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Showing papers by "University of North Carolina at Chapel Hill published in 1999"


Journal ArticleDOI
01 Sep 1999-Gut
TL;DR: A committee consensus approach, including criticism from multinational expert reviewers, was used to revise the diagnostic criteria and update diagnosis and treatment recommendations, based on research results.
Abstract: The Rome diagnostic criteria for the functional bowel disorders and functional abdominal pain are used widely in research and practice. A committee consensus approach, including criticism from multinational expert reviewers, was used to revise the diagnostic criteria and update diagnosis and treatment recommendations, based on research results. The terminology was clarified and the diagnostic criteria and management recommendations were revised. A functional bowel disorder (FBD) is diagnosed by characteristic symptoms for at least 12 weeks during the preceding 12 months in the absence of a structural or biochemical explanation. The irritable bowel syndrome, functional abdominal bloating, functional constipation, and functional diarrhea are distinguished by symptom-based diagnostic criteria. Unspecified FBD lacks criteria for the other FBDs. Diagnostic testing is individualized, depending on patient age, primary symptom characteristics, and other clinical and laboratory features. Functional abdominal pain (FAP) is defined as either the FAP syndrome, which requires at least six months of pain with poor relation to gut function and loss of daily activities, or unspecified FAP, which lacks criteria for the FAP syndrome. An organic cause for the pain must be excluded, but aspects of the patient's pain behavior are of primary importance. Treatment of the FBDs relies upon confident diagnosis, explanation, and reassurance. Diet alteration, drug treatment, and psychotherapy may be beneficial, depending on the symptoms and psychological features.

2,528 citations


Journal ArticleDOI
TL;DR: In this paper, the authors introduce the concept of workplace incivility and explain how it can potentially spiral into increasingly intense aggressive behaviors, and examine what happens at key points: the starting and tipping points.
Abstract: In this article we introduce the concept of workplace incivility and explain how incivility can potentially spiral into increasingly intense aggressive behaviors. To gain an understanding of the mechanisms that underlie an “incivility spiral,” we examine what happens at key points: the starting and tipping points. Furthermore, we describe several factors that can facilitate the occurrence and escalation of an incivility spiral and the secondary spirals that can result. We offer research propositions and discuss implications of workplace incivility for researchers and practitioners.

2,527 citations


Journal ArticleDOI
14 May 1999-Cell
TL;DR: Electron microscopy reported here demonstrated that TRF2 can remodel linear telomeric DNA into large duplex loops (t loops) in vitro, which may provide a general mechanism for the protection and replication of telomeres.

2,413 citations


Journal ArticleDOI
TL;DR: Two important processes have occurred to legitimize these conditions, and to increase attention toward the research and clinical care of patients with functional gastrointestinal disorders (FGID), a shift in conceptualizing these disorders from a disease-based, reductionistic model, to a more integrated, biopsychosocial model of illness.

2,274 citations


Journal ArticleDOI
27 Oct 1999-JAMA
TL;DR: The estimated number of annual deaths attributable to obesity among US adults is approximately 280000 based onHRs from all subjects and 325000 based on HRs from only nonsmokers and never-smokers.
Abstract: ContextObesity is a major health problem in the United States, but the number of obesity-attributable deaths has not been rigorously estimated.ObjectiveTo estimate the number of deaths, annually, attributable to obesity among US adults.DesignData from 5 prospective cohort studies (the Alameda Community Health Study, the Framingham Heart Study, the Tecumseh Community Health Study, the American Cancer Society Cancer Prevention Study I, and the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study) and 1 published study (the Nurses' Health Study) in conjunction with 1991 national statistics on body mass index distributions, population size, and overall deaths.SubjectsAdults, 18 years or older in 1991, classified by body mass index (kg/m2) as overweight (25-30), obese (30-35), and severely obese (>35).Main Outcome MeasureRelative hazard ratio (HR) of death for obese or overweight persons.ResultsThe estimated number of annual deaths attributable to obesity varied with the cohort used to calculate the HRs, but findings were consistent overall. More than 80% of the estimated obesity-attributable deaths occurred among individuals with a body mass index of more than 30 kg/m2. When HRs were estimated for all eligible subjects from all 6 studies, the mean estimate of deaths attributable to obesity in the United States was 280,184 (range, 236,111-341,153). Hazard ratios also were calculated from data for nonsmokers or never-smokers only. When these HRs were applied to the entire population (assuming the HR applied to all individuals), the mean estimate for obesity-attributable death was 324,940 (range, 262,541-383,410).ConclusionsThe estimated number of annual deaths attributable to obesity among US adults is approximately 280,000 based on HRs from all subjects and 325,000 based on HRs from only nonsmokers and never-smokers.

1,954 citations


Journal ArticleDOI
02 Sep 1999-Nature
TL;DR: A role for NF-κB in growth factor signalling is established and an anti-apoptotic Ras/PI(3)K/Akt/IKK/NF-κBs pathway is defined, thus linking anti-APoptotic signalling with transcription machinery.
Abstract: The mechanisms of cell proliferation and transformation are intrinsically linked to the process of apoptosis: the default of proliferating cells is to die unless specific survival signals are provided1,2. Platelet-derived growth factor (PDGF) is a principal survival factor that inhibits apoptosis and promotes proliferation1, but the mechanisms mediating its anti-apoptotic properties are not completely understood. Here we show that the transcription factor NF-κB3,4,5 is important in PDGF signalling. NF-κB transmits two signals: one is required for the induction of proto-oncogene c-myc and proliferation, and the second, an anti-apoptotic signal, counterbalances c-Myc cytotoxicity. We have traced a putative pathway whereby PDGF activates NF-κB through Ras and phospatidylinositol-3-kinase (PI(3)K) to the PKB/Akt protein kinase and the IκB kinase (IKK); NF-κB thus appears to be a target of the anti-apoptotic Ras/PI(3)K/Akt pathway6,7. We show that, upon PDGF stimulation, Akt transiently associates in vivo with IKK and induces IKK activation. These findings establish a role for NF-κB in growth factor signalling and define an anti-apoptotic Ras/PI(3)K/Akt/IKK/NF-κB pathway, thus linking anti-apoptotic signalling with transcription machinery.

1,819 citations


Journal ArticleDOI
TL;DR: This paper examined the antecedents, consequences, and mediational role of team empowerment using 111 work teams in four organizations and found that empowered teams were more productive and proactive than less empowered teams and had higher levels of customer service, job satisfaction and organizational and team commitment.
Abstract: We examined the antecedents, consequences, and mediational role of team empowerment using 111 work teams in four organizations. The results indicated that the actions of external leaders, the production/service responsibilities given to teams, team-based human resources policies, and the social structure of teams all worked to enhance employee team empowerment experiences. More empowered teams were also more productive and proactive than less empowered teams and had higher levels of customer service, job satisfaction, and organizational and team commitment.

1,793 citations


Journal ArticleDOI
TL;DR: In this paper, the authors contribute to the emerging body of knowledge on buyer-seller relationships in business markets, focusing on the relationship between buyers and sellers in the context of marketing managers and scholars.
Abstract: During the past decade, marketing managers and scholars have focused increased attention on buyer–seller relationships in business markets. This article contributes to the emerging body of knowledg...

1,783 citations


Journal ArticleDOI
TL;DR: In this article, the authors investigated how similarity changes with distance in biological communities, and explored whether growth form, dispersal type, rarity, or support affected the rate of distance decay in similarity.
Abstract: Aim Our aim was to understand how similarity changes with distance in biological communities, to use the distance decay perspective as quantitative technique to describe biogeographic pattern, and to explore whether growth form, dispersal type, rarity, or support affected the rate of distance decay in similarity. Location North American spruce-fir forests, Appalachian montane spruce-fir forests. Methods We estimated rates of distance decay through regression of log-transformed compositional similarity against distance for pairwise comparisons of thirty-four white spruce plots and twenty-six black spruce plots distributed from eastern Canada to Alaska, six regional floras along the crest of the Appalachians, and six regional floras along the east‐west extent of the boreal forest. Results Similarity decreased significantly with distance, with the most linear models relating the log of similarity to untransformed distance. The rate of similarity decay was 1.5‐1.9 times higher for vascular plants than for bryophytes. The rate of distance decay was highest for berry-fruited and nut-bearing species (1.7 times higher than plumose-seeded species and 1.9 times higher than microseeded/spore species) and 2.1 times higher for herbs than woody plants. There was no distance decay for rare species, while species of intermediate frequency had 2.0 times higher distance decay rates than common species. The rate of distance decay was 2.7 times higher for floras from the fragmented Appalachians than for floras from the contiguous boreal forest. Main conclusions The distance decay of similarity can be caused by either a decrease in environmental similarity with distance (e.g. climatic gradients) or by limits to dispersal and niche width differences among taxa. Regardless of cause, the distance decay of similarity provides a simple descriptor of how biological diversity is distributed and therefore has consequences for conservation strategy.

1,529 citations


Journal ArticleDOI
TL;DR: In this article, the authors propose a method for the identification of the most likely candidate species of a given species from a set of known species: a.k.a. a. nomenclature.

1,466 citations


Journal ArticleDOI
TL;DR: In this paper, the authors investigate if the use of a Big 6 auditor is increasing the propensity of a firm's endogenous propensity to generate accruals and find that high-accrual firms have greater scope for aggressive and/or opportunistic strategies.
Abstract: This study investigates if the use of a Big 6 auditor is increasing in the firm's endogenous propensity to generate accruals. High‐accrual firms have greater scope for aggressive and/or opportunist...

Journal ArticleDOI
TL;DR: It is shown that NF-κB also promotes cell growth in embryonic fibroblasts, correlating with its regulation of cyclin D1, and is identified as an important transcriptional target of NF-α, revealing a mechanism to explain how NF-β is involved in the early phases of the cell cycle to regulate cell growth and differentiation.
Abstract: Accumulating evidence implicates the transcription factor NF-kappaB as a positive mediator of cell growth, but the molecular mechanism(s) involved in this process remains largely unknown. Here we use both a skeletal muscle differentiation model and normal diploid fibroblasts to gain insight into how NF-kappaB regulates cell growth and differentiation. Results obtained with the C2C12 myoblast cell line demonstrate that NF-kappaB functions as an inhibitor of myogenic differentiation. Myoblasts generated to lack NF-kappaB activity displayed defects in cellular proliferation and cell cycle exit upon differentiation. An analysis of cell cycle markers revealed that NF-kappaB activates cyclin D1 expression, and the results showed that this regulatory pathway is one mechanism by which NF-kappaB inhibits myogenesis. NF-kappaB regulation of cyclin D1 occurs at the transcriptional level and is mediated by direct binding of NF-kappaB to multiple sites in the cyclin D1 promoter. Using diploid fibroblasts, we demonstrate that NF-kappaB is required to induce cyclin D1 expression and pRb hyperphosphorylation and promote G(1)-to-S progression. Consistent with results obtained with the C2C12 differentiation model, we show that NF-kappaB also promotes cell growth in embryonic fibroblasts, correlating with its regulation of cyclin D1. These data therefore identify cyclin D1 as an important transcriptional target of NF-kappaB and reveal a mechanism to explain how NF-kappaB is involved in the early phases of the cell cycle to regulate cell growth and differentiation.

Journal ArticleDOI
TL;DR: Several novel purification strategies that involve the use of non-ionic iodixanol gradients followed by ion exchange or heparin affinity chromatography by either conventional or HPLC columns are reported, which result in more than 50% recovery of rAAV from a crude lysate and routinely produce vector that is more than 99% pure.
Abstract: Conventional methods for rAAV purification that are based on cesium chloride ultracentrifugation have often produced vector preparations of variable quality and resulted in significant loss of particle infectivity. We report here several novel purification strategies that involve the use of non-ionic iodixanol gradients followed by ion exchange or heparin affinity chromatography by either conventional or HPLC columns. These methods result in more than 50% recovery of rAAV from a crude lysate and routinely produce vector that is more than 99% pure. More importantly, the new purification procedures consistently produce rAAV stocks with particle-to-infectivity ratios of less than 100, which is significantly better than conventional methods. The new protocol increases the overall yield of infectious rAAV by at least 10-fold and allows for the complete purification of rAAV in 1 working day. Several of these methods should also be useful for large-scale production.

Journal ArticleDOI
TL;DR: In this paper, the authors discuss the management of the natural environment is becoming an increasingly important issue to manufacturing firms, yet their managers are also challenged to implement changes that improve competitiveness.
Abstract: Management of the natural environment is becoming an increasingly important issue to manufacturing firms, yet their managers are also challenged to implement changes that improve competitiveness. T...

Journal ArticleDOI
TL;DR: A caretaker role for BRCA1 is demonstrated in preserving genomic integrity by promoting homologous recombination and limiting mutagenic nonhomologous repair processes.

Journal ArticleDOI
TL;DR: There is a high rate of relapse within 5 years of recovery from a first episode of schizophrenia and schizoaffective disorder, and this risk is diminished by maintenance antipsychotic drug treatment.
Abstract: Background We examined relapse after response to a first episode of schizophrenia or schizoaffective disorder. Methods Patients with first-episode schizophrenia were assessed on measures of psychopathologic variables, cognition, social functioning, and biological variables and treated according to a standardized algorithm. The sample for the relapse analyses consisted of 104 patients who responded to treatment of their index episode and were at risk for relapse. Results Five years after initial recovery, the cumulative first relapse rate was 81.9% (95% confidence interval [CI], 70.6%-93.2%); the second relapse rate was 78.0% (95% CI, 46.5%-100.0%). By 4 years after recovery from a second relapse, the cumulative third relapse rate was 86.2% (95% CI, 61.5%-100.0%). Discontinuing antipsychotic drug therapy increased the risk of relapse by almost 5 times (hazard ratio for an initial relapse, 4.89 [99% CI, 2.49-9.60]; hazard ratio for a second relapse, 4.57 [99% CI, 1.49-14.02]). Subsequent analyses controlling for antipsychotic drug use showed that patients with poor premorbid adaptation to school and premorbid social withdrawal relapsed earlier. Sex, diagnosis, obstetric complications, duration of psychotic illness before treatment, baseline symptoms, neuroendocrine measures, methylphenidate hydrochloride challenge response, neuropsychologic and magnetic resonance imaging measures, time to response of the initial episode, adverse effects during treatment, and presence of residual symptoms after the initial episode were not significantly related to time to relapse. Conclusions There is a high rate of relapse within 5 years of recovery from a first episode of schizophrenia and schizoaffective disorder. This risk is diminished by maintenance antipsychotic drug treatment.

Journal ArticleDOI
TL;DR: In this article, a modification in the three-dimensional Ewald summation technique was proposed for calculations of long-range Coulombic forces for systems with a slab geometry that are periodic in two dimensions and have a finite length in the third dimension.
Abstract: We propose a modification in the three-dimensional Ewald summation technique for calculations of long-range Coulombic forces for systems with a slab geometry that are periodic in two dimensions and have a finite length in the third dimension. The proposed method adds a correction term to the standard Ewald summation formula. To test the current method, molecular dynamics simulations on water between Pt(111) walls have been carried out. For a more direct test, the calculation of the pair forces between two point charges has been also performed. An excellent agreement with the results from simulations using the rigorous two dimensional Ewald summation technique were obtained. We observed that a significant reduction in computing time can be achieved when the proposed modification is used.

Journal ArticleDOI
TL;DR: In this article, a large sample of hedge fund data from 1988-1995 was used to find that hedge funds consistently outperform mutual funds, but not standard market indices, and the impact of six data-conditioning biases was explored.
Abstract: Hedge funds display several interesting characteristics that may influence performance, including: flexible investment strategies, strong managerial incentives, substantial managerial investment, sophisticated investors, and limited government oversight. Using a large sample of hedge fund data from 1988-1995, we find that hedge funds consistently outperform mutual funds, but not standard market indices. Hedge funds, however, are more volatile than both mutual funds and market indices. Incentive fees explain some of the higher performance, but not the increased total risk. The impact of six data-conditioning biases is explored. We find evidence that positive and negative survival-related biases offset each other. HEDGE FUNDS HAVE BEEN IN EXISTENCE for almost 50 years. However, their recent growth has increased their prominence in the financial markets and the business press. Since the late 1980s, the number of hedge funds has risen by more than 25 percent per year. The rate of growth in hedge fund assets has been even more rapid. In 1997, there were more than 1200 hedge funds managing a total of more than $200 billion. Though the number and size of hedge funds are small relative to mutual funds, their growth reflects the importance of this alternative investment vehicle for institutional investors and wealthy individual investors.' As the name implies, hedge funds began as investment partnerships that could take long and short positions. They have evolved into a multifaceted organizational structure that defies simple definition. There are, however, a

Journal ArticleDOI
TL;DR: Protocols have been developed for nonmydriatic fundus photography and for evaluation of retinal vascular abnormalities in the ARIC Study and several microvascular changes were significantly associated with higher blood pressure, controlling for gender, race, age, and smoking status.

Journal ArticleDOI
20 Aug 1999-Cell
TL;DR: The generation of mice expressing only 5% of normal levels of the essential NMDAR1 (NR1) subunit is reported, supporting a model in which reduced NMDA receptor activity results in schizophrenic-like behavior and reveals how pharmacological manipulation of monoaminergic pathways can affect this phenotype.

Journal ArticleDOI
TL;DR: This article found that stock price reactions to independent director appointments are significantly lower when the CEO is involved in the selection of new directors compared to when no CEO involvement is required, and they found that companies remove CEOs from involvement in board selection.
Abstract: We study whether CEO involvement in the selection of new directors influences the nature of appointments to the board. When the CEO serves on the nominating committee or no nominating committee exists, firms appoint fewer independent outside directors and more gray outsiders with conflicts of interest. Stock price reactions to independent director appointments are significantly lower when the CEO is involved in director selection. Our evidence may illuminate a mechanism used by CEOs to reduce pressure from active monitoring, and we find a recent trend of companies removing CEOs from involvement in director selection.

Journal ArticleDOI
TL;DR: Markers of inflammation are associated with the development of diabetes in middle-aged adults, and autoimmunity may partly explain these associations, which probably reflect the pathogenesis of type 2 diabetes.

Journal ArticleDOI
TL;DR: It is demonstrated that the activation of NF-κB in response to chemotherapy is a principal mechanism of inducible tumor chemoresistance, and the inhibition of NF -κB is established as a new approach to adjuvant therapy in cancer treatment.
Abstract: Control of inducible chemoresistance: Enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-κB

Journal ArticleDOI
TL;DR: The findings indicate that subtle symptoms of autism are present at 9–12 months, and suggest that early assessment procedures need to consider sensory processing/sensory-motor functions in addition to social responses during infancy.
Abstract: This retrospective video study explored the usefulness of sensory-motor measures in addition to social behaviors as early predictors of autism during infancy. Three groups included 11 children with autism, 10 with developmental disabilities, and 11 typically developing children. Home videos were edited to obtain a 10-minute cross-section of situations at 9-12 months for each subjects. Using interval scoring, raters coded several behavioral categories (i.e., Looking, Affect, Response to Name, Anticipatory Postures, Motor/Object Stereotypies, Social Touch, Sensory Modulation). Nine items, in combination, were found to discriminate the three groups with a correct classification rate of 93.75%. These findings indicate that subtle symptoms of autism are present at 9-12 months, and suggest that early assessment procedures need to consider sensory processing/sensory-motor functions in addition to social responses during infancy. Furthermore, prior to a time that they reported autistic symptoms, caregivers used compensatory strategies to increase the saliency of stimuli in order to engage their children more successfully; these strategies may provide a window for earlier diagnosis.

Journal ArticleDOI
01 Jul 1999-Neuron
TL;DR: A novel family of postsynaptic density proteins, termed Shank, that binds via its PDZ domain to the C terminus of PSD-95-associated protein GKAP, and may function as a scaffold protein in the PSD, potentially cross-linking NMDA receptor/PSD- 95 complexes and coupling them to regulators of the actin cytoskeleton.

Journal ArticleDOI
TL;DR: Specific detailed recommendations for each level have been established in this document, which are intended to improve the rate of early suspicion and diagnosis of, and therefore early intervention for, autism.
Abstract: The Child Neurology Society and American Academy of Neurology recently proposed to formulate Practice Parameters for the Diagnosis and Evaluation of Autism for their memberships. This endeavor was expanded to include representatives from nine professional organizations and four parent organizations, with liaisons from the National Institutes of Health. This document was written by this multidisciplinary Consensus Panel after systematic analysis of over 2,500 relevant scientific articles in the literature. The Panel concluded that appropriate diagnosis of autism requires a dual-level approach: (a) routine developmental surveillance, and (b) diagnosis and evaluation of autism. Specific detailed recommendations for each level have been established in this document, which are intended to improve the rate of early suspicion and diagnosis of, and therefore early intervention for, autism.

Journal ArticleDOI
10 Dec 1999-Science
TL;DR: Global transposon mutagenesis was used to identify nonessential genes in an effort to learn whether the naturally occurring gene complement is a true minimal genome under laboratory growth conditions, and suggests that 265 to 350 of the 480 protein-coding genes of M. genitalium are essential under laboratory growing conditions.
Abstract: Mycoplasma genitalium with 517 genes has the smallest gene complement of any independently replicating cell so far identified. Global transposon mutagenesis was used to identify nonessential genes in an effort to learn whether the naturally occurring gene complement is a true minimal genome under laboratory growth conditions. The positions of 2209 transposon insertions in the completely sequenced genomes of M. genitalium and its close relative M. pneumoniae were determined by sequencing across the junction of the transposon and the genomic DNA. These junctions defined 1354 distinct sites of insertion that were not lethal. The analysis suggests that 265 to 350 of the 480 protein-coding genes of M. genitalium are essential under laboratory growth conditions, including about 100 genes of unknown function.

Journal ArticleDOI
TL;DR: Calcium supplementation is associated with a significant - though moderate - reduction in the risk of recurrent colorectal adenomas, independent of initial dietary fat and calcium intake.
Abstract: Background and Methods Laboratory, clinical, and epidemiologic evidence suggests that calcium may help prevent colorectal adenomas. We conducted a randomized, double-blind trial of the effect of supplementation with calcium carbonate on the recurrence of colorectal adenomas. We randomly assigned 930 subjects (mean age, 61 years; 72 percent men) with a recent history of colorectal adenomas to receive either calcium carbonate (3 g [1200 mg of elemental calcium] daily) or placebo, with follow-up colonoscopies one and four years after the qualifying examination. The primary end point was the proportion of subjects in whom at least one adenoma was detected after the first follow-up endoscopy but up to (and including) the second follow-up examination. Risk ratios for the recurrence of adenomas were adjusted for age, sex, lifetime number of adenomas before the study, clinical center, and length of the surveillance period. Results The subjects in the calcium group had a lower risk of recurrent adenomas. Among the...

Journal ArticleDOI
TL;DR: This review summarizes recent developments in transfusion medicine that have affected the field and the identification of patients most likely to benefit from blood conservation.
Abstract: Blood transfusion and blood conservation (techniques or strategies to avoid the need for blood) are complementary activities that constitute the clinical arena of transfusion medicine. Recent improvements in the safety of the blood supply and the increasing costs associated with transfusion therapies have led to a reevaluation of the clinical practices of blood transfusion and blood conservation. Among the issues that have been reevaluated are the threshold for transfusion at which the benefits outweigh the risks and the identification of patients most likely to benefit from blood conservation. This review summarizes recent developments in transfusion medicine that have affected the . . .

Proceedings ArticleDOI
01 Jul 1999
TL;DR: The authors showed that subjective presence significantly correlated with subjects' degree of association with their virtual bodies (avatars), suggesting that substantial potential presence gains can be had from tracking all limbs and customizing avatar appearance.
Abstract: A study by Slater, et al., [1995] indicated that naive subjects in an immersive virtual environment experience a higher subjective sense of presence when they locomote by walking-in-place (virtual walking) than when they push-button-fly (along the floor plane). We replicated their study, adding real walking as a third condition. Our study confirmed their findings. We also found that real walking is significantly better than both virtual walking and flying in ease (simplicity, straightforwardness, naturalness) as a mode of locomotion. The greatest difference in subjective presence was between flyers and both kinds of walkers. In addition, subjective presence was higher for real walkers than virtual walkers, but the difference was statistically significant only in some models. Follow-on studies show virtual walking can be substantially improved by detecting footfalls with a head accelerometer. As in the Slater study, subjective presence significantly correlated with subjects' degree of association with their virtual bodies (avatars). This, our strongest statistical result, suggests that substantial potential presence gains can be had from tracking all limbs and customizing avatar appearance. An unexpected by-product was that real walking through our enhanced version of Slater's visual-cliff virtual environment (Figure 1) yielded a strikingly compelling virtual experience - The strongest we and most of our visitors have yet experienced. The most needed system improvement is the substitution of wireless technology for all links to the user. Copyright ACM 1999.