bluuebunny/crossref_metadata_2025 huggingface dataset:
Aerobic Capacity, Strength, Flexibility, and Activity Level in Unimpaired Extremely Low Birth Weight (≤800 g) Survivors at 17 Years of Age Compared With Term-Born Control Subjects
Authors: Rogers Marilyn , Fay Taryn B. , Whitfield Michael F. , Tomlinson Jill , Grunau Ruth E.
Published: July 2005

Objectives. To compare aerobic capacity, strength, flexibility, and activity level in extremely low birth weight (ELBW) adolescents at 17 years of age with term-born control subjects.

Methods. Fifty-three ELBW teens of birth weight ≤800 g were assessed at 17.3 years (16.3–19.7 years; birth weight: 720 g [520–800 g]; gestation: 26 weeks [23–29 weeks]) along with term-born control subjects (n = 31) at age 17.8 years (16.5–19.0 years; birth weight: 3506 g [3068–4196 g]; gestation: weeks 40 [39–42 weeks]). ELBW and control teens were assessed by a pediatric physiotherapist and completed components of the Canadian Physical Activity, Fitness and Lifestyle Appraisal and a self-assessment fitness and activity questionnaire. Continuous data were analyzed using MANOVA (group, gender) followed by t tests; categorical data were analyzed using the χ2 test.

Results. ELBW teens had lower aerobic capacity, grip strength, leg power, and vertical jump; could do fewer push-ups; had less abdominal strength as measured by curl-ups; had less lower back flexibility; and had tighter hamstrings. ELBW teens reported less previous and current sports participation, lower physical activity level, and poorer coordination compared with term-born control subjects. ELBW teens were also found to have more difficulty with maintenance of rhythm and cadence. Although ELBW teens rated themselves lower on all measures of sporting activity, they were as happy with their level of fitness as the control subjects.

Conclusions. Compared with term-born control subjects, there are significant differences in motor performance in unimpaired ELBW survivors in late adolescence, reflected in aerobic capacity, strength, endurance, flexibility, and activity level. We conclude that these differences in fitness and physical activity are related to the interaction of effects of premature birth on the motor system together with a more inactive lifestyle. These findings have potential implications for later adult health problems.
Improvement in Bone Mineral Density and Body Composition in Survivors of Childhood Acute Lymphoblastic Leukemia: A 1-Year Prospective Study
Authors: Marinovic Daniela , Dorgeret Sophie , Lescoeur Brigitte , Alberti Corinne , Noel Michèle , Czernichow Paul , Sebag Guy , Vilmer Etienne , Léger Juliane
Published: July 2005

Objectives. Abnormalities in bone mineral density (BMD), body composition, and bone metabolism have been reported in children who were treated for acute lymphoblastic leukemia (ALL) during and after completion of therapy. However, these studies are cross-sectional, and no longitudinal data are available in a large group of patients after completion of therapy. In the present study, 1-year longitudinal changes in BMD, body composition, and bone metabolism were evaluated in children with ALL during the first 3 years after completion of therapy without cranial irradiation.

Methods. BMD of total body (TB; g/cm2), areal and apparent volumetric lumbar spine (L2–L4), lean body mass, and percentage of body fat were measured by dual-energy x-ray absorptiometry in 37 children (median age: 7.9 years; range: 4.7–20.6 years) who were treated for ALL at a median age of 3.3 years (range: 1.1–16.6 years), after a median time of 2.2 years after the completion of treatment, and after a 1-year follow-up period. Two control subjects (n = 74) who were matched for gender, age, and pubertal stage were also longitudinally investigated for body composition for 1 year. Usual serum biochemical markers of calcium metabolism and bone turnover were measured in patients during the study period.

Results. A slight decrease in TB BMD was found after a median time of 2.2 years after the completion of therapy for ALL in childhood. Patients showed a significantly lower median TB BMD when evaluated <1.5 years as compared with those at ≥1.5 years since completion of therapy. At the time of first evaluation, the percentage of body fat mass was significantly higher and patients were physically less active than their matched control subjects. Although, as expected, during the 1 year of follow-up both groups showed an annual increment in their BMD measurements, a significantly higher increase in TB BMD was observed in patients in comparison with control subjects. During this same period, the increase in the percentage of body fat mass was slightly lower in ALL patients as compared with control subjects. At the end of the follow-up year, BMD, body-composition parameters, and physical activity of ALL patients were similar to those observed in matched control subjects. Serum biochemical markers of bone turnover were normal at both evaluations.

Conclusions. A significant increase in TB BMD and a tendency to a lesser increase in percentage of body fat mass were observed during the study period in ALL patients as compared with chronological age-, gender-, and pubertal stage–matched control subjects. These findings suggest a positive effect of long-term completion therapy and increase in physical activity on BMD, body composition, and bone metabolism in patients who have been treated for ALL.
Croup Hospitalizations in Ontario: A 14-Year Time-Series Analysis
Authors: Segal Audrey O. , Crighton Eric J. , Moineddin Rahim , Mamdani Muhammad , Upshur Ross E.G.
Published: July 2005

Objective. Croup is the most common form of airway obstruction in children. Known to be primarily viral, the seasonality of croup has been examined largely through its association with the human parainfluenza viruses. This study examined the seasonal pattern of croup hospitalizations in relation to age and gender for the province of Ontario during a 14-year period.

Methods. A retrospective, population-based study design was used to examine seasonal and temporal patterns of croup hospitalizations from April 1, 1988, to March 31, 2002. All residents of Ontario who were aged 0 to 4 years and eligible for universal health coverage during the study period were included for analysis. Time-series analyses then were conducted on monthly aggregations of hospitalizations.

Results. This study found strong evidence of croup hospitalization seasonality, with a biennial midautumn peak and annual summer trough, evident throughout the 14-year study period (Fisher's κ = 51.11; Bartlett Kolmogorov Smirnov = 0.552). The pattern was observed in all children aged 0 to 4, although boys were hospitalized 2 times more often than girls of the same age. Rates of croup hospitalization were lower for children aged 1 to 4 years than for children aged 0 to <1. A marked decrease in croup hospitalizations was observed after the winter of 1993/1994 and continued to decrease in a step-wise manner for the remainder of the study period.

Conclusions. This study delineates a clear biennial pattern of seasonal croup hospitalizations, varying by age and gender, with a large decrease in hospitalizations after the winter of 1993/1994. It is expected that these findings will have important implications for the treatment and management of childhood croup.
Acute Arsenic Poisoning in Two Siblings
Authors: Lai Melisa W , Boyer Edward W , Kleinman Monica E , Rodig Nancy M , Ewald Michele Burns
Published: July 2005

We report a case series of acute arsenic poisoning of 2 siblings, a 4-month-old male infant and his 2-year-old sister. Each child ingested solubilized inorganic arsenic from an outdated pesticide that was misidentified as spring water. The 4-month-old child ingested a dose of arsenic that was lethal despite extraordinary attempts at arsenic removal, including chelation therapy, extracorporeal membrane oxygenation, exchange transfusion, and hemodialysis. The 2-year-old fared well with conventional therapy.
Heat Stress From Enclosed Vehicles: Moderate Ambient Temperatures Cause Significant Temperature Rise in Enclosed Vehicles
Authors: McLaren Catherine , Null Jan , Quinn James
Published: July 2005

Objective. Each year, children die from heat stroke after being left unattended in motor vehicles. In 2003, the total was 42, up from a national average of 29 for the past 5 years. Previous studies found that on days when ambient temperatures exceeded 86°F, the internal temperatures of the vehicle quickly reached 134 to 154°F. We were interested to know whether similarly high temperatures occurred on clear sunny days with more moderate temperatures. The objective of this study was to evaluate the degree of temperature rise and rate of rise in similar and lower ambient temperatures. In addition, we evaluated the effect of having windows “cracked” open.

Methods. In this observational study, temperature rise was measured continuously over a 60-minute period in a dark sedan on 16 different clear sunny days with ambient temperatures ranging from 72 to 96°F. On 2 of these days, additional measurements were made with the windows opened 1.5 inches. Analysis of variance was used to compare how quickly the internal vehicle temperature rose and to compare temperature rise when windows were cracked open 1.5 inches.

Results. Regardless of the outside ambient temperature, the rate of temperature rise inside the vehicle was not significantly different. The average mean increase was 3.2°F per 5-minute interval, with 80% of the temperature rise occurring during the first 30 minutes. The final temperature of the vehicle depended on the starting ambient temperature, but even at the coolest ambient temperature, internal temperatures reached 117°F. On average, there was an ∼40°F increase in internal temperature for ambient temperatures spanning 72 to 96°F. Cracking windows open did not decrease the rate of temperature rise in the vehicle (closed: 3.4°F per 5 minutes; opened: 3.1°F per 5 minutes or the final maximum internal temperature.

Conclusions. Even at relatively cool ambient temperatures, the temperature rise in vehicles is significant on clear, sunny days and puts infants at risk for hyperthermia. Vehicles heat up rapidly, with the majority of the temperature rise occurring within the first 15 to 30 minutes. Leaving the windows opened slightly does not significantly slow the heating process or decrease the maximum temperature attained. Increased public awareness and parental education of heat rise in motor vehicles may reduce the incidence of hyperthermia death and improve child passenger safety.
The Cost of Containing One Case of Measles: The Economic Impact on the Public Health Infrastructure—Iowa, 2004
Authors: Dayan Gustavo H. , Ortega-Sánchez Ismael R. , LeBaron Charles W. , Quinlisk M. Patricia ,   and the Iowa Measles Response Team
Published: July 2005

Background. In February 2004, students from a college in Iowa, with a high proportion of nonmedical exemptions to vaccination, traveled to India; one fourth of the students contracted measles while there. One exposed, susceptible student returned home during his infectious period, necessitating 2 months of containment efforts in Iowa.

Objective. The objective of this study was to measure the direct costs of measles containment from a public health system perspective.

Methods. We evaluated activities performed, personnel time/materials allocated, and direct costs incurred in 2004 US dollars by the Iowa public health infrastructure. The study period was defined as March 5, 2004 (when the Iowa Department of Public Health was first contacted about the case), through May 12, 2004 (when a final meeting was held on the containment effort).

Results. A total of 2525 hours of personnel time were expended to review flight manifests, contact exposed passengers, set up vaccination clinics, trace >1000 potentially exposed contacts, and institute and enforce quarantine orders for vaccination refusers. Two thousand twenty-five phone calls were received from the public, and 2243 miles were driven by staff. The temporal distribution of personnel time was characterized by marked peaks at the report of potential secondary cases. The total estimated cost was $ 142452.

Conclusions. The direct cost to the public health infrastructure of containing 1 case of measles was far greater than the estimated cost of uncomplicated individual illness (less than $100). Economic analyses of vaccine-preventable diseases may need to go beyond the costs of individual illness to account for the costs of protecting society.
Obesity Rather Than Severity of Sleep-Disordered Breathing as the Major Determinant of Insulin Resistance and Altered Lipidemia in Snoring Children
Authors: Tauman Riva , O’Brien Louise M. , Ivanenko Anna , Gozal David
Published: July 2005

Objective. Sleep-disordered breathing (SDB) is associated with insulin resistance and dyslipidemia in adults and in obese children. However, the prevalence of such metabolic abnormalities among snoring children is unknown. This study was done to prospectively assess the relative contribution of SDB and obesity to metabolic disturbances in a large cohort of snoring children.

Methods. Measurements of fasting serum glucose, insulin, and lipids were obtained after polysomnographic evaluation in 116 snoring children and in 19 control subjects. Insulin resistance was assessed using the insulin/glucose ratio (I/G ratio) and homeostasis model assessment (HOMA).

Results. A total of 135 children (79 boys; mean age: 8.9 ± 3.5 years) were studied. Sixty-four children had moderate to severe SDB (AHI = 5 per hour of total sleep time [TST]), 52 had mild SDB (AHI = 1 but <5 per hour of TST), and 19 were control subjects (AHI <1 per hour of TST). Seventy of these children were obese. No significant correlations were found between AHI, lowest arterial oxygen saturation, or arousal index and serum insulin, serum glucose, I/G ratio, HOMA, or serum lipids for either the whole group or the obese children only. However, significant positive correlations were found between I/G ratio and relative BMI (relBMI; r = 0.58), HOMA and relBMI (r = 0.52), triglycerides and relBMI (r = 0.30), and high-density lipoprotein and relBMI (r = 0.50). No significant differences were found in relBMI, I/G ratio, and lipid levels between boys and girls.

Conclusions. Among children with suspected SDB, insulin resistance and dyslipidemia seem to be determined primarily by the degree of body adiposity rather than by the severity of SDB.
Model Contractual Language for Medical Necessity for Children
Authors:   Committee on Child Health Financing
Published: July 2005

The term “medical necessity” is used by Medicare and Medicaid and in insurance contracts to refer to medical services that are generally recognized as appropriate for the diagnosis, prevention, or treatment of disease and injury. There is no consensus on how to define and apply the term and the accompanying rules and regulations, and as a result there has been substantial variation in medical-necessity definitions and interpretations. With this policy statement, the American Academy of Pediatrics hopes to encourage insurers to adopt more consistent medical-necessity definitions that take into account the needs of children.
Adolescent Pregnancy: Current Trends and Issues
Authors: Klein Jonathan D. ,   and the Committee on Adolescence
Published: July 2005

The prevention of unintended adolescent pregnancy is an important goal of the American Academy of Pediatrics and our society. Although adolescent pregnancy and birth rates have been steadily decreasing, many adolescents still become pregnant. Since the last statement on adolescent pregnancy was issued by the Academy in 1998, efforts to prevent adolescent pregnancy have increased, and new observations, technologies, and prevention effectiveness data have emerged. The purpose of this clinical report is to review current trends and issues related to adolescent pregnancy, update practitioners on this topic, and review legal and policy implications of concern to pediatricians.
On Gödel's Way In: The Influence of Rudolf Carnap
Authors: Goldfarb Warren
Published: July 2005

The philosopher Rudolf Carnap (1891–1970), although not himself an originator of mathematical advances in logic, was much involved in the development of the subject. He was the most important and deepest philosopher of the Vienna Circle of logical positivists, or, to use the label Carnap later preferred, logical empiricists. It was Carnap who gave the most fully developed and sophisticated form to the linguistic doctrine of logical and mathematical truth: the view that the truths of mathematics and logic do not describe some Platonistic realm, but rather are artifacts of the way we establish a language in which to speak of the factual, empirical world, fallouts of the representational capacity of language. (This view has its roots in Wittgenstein's Tractatus, but Wittgenstein's remarks on mathematics beyond first-order logic are notoriously sparse and cryptic.) Carnap was also the thinker who, after Russell, most emphasized the importance of modern logic, and the distinctive advances it enables in the foundations of mathematics, to contemporary philosophy. It was through Carnap's urgings, abetted by Hans Hahn, once Carnap arrived in Vienna as Privatdozent in philosophy in 1926, that the Vienna Circle began to take logic seriously and that positivist philosophy began to grapple with the question of how an account of mathematics compatible with empiricism can be given (see Goldfarb 1996).

A particular facet of Carnap's influence is not widely appreciated: it was Carnap who introduced Kurt Gödel to logic, in the serious sense. Although Gödel seems to have attended a course of Schlick's on philosophy of mathematics in 1925–26, his second year at the University, he did not at that time pursue logic further, nor did the seminar leave much of a trace on him. In the early summer of 1928, however, Carnap gave two lectures to the Circle which Gödel attended, or so I surmise. At these occasions, Carnap presented material from his manuscript treatise, Untersuchungen zur allgemeinen Axiomatik, that is, “Investigations into general axiomatics”, which dealt with questions of consistency, completeness and categoricity. Carnap later circulated this material to various people including Gödel.
What did Gödel Believe and When did He believe It?
Authors: Davis Martin
Published: July 2005

Gödel has emphasized the important role that his philosophical views had played in his discoveries. Thus, in a letter to Hao Wang of December 7, 1967, explaining why Skolem and others had not obtained the completeness theorem for predicate calculus, Gödel wrote:

This blindness (or prejudice, or whatever you may call it) of logicians is indeed surprising. But I think the explanation is not hard to find. It lies in a widespread lack, at that time, of the required epistemological attitude toward metamathematics and toward non-finitary reasoning. …I may add that my objectivist conception of mathematics and metamathematics in general, and of transfinite reasoning in particular, was fundamental also to my other work in logic.How indeed could one think of expressing metamathematics in the mathematical systems themselves, if the latter are considered to consist of meaningless symbols which acquire some substitute of meaning only through metamathematics?Or how could one give a consistency proof for the continuum hypothesis by means of my transfinite model Δ if consistency proofs have to be finitary?In a similar vein, Gödel has maintained that the “realist” or “Platonist” position regarding sets and the transfinite with which he is identified was part of his belief system from his student days. This can be seen in Gödel's replies to the detailed questionnaire prepared by Burke Grandjean in 1974. Gödel prepared three tentative mutually consistent replies, but sent none of them.
Gödel's Conceptual Realism
Authors: Donald A. Martin
Published: July 2005

Kurt Gödel is almost as famous—one might say “notorious”—for his extreme platonist views as he is famous for his mathematical theorems. Moreover his platonism is not a myth; it is well-documented in his writings. Here are two platonist declarations about set theory, the first from his paper about Bertrand Russell and the second from the revised version of his paper on the Continuum Hypotheses.

Classes and concepts may, however, also be conceived as real objects, namely classes as “pluralities of things” or as structures consisting of a plurality of things and concepts as the properties and relations of things existing independently of our definitions and constructions.It seems to me that the assumption of such objects is quite as legitimate as the assumption of physical bodies and there is quite as much reason to believe in their existence.But, despite their remoteness from sense experience, we do have something like a perception also of the objects of set theory, as is seen from the fact that the axioms force themselves upon us as being true. I don't see any reason why we should have less confidence in this kind of perception, i.e., in mathematical intuition, than in sense perception.

The first statement is a platonist declaration of a fairly standard sort concerning set theory. What is unusual in it is the inclusion of concepts among the objects of mathematics. This I will explain below. The second statement expresses what looks like a rather wild thesis.
Gödel's Reformulation of Gentzen's First Consistency Proof For Arithmetic: The No-Counterexample Interpretation
Authors: Tait W. W.
Published: July 2005

The last section of “Lecture at Zilsel's” [9, §4] contains an interesting but quite condensed discussion of Gentzen's first version of his consistency proof forPA[8], reformulating it as what has come to be called theno-counterexample interpretation. I will describe Gentzen's result (in game-theoretic terms), fill in the details (with some corrections) of Gödel's reformulation, and discuss the relation between the two proofs.
Quantum logic as motivated by quantum computing
Authors: Dunn J. Michael , Hagge Tobias J. , Moss Lawrence S. , Wang Zhenghan
Published: July 2005

§1. Introduction. Our understanding of Nature comes in layers, so should the development of logic. Classic logic is an indispensable part of our knowledge, and its interactions with computer science have recently dramatically changed our life. A new layer of logic has been developing ever since the discovery of quantum mechanics. G. D. Birkhoff and von Neumann introduced quantum logic in a seminal paper in 1936 [1]. But the definition of quantum logic varies among authors (see [2]). How to capture the logic structure inherent in quantum mechanics is very interesting and challenging. Given the close connection between classical logic and theoretical computer science as exemplified by the coincidence of computable functions through Turing machines, recursive function theory, and λ-calculus, we are interested in how to gain some insights about quantum logic from quantum computing. In this note we make some observations about quantum logic as motivated by quantum computing (see [5]) and hope more people will explore this connection.

The quantum logic as envisioned by Birkhoff and von Neumann is based on the lattice of closed subspaces of a Hilbert space, usually an infinite dimensional one. The quantum logic of a fixed Hilbert space ℍ in this note is the variety of all the true equations with finitely many variables using the connectives meet, join and negation. Quantum computing is theoretically based on quantum systems with finite dimensional Hilbert spaces, especially the states space of a qubit ℂ2. (Actually the qubit is merely a convenience.
On the type-definability of the binding group in simple theories
Authors: Hart Bradd , Shami Ziv
Published: July 2005

Let T be simple, work in Ceq over a boundedly closed set. Let p Є S(∅) be internal in a quasi-stably-embedded type-definable set Q (e.g., Q is definable or stably-embedded) and suppose (p, Q) is ACL-embedded in Q (see definitions below). Then Aut(p/Q) with its action on pc is type-definable in Ceq over ∅. In particular, if p Є S(∅) is internal in a stably-embedded type-definable set Q, and pc ⋃ Q is stably-embedded, then Aut(p/Q) is type-definable with its action on pc.
Expansions of o-minimal structures by fast sequences
Authors: Friedman Harvey , Miller Chris
Published: July 2005

Let ℝ be an o-minimal expansion of (ℝ, <, +) and (ϕk)kЄℕbe a sequence of positive real numbers such that limtk→+∞f(ϕk)/ϕk+1 = 0 for everyf: ℝ → ℝ definable in ℜ (Such sequences always exist under some reasonable extra assumptions on ℜ, in particular, if ℜ is exponentially bounded or if the language is countable.) Then (ℜ, (S)) is d-minimal. whereSranges over all subsets of cartesian powers of the range ofϕ.
Randomness, relativization and Turing degrees
Authors: Nies André , Stephan Frank , Terwijn Sebastiaan A.
Published: July 2005

We compare various notions of algorithmic randomness. First we consider relativized randomness. A set is n-random if it is Martin-Löf random relative to ∅(n − 1). We show that a set is 2-random if and only if there is a constant c such that infinitely many initial segments x of the set are c-incompressible: C(x) ≥ ∣x∣ − c. The ‘only if’ direction was obtained independently by Joseph Miller. This characterization can be extended to the case of time-bounded C-complexity.

Next we prove some results on lowness. Among other things, we characterize the 2-random sets as those l-random sets that are low for Chaitin's Ω. Also, 2-random sets form minimal pairs with 2-generic sets. The r.e. low for Ω. sets coincide with the r.e. K-trivial ones.

Finally we show that the notions of Martin-Löf randomness, recursive randomness, and Schnorr randomness can be separated in every high degree while the same notions coincide in every non-high degree. We make some remarks about hyperimmune-free and PA-complete degrees.
The Church-Rosser property in symmetric combinatory logic
Authors: Bimbó Katalin
Published: July 2005

Symmetic combinatory logic with the symmetric analogue of a combinatorially complete base (in the form of symmetric λ-calculus) is known to lack the Church-Rosser property. We prove a muchstrongertheorem that no symmetric combinatory logic that containsat least two proper symmetric combinatoryhas the Church-Rosser property. Although the statement of the result looks similar to an earlier one concerning dual combinatory logic,the proof is differentbecause symmetric combinators may form redexes in both left and right associated terms. Perhaps surprisingly, we are also able to show that certain symmetric combinatory logics that include justone particular constantare not confluent. This result (beyond other differences) clearly sets apart symmetric combinatory logic from dual combinatory logic, since all dual combinatory systems with a single combinator or a single dual combinator are Church-Rosser. Lastly, we prove that a symmetric combinatory logic that contains the fixed point and the one-place identity combinator has the Church-Rosser property.
Asymptotic theory of modules of separably closed fields
Authors: Point Françoise
Published: July 2005

We consider the reduct to the module language of certain theories of fields with a non surjective endomorphism. We show in some cases the existence of a model companion. We apply our results for axiomatizing the reduct to the theory of modules of non principal ultraproducts of separably closed fields of fixed but non zero imperfection degree.
Structured pigeonhole principle, search problems and hard tautologies
Authors: Krajíček Jan
Published: July 2005

We consider exponentially large finite relational structures (with the universe {0, 1}n) whose basic relations are computed by polynomial size (nO(1)) circuits. We study behaviour of such structures when pulled back by P/poly maps to a bigger or to a smaller universe. In particular, we prove that:

1. If there exists a P/poly map g: {0, 1}n → {0, 1}m, n < m, iterable for a proof system then a tautology (independent of g) expressing that a particular size n set is dominating in a size 2n tournament is hard for the proof system.

2. The search problem WPHP. decoding RSA or finding a collision in a hashing function can be reduced to finding a size m homogeneous subgraph in a size 22m graph.

Further we reduce the proof complexity of a concrete tautology (expressing a Ramsey property of a graph) in strong systems to the complexity of implicit proofs of implicit formulas in weak proof systems.
Upward categoricity from a successor cardinal for tame abstract classes with amalgamation
Authors: Lessmann Olivier
Published: July 2005

This paper is devoted to the proof of the following upward categoricity theorem: Let be a tame abstract elementary class with amalgamation, arbitrarily large models, and countable Löwenheim-Skolem number. If is categorical in ℵ then is categorical in every uncountable cardinal. More generally, wc prove that if is categorical in a successor cardinal λ+ then is categorical everywhere above λ+.
Une fonction de Kolchin pour les corps imparfaits de degré d'imperfection fini
Authors: Delon Françoise
Published: July 2005

Non-perfect separably closed fields are stable, and not superstable. As a result, not all types can be ranked. We develop here a new tool, a “semi-rank”, which takes values in the non-negative reals, and gives a sufficient condition for forking of types. This semi-rank is built up from a transcendence function, analogous to the one considered by Kolehin in the context of differentially closed fields. It yields some orthogonality and stratification results.
Chaos Theory
Authors: Wolff R. C. L.
Published: July 2005

A system is chaotic if it is governed by a set of deterministic equations, but displays erratic, apparently random, behavior. The mathematical structure may be the iteration of linked difference equations in discrete time, or the evolution of a set of linked differential equations in continuous time. Stochastic interpretations, especially those involving time series analysis, are described.
Blinding or Masking
Authors: Day Simon J.
Published: July 2005

The need for blinding in clinical trials and epidemiological studies is reviewed and its importance stressed. Various reasons for blinding include the potential for patient bias, bias in patient management and evaluation, bias in data management and study management. Blinding and unblinding interim analyses need special attention, and procedures for emergency unblinding need to be available.

Four levels of blinding are described from the slightly ambiguous term “single‐blind” through to quadruple‐blinding. Methods to maintain the blind at various stages such as use of placebos, “double‐dummy” designs, and sham procedures are discussed.

Finally, some of the difficulties of blinding are highlighted. Often, it may be ineffective and reporting of the achieved quality of blinding is recommended. There are special issues with regard to equivalence studies, and regulatory guidance exists discussing many issues included in this article.
Intention to Treat Analysis
Authors: Ellenberg Jonas H.
Published: July 2005

In a randomized clinical trial design for the comparison of treatments, subjects are randomly assigned to different treatments. The intention‐to‐treat principle requires that any comparison of the treatments be based upon comparison of all patients in the treatment groups to which they were randomly assigned. This approach maintains the benefits of randomization, one of which is that the characteristics of the group of patients receiving the different treatments should be roughly equivalent at the onset of the trial.

Several conditions can influence the actual versus intended protocol under which subjects are studied including: nonadherence to the assigned treatment regimen, or termination of participation prior to outcome measurement. Investigators may attempt to compare groups defined by factors that might be influenced by the treatments under test, for example, the comparison of only those patients in the trial that actually complied with the prescribed treatments. Any observed differences among treatment groups constructed in this manner may be due not to treatment, but to factors associated with compliance.
Actuarial Methods
Authors: Haberman Steven
Published: July 2005

Actuarial methods overlap with biostatistics in a number of important areas including the development and application of the survival model, and its extensions—the multiple decrement and multiple state models; projections of populations that involve extrapolations of demographic and biostatistical rates and probabilities; parametric and nonparametric methods of smoothing and curve fitting (known as graduation); and risk classification. In each of these areas, actuarial science has followed the innovations in statistical and biostatistical theory and application and developed these further for specific actuarial applications.
Birthweight
Authors: Macfarlane Alison
Published: July 2005

The World Health Organization defines birthweight as the first weight of the fetus or baby after birth. It also defines low birthweight, very low birthweight and extremely low birthweight. The limited definition of “prematurity”, based on birthweight, was abandoned in the 1970s and replaced by a definition of preterm birth based on gestational age.
Standardization Methods
Authors: Inskip Hazel
Published: July 2005

Standardization methods are used to adjust for the effects of age and sex, and possibly other factors, in the comparison of mortality or disease rates between two or more populations. Such methods have a long history, particularly for the comparison of mortality rates. The two methods that are most widely used are known as direct and indirect standardization and the mortality ratios that are derived from these are known respectively as the Comparative Mortality Figure and the Standardized Mortality Ratio. When the populations at risk are hard to define, methods involving the proportions of deaths from specific causes can be used. More recently, different approaches involving modeling have been developed to adjust rates for the effects of age and other confounding factors.
Cancer Registries
Authors: Hankey B. , Fritz April
Published: July 2005

We review the history of cancer surveillance and distinguish hospital‐based from population‐based cancer registries. Registry operations include case ascertainment, abstracting and coding, data collection, quality control, and producing statistics on health outcomes. The characteristics of the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program are described, and we give web site addresses that describe SEER procedures, facilities for making data and analytical tools available, and a strategic plan for cancer surveillance research.
Case–Control Study, Nested
Authors: Langholz Bryan
Published: July 2005

Nested case–control studies refer to a class of cohort sampling designs used in epidemiologic research. This article describes the general principles, analysis methods, statistical properties, and relationship to other approaches. Methods are illustrated by studies from the epidemiological literature.
Case–Control Study, Sequential
Authors: O'Neill Robert T.
Published: July 2005

Recruitment of cases and controls for a case–control study can take an appreciable amount of time. There is potential for shortening the duration of a case–control study and reducing the numbers of required cases and controls by analyzing the accruing data sequentially and perhaps by stopping accrual early if a definitive early decision can be reached. We discuss the Wald sequential probability ratio test and group sequential tests for 1:1 matched case–control designs and tabulate the average reductions in sample sizes obtained by sequential procedures, compared with fixed sample size designs.
Confounder
Authors: Gail Mitchell H.
Published: July 2005

A confounder is a variable that alters the association between an exposure and a disease. A confounder is associated with disease risk in unexposed subjects, is not affected by exposure or disease, and is associated with exposure in the source population. Methods to control confounding are mentioned, as is a definition of confounding based on a counterfactual theory of causal effects.
Confounder Summary Score
Authors: Greenland Sander
Published: July 2005

Consider an observational study of the effect of an “exposure” variable
X
on an outcome variable
Y
in which multiple confounders must be controlled. Simultaneous stratification on all observed confounder combinations may lead to many uninformative strata (i.e. strata in which there is either no variation in the exposure or no variation in the outcome). The usual method of coping with this problem is to estimate exposure effects from coefficients in a regression model for the dependence of the outcome on the exposure and confounders. Confounder summary scores are alternatives that use fitted models to define strata.
Cumulative Hazard
Authors: Gail Mitchell H.
Published: July 2005

Cumulative hazard is the integrated hazard rate.
Cumulative Incidence
Authors: Gail Mitchell H.
Published: July 2005

Cumulative risk is the proportion of individuals in a cohort who develop disease in a defined time period.
Descriptive Epidemiology
Authors: Gail Mitchell H.
Published: July 2005

Descriptive epidemiology is defined and contrasted with analytic epidemiology.
Ecologic Study
Authors: Morgenstern Hal
Published: July 2005

An ecologic study focuses on the comparison of groups rather than individuals; thus, individual‐level data are missing on the joint distribution of variables within groups. The purpose of an ecologic analysis may be to make biologic inferences about effects on individual risks or to make ecologic inferences about effects on group rates. Ecologic study designs may be classified on two dimensions: (a) whether or not the primary exposure is measured; and (b) whether subjects are grouped by place, time, or place and time. Despite practical advantages of ecologic studies, there are several methodologic problems that severely limit causal inference, including ecologic and cross‐level bias, problems of confounder control, within‐group misclassification, lack of adequate data, temporal ambiguity, collinearity, and migration across groups. Even when the study objective is to estimate ecologic effects, individual‐level data are generally needed to make valid causal inferences, preferably using multilevel analysis.
Effect Modification
Authors: McKnight Barbara
Published: July 2005

Effect modification occurs when a measure of the association between an exposure and the risk of disease is modified, or changes, with values of a third variable called the
effect modifier
. For a given measure of association between exposure and disease risk, there is usually a corresponding regression model scale on which the presence of effect modification corresponds to the presence of statistical interaction between exposure and the effect modifying variable. This correspondence is described for several additive and multiplicative measures of association.
Fixed Population
Authors: Gail Mitchell H.
Published: July 2005

A fixed population is defined and contrasted with a dynamic population.
Frequency Matching
Authors: Gail Mitchell H.
Published: July 2005

Frequency matching is a sampling design used in case–control studies to assure that cases and controls have the same distributions over strata defined by matching factors. Frequency matching is also used in cohort studies to insure that exposed and unexposed individuals have the same distributions over strata defined by known risk factors.
Geographic Epidemiology
Authors: Bithell John F.
Published: July 2005

Geographical analysis of epidemiologic data may be useful in modeling risk as a function of geographic covariates, testing hypotheses, mapping disease patterns, identifying areas of high risk, or detecting clusters. Distinctions are drawn between case dependence and independence (the latter not requiring a spatially correlated error structure), and between areal and continuous data. Various models are described, and attention is given to disease mapping (involving data smoothing) and clustering.
Odds
Authors: Gail Mitchell H.
Published: July 2005

If an event
E
has probability Pr(
E
), the odds of the event is defined as Pr(
E
)/[1 − Pr(
E
)].
Relative Odds
Authors: Gail Mitchell H.
Published: July 2005

The relative odds, or odds ratio, is the ratio of the odds of disease in an exposed cohort divided by that in an unexposed cohort.
Risk
Authors: Gail Mitchell H.
Published: July 2005

Risk is the probability that an individual without disease will develop disease over a defined age or time interval.
Decision Analysis in Diagnosis and Treatment Choice
Authors: Tosteson Anna N. A.
Published: July 2005

Decision analysis, a quantitative approach to decision making under conditions of uncertainty, is introduced and its use in clinical decision making is described. Decision analysis identifies the optimal course of action as that which maximizes (or minimizes) the expected value of the outcome as specified by the decision maker. Through sensitivity analysis, the parameters that affect the optimal course of action are identified. The expected value of clinical information and perfect information are defined in the context of a clinical example.
Diagnostic Test Accuracy
Authors: Walter Stephen D.
Published: July 2005

This entry discusses accuracy for a diagnostic test in terms of the disease prevalence, and test sensitivity and specificity. Clinical implications of test errors are mentioned as well as alternative ways to assess accuracy.
Dose‐response in Pharmacoepidemiology
Authors: Murphy J. R.
Published: July 2005

Pharmacoepidemiology deals with the action of drugs within a population. Because of differences in the method of data collection, estimation of pharmacoepidemiologic dose–response parameters is somewhat different from that in biological assay or clinical trials. Pharmacodynamic models to estimate these parameters are reviewed, with a specification of appropriate dose–response variables. Parameter estimation is described, together with mention of appropriate software to do so.
Drug Approval and Regulation
Authors: Lewis John A. , Jones David R.
Published: July 2005

Before it can be marketed, any new medicinal product generally requires the regulatory approval of the appropriate governmental agency. This article describes the contribution of statistics and statisticians to the regulatory process. It addresses the role of statisticians within regulatory agencies worldwide. It provides an explanation of the various ways in which statistical assessment is carried out within the major regulatory agencies. It concludes by considering the statistical aspects of the regulatory application written by the applicant company to support their claims for their medicinal product.
Incubation Period of Infectious Diseases
Authors: Brookmeyer Ron
Published: July 2005

The incubation period is the time interval between exposure to a disease‐causing agent and the onset of symptomatic disease. For example, the incubation period of an infectious disease refers to the time interval between infection or exposure to a viral or bacterial agent and the onset of symptomatic (clinical) disease. The incubation period is also called the clinical latency period. The focus of this article is on modeling and estimating the incubation period of infectious diseases. However, some of the ideas may also be applicable to the incubation period of noninfectious disease, for example, the incubation period of radiation‐induced cancer that refers to the time interval from radiation exposure to cancer diagnosis. Alternative designs for the estimation of an incubation period are reviewed, and methods to synthesize studies on incubation periods are mentioned.
Natural History Study of Prognosis
Authors: Cnaan Avital
Published: July 2005

Prognosis refers to the probable outcome of an attack of disease. The traditional definition would describe the evolution of disease in the absence of medical intervention, but nowadays we may also include the term “clinical course” to describe the natural history of a disease that has been affected by medical intervention. Various design considerations are reviewed for the study of natural history, including the use of cohort studies, the various biases that may affect such studies, and the definition of time zero as a clearly defined starting point. Other topics include the analysis of dichotomous outcomes, survival analysis and longitudinal data analysis. Combination of data from several studies, and situations involving multiple outcomes are also mentioned.
Normal Clinical Values, Design of a Study
Authors: Harris Eugene K.
Published: July 2005

This entry describes the estimation of normal ranges for clinical variables. A key issue is the identification of the appropriately healthy segment of the general population, and ways in which it can be sampled without bias. Techniques such as convenience sampling often do involve potential bias. Topics such as exclusion and partitioning criteria for the sampling are described. Sample size determination for establishing normal limits is reviewed.
Observer Reliability and Agreement
Authors: De Vet H.
Published: July 2005

The termsobserver reliabilityandobserver agreementrepresent different concepts. Reliability coefficients express the ability to differentiate between subjects. Agreement parameters determine whether the same value is achieved if a measurement is repeated. Parameters for reliability are ICCs for measurements on an interval scale. Parameters for agreement are kappa for measurements on a nominal scale, weighted kappa for an ordinal scale, and levels of agreement for measurements on an interval scale.

Assessing observer reliability and agreement is essential for the interpretation of clinical observations in research and medical practice. Moreover, only if the sources of measurement errors are known, can they be anticipated, thereby improving the quality of measurements.
Screening, Models of
Authors: Stevenson Chris
Published: July 2005

This article describes models for disease screening and how they have developed in recent years. The discussion focuses on screening for cancer, because most of the methodological advances in screening design and evaluation have concerned cancer screening. The first part of the article describes the characteristics of these models and illustrates them with a discussion of a simple screening model. The second part describes the development, strengths, and weaknesses of the two main types of screening model—analytic and simulation models—with a particular focus on microsimulation models. The third part discusses model fitting and validation, and the final part briefly describes models for diseases other than cancer—in particular, models for screening for infectious diseases—and discusses the current state and possible future directions for models of disease screening.
Sensitivity
Authors: Walter Stephen D.
Published: July 2005

The sensitivity of a diagnostic or screening test is defined, and a relation to the test likelihood ratio is described. Clinical implications are mentioned. Alternative uses of the term “sensitivity” are also mentioned, in the context of measuring devices, outlier detection, and robustness.
Age‐of‐Onset Estimation
Authors: Siegmund K.
Published: July 2005

Age of onset estimates are crucial to clinical management and designing disease prevention studies. For many diseases, age is the primary risk factor. Age of onset is censored if a person is unaffected. Two different modeling philosophies are possible: to assume a mixture of susceptible and nonsusceptible individuals in the population, or to assume that all individuals are susceptible and would become affected if only they lived long enough. Variability of age of onset as a function of exposures can be modeled through the hazard. Designs possible to estimate age of onset parameters are: case—control family studies, kin—cohort studies, and the study of high‐risk families. Age‐specific penetrances can be estimated using a likelihood, pseudolikelihood, marginal likelihood, weighted score, or the method of moments.