bluuebunny/crossref_metadata_2025 huggingface dataset:
What Drives Employment Relationships in Taxicab Organizations? Linking Agency to Firm Capabilities and Strategic Opportunities
Authors: Sherer Peter D. , Rogovsky Nikolai , Wright Norman
Published: October 2008

Agency theorists argue that organizations typically get little value from using employees and that they should instead use nonemployees operating fully as residual claimants. Yet, even in a context where those theorists would predict virtually no employees—taxicab organizations—they are common. What drives the use of employment relationships in these organizations? The authors show how employment relationships are linked to firm capabilities and strategic opportunities in a sample of taxicab organizations, relying on arguments about the linkage of employment to the internal liquidity of labor, organizational routines, and internal cooperation. The theoretical arguments and findings suggest what organizations gain by having employment relationships and show that integrating the agency theoretic argument with the other theoretical arguments leads toward a resource-based view of strategy and human resources. The authors highlight the importance of embedding arguments on the internal management of human resources in the strategic and competitive context in which organizations operate. Their arguments also have implications for the resource-based approach to strategy in mapping the resource space of human assets in organizations and, within that space, directing attention to how organizations gain sustainable competitive advantage through managing human resources.
A Round-Trip Location Problem on a Tree Graph
Authors: Chan Albert W. , Francis Richard L.
Published: October 2008

The problem considered is to locate one new facility with respect to a finite number of pairs of existing facilities on, a tree graph, which typically represents a road network, so as to minimize the maximum cost, where cost are linear increasing functions of the round-trip distance a vehicle based at the new facility travels via a pair of existing facilities. Based on an attainable lower bound for the minimax problem, an algorithm is developed that yields all optimal solutions to the problem.
Convergence and Descent in the Fermat Location Problem
Authors: Ostresh Lawrence M.
Published: October 2008

The Fermat location problem is to find a point whose sum of weighted distances from m given points (vertices) is a minimum. The best known method of solution is an iterative scheme devised by Weiszfeld in 1937, which converges to the unique minimum point unless one of the iterates happens to “land” on a nonoptimal vertex. The convergence proof of this scheme depends on two theorems, one of which (descent theorem) states that the objective function strictly decreases at each step. This paper extends the descent theorem by proving: (1) there is a “ball” whose radius and center depend on the Weiszfeld iteration, such that any algorithm whose iterates are “in the ball” or “on its surface” is a descent algorithm; (2) under certain circumstances, one or more of the vertices may be deleted, although the weight(s) are taken into account, and the Weiszfeld algorithm retains its descent property. In general there are several subsets of vertices which may be deleted, and for each subset, a corresponding iterate; (3) the convex hull of these iterates is such that all points within it have the descent property. Examples of the potential application of these extensions are given, including the construction of a modified Weiszfeld algorithm that without exception converges to the optimum. Beyond that, it is hoped the theorems may in time be useful in proving the descent property of yet to be discovered, very fast, nongradient algorithms.
A Maximum Entropy Combined Distribution and Assignment Model Solved by Benders Decomposition
Authors: Jörnsten Kurt O.
Published: October 2008

The combined distribution and assignment problem has been studied by many authors. The problems examined have been of different types. Some authors focus their attention on the user optimized combined distribution and assignment problem whereas others study a system optimized version. Apart from this difference there is also a difference in the way the distribution part and the assignment part are incorporated into the models. In this paper we study a combined distribution and assignment problem with entropy objective and cost constraints and give an algorithm based on Benders decomposition for its solution. The resulting solution method will be a “dual” method.
Dynamic Repositioning of Indistinguishable Service Units on Transportation Networks
Authors: Berman Oded
Published: October 2008

The repositioning of urban emergency units is examined analytically using the methodology of Markovian Decision Processes. In practice urban emergency vehicles (e.g., fire engines) are constantly subject to repositioning in order to assure a proper posture for responding quickly to future demands. The analysis assumes that there are q indistinguishable servers on the network located initially at q nodes—“The Home Locations.” Depending on the status of other server locations, any available server can be moved to any other vacant location in the network. The states of the system are defined according to the status of each location (occupied or vacant). The policy space consists of decisions on where and when to move service units for any possible state. The objective is to minimize the long term expected cost (in time units) of operating the system.
The Effect of Car Size on Headways in Freely Flowing Freeway Traffic
Authors: Wasielewski Paul
Published: October 2008

In order to determine the effect of car size on freeway capacity, headways were measured and vehicles classified by size for 20,500 vehicles in near-capacity traffic on a Detroit freeway. The data were obtained using a videotape recorder system. Vehicle arrival times were measured from a videotaped image of the oncoming traffic using a photodetector mounted on the monitor screen. Size classifications were made by an observer from the pictures of each vehicle on the monitor. Average headways increased monotonically with lead car size from 1.87 s for “small” cars to 2.02 s for “large” cars. These differences are significantly greater than the differences expected from the greater road space occupied by the larger cars if the front bumper to rear bumper separation were independent of car size. The effect of following car size was nonmonotonic with the shortest average headways, 1.90 s, observed for “medium” following cars, and essentially equal headways of 1.99 s for “small” cars and 2.00 s for “large” cars. The observed car size effects were found for long as well as for short headways. The net result of these effects would be an 8% increase in freeway capacity if the cars observed in the study were all replaced with small (subcompact) cars.
A Class of Train-Scheduling Problems
Authors: Assad Arjang A.
Published: October 2008

We relate the question of determining stop-schedules for trains that deliver traffic on a line of stations to the maximization of submodular set functions. We prove that a greedy algorithm is optimal under certain assumptions and report computational experience on the performance of the greedy heuristic as compared to the exact algorithm when the optimality of the greedy heuristic cannot be guaranteed.
Medi-Centers of a Tree
Authors: Handler Gabriel Y.
Published: October 2008

While relatively efficient algorithms are now available for minisum (“median”) and minimax (“center”) network location problems, little attention has been focused on the often realistic cases where both criteria are combined in a single formulation. This paper presents a contribution to the study of such “medi-center” problems. Efficient algorithms are developed for locating a single facility on a tree. The simplicity and efficiency of the algorithms are due to a fundamental convexity property of tree networks.
A Stochastic Model of the Dynamic Vehicle Allocation Problem
Authors: Powell Warren B.
Published: October 2008

The stochastic vehicle allocation problem addresses the movement of vehicles between locations over a given planning horizon. The demand for vehicles to carry loads between locations is uncertain, and vehicles are assumed to be able to handle several loads over the course of the planning horizon. This requires tracking the movement of both loaded and empty vehicles, resulting in a network with stochastic flows. The methodology represents the flows of vehicles over the network explicitly as random variables, taking advantage of the acyclic structure of the time space network. The decision variables are formulated in terms of sending a certain fraction of the supply of vehicles at a node (which is random) over each of the outbound links. The result is a nonseparable objective function with a very simple constraint structure which lends itself readily to the Frank-Wolfe algorithm. Numerical experiments suggest very good computational efficiency.
Exact and Heuristic Algorithms for the Optimum Communication Spanning Tree Problem
Authors: Ahuja R. K. , Murty V. V. S.
Published: October 2008

Network design problems have been widely investigated in the literature. In this paper, we study one such design problem, known as the Optimum Communication Spanning Tree (OCST) problem. We develop an exact algorithm based on the branch and bound approach and a heuristic algorithm to solve the problem. The branch and bound algorithm uses the lower planes recently developed by the authors. Reoptimization of subproblems is extensively used to reduce computation. The heuristic algorithm is a two-phase algorithm: tree-building algorithm and tree-improvement algorithm. These algorithms have been tested on randomly generated Euclidean and non-Euclidean problems and results of these investigations are described. The branch and bound algorithm is able to solve moderately large sized problems in reasonable time. The two-phase heuristic algorithm has produced excellent results by providing optimal solutions for all the problems tested. Further, it is capable of solving problems of size 100 nodes and 1,000 arcs in about 30 seconds on DEC 10.
Trajectory Analysis of the Stochastic Queue Median in a Plane with Rectilinear Distances
Authors: Brandeau Margaret L. , Chiu Samuel S.
Published: October 2008

In this paper we analyze the trajectory of stochastic queue median (SQM) location problem in a planar region with a rectilinear travel metric. The location objective is to minimize expected response time to customers (that is, travel time plus queue delay). We introduce a methodology for parametric analysis of planar location problems which is potentially applicable to other location problems as well. Using the methodology, we demonstrate strong parallels between our planar SQM problem and the same problem on a tree network. We show how the optimal SQM location must occur in a certain region of the plane. Given a mild regularity condition, we develop trajectory results for the optimal location as a function of the customer call rate, and we derive a simple necessary and sufficient ratio condition which characterizes points on the optimal trajectory, and present an algorithm for finding that trajectory. We also analyze the problem in the degenerate case when the regularity condition is violated. Finally, we extend our results to the planar stochastic expected queue median problem, which incorporates stochastic travel times.
Stop Probability and Delay Estimations at Low Volumes for Semi-Actuated Traffic Signals
Authors: Luh John Z. , Lee Chung-Yee
Published: October 2008

Semi-actuated signals have been widely used on arterials, since they provide flexible controls for minor street traffic to reduce delays and stops. It is very important to estimate average delays and stops under such signal control in designing timing plans or evaluating operational performance. Unfortunately, the literature offers very few methods dealing exclusively with semi-actuated signals in estimating delays and stops. A common approach is to estimate average green times, then to apply a model for pretimed signals to calculate delays and stops. This method produces reasonable approximations when traffic volumes are moderate to high. When traffic volumes are low, however, this method produces biased approximations since it does not consider phase skipping due to lack of traffic demand. This paper presents an analytical method to directly estimate stop probability and average delay for semi-actuated signals at low volumes, under both isolated and coordinated controls. This method uses probability theory and stochastic processes to consider the various cycle lengths and green times under such signal control with simplified assumptions. A comparison with the results of a simulation demonstrates the validity of the method.
Routing Container Ships Using Lagrangean Relaxation and Decomposition
Authors: Rana Krishan , Vickson R. G.
Published: October 2008

International shipping is a multibillon dollar business and shipping companies may expect large benefits from improving the routing and scheduling processes of their ships. In this paper, we describe a container-ship routing scenario in which a shipping company provides services to a network of ports. We formulate a mathematical programming model that maximizes total profit (i.e., revenue minus operating costs) for multiple ships and determines: (a) the optimal sequence of ports of call for each ship, (b) the number of trips each ship makes in a planning horizon, and (c) the amount of cargo transported between any two ports by each ship. The model contains discrete, 0–1 and continuous variables, and nonlinear complicating constraints. The multiple container ship model is quite different from those of vehicle routing and traveling salesman problems. We use a decomposition method for the model as well as for the network in order to solve the problem. Several problems on 10- to 20-port networks are solved and the results presented.
En Route Sector Capacity Model
Authors: Janić Milan , Tošić Vojin
Published: October 2008

This paper presents a model for calculating the capacity of an en route sector of an air traffic control system from the geometric point of view. The model is based on the concept of expected capacity under saturation conditions, i.e., in the presence of continuous demand for service. The model could be used for planning purposes such as sector capacity calculations and capacity sensitivity analysis for different traffic scenarios. A sensitivity analysis can be performed varying such parameters as: sector geometry (number of entry points and air routes' configuration), characteristics of the sector's expected traffic (arriving traffic distribution between entry points and flight levels for each of those points, the characteristics of requests for level changes while in the sector, aircraft mix at the entry points) and air traffic control separation rules.
Locating Discretionary Service Facilities Based on Probabilistic Customer Flows
Authors: Berman Oded , Krass Dmitry , Xu Chen Wei
Published: October 2008

In this paper, we consider the problem of locating discretionary facilities on a network. In contrast to previous work in the area, we no longer assume that information on customers' flows along all paths of the network is known (in practice such information is rarely available). Assuming that the fraction of customers that travel from any node to any adjacent node in the network is available, the problem of locating the facilities so as to maximize the fraction of customers that pass by a facility before reaching their destination is formulated as a nonlinear Integer Program. It is shown that by employing the theory of constrained Markov Decision Processes this problem can be reformulated as a linear Mixed Integer Program. The paper presents some preliminary computational results for this formulation as well as results for a greedy heuristic algorithm.
Sources of Productivity Increases in the U.S. Passenger Airline Industry
Authors: Murphy Neil B.
Published: October 2008

The purpose of this paper is to estimate cost junctions for the U.S. passenger airline industry in order to determine the sources of recent observed productivity increases. A cost function is derived from the Cobb-Douglas production function, and the parameters of that reduced form equation are estimated. Special attention is given to effect of technology on costs. In general, it was found that there seem to be no scale economies present in the production of available seat miles, but that the level of technology has a substantial impact on cost and productivity.
Incorporating Insurance Costs in Hazardous Materials Routing Models
Authors: Verter Vedat , Erkut Erhan
Published: October 2008

The economic loss associated with the involvement of a hazardous materials truck in an accident can be very high. Although the immediate costs are usually borne by an insurer, the carrier would incur an increase in its future insurance costs as a result. Thus, a hazardous materials carrier can benefit from considering its long-term insurance costs in routing the required shipments. In this paper, we introduce the hazardous materials routing problem under insurance costs. We present a solution methodology that facilitates evaluation of alternative routing policies. The proposed methodology involves solution of a manageable number of shortest path problems in determining the most appropriate route(s). We argue that, for each shipment, the route to be taken by the truck should be determined on the basis of the expected increase in insurance costs due to a possible accident as well as the cost of transportation.
Applications of Non-Order-Preserving Path Selection of Hazmat Routing
Authors: Nembhard David A. , White Chelsea C.
Published: October 2008

In this paper, we consider the problem of determining a path that maximizes a multi-attribute, non-order-preserving value function. The motivating application is the determination of a most preferred path for transporting hazardous materials based on transportation cost and risk to population. A sub-path of an optimal path may not be optimal for a non-order-preserving value function, implying that a traditional application of dynamic programming may intentionally or unintentionally produce sub-optimal paths. We consider two approximation procedures for two general cases, the q = 0 case and the q > 0 case, where q is the number of required intermediate stops between origin and destination. The first approximation procedure involves applying dynamic programming as if a sub-path of an optimal path were always optimal. The second approximation procedure involves determining a linear order-preserving criterion that approximates the non-order-preserving value function and then applying dynamic programming. We use the best-first search algorithm BU* to determine optimal routes for both the q = 0 and q < 0 cases. We examine the frequency and magnitude of the resulting sub-optimalities for a multi-attribute value model based on a six-county road network that includes Cleveland, Ohio. Numerical results show that if one of the two approximations is used, significant sub-optimalities can occur over a wide range of decision maker preferences. Both approximations can produce sub-optimality error magnitudes of over 50%.
A Probabilistic Approach to Evaluate Strategies for Selecting a Parking Space
Authors: Cassady C. Richard , Kobza John E.
Published: October 2008

Upon entering the parking lot of a facility, a driver must select a parking space. This paper proposes and evaluates strategies which are intended to find a “good” parking space. Three performance measures are defined for evaluating the “goodness” of a selected parking space. One of these is based on the amount of walking required of the customer, another is based on the amount of driving required, and the third is a combination of the first two and represents the time required for the customer to reach the front door of the facility. Two strategies are defined for selecting a parking space. The first is simple and somewhat conservative, whereas the second strategy is more complicated and aggressive. A probabilistic approach is used to evaluate the three performance measures for each strategy using a parking lot of somewhat “typical” configuration. This approach treats driver decisions and parking space availability as random experiments, and uses conditional probability to evaluate the performance of the strategies.
Ship Routing Through Altimetry-Derived Ocean Currents
Authors: McCord Mark R. , Lee Young-Kyun , Lo Hong Kam
Published: October 2008

We investigate the potential of strategic ship routing through dynamic currents derived from satellite altimetry by simulating current patterns in a dynamic Gulf Stream region to reflect present and improved current estimation capabilities, using dynamic programming to determine approximately 3-day routes through the current patterns, and estimating relative fuel savings that would be obtained if a 16-knot ship followed these rather than great circle routes. When simulating the use of a modified hydrographic approach to derive directly-gridded current velocities from an orbiting altimeter, reflective of present capabilities, an average fuel savings of 2.5% is calculated over 486 simulated voyages. A 5.8% average fuel savings is calculated when the bias associated with the modified hydrographic estimation approach is eliminated but the spatial-temporal sampling limitation associated with satellite orbits remains. Eliminating both the bias and the sampling limitation, which could be achieved with a current nowcasting model, produces 11.1% average fuel savings. Error-free forecasts lead to only slight marginal improvements over error-free nowcasts. Analysis by route characteristics indicates that the contribution of strategic routing is much better on with-current voyages—when the ship is traveling in the general direction of the primary current flow—than on counter-current voyages. We conclude that beneficial strategic routing through altimetry-derived current patterns is feasible using present capabilities on with-current voyages, but that overall performance and applicability would be substantially improved with the development of a current nowcasting model.
Human Judgment and Analytical Derivation of Ride Quality
Authors: Liu Chiu , Gazis Denos C. , Kennedy Thomas W.
Published: October 2008

Questions concerning when a road ceases to serve the public well or has failed are closely related to the ride quality of the road. The quantification of the rideability or serviceability of road deals with the human rating of ride quality. For the most thorough rating, a select panel of raters has been used to rate a road section after having either driven or ridden over the section. The average of the ratings may be called the present serviceability rating (PSR). Given a set of PSR covering a wide spectrum of roads of different surface characteristics, the essential question is how to explain the PSR in terms of the explanatory variables describing human sensitivity in some relevant functional form. It is apparent that a rater responds to the vibration environment in a moving vehicle induced by the longitudinal roughness of a road. This paper presents an analytical model connecting the characteristics of a road profile, and the dynamic response of a vehicle to the profile, to the human ratings of the ride quality. Analytical expressions for various dynamic indices in a moving vehicle are derived. Very good agreement between the model prediction and the ratings is demonstrated using actual field data. Obtaining a good model prediction would give the means of obtaining a rating of road quality comparable to that provided by experts, without the associated expense of employing such experts.
The Method of Competing Links
Authors: Halder Alan K.
Published: October 2008

A problem that is of interest in transportation planning, as well as other fields, is the effect on some or all of the shortest routes through a network, of increasing the length of a link in the network, or removing a link completely. A method is described for handling this problem, by establishing a subset of links, one of which must be contained in any alternative shortest path. These are referred to as the competing links. It is shown that this method has applications going beyond the particular problem cited. It may be applied to measuring the effects of altering some of the links in a network subjected to congested flow. The results presented for the algorithm compare very favorably with alternative procedures. It is suggested that the algorithm could be used in the development of networks which are, in some sense, optimal.
Delay at a Fixed Time Traffic Signal—II: Numerical Comparisons of some Theoretical Expressions
Authors: Hutchinson T. P.
Published: October 2008

Numerical comparisons of several expressions for the average delay to traffic passing a fixed time traffic signal have been made for a wide range of values of the arrival rate, saturation flow, cycle time, proportion of the cycle effectively green, and variance-to-mean ratio of the number of arrivals per cycle (I-ratio). The values of average delay given by Miller's, Newell's, and Webster's simplified expressions, and by a new modification of the last incorporating the I-ratio are compared with the value given by Webster's full expression. The differences are not usually more than 10 per cent when I = 1, but the importance of the I-ratio is shown by the differences reaching about 50 percent at high degrees of saturation when I = 1.5. The differences between the values of the various expressions are also compared with the effects on the value of Webster's full expression of given errors in the parameters. These effects are found to be large enough to make it difficult to distinguish experimentally between the various expressions when the I-ratio is near to 1 except by extensive measurements. Because of this the choice between expressions is often a matter of convenience of computation, and this choice is briefly discussed.
A Car-Following Model Relating Reaction Times and Temporal Headways to Accident Frequency
Authors: Brill Edward A.
Published: October 2008

This paper deals with a car-following model relating driver reaction time, temporal headway and deceleration response to accident frequency. The central goal is to assess the sensitivity of collision probability to a shift in expected reaction time. This problem reduces to determining the sensitivity of the probability of ruin to changes in the drift of the process of cumulative differences between reaction times and temporal headways. A diffusion-type approximation is used and it is shown that additive changes in mean reaction time correspond to multiplicative changes in collision probability. A numerical example is given to illustrate the potential effects of a mere 0.1 sec decrease in mean reaction time.
A Note on Computational Simplifications in Solving Generalized Transportation Problems
Authors: Glover Fred , Klingman D.
Published: October 2008

Efficient techniques are given for implementing the pricing-out and change-of-basis procedures for generalized transportation problems. Our approach avoids the necessity to “parameterize” the calculations, which is the more standard procedure. In addition, we show that the pricing-out and change-of-basis procedures can be organized in a manner that permits the calculations for one to be utilized in the other, further reducing total computational effort.
Elevator Systems for Tall Buildings Part II: Mixed-Mode Elevator Systems
Authors: Mitric Slobodan
Published: October 2008

Models of two types of mixed-mode elevator systems are presented; in the first, elevators in a tall building operate partly in an express mode and partly in a local mode. The second system contains both express-mode and local-mode elevators, but any one elevator is either an express or a local. It is found that the general strategies to be followed in elevator design, with the objective of conserving the useful floor area, are (in order indicative of the increasing positive effect): (a) keep the service zone of an elevator as small as possible, (b) separate express from local elevators, (c) use only express elevators, and (d) split express elevators on all long runs.
Balancing rigour and relevance in guideline development for depression: The case for comprehensive cohort studies
Authors: Barkham Michael. , Parry Glenys.
Published: November 2008

Purpose. Clinical guidelines for the treatment of depression have not yet realized their potential for improving the delivery of the psychological therapies within national healthcare systems. Current guidelines emphasize treatment efficacy and issues in service delivery are relatively neglected. Hence, there is a hierarchy of evidence in which randomized efficacy trials are given primacy over naturalistic (i.e. practice‐based) data. Such a strategy is inadequate to address important questions about best delivery of safe and acceptable psychological therapies and exacerbates divisions between research and practice communities.

Methods. Selected narrative review.

Results. Both randomized controlled trials and practice‐based studies have shortcomings that can be ameliorated by the adoption of practical clinical trials embedded within large cohort studies – that is, comprehensive cohort studies.

Conclusions. Comprehensive cohort studies have the potential to deliver an evidence base which is both rigorous and relevant. This could satisfy the scientific community as well as allowing practitioners and service users to be fully involved and committed to the process of collecting evidence and implementing guidance. We argue this would be a sound foundation upon which to build an evidence base upon which to develop future clinical guidelines for depression.
History, context, process, and rationale for the development of clinical guidelines
Authors: Pilling Stephen.
Published: November 2008

This paper sets out the rationale and process for the development of clinical guidelines, particularly as they apply to psychological therapies and mental health more generally. The methods by which they are produced are briefly reviewed and some commonly identified problems associated with guideline development are also discussed. The evidence for their effective implementation is reviewed and likely future development in clinical guidelines in mental health and psychological therapies are discussed.
Investigation of Irradiation Hardening and Embrittlement of Zr-2.5%Nb Alloy with High-Energy (e,γ)-Beams
Authors: Parkhomenko O. , Grytsyna V. , Chernyayeva T. , Azhazha V. , Krasnorutskyy V. , Ozhigov L. , Savchenko V.
Published: November 2008

The paper researches into the effect of the initial structural condition of Zr-2.5%Nb alloy, which is widely used in reactor engineering to manufacture reactor core components (mainly as a structural material for RBMK and CANDU pressure tubes), and of irradiation conditions (temperature, applied stress) on irradiation hardening and embrittlement. The reactor damage of Zr-2.5%Nb alloy was modeled with a method of high-energy 225 MeV (e,γ)-beam irradiation, which allows samples to be irradiated under strictly controlled stress conditions. The research has been carried out on Zr-2.5%Nb alloy exposed to four types of thermo-mechanical treatment. It has been found that the alloy is susceptible to intensive irradiation embrittlement irrespective of its initial condition, and the intensity of Zr-2.5%Nb irradiation hardening greatly depends on pre-treatment. In contrast to other conditions, Zr-2.5%Nb alloy is virtually not susceptible to irradiation hardening after high-speed high-frequency (SHF) heating, quenching, and subsequent annealing in the high-temperature range of the α-region, during which the double-phase α+βNb state with high dispersion of βNb (∼1023 m−3) precipitates develops. The obtained results are in good agreement with the post-reactor irradiation tensile test results. The study demonstrates the efficiency of high-energy (e,γ)-beam irradiation for investigating the irradiation hardening and embrittlement of zirconium alloys.
Nur7Is a Nonsense Mutation in the Mouse Aspartoacylase Gene That Causes Spongy Degeneration of the CNS
Authors: Traka Maria , Wollmann Robert L. , Cerda Sonia R. , Dugas Jason , Barres Ben A. , Popko Brian
Published: November 2008

Aspartoacylase (ASPA) is an oligodendrocyte-restricted enzyme that catalyzes the hydrolysis of neuronally derivedN-acetylaspartate (NAA) to acetate and aspartic acid. ASPA deficiency leads to the fatal childhood autosomal recessive leukodystrophy Canavan disease (CD). Here we demonstrate that the previously described ENU-inducednur7mouse mutant is caused by a nonsense mutation, Q193X, in theAspagene (Aspanur7). HomozygousAspanur7nur7mice do not express detectable Aspa protein and display an early-onset spongy degeneration of CNS myelin with increased NAA levels similar to that observed in CD patients. In addition, CNS regions rich in neuronal cell bodies also display vacuolization. Interestingly, distinct myelin rich areas, such as the corpus callosum, optic nerve, and spinal cord white matter appear normal inAspanur7/nur7mice. Reduced cerebroside synthesis has been demonstrated in CD patients and animal models. To determine the potential relevance of this observation in disease pathogenesis, we generatedAspanur7/nur7mice that were heterozygous for a null allele of the gene that encodes the enzyme UDP-galactose:ceramide galactosyltransferase (Cgt), which is responsible for catalyzing the synthesis of the abundant myelin galactolipids. Despite reduced amounts of cerebrosides, theAspanur7/nur7;Cgt+/−mice were not more severely affected than theAspanur7mutants, suggesting that diminished cerebroside synthesis is not a major contributing factor in disease pathogenesis. Furthermore, we found that myelin degeneration leads to significant axonal loss in the cerebellum of olderAspanur7mutants. This finding suggests that axonal pathology caused by CNS myelin defects may underlie the neurological disabilities that CD patients develop at late stages of the disease.
Childhood Sleep Time and Long-Term Risk for Obesity: A 32-Year Prospective Birth Cohort Study
Authors: Landhuis Carl Erik , Poulton Richie , Welch David , Hancox Robert John
Published: October 2008

OBJECTIVE. Associations between short sleep duration and increased BMI have been found in children and adults. However, it is not known whether short sleep time during childhood has long-term consequences. We assessed the association between sleep time in childhood and adult BMI in a birth cohort.

METHODS. Study members were a general-population birth cohort of 1037 participants (502 female) who were born in Dunedin, New Zealand, between April 1972 and March 1973. Parental reports of bedtimes and rising times collected at ages 5, 7, 9, and 11 years were used to estimate childhood sleep time. Linear regression analysis was used to analyze the association between childhood sleep time and BMI measured at 32 years of age.

RESULTS. Shorter childhood sleep times were significantly associated with higher adult BMI values. This association remained after adjustment for adult sleep time and the potential confounding effects of early childhood BMI, childhood socioeconomic status, parental BMIs, child and adult television viewing, adult physical activity, and adult smoking. In logistic regression analyses, more sleep time during childhood was associated with lower odds of obesity at 32 years of age. This association was significant after adjustment for multiple potential confounding factors.

CONCLUSIONS. These findings suggest that sleep restriction in childhood increases the long-term risk for obesity. Ensuring that children get adequate sleep may be a useful strategy for stemming the current obesity epidemic.
Trends in the Prevalence of Chronic Medication Use in Children: 2002–2005
Authors: Cox Emily R. , Halloran Donna R. , Homan Sharon M. , Welliver Sherry , Mager Douglas E.
Published: October 2008

OBJECTIVE. Our goal was to estimate the quarterly prevalence of and evaluate trends for chronic medication use in children.

PATIENTS AND METHODS. A cross-sectional study of ambulatory prescription claims data from 2002 to 2005 was conducted for a nationally representative sample of >3.5 million commercially insured children who were 5 to 19 years old. Prevalence of chronic medication use was measured quarterly for antihypertensives, antihyperlipidemics, type 2 antidiabetics, antidepressants, attention-deficit disorder and attention-deficit/hyperactivity disorder medications, and asthma-controller therapy.

RESULTS. First-quarter 2002 baseline prevalence of chronic medication use per 1000 child beneficiaries ranged from a high of 29.5 for antiasthmatics to a low of 0.27 for antihyperlipidemics. Except for asthma medication use, prevalence rates were higher for older teens aged 15 to 19 years. During the study period, the prevalence rate for type 2 antidiabetic agents doubled, driven by 166% and 135% increases in prevalence among females aged 10 to 14 and 15 to 19 years, respectively. Therapy classes with double-digit growth in prevalence of use were asthma medications (46.5%), attention-deficit disorder and attention-deficit/hyperactivity disorder medications (40.4%), and antihyperlipidemics (15%). Prevalence of use growth was more moderate for antihypertensives and antidepressants (1.8%). Rates of growth were dramatically higher among girls than boys for type 2 antidiabetics (147% vs 39%), attention-deficit disorder and attention-deficit/hyperactivity disorder medications (63% vs 33%), and antidepressants (7% vs −4%).

CONCLUSIONS. Prevalence of chronic medication use in children increased across all therapy classes evaluated. Additional study is needed into the factors influencing these trends, including growth in chronic disease risk factors, greater awareness and screening, and greater affinity toward early use of drug therapy in children.
Early Detection of Airway Wall Remodeling and Eosinophilic Inflammation in Preschool Wheezers
Authors: Mahr Todd A.
Published: October 2008

Saglani S, Payne DN, Zhu J, et al. Am J Respir Crit Care Med. 2007;176(9):858–864

PURPOSE OF THE STUDY. Eosinophilic airway inflammation and epithelial reticular basement membrane (RBM) thickening, absent in wheezy infants, may be present in preschool-aged children with severe, recurrent wheeze. This study compared RBM thickness and inflammation in endobronchial biopsies from wheezy preschool-aged children and age-matched control subjects.

STUDY POPULATION. Tissue for endobronchial biopsy was obtained from wheezy preschool-aged children (aged 3 months to 5 years) who were undergoing a clinically indicated fiber-optic bronchoscopy. Nonasthmatic controls were subjects undergoing fiber-optic bronchoscopy to investigate stridor.

METHODS. There were 16 children (median age: 29 months) with wheezing confirmed by video questionnaire (confirmed wheezers), 14 children (median age: 17 months) with reported wheeze (reported wheeze), and 10 (median age: 10 months) control subjects. Biopsy specimens were examined to compare eosinophilic inflammation (volume fraction of immunologically distinct inflammatory cells) and RBM thickness between the groups.

RESULTS. Median RBM thickness was 4.6 μm in children with confirmed wheezing compared with 3.5 μm in those with reported wheezing and 3.8 μm in controls. Median values for eosinophil density were 1.07% in confirmed wheezers, 0.72% in reported wheezers, and 0.0% in controls. Eosinophilic inflammation was significantly greater in confirmed wheezers compared with control subjects (P < .05). There were no between-group differences for any other inflammatory cell phenotype.

CONCLUSIONS. The characteristic pathologic features of asthma in adults and school-aged children develop in preschool-aged children with confirmed wheeze between the ages of 1 and 3 years, a time when intervention may modify the natural history of asthma.

REVIEWER COMMENTS. This study reconfirms that pathologic evidence of asthma can be found as early as 1 to 3 years of age. This also seems to relate to the time when lung-function abnormalities appear in preschool-aged persistent wheezers. Treatment during this critical period may affect the natural history of asthma.
Value of the Bronchodilator Response in Assessing Controller Naïve Asthmatic Children
Authors: James John M.
Published: October 2008

Galant SP, Morphew T, Amaro S, Liao O. J Pediatr. 2007;151(5):457–462

PURPOSE OF THE STUDY. To define the bronchodilator response (BDR) cutoff point that best identified asthma to determine the frequency of abnormal spirometry results across severity.

STUDY POPULATION. Children with asthma (n = 346) and 51 children without asthma, aged 4 to 17 years, who met entry criteria for spirometry were identified.

METHODS. Controller-naive children were evaluated with clinical criteria alone to establish a diagnosis of asthma and severity classification and then compared with the BDR, which was calculated as the percentage change from the initial forced expiratory volume in 1 second (FEV1). Receiver operator characteristic analysis determined the cutoff point for asthma diagnosis that gave the best combination of sensitivity and specificity.

RESULTS. The mean BDR in asthmatic subjects was 8.6% (95% confidence interval: 7.5%–9.8%), compared with 2.2% (95% confidence interval: 0.2%–4.3%) for the nonasthmatic subjects (P < .001). A BDR of ≥9% best differentiated these populations with a sensitivity rate of 42.5% and a specificity rate of 86.3%. Abnormal spirometry results, defined as a BDR of ≥9%, an FEV1 of <80% predicted, or both, ranged from 44.4% for mild-intermittent bronchial asthma to 57.0% for severe-persistent bronchial asthma.

CONCLUSIONS. Spirometric criteria that include BDR can potentially identify children who have clinically mild asthma and might benefit from controller therapy.

REVIEWER COMMENTS. What a breath of fresh air (pardon the pun). Establishing a firm diagnosis of asthma in pediatric patients can be, at times, a real challenge. Clinical history, physical examination, and a low FEV1 are all very useful in the diagnosis, but there are convincing data in children showing that an isolated, baseline FEV1 is not a good measure of the presence of asthma or its severity. The findings from this investigation demonstrate that detecting bronchodilator responsiveness (ie, 9% cutoff value for improvement in FEV1 after inhaled albuterol by metered-dose inhaler or nebulizer) can certainly aid in the diagnosis of asthma in children. A prospective assessment of this cutoff value in an unselected cohort of subjects, as well as the use of a single delivery system for the inhaled albuterol, will need to be investigated further to establish this measure as a useful diagnostic test for asthma in pediatric patients. Ultimately, use of the BDR in combination with baseline FEV1 should help clinicians detect a population of children with asthma and which children would benefit the most from therapeutic interventions such as inhaled corticosteroids.
Solid Food Introduction in Relation to Eczema: Results From a Four-Year Prospective Birth Cohort Study
Authors: James John M.
Published: October 2008

Filipiak B, Zutavern A, Koletzko S, et al. J Pediatr. 2007;151(4):352–358

PURPOSE OF THE STUDY. To assess the association between the introduction of solid foods in the first 12 months and the occurrence of eczema during the first 4 years of life in a prospective study of newborns.

METHODS. Data were taken from annually administered questionnaires from a large birth cohort (recruited 1995–1998) comprising an intervention and a nonintervention group. Outcomes were doctor-diagnosed and symptomatic eczema. Multiple generalized estimation equation models were performed for the 2 study groups.

RESULTS. From the 5991 recruited infants, 4753 (79%) were followed up. The 2 study groups were different in their family risk of allergies and feeding practices. No association was found between the time of introduction of solids or the diversity of solids and eczema. In the nonintervention group, a decreased risk was observed for avoidance of soybean/nuts, but an increased risk was seen in doctor-diagnosed eczema for the avoidance of egg in the first year.

CONCLUSIONS. The evidence from this study supports neither a delayed introduction of solids beyond the fourth month nor a delayed introduction of the most potentially allergenic solids beyond the sixth month of life for the prevention of eczema. However, effects under more extreme conditions cannot be ruled out.

REVIEWER COMMENTS. The dilemma of when to introduce solid foods during infancy continues. The data from this investigation support the notion that it is unnecessary to delay solid foods beyond the fourth month of life or allergenic solid foods beyond the sixth month of life to prevent eczema. Specifically, this investigation found no significant effect of timing or diversity of solid foods on eczema outcomes to 4 years of age. The duration of exclusive breastfeeding as compared with the timing of introduction of solid foods, including both formulas made with whole cow's milk or soy proteins, as well as extensively hydrolyzed casein and partially hydrolyzed whey protein formulas, were examined. It is interesting to note that findings from this investigation seem to indicate that there may be a period of immunologic immaturity during which whole protein in large amounts, whether solid or liquid, may promote the development of atopic disease. These data should help to settle the argument of when to introduce solid foods during infancy for the prevention of eczema and will have a direct impact on global recommendations dealing with this clinical issue.
Identification of Host Proteins Required for HIV Infection Through a Functional Genomic Screen
Authors: Church Joseph A.
Published: October 2008

Brass AL, Dykxhoorn DM, Benita Y, et al. Science. 2008;319(5865):921–926

PURPOSE OF THE STUDY. The HIV genome encodes only 15 proteins and, therefore, must use multiple host-cell collaborators for successful replication and transmission. Required host-derived proteins include CD4 as the primary virus receptor and chemokine receptors as coreceptors. This study identified multiple other host proteins required for HIV activity.

METHODS. Human cells known to be susceptible to HIV were exposed in vitro to HIV. Using small interfering RNAs able to inhibit each known gene in the human genome 1 at a time, the investigators tested whether HIV could establish an infection and copy itself. HIV dependence on >21 000 human genes was examined.

RESULTS. More than 250 human genes were identified to be required for efficient HIV replication. Termed “HIV-dependency factors,” the products of these genes are known to participate in a broad array of cellular functions and implicate unsuspected pathways in the virus life cycle.

CONCLUSIONS. The extraordinary dependence of HIV on human host proteins for efficient transmission and replication provides many new potential targets for antiretroviral therapy.

REVIEWER COMMENTS. An example of targeting host proteins is the use of chemokine receptor 5 (CCR5) inhibitors. Many people with CCR5 deficiency are very resistant to HIV infection yet have limited if any clinical consequences. Maraviroc CCR5 inhibitor is approved for treatment for HIV infection. This study identified many more such potential targets.