times slower than those typically used in climate models. These slower rates for converting from volatile or hydrophobic to condensed and hygroscopic organic compounds increase carbonaceous particle burdens in climate models by 70%, producing organic aerosol climate forcings of as much as –0.8 watt per square meter cooling and +0.3 watt per square meter warming.
Leading-Edge Vortex Lifts Swifts
Authors: Videler J. J. , Stamhuis E. J. , Povel G. D. E.
Published: December 2004

The current understanding of how birds fly must be revised, because birds use their hand-wings in an unconventional way to generate lift and drag. Physical models of a common swift wing in gliding posture with a 60° sweep of the sharp hand-wing leading edge were tested in a water tunnel. Interactions with the flow were measured quantitatively with digital particle image velocimetry at Reynolds numbers realistic for the gliding flight of a swift between 3750 and 37,500. The results show that gliding swifts can generate stable leading-edge vortices at small (5° to 10°) angles of attack. We suggest that the flow around the arm-wings of most birds can remain conventionally attached, whereas the swept-back hand-wings generate lift with leading-edge vortices.
Transient Uplift After a 17th-Century Earthquake Along the Kuril Subduction Zone
Authors: Sawai Yuki , Satake Kenji , Kamataki Takanobu , Nasu Hiroo , Shishikura Masanobu , Atwater Brian F. , Horton Benjamin P. , Kelsey Harvey M. , Nagumo Tamotsu , Yamaguchi Masaaki
Published: December 2004

In eastern Hokkaido, 60 to 80 kilometers above a subducting oceanic plate, tidal mudflats changed into freshwater forests during the first decades after a 17th-century tsunami. The mudflats gradually rose by a meter, as judged from fossil diatom assemblages. Both the tsunami and the ensuing uplift exceeded any in the region's 200 years of written history, and both resulted from a shallow plate-boundary earthquake of unusually large size along the Kuril subduction zone. This earthquake probably induced more creep farther down the plate boundary than did any of the region's historical events.
Hypoxic pulmonary vasoconstriction: role of ion channels
Authors: Mauban Joseph R. H. , Remillard Carmelle V. , Yuan Jason X.-J.
Published: December 2004

Acute hypoxia induces pulmonary vasoconstriction and chronic hypoxia causes structural changes of the pulmonary vasculature including arterial medial hypertrophy. Electro- and pharmacomechanical mechanisms are involved in regulating pulmonary vasomotor tone, whereas intracellular Ca2+serves as an important signal in regulating contraction and proliferation of pulmonary artery smooth muscle cells. Herein, we provide a basic overview of the cellular mechanisms involved in the development of hypoxic pulmonary vasoconstriction. Our discussion focuses on the roles of ion channels permeable to K+and Ca2+, membrane potential, and cytoplasmic Ca2+in the development of acute hypoxic pulmonary vasoconstriction and chronic hypoxia-mediated pulmonary vascular remodeling.
Robert Boyle’s landmark book of 1660 with the first experiments on rarified air
Authors: West John B.
Published: December 2004

In 1660, Robert Boyle (1627–1691) published his landmark book New Experiments Physico-Mechanicall, Touching the Spring of the Air, and its Effects… in which he described the first controlled experiments of the effects of reducing the pressure of the air. Critical to this work was the development of an air pump by Boyle with Robert Hooke (1635–1703). For the first time, it was possible to observe physical and physiological processes at both normal and reduced barometric pressures. The air pump was described in detail, although the exact design of the critical piston is unclear. Boyle reported 43 separate experiments, which can conveniently be divided into 7 groups. The first experiments were on the “spring of the air,” that is the pressure developed by the air when its volume was changed. Several experiments described the behavior of the barometer invented by Torricelli just 16 years before when it was introduced into the low-pressure chamber. The behavior of burning candles was discussed, although this emphasized early misunderstandings of the nature of combustion. There were some physiological observations, although these were later extended by Boyle and Hooke. The effects of the low pressure on such diverse physical phenomena as magnetism, sound propagation, behavior of a pendulum, evolution of gases from liquids, and the behavior of smoke were described. This classic book is brimming with enthusiasm and fresh ideas even for today and deserves to be better known.
Two-Photon Microscopy of Cells and Tissue
Authors: Rubart Michael
Published: December 2004

Two-photon excitation fluorescence imaging provides thin optical sections from deep within thick, scattering specimens by way of restricting fluorophore excitation (and thus emission) to the focal plane of the microscope. Spatial confinement of two-photon excitation gives rise to several advantages over single-photon confocal microscopy. First, penetration depth of the excitation beam is increased. Second, because out-of-focus fluorescence is never generated, no pinhole is necessary in the detection path of the microscope, resulting in increased fluorescence collection efficiency. Third, two-photon excitation markedly reduces overall photobleaching and photodamage, resulting in extended viability of biological specimens during long-term imaging. Finally, localized excitation can be used for photolysis of caged compounds in femtoliter volumes and for diffusion measurements by two-photon fluorescence photobleaching recovery. This review aims to provide an overview of the use of two-photon excitation microscopy. Selected applications of this technique will illustrate its excellent suitability to assess cellular and subcellular events in intact, strongly scattering tissue. In particular, its capability to resolve differences in calcium dynamics between individual cardiomyocytes deep within intact, buffer-perfused hearts is demonstrated. Potential applications of two-photon laser scanning microscopy as applied to integrative cardiac physiology are pointed out.
Cross-Culture Comparison of Tax Morale and Tax Compliance: Evidence from Costa Rica and Switzerland
Authors: Torgler Benno
Published: December 2004

This paper analyzes the effects of internal and external social norms on tax morale and tax compliance behavior. Field data and data derived from laboratory experiments are used to examine tax morale and tax compliance behavior in Costa Rica and Switzerland. The results indicate that internal and external social norms have a significant effect on tax morale and tax compliance.
Work Relations Between Immigrants and Old-Timers in an Israeli Organization: Social Interactions and Inter-Group Attitudes
Authors: Remennick Larissa
Published: December 2004

Although immigrant workers have become an integral part of most organizations in immigrant-receiving countries, there is surprisingly little research on cross-cultural work relations, especially in the professional/white-collar sector. In Israel, where former Soviet immigrants comprise over 20 percent of the Jewish population, the presence of Russian-speaking workers and professionals is dense in almost every workplace.The current qualitative study is focused on everyday work relations and inter-group attitudes between long-time Israeli residents and recent Russian-speaking immigrants in the context of a medical organization. Twenty-five interviews with the veteran and new immigrant workers (conducted in Hebrew and in Russian) indicate that these groups diligently guard their social borders and separate identities, and share similar critical opinions on each other’s work ethic and competence. Conflicts arise around the issues of educational and work status gaps, relations with supervisors, and language use. The continuing use of Russian by immigrant workers is interpreted by Hebrew-speakers as a sign of their separatism and anti-Israeli outlook. The underlying mechanisms of mutual stereotyping are discussed.
Empire, Race, and Ethnicity
Authors: Rex John
Published: December 2004

The year 2005 will mark sixty years since the end of the Second World War. During that time, social scientists have tried to conceptualize the world in terms of race and ethnic relations. Old imperial orders collapsed and a process of liberation from White domination in South Africa had already begun within the context of the Cold War. At the same time, a process of modernization began in the imperial metropolises, leading to the emergence of a kind of Welfare State designed to overcome class conflict, but having to cope with the integration of sub-national and migrant minorities. In 1989, the bipolar power situation, internationally, ended with the collapse of Communism. There occurred a new transfer of populations; refugees replaced economic migrants as the principle group that had either to be integrated or become the major focus of national conflicts. Internationally, American world hegemony came into being. America and its subordinate allies saw themselves as faced with a wide range of resistance taking the form of terrorism, but also with new rogue states as their enemies. This paper reviews the ways in which race and ethnic relations have been conceptualized at various stages in this process.
Why Women are at War with Chevron: Nigerian Subsistence Struggles against the International Oil Industry
Authors: Turner Terisa E. , Brownhill Leigh S.
Published: December 2004

This study is an inquiry into why women were at war with oil companies in Nigeria and how they internationalized their struggle. Employing the Midnight Notes Collective's concept of “the new enclosures”; Shiva, Mies, and Bennholdt-Thomsen's “subsistence perspective”; and McMurtry's concept of the “civil commons,” the study elaborates a “gendered class analysis” to consider the social anatomy of coordinated global actions by producers and consumers of oil. Part one examines the period from July 2002 to February 2003. Nigerian women occupied oil terminals and flow stations and inspired global protests against war and oil companies. Part two considers widespread Nigerian workers’ strikes in the period from February 2003 to July 2003. These included work stoppages in transport, the oil industry, and the public service; a two-week seizure by oil workers of four Trans-ocean deep-sea platforms and an eight-day general strike against increases in the price of petroleum products. Part three analyzes the July-September 2003 period. From 10 July 2003 peasant women occupied oil facilities throughout the Delta. As official government neared collapse, village and clan-based organizations assumed much of the responsibility for the oversight of their own communities. By September 2003, insurgents shut down some 40 percent of Nigerian crude oil production capacity. Villagers denied oil companies all physical access to the western Delta. Chevron/Texaco, Shell, other majors and their contractors evacuated their Warri headquarters. The autonomous village organizations, linked to each other through regional solidarity networks, coordinated pan-Delta defense against Nigerian and U.S. military counterinsurgency. The study concludes with an analysis of the roots of insurgent power and direct deals in oil.
Sexual Satisfaction of Married Urban Chinese
Authors: Ji Jianjun , Norling Andrea M.
Published: December 2004

While there is literature on family life satisfaction for married Chinese, there are few studies concerning marital sexual life satisfaction. Using data from the 1993 China Housing Survey conducted in the two major metropolitan cities of Shanghai and Tianjin, this study explores factors that are associated with sexual satisfaction of married urban Chinese. Ordinary Least Squares (OLS) is employed to estimate the effects of family relationships, socioeconomic status, division of house labor, and demographic characteristics on sexual satisfaction. Differences in sexual satisfaction among married men and women are also examined. The results show that family relationships and sexual satisfaction are closely correlated throughout all models. Socioeconomic status and division of house labor are partially correlated. Demographic-related characteristics, however, have little influence on sexual satisfaction. The correlations with sexual satisfaction between married men and women show more similarity than disparity.
Policy Issues and Empirical Assessment of Economic Performance: The Cases of African Countries, 1970-1999
Authors: Doamekpor Francois K.
Published: December 2004

This study uses international data to examine the relationship between economic performance and its determinants for selected countries in the African Region. Performance is defined as a positive increase in the average growth rate of the gross domestic product. The study covers approximately 30 years, 1970 through 1999, and involves 42 African countries. After controlling for the effects of geographic location and years of independent policy-making, the results indicate that capital and exports contributed significantly to the growth of the gross domestic product. Labor, on the other hand, did not conform to the hypothesized formulation of a positive effect on output growth.
Determinants of Foreign Direct Investment in Africa
Authors: Onyeiwu Steve , Shrestha Hemanta
Published: December 2004

Despite economic and institutional reform in Africa during the past decade, the flow of Foreign Direct Investment (FDI) to the region continues to be disappointing and uneven. In this study we use the fixed and random effects models to explore whether the stylized determinants of FDI affect FDI flows to Africa in conventional ways. Based on a panel dataset for 29 African countries over the period 1975 to 1999, the paper identifies the following factors as significant for FDI flows to Africa: economic growth, inflation, openness of the economy, international reserves, and natural resource availability. Contrary to conventional wisdom, political rights and infrastructures were found to be unimportant for FDI flows to Africa. The significance of a variable for FDI flows to Africa was found to be dependent on whether country- and time-specific effects are fixed or stochastic.
Paternity After Adolescent Varicocele Repair
Authors: Salzhauer Elan W. , Sokol Alex , Glassberg Kenneth I.
Published: December 2004

Objective. Varicocelectomy has long been a therapeutic modality used in the treatment of male infertility. In the past decade, adolescent varicocelectomy has become a frequent procedure to preserve testicular growth and to help prevent future infertility. Because our clinical population includes a large portion of orthodox Jews who traditionally marry early and are forbidden to use birth control by religious law, we thought that by studying our patients, we might be able to accelerate our follow-up regarding paternity. In addition, we wanted to learn whether adolescent varicocelectomy might have any negative impact.

Methods. Questionnaires inquiring as to the marital and paternity status, postoperative course, and complications were sent to 50 patients who had undergone a unilateral or bilateral varicocele repair during adolescence and who were at least 21 years old at the time of this review. In addition, a careful chart review was performed to examine the perioperative and postoperative parameters of each respondent.

Results. Of the 43 responses (86% response rate), 18 of 18 patients who had attempted to father a child were successful. The remaining 25 were not married or had never attempted to father a child. In the paternity group, 10 of the fathers had undergone an Ivanissevich repair; the remaining 8 had a Palomo repair. Sixteen of the 18 had unilateral varicocelectomies, and 2 underwent bilateral repairs. Of those with a unilateral varicocele, the indication for surgery in 10 was a grade 2 to 3 varicocele associated with a >20% volume difference when compared with the right testicle. Three had 10% to 20% volume loss, whereas the remaining three had unusually large grade 3 varicoceles without concurrent volume difference.

Conclusions. Varicocelectomy in the adolescent population has been proposed as a therapeutic intervention to preserve both fertility and testicular growth. Although not showing a cause-and-effect relationship, it is our contention that varicocelectomy in adolescence at worst does no harm and at best preserves fertility.
Indicators of Acute Bacterial Meningitis in Children at a Rural Kenyan District Hospital
Authors: Berkley James A. , Versteeg Anne C. , Mwangi Isaiah , Lowe Brett S. , Newton Charles R. J. C.
Published: December 2004

Objective. Acute bacterial meningitis remains an important cause of death and neurologic sequelae in African children. The clinical features of meningitis are often nonspecific and in this setting may overlap with those of malaria. Early diagnosis and appropriate antibiotic treatment are perhaps the most important steps in management, but published data suggest that fewer than half of the cases of childhood meningitis are identified at first assessment in hospitals in this region. The objective of this study was to identify clinical indicators of acute bacterial meningitis by examining components of the World Health Organization Integrated Management of Childhood Illness (IMCI) referral criteria for meningitis (lethargy, unconsciousness, inability to feed, stiff neck, or seizures) and other symptoms and signs.

Methods. Kilifi District Hospital, serving ∼200 000 people in a rural, malaria-endemic area of the Kenyan coast, was studied. A Kenya Medical Research Institute research center is located at the hospital. All pediatric admissions aged ≥60 days between June 2001 and July 2002 were eligible.

Results. A total of 91 (2.0%) of 4582 admissions had meningitis, including 77 (4.0%) of 1929 of those who met the IMCI referral criteria for meningitis at admission (sensitivity: 85%; specificity: 59%). Independent indicators of the presence of meningitis were a bulging fontanel, neck stiffness, cyanosis, impaired consciousness, partial seizures, and seizures outside the febrile convulsions age range. One or more of these indicators was present in 895 (19%) of admissions, 72 (8.0%) of whom had meningitis (sensitivity: 79%; specificity: 80%). Independent indicators of the absence of meningitis were the absence of a history of fever, a history of diarrhea, and a positive malaria slide. The area under the receiver operating characteristic curve for a set of simple screening rules based on the positive indicators identified was 0.88 (95% confidence interval: 0.85–0.92).

Conclusions. The presence of ≥1 of a bulging fontanel, neck stiffness, cyanosis, impaired consciousness, partial seizures, and seizures outside the febrile convulsions age range is a clear indication for lumbar puncture and/or presumptive treatment. However, careful observation and reassessment may be the only practical way to identify one fifth of meningitis cases in this setting.
Economic Analysis of Palivizumab in Infants With Congenital Heart Disease
Authors: Yount Laura E. , Mahle William T.
Published: December 2004

Objective. Palivizumab has been shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations by 45% in children with congenital heart disease (CHD). The American Academy of Pediatrics has recommended that infants with hemodynamically significant CHD be considered for palivizumab. However, the economic implications of palivizumab prophylaxis in the CHD population have not been evaluated. In the present study, we sought to examine the cost savings and cost utility of RSV prophylaxis with palivizumab in children with CHD.

Methods. Probabilities of hospitalization and efficacy of prophylaxis were based on published results. Costs of hospitalization were derived from a published analysis of bronchiolitis hospitalization costs from a consortium of children's hospitals. A hypothetical cohort of 10 000 CHD patients (half of whom would receive palivizumab) was created to calculate cost-savings and cost-utility. To assess cost utility, we assumed that by reducing hospitalization, palivizumab would reduce RSV-related hospital mortality, generally reported to be 3% in CHD patients. Sensitivity analysis was performed.

Results. On the basis of a protocol of 5 monthly doses of palivizumab, the cost of prophylaxis for 1 RSV season was calculated as $6160 per patient. After accounting for impact on direct and indirect costs of hospitalization, administration of palivizumab to 5000 CHD patients would result in a net loss of $20 415 753. If one assumes that palivizumab confers a survival benefit, then the cost of life-year saved is $100 338 and cost of quality-adjusted life-year saved is $114 337.

Conclusions. The cost of palivizumab prophylaxis was high relative to benefits realized. Given the large number of CHD patients who might be considered candidates for RSV prophylaxis (>6000 patients per year in United States) routine use of palivizumab in young children with hemodynamically significant CHD needs to be evaluated further.
End-of-Life After Birth: Death and Dying in a Neonatal Intensive Care Unit
Authors: Singh Jaideep , Lantos John , Meadow William
Published: December 2004

Objective. In canonical modern bioethics, withholding and withdrawing medical interventions for dying patients are considered morally equivalent. However, electing not to administer cardiopulmonary resuscitation (CPR) struck us as easily distinguishable from withdrawing mechanical ventilation. Moreover, withdrawing mechanical ventilation from a moribund infant “feels” different from withdrawing mechanical ventilation from a hemodynamically stable child with a severe neurologic insult. Most previous descriptions of withdrawing and withholding intervention in the neonatal intensive care unit (NICU) have blurred many of these distinctions. We hypothesized that clarifying them would more accurately portray the process of end-of-life decision-making in the NICU.

Methods. We reviewed the charts of all newborn infants who had birth weight >400 g and died in our hospital in 1988, 1993, and 1998 and extracted potential ethical issues (resuscitation, withdrawal, withholding, CPR, do-not-resuscitate orders, neurologic prognosis, ethics consult) surrounding each infant's death.

Results. Using traditional definitions, roughly half of all deaths in our NICU in 1993 and 1998 were associated with “withholding or withdrawing.” In addition, by 1998, >40% of our NICU deaths could be labeled “active withdrawal,” reflecting the extubation of infants regardless of their physiologic instability. This practice is growing over time. However, 2 important conclusions arise from our more richly elaborated descriptions of death in the NICU. First, when CPR was withheld, it most commonly occurred in the context of moribund infants who were already receiving ventilation and dopamine. Physiologically stable infants who were removed from mechanical ventilation for quality-of-life reasons accounted for only 3% of NICU deaths in 1988, 16% of NICU deaths in 1993, and 13% of NICU deaths in 1998. Moreover, virtually none of these active withdrawals took place in premature infants. Second, by 1998 infants, who died without CPR almost always had mechanical ventilation withdrawn. Finally, the median and average day of death for 100 nonsurvivors who received full intervention did not differ significantly from the 78 nonsurvivors for whom intervention was withheld.

Conclusions. In our unit, a greater and greater percentage of doomed infants die without ever receiving chest compressions or epinephrine boluses. Rather, we have adopted a nuanced approach to withdrawing/withholding NICU intervention, providing what we hope is a humane approach to end-of-life decisions for doomed NICU infants. We suggest that ethical descriptions that reflect these nuances, distinguishing between withholding and withdrawing interventions from physiologically moribund infants or physiologically stable infants with morbid neurologic prognoses, provide a more accurate reflection of the circumstances of dying in the NICU.
Prevalence and Correlates of High-Quality Basic Pediatric Preventive Care
Authors: Zuckerman Barry , Stevens Gregory D. , Inkelas Moira , Halfon Neal
Published: December 2004

Background. The list of recommended pediatric preventive services has grown considerably in the past decade, and clinician variability, clinician distribution, and other correlates of provision of these basic preventive services (BPS) are not known.

Objective. To describe the proportion of high-quality basic pediatric preventive services, exclusive of immunizations, reported by parents and to identify sociodemographic and health system predictors and health service correlates of provision of these services.

Study Design. The study used cross-sectional data on 2041 children, 4 to 35 months of age, in the 2000 National Survey of Early Childhood Health.

Outcome Measures. The BPS measure assesses the receipt of (1) developmental assessment, (2) injury prevention counseling, (3) screening for parental smoking, (4) guidance on reading to the child, and (5) guidance on 14 other topics (assessed as a composite score). The BPS scale categorizes the receipt of services as excellent, good, fair, or poor.

Results. Most children received excellent (34.9%) or good (31.5%) care, but many received fair (24.9%) or poor (8.7%) care. Sociodemographic and health care factors such as race/ethnicity, insurance, and practice setting were not associated with BPS levels. Higher BPS scores were associated with parental reports of longer well-child visits, more counseling regarding family and community risk factors, lower rates of delayed or missed care, and greater satisfaction.

Conclusions. Two thirds of children receive good or excellent basic preventive care, as determined with this composite, and no disparities according to race/ethnicity, income, or health insurance status of families (which are often found to be associated with health care access) were found. This equitable distribution of high-quality care suggests a high level of clinician professionalism. Duration of visits may be a key factor to improve quality of care. Because of its association with other services, processes, and outcomes of care, the BPS scale may serve as a useful construct for monitoring quality and stimulating efforts to improve national pediatric preventive care.
Influence of Sleep Position Experience on Ability of Prone-Sleeping Infants to Escape From Asphyxiating Microenvironments by Changing Head Position
Authors: Paluszynska Dorota A. , Harris Kathleen A. , Thach Bradley T.
Published: December 2004

Objective. Several studies have found that back- or side-sleeping infants who are inexperienced in prone sleeping are at much higher risk for sudden infant death syndrome (SIDS) when they turn to prone or are placed prone for sleep compared with infants who normally sleep prone. Moreover, such inexperienced infants are more likely to be found in the face-down position at death after being placed prone compared with SIDS infants who are experienced in prone sleeping. We hypothesized that lack of experience in prone sleeping is associated with increased difficulty in changing head position to avoid an asphyxiating sleep environment.

Methods. We studied 38 healthy infants while they slept prone. Half of these were experienced and half were inexperienced in prone sleeping. To create a mildly asphyxiating microenvironment, we placed infants to sleep prone with their faces covered by soft bedding. We recorded inspired CO2 (CO2I), electrocardiogram, and respiration, and we videotaped head movements. Also, we assessed gross motor development (Denver Development Scale).

Results. When sleeping prone, with their faces covered by bedding, all infants experienced mild asphyxia as a result of rebreathing. All aroused and attempted escape from this environment. Infants used 3 stereotyped head-repositioning strategies. The least effective was nuzzling into the bedding with occasional brief head lifts. More effective were head lifts combined with a head turn. Some infants, however, could turn only to 1 side, right or left. Infants who were inexperienced in prone sleeping had less effective protective behaviors than experienced infants. Infant age did not correlate with efficacy of protective behaviors. Infants who were experienced in prone sleep had advanced gross motor development compared with inexperienced infants.

Conclusion. Infants who are inexperienced in prone sleeping have decreased ability to escape from asphyxiating sleep environments when placed prone. These observations potentially explain the increased risk associated with prone sleep in infants who are inexperienced. The increased occurrence of the face-down position in such infants is also potentially explained. These findings suggest that airway protective behaviors may be acquired through the mechanism of operant conditioning (learning).
Direct Cost Analyses of Palivizumab Treatment in a Cohort of At-Risk Children: Evidence From the North Carolina Medicaid Program
Authors: Wegner Steven , Vann Julie Jacobson , Liu Gordon , Byrns Patricia , Cypra Clement , Campbell William , Stiles Alan
Published: December 2004

Objective. Use of palivizumab prophylactic therapy reduces the occurrence of hospitalizations for serious respiratory syncytial virus (RSV) lower respiratory tract infections in at-risk infants. The direct cost-benefit of palivizumab prophylaxis for infants who are born at 32 to 35 weeks' estimated gestational age (EGA) during their first year of life has not been systematically examined. The objective of this study was to compare the direct costs of palivizumab prophylaxis and RSV treatment in infants who were born at 32 to 35 weeks EGA and received and did not receive palivizumab.

Methods. A cohort study was performed of infants who were younger than 1 year and were enrolled in an enhanced primary care case management model within the North Carolina Medicaid Program. Comparisons were made between infants who received (Synagis prophylaxis group) and did not receive palivizumab (nonprophylaxis group) during the study period. Cost was examined using the sum of Medicaid paid services for prophylaxis with palivizumab and treatment for RSV infections that occurred between October 1, 2002, and May 31, 2003. The Anderson framework was used to specify the regression cost models to compare the participants who received (Synagis prophylaxis) and did not receive (nonprophylaxis group) palivizumab. The primary outcomes were actual 7-month seasonal costs and standardized seasonal costs adjusting for the varied months of infant participation.

Results. The study sample included 185 Synagis prophylaxis and 182 nonprophylaxis participants who met the inclusion criteria. The average per-person total cost of RSV care and prophylaxis was $5117 for the Synagis prophylaxis group and $371 for the nonprophylaxis group. Five hospitalizations occurred in the prophylaxis group, and 12 occurred in the nonprophylaxis group (odds ratio: 0.27). No deaths occurred in either group.

Conclusions. Palivizumab administered to infants who were born at 32 to 35 weeks' EGA did not provide direct cost savings related to hospitalization or ambulatory care in a Medicaid population. The primary difference in cost between the groups was attributable to the palivizumab prophylaxis.
Benefits of the Nonfasting Ketogenic Diet Compared With the Initial Fasting Ketogenic Diet
Authors: Kim Dong Wook , Kang Hoon Chul , Park Jung Chae , Kim Heung Dong
Published: December 2004

Objective. The ketogenic diet (KD) is traditionally introduced with an initial period of fasting and fluid restriction that is difficult and sometimes complicated by moderate dehydration. This investigation compares the efficacy and tolerability of the nonfasting ketogenic diet (NFKD) and the conventional initial-fasting ketogenic diet (IFKD).

Methods. Forty-one children with intractable epilepsy were treated with the NFKD, beginning with a gradual increase in calories with no initial fasting or fluid restriction. This NFKD population was compared retrospectively with 83 recent historical control subjects who were treated with the IFKD. Efficacy, tolerability, time until strong ketosis, and occurrence of complications were compared.

Results. Fourteen (34.1%) patients became seizure-free for at least 3 months after the NFKD, compared with 29 (34.9%) after the IFKD. There was no significant difference in days until strong urinary ketosis between the 2 groups. The incidence of hypoglycemia was also not significantly different between the groups as most other laboratory findings, although the blood urea nitrogen was elevated in 24.1% of the IFKD group and in only 12.2% of the NFKD patients without statistical significance. Conversely, moderate dehydration was significantly less frequent in the NFKD group (12.2%) than in the IFKD group (62.7%). Finally, these results were reflected to the shortening of the hospitalization period in the NFKD group.

Conclusions. These observations suggest that initial fasting and fluid restriction are not essential for the KD and that the tolerability of this treatment may be improved. These data support our intention to conduct a formal, prospective, randomized trial comparing 2 forms of the KD.
On-Time Immunization Rates Among Children Who Enter Chicago Public Schools
Authors: Dominguez Samuel R. , Parrott J. Scott , Lauderdale Diane S. , Daum Robert S.
Published: December 2004

Objective. A primary objective of the Healthy People 2010 initiatives is to increase on-time immunization rates during the first 2 years of life and to decrease racial disparities in coverage. The objective of this study was to determine on-time immunization coverage rates among infants and toddlers stratified by race/ethnicity in a large metropolitan center.

Methods. A retrospective cohort study that was based on immunization records in the Chicago Public Schools computerized database was conducted using all 67376 children who completed kindergarten in 2001 and 2002.

Results. On-time immunization rates in Chicago public school children are low (31% at 7 months, 32% at 19 months, 59% at 36 months). At 19 months of age and thereafter, Hispanic children had the highest rate of on-time immunization coverage. Among children <48 months old, black children had the lowest rates of up-to-date immunization status. At 48 months of age, the up-to-date rate for black children improved to a rate similar to white children (58%) and by school entry surpassed the up-to-date rate for white children (71%). Compared with the recommended 2, 4, 6, and 15 to 18 months schedule, black children received 4 doses of diphtheria/tetanus/acellular pertussis at a mean age of 10.0, 14.6, 20.4, and 34.5 months of age. In contrast, Hispanic children received the same doses at a mean of 4.5, 7.4, 11.0, and 25.1 month of age. In addition, ∼25% of black children received the majority of their vaccinations >12 months later than the recommended time intervals.

Conclusions. Striking immunization delay still exists during the infant and toddler years. Targeted efforts are needed to increase on-time immunization rates and to decrease racial disparity in immunization coverage.
Hypotensive Extremely Low Birth Weight Infants Have Reduced Cerebral Blood Flow
Authors: Munro Michael J. , Walker Adrian M. , Barfield Charles P.
Published: December 2004

Objectives. Whether extremely low birth weight (ELBW) infants are at risk of cerebral hypoperfusion is uncertain because key issues concerning their cerebral blood flow (CBF) and mean arterial pressure (MAP) are unresolved: (1) whether CBF is pressure-passive or autoregulated; (2) the normal level of MAP; and (3) whether inotropic drugs used to increase MAP might inadvertently impair CBF. We addressed these issues in ELBW infants undergoing intensive care.

Methods. CBF (measured by near-infrared spectroscopy) and MAP were measured in 17 infants aged 1.5 to 40.5 hours.

Results. Five infants remained normotensive (MAP 37 ± 2 mm Hg, [mean ± SEM]); twelve became hypotensive (MAP 25 ± 1 mm Hg) and were treated with dopamine (10–30 μg · kg−1 per min). CBF of hypotensive infants (14 ± 1 mL · 100 g−1 per min) was lower than the CBF of normotensive infants (19 ± mL · 100 g−1 per min). After commencement of dopamine in hypotensive infants, MAP increased (29 ± 1 mm Hg) and CBF also increased (18 ± 1 mL · 100g−1 per min). CBF was correlated with MAP in hypotensive infants before (R = 0.62) and during (R = 0.67) dopamine, but not in normotensive infants. A breakpoint was identified in the CBF versus MAP autoregulation curve of untreated infants at MAP = 29 mm Hg; no breakpoint was evident in dopamine-treated infants.

Conclusions. In ELBW infants (1) cerebral autoregulation is functional in normotensive but not hypotensive infants; (2) a breakpoint exists at ∼30 mm Hg in the CBF-MAP autoregulation curve; and (3) dopamine improves both MAP and CBF.
Gaps in the Evidence for Well-Child Care: A Challenge to Our Profession
Authors: Moyer Virginia A. , Butler Margaret
Published: December 2004

Background. Up to one third of visits to pediatricians involve health supervision (well-child care), and recommendations for office-based preventive interventions have dramatically expanded. We reviewed the evidence for the effectiveness of these interventions.

Methods. The well-child care recommendations of 7 major North American organizations were tabulated. Three types of health supervision interventions were recommended, ie, behavioral counseling, screening, and prophylaxis. For recommendations common to at least 2 of the 7 organizations, evidence of effectiveness was sought from systematic reviews and clinical trials. Immunizations were not considered for this review, because they have been reviewed elsewhere.

Results. Forty-two preventive interventions were recommended by ≥2 of the organizations. Limited clinical trials show that counseling can change some health risk behaviors; repeated intensive counseling is most likely to be effective. Harmful effects were shown for a few behavioral counseling interventions. Trials have been conducted for only 2 of the recommended screening interventions; therefore, rigorous evidence supporting screening is very limited. Trials support the use of folate to prevent neural tube defects, trials of iron supplementation do not address developmental outcomes, and trials were not found for the other recommended prophylactic interventions.

Conclusions. Limited direct evidence was found to support the recommended interventions. Because a large number of interventions are routinely recommended and often mandated and because the implementation of any recommendation may cause harm (including the displacement of other beneficial activities), these recommendations should be based on the strongest possible evidence. When recommendations are made, supporting evidence should be clearly stated.