Showing papers by "Harvard University published in 2000"

Bowling Alone: The Collapse and Revival of American Community

Abstract: BOWLING ALONE warns Americans that their stock of "social capital", the very fabric of their connections with each other, has been accelerating down. Putnam describes the resulting impoverishment of their lives and communities. Drawing on evidence that includes nearly half a million interviews conducted over a quarter of a century in America, Putnam shows how changes in work, family structure, age, suburban life, television, computers, women's roles and other factors are isolating Americans from each other in a trend whose reflection can clearly be seen in British society. We sign 30 percent fewer petitions than we did ten years ago. Membership in organisations- from the Boy Scouts to political parties and the Church is falling. Ties with friends and relatives are fraying: we're 35 percent less likely to visit our neighbours or have dinner with our families than we were thirty years ago. We watch sport alone instead of with our friends. A century ago, American citizens' means of connecting were at a low point after decades of urbanisation, industrialisation and immigration uprooted them from families and friends. That generation demonstrated a capacity for renewal by creating the organisations that pulled Americans together. Putnam shows how we can learn from them and reinvent common enterprises that will make us secure, productive, happy and hopeful.

Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.

Abstract: Background Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml per kilogram of body weight and may cause stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome. We therefore conducted a trial to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these patients. Methods Patients with acute lung injury and the acute respiratory distress syndrome were enrolled in a multicenter, randomized trial. The trial compared traditional ventilation treatment, which involved an initial tidal volume of 12 ml per kilogram of predicted body weight and an airway pressure measured after a 0.5-second pause at the end of inspiration (plateau pressure) of 50 cm of water or less, with ventilation with a lower tidal volume, which involved an initial tidal volume of 6 ml per kilogram of predicted body weight and a plateau pressure of 30 cm of water or less. The primary outcomes were death before a patient was discharged home and was breathing without assistance and the number of days without ventilator use from day 1 to day 28. Results The trial was stopped after the enrollment of 861 patients because mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes (31.0 percent vs. 39.8 percent, P=0.007), and the number of days without ventilator use during the first 28 days after randomization was greater in this group (mean [+/-SD], 12+/-11 vs. 10+/-11; P=0.007). The mean tidal volumes on days 1 to 3 were 6.2+/-0.8 and 11.8+/-0.8 ml per kilogram of predicted body weight (P Conclusions In patients with acute lung injury and the acute respiratory distress syndrome, mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use.

Angiogenesis in cancer and other diseases

Abstract: Pathological angiogenesis is a hallmark of cancer and various ischaemic and inflammatory diseases Concentrated efforts in this area of research are leading to the discovery of a growing number of pro- and anti-angiogenic molecules, some of which are already in clinical trials The complex interactions among these molecules and how they affect vascular structure and function in different environments are now beginning to be elucidated This integrated understanding is leading to the development of a number of exciting and bold approaches to treat cancer and other diseases But owing to several unanswered questions, caution is needed

GPSR: greedy perimeter stateless routing for wireless networks

Abstract: We present Greedy Perimeter Stateless Routing (GPSR), a novel routing protocol for wireless datagram networks that uses the positions of routers and a packet's destination to make packet forwarding decisions. GPSR makes greedy forwarding decisions using only information about a router's immediate neighbors in the network topology. When a packet reaches a region where greedy forwarding is impossible, the algorithm recovers by routing around the perimeter of the region. By keeping state only about the local topology, GPSR scales better in per-router state than shortest-path and ad-hoc routing protocols as the number of network destinations increases. Under mobility's frequent topology changes, GPSR can use local topology information to find correct new routes quickly. We describe the GPSR protocol, and use extensive simulation of mobile wireless networks to compare its performance with that of Dynamic Source Routing. Our simulations demonstrate GPSR's scalability on densely deployed wireless networks.

Biotic invasions: causes, epidemiology, global consequences, and control

Abstract: Biotic invaders are species that establish a new range in which they proliferate, spread, and persist to the detriment of the environment. They are the most important ecological outcomes from the unprecedented alterations in the distribution of the earth's biota brought about largely through human transport and commerce. In a world without borders, few if any areas remain sheltered from these im- migrations. The fate of immigrants is decidedly mixed. Few survive the hazards of chronic and stochastic forces, and only a small fraction become naturalized. In turn, some naturalized species do become invasive. There are several potential reasons why some immigrant species prosper: some escape from the constraints of their native predators or parasites; others are aided by human-caused disturbance that disrupts native communities. Ironically, many biotic invasions are apparently facilitated by cultivation and husbandry, unintentional actions that foster immigrant populations until they are self-perpetuating and uncontrollable. Whatever the cause, biotic invaders can in many cases inflict enormous environmental damage: (1) Animal invaders can cause extinctions of vulnerable native species through predation, grazing, competition, and habitat alteration. (2) Plant invaders can completely alter the fire regime, nutrient cycling, hydrology, and energy budgets in a native ecosystem and can greatly diminish the abundance or survival of native species. (3) In agriculture, the principal pests of temperate crops are nonindigenous, and the combined expenses of pest control and crop losses constitute an onerous "tax" on food, fiber, and forage production. (4) The global cost of virulent plant and animal diseases caused by parasites transported to new ranges and presented with susceptible new hosts is currently incalculable. Identifying future invaders and taking effective steps to prevent their dispersal and establishment con- stitutes an enormous challenge to both conservation and international commerce. Detection and management when exclusion fails have proved daunting for varied reasons: (1) Efforts to identify general attributes of future invaders have often been inconclusive. (2) Predicting susceptible locales for future invasions seems even more problematic, given the enormous differences in the rates of arrival among potential invaders. (3) Eradication of an established invader is rare, and control efforts vary enormously in their efficacy. Successful control, however, depends more on commitment and continuing diligence than on the efficacy of specific tools themselves. (4) Control of biotic invasions is most effective when it employs a long-term, ecosystem- wide strategy rather than a tactical approach focused on battling individual invaders. (5) Prevention of invasions is much less costly than post-entry control. Revamping national and international quarantine laws by adopting a "guilty until proven innocent" approach would be a productive first step. Failure to address the issue of biotic invasions could effectively result in severe global consequences, including wholesale loss of agricultural, forestry, and fishery resources in some regions, disruption of the ecological processes that supply natural services on which human enterprise depends, and the creation of homogeneous, impoverished ecosystems composed of cosmopolitan species. Given their current scale, biotic invasions have taken their place alongside human-driven atmospheric and oceanic alterations as major agents of global change. Left unchecked, they will influence these other forces in profound but still unpredictable ways.

The genome sequence of Drosophila melanogaster

Abstract: The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.

Increasing Returns, Path Dependence, and the Study of Politics

Abstract: It is increasingly common for social scientists to describe political processes as “path dependent.” The concept, however, is often employed without careful elaboration. This article conceptualizes path dependence as a social process grounded in a dynamic of “increasing returns.” Reviewing recent literature in economics and suggesting extensions to the world of politics, the article demonstrates that increasing returns processes are likely to be prevalent, and that good analytical foundations exist for exploring their causes and consequences. The investigation of increasing returns can provide a more rigorous framework for developing some of the key claims of recent scholarship in historical institutionalism: Specific patterns of timing and sequence matter; a wide range of social outcomes may be possible; large consequences may result from relatively small or contingent events; particular courses of action, once introduced, can be almost impossible to reverse; and consequently, political development is punctuated by critical moments or junctures that shape the basic contours of social life.

Information Asymmetry, Corporate Disclosure and the Capital Markets: A Review of the Empirical Disclosure Literature

Abstract: Corporate disclosure is critical for the functioning of an efficient capital market. Firms provide disclosure through regulated financial reports, including the financial statements, footnotes, management discussion and analysis, and other regulatory filings. In addition, some firms engage in voluntary communication, such as management forecasts, analysts? presentations and conference calls, press releases, internet sites, and other corporate reports. Finally, there are disclosures about firms by information intermediaries, such as financial analysts, industry experts, and the financial press.

Measuring the thickness of the human cerebral cortex from magnetic resonance images

Abstract: Accurate and automated methods for measuring the thickness of human cerebral cortex could provide powerful tools for diagnosing and studying a variety of neurodegenerative and psychiatric disorders. Manual methods for estimating cortical thickness from neuroimaging data are labor intensive, requiring several days of effort by a trained anatomist. Furthermore, the highly folded nature of the cortex is problematic for manual techniques, frequently resulting in measurement errors in regions in which the cortical surface is not perpendicular to any of the cardinal axes. As a consequence, it has been impractical to obtain accurate thickness estimates for the entire cortex in individual subjects, or group statistics for patient or control populations. Here, we present an automated method for accurately measuring the thickness of the cerebral cortex across the entire brain and for generating cross-subject statistics in a coordinate system based on cortical anatomy. The intersubject standard deviation of the thickness measures is shown to be less than 0.5 mm, implying the ability to detect focal atrophy in small populations or even individual subjects. The reliability and accuracy of this new method are assessed by within-subject test-retest studies, as well as by comparison of cross-subject regional thickness measures with published values.

The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans

Abstract: The C. elegans heterochronic gene pathway consists of a cascade of regulatory genes that are temporally controlled to specify the timing of developmental events1. Mutations in heterochronic genes cause temporal transformations in cell fates in which stage-specific events are omitted or reiterated2. Here we show that let-7 is a heterochronic switch gene. Loss of let-7 gene activity causes reiteration of larval cell fates during the adult stage, whereas increased let-7 gene dosage causes precocious expression of adult fates during larval stages. let-7 encodes a temporally regulated 21-nucleotide RNA that is complementary to elements in the 3′ untranslated regions of the heterochronic genes lin-14, lin-28, lin-41, lin-42 and daf-12, indicating that expression of these genes may be directly controlled by let-7. A reporter gene bearing the lin-41 3′ untranslated region is temporally regulated in a let-7-dependent manner. A second regulatory RNA, lin-4, negatively regulates lin-14 and lin-28 through RNA–RNA interactions with their 3′ untranslated regions3,4. We propose that the sequential stage-specific expression of the lin-4 and let-7 regulatory RNAs triggers transitions in the complement of heterochronic regulatory proteins to coordinate developmental timing.

Marginal Structural Models and Causal Inference in Epidemiology

Abstract: In observational studies with exposures or treatments that vary over time, standard approaches for adjustment of confounding are biased when there exist time-dependent confounders that are also affected by previous treatment. This paper introduces marginal structural models, a new class of causal models that allow for improved adjustment of confounding in those situations. The parameters of a marginal structural model can be consistently estimated using a new class of estimators, the inverse-probability-of-treatment weighted estimators.

Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation.

Abstract: PD-1 is an immunoinhibitory receptor expressed by activated T cells, B cells, and myeloid cells. Mice deficient in PD-1 exhibit a breakdown of peripheral tolerance and demonstrate multiple autoimmune features. We report here that the ligand of PD-1 (PD-L1) is a member of the B7 gene family. Engagement of PD-1 by PD-L1 leads to the inhibition of T cell receptor-mediated lymphocyte proliferation and cytokine secretion. In addition, PD-1 signaling can inhibit at least suboptimal levels of CD28-mediated costimulation. PD-L1 is expressed by antigen-presenting cells, including human peripheral blood monocytes stimulated with interferon gamma, and activated human and murine dendritic cells. In addition, PD-L1 is expressed in nonlymphoid tissues such as heart and lung. The relative levels of inhibitory PD-L1 and costimulatory B7-1/B7-2 signals on antigen-presenting cells may determine the extent of T cell activation and consequently the threshold between tolerance and autoimmunity. PD-L1 expression on nonlymphoid tissues and its potential interaction with PD-1 may subsequently determine the extent of immune responses at sites of inflammation.

Location, Competition, and Economic Development: Local Clusters in a Global Economy

Abstract: Economic geography during an era of global competition involves a paradox. It is widely recognized that changes in technology and competition have diminished many of the traditional roles of location. Yet clusters, or geographic concentrations of interconnected companies, are a striking feature of virtually every national, regional, state, and even metropolitan economy, especially in more advanced nations. The prevalence of clusters reveals important insights about the microeconomics of competition and the role of location in competitive advantage. Even as old reasons for clustering have diminished in importance with globalization, new influences of clusters on competition have taken on growing importance in an increasingly complex, knowledge-based, and dynamic economy. Clusters represent a new way of thinking about national, state, and local economies, and they necessitate new roles for companies, government, and other institutions in enhancing competitiveness.

International Data on Educational Attainment Updates and Implications

Abstract: This paper presents a data set that improves the measurement of educational attainment for a broad group of countries. We extend our previous estimates of educational attainment for the population over age 15 and over age 25 up to 1995 and provide projections for 2000. We discuss the estimation method for the measures of educational attainment and relate our estimates to alternative international measures of human capital stocks.

Neuronal plasticity: increasing the gain in pain.

Abstract: We describe those sensations that are unpleasant, intense, or distressing as painful. Pain is not homogeneous, however, and comprises three categories: physiological, inflammatory, and neuropathic pain. Multiple mechanisms contribute, each of which is subject to or an expression of neural plasticity-the capacity of neurons to change their function, chemical profile, or structure. Here, we develop a conceptual framework for the contribution of plasticity in primary sensory and dorsal horn neurons to the pathogenesis of pain, identifying distinct forms of plasticity, which we term activation, modulation, and modification, that by increasing gain, elicit pain hypersensitivity.

Fabrication of microfluidic systems in poly(dimethylsiloxane)

Abstract: Microfluidic devices are finding increasing application as analytical systems, biomedical devices, tools for chemistry and biochemistry, and systems for fundamental research. Conventional methods of fabricating microfluidic devices have centered on etching in glass and silicon. Fabrication of microfluidic devices in poly(dimethylsiloxane) (PDMS) by soft lithography provides faster, less expensive routes than these conventional methods to devices that handle aqueous solutions. These soft-lithographic methods are based on rapid prototyping and replica molding and are more accessible to chemists and biologists working under benchtop conditions than are the microelectronics-derived methods because, in soft lithography, devices do not need to be fabricated in a cleanroom. This paper describes devices fabricated in PDMS for separations, patterning of biological and nonbiological material, and components for integrated systems.

Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta.

Abstract: Apoptosis, or cellular suicide, is important for normal development and tissue homeostasis, but too much or too little apoptosis can also cause disease. The family of cysteine proteases, the so- called caspases, are critical mediators of programmed cell death, and thus far 14 family members have been identified. Some of these, such as caspase-8, mediate signal transduction downstream of death receptors located on the plasma membrane. Others, such as caspase-9, mediate apoptotic signals after mitochondrial damage. Stress in the endoplasmic reticulum (ER) can also result in apoptosis. Here we show that caspase-12 is localized to the ER and activated by ER stress, including disruption of ER calcium homeostasis and accumulation of excess proteins in ER, but not by membrane- or mitochondrial-targeted apoptotic signals. Mice that are deficient in caspase-12 are resistant to ER stress-induced apoptosis, but their cells undergo apoptosis in response to other death stimuli. Furthermore, we show that caspase-12-deficient cortical neurons are defective in apoptosis induced by amyloid-beta protein but not by staurosporine or trophic factor deprivation. Thus, caspase-12 mediates an ER-specific apoptosis pathway and may contribute to amyloid-beta neurotoxicity.

Theory of the Firm: Managerial Behavior, Agency Costs and Ownership Structure

Abstract: This paper integrates elements from the theory of agency, the theory of property rights and the theory of finance to develop a theory of the ownership structure of the firm. We define the concept of agency costs, show its relationship to the ‘separation and control’ issue, investigate the nature of the agency costs generated by the existence of debt and outside equity, demonstrate who bears costs and why, and investigate the Pareto optimality of their existence. We also provide a new definition of the firm, and show how our analysis of the factors influencing the creation and issuance of debt and equity claims is a special case of the supply side of the completeness of markets problem. The directors of such [joint-stock] companies, however, being the managers rather of other people’s money than of their own, it cannot well be expected, that they should watch over it with the same anxious vigilance with which the partners in a private copartnery frequently watch over their own. Like the stewards of a rich man, they are apt to consider attention to small matters as not for their master’s honour, and very easily give themselves a dispensation from having it. Negligence and profusion, therefore, must always prevail, more or less, in the management of the affairs of such a company. — Adam Smith (1776)

Gastrointestinal Toxicity With Celecoxib vs Nonsteroidal Anti-inflammatory Drugs for Osteoarthritis and Rheumatoid Arthritis: The CLASS Study: A Randomized Controlled Trial

Abstract: ContextConventional nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a spectrum of toxic effects, notably gastrointestinal (GI) effects, because of inhibition of cyclooxygenase (COX)-1. Whether COX-2–specific inhibitors are associated with fewer clinical GI toxic effects is unknown.ObjectiveTo determine whether celecoxib, a COX-2–specific inhibitor, is associated with a lower incidence of significant upper GI toxic effects and other adverse effects compared with conventional NSAIDs.DesignThe Celecoxib Long-term Arthritis Safety Study (CLASS), a double-blind, randomized controlled trial conducted from September 1998 to March 2000.SettingThree hundred eighty-six clinical sites in the United States and Canada.ParticipantsA total of 8059 patients (≥18 years old) with osteoarthritis (OA) or rheumatoid arthritis (RA) were enrolled in the study, and 7968 received at least 1 dose of study drug. A total of 4573 patients (57%) received treatment for 6 months.InterventionsPatients were randomly assigned to receive celecoxib, 400 mg twice per day (2 and 4 times the maximum RA and OA dosages, respectively; n = 3987); ibuprofen, 800 mg 3 times per day (n = 1985); or diclofenac, 75 mg twice per day (n = 1996). Aspirin use for cardiovascular prophylaxis (≤325 mg/d) was permitted.Main Outcome MeasuresIncidence of prospectively defined symptomatic upper GI ulcers and ulcer complications (bleeding, perforation, and obstruction) and other adverse effects during the 6-month treatment period.ResultsFor all patients, the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 0.76% vs 1.45% (P = .09) and 2.08% vs 3.54% (P = .02), respectively. For patients not taking aspirin, the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 0.44% vs 1.27% (P = .04) and 1.40% vs 2.91% (P = .02). For patients taking aspirin, the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 2.01% vs 2.12% (P = .92) and 4.70% vs 6.00% (P = .49). Fewer celecoxib-treated patients than NSAID-treated patients experienced chronic GI blood loss, GI intolerance, hepatotoxicity, or renal toxicity. No difference was noted in the incidence of cardiovascular events between celecoxib and NSAIDs, irrespective of aspirin use.ConclusionsIn this study, celecoxib, at dosages greater than those indicated clinically, was associated with a lower incidence of symptomatic ulcers and ulcer complications combined, as well as other clinically important toxic effects, compared with NSAIDs at standard dosages. The decrease in upper GI toxicity was strongest among patients not taking aspirin concomitantly.

The TIMI Risk Score for Unstable Angina/Non–ST Elevation MI: A Method for Prognostication and Therapeutic Decision Making

Abstract: ContextPatients with unstable angina/non–ST-segment elevation myocardial infarction (MI) (UA/NSTEMI) present with a wide spectrum of risk for death and cardiac ischemic events.ObjectiveTo develop a simple risk score that has broad applicability, is easily calculated at patient presentation, does not require a computer, and identifies patients with different responses to treatments for UA/NSTEMI.Design, Setting, and PatientsTwo phase 3, international, randomized, double-blind trials (the Thrombolysis in Myocardial Infarction [TIMI] 11B trial [August 1996–March 1998] and the Efficacy and Safety of Subcutaneous Enoxaparin in Unstable Angina and Non-Q-Wave MI trial [ESSENCE; October 1994–May 1996]). A total of 1957 patients with UA/NSTEMI were assigned to receive unfractionated heparin (test cohort) and 1953 to receive enoxaparin in TIMI 11B; 1564 and 1607 were assigned respectively in ESSENCE. The 3 validation cohorts were the unfractionated heparin group from ESSENCE and both enoxaparin groups.Main Outcome MeasuresThe TIMI risk score was derived in the test cohort by selection of independent prognostic variables using multivariate logistic regression, assignment of value of 1 when a factor was present and 0 when it was absent, and summing the number of factors present to categorize patients into risk strata. Relative differences in response to therapeutic interventions were determined by comparing the slopes of the rates of events with increasing score in treatment groups and by testing for an interaction between risk score and treatment. Outcomes were TIMI risk score for developing at least 1 component of the primary end point (all-cause mortality, new or recurrent MI, or severe recurrent ischemia requiring urgent revascularization) through 14 days after randomization.ResultsThe 7 TIMI risk score predictor variables were age 65 years or older, at least 3 risk factors for coronary artery disease, prior coronary stenosis of 50% or more, ST-segment deviation on electrocardiogram at presentation, at least 2 anginal events in prior 24 hours, use of aspirin in prior 7 days, and elevated serum cardiac markers. Event rates increased significantly as the TIMI risk score increased in the test cohort in TIMI 11B: 4.7% for a score of 0/1; 8.3% for 2; 13.2% for 3; 19.9% for 4; 26.2% for 5; and 40.9% for 6/7 (P<.001 by χ2 for trend). The pattern of increasing event rates with increasing TIMI risk score was confirmed in all 3 validation groups (P<.001). The slope of the increase in event rates with increasing numbers of risk factors was significantly lower in the enoxaparin groups in both TIMI 11B (P = .01) and ESSENCE (P = .03) and there was a significant interaction between TIMI risk score and treatment (P = .02).ConclusionsIn patients with UA/NSTEMI, the TIMI risk score is a simple prognostication scheme that categorizes a patient's risk of death and ischemic events and provides a basis for therapeutic decision making.

Printing proteins as microarrays for high-throughput function determination.

Abstract: Systematic efforts are currently under way to construct defined sets of cloned genes for high-throughput expression and purification of recombinant proteins To facilitate subsequent studies of protein function, we have developed miniaturized assays that accommodate extremely low sample volumes and enable the rapid, simultaneous processing of thousands of proteins A high-precision robot designed to manufacture complementary DNA microarrays was used to spot proteins onto chemically derivatized glass slides at extremely high spatial densities The proteins attached covalently to the slide surface yet retained their ability to interact specifically with other proteins, or with small molecules, in solution Three applications for protein microarrays were demonstrated: screening for protein-protein interactions, identifying the substrates of protein kinases, and identifying the protein targets of small molecules

Don't go it alone: alliance network composition and startups' performance in Canadian biotechnology

Abstract: We combine theory and research on alliance networks and on new firms to investigate the impact of variation in startups’ alliance network composition on their early performance. We hypothesize that startups can enhance their early performance by 1) establishing alliances, 2) configuring them into an efficient network that provides access to diverse information and capabilities with minimum costs of redundancy, conflict, and complexity, and 3) judiciously allying with potential rivals that provide more opportunity for learning and less risk of intra-alliance rivalry. An analysis of Canadian biotech startups’ performance provides broad support for our hypotheses, especially as they relate to innovative performance. Overall, our findings show how variation in the alliance networks startups configure at the time of their founding produces significant differences in their early performance, contributing directly to an explanation of how and why firm age and size affect firm performance. We discuss some clear, but challenging, implications for managers of startups. Copyright © 2000 John Wiley & Sons, Ltd.

Inequality and Growth in a Panel of Countries

Abstract: Evidence from a broad panel of countries shows little overall relation between income inequality and rates of growth and investment. For growth, higher inequality tends to retard growth in poor countries and encourage growth in richer places. The Kuznets curve—whereby inequality first increases and later decreases during the process of economic development—emerges as a clear empirical regularity. However, this relation does not explain the bulk of variations in inequality across countries or over time.

A clonogenic common myeloid progenitor that gives rise to all myeloid lineages

Abstract: Haematopoietic stem cells give rise to progeny that progressively lose self-renewal capacity and become restricted to one lineage. The points at which haematopoietic stem cell-derived progenitors commit to each of the various lineages remain mostly unknown. We have identified a clonogenic common lymphoid progenitor that can differentiate into T, B and natural killer cells but not myeloid cells. Here we report the prospective identification, purification and characterization, using cell-surface markers and flow cytometry, of a complementary clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Common myeloid progenitors give rise to either megakaryocyte/erythrocyte or granulocyte/macrophage progenitors. Purified progenitors were used to provide a first-pass expression profile of various haematopoiesis-related genes. We propose that the common lymphoid progenitor and common myeloid progenitor populations reflect the earliest branch points between the lymphoid and myeloid lineages, and that the commitment of common myeloid progenitors to either the megakaryocyte/erythrocyte or the granulocyte/macrophage lineages are mutually exclusive events.

How Taxing is Corruption on International Investors

Abstract: This paper studies the effect of corruption on foreign direct investment. The sample covers bilateral investment from twelve source countries to 45 host countries. There are two central findings. First, a rise in either the tax rate on multinational firms or the corruption level in a host country reduces inward foreign direct investment (FDI). In a benchmark estimation, an increase in the corruption level from that of Singapore to that of Mexico would have the same negative effect on inward FDI as raising the tax rate by fifty percentage points. Second, American investors are averse to corruption in host countries, but not necessarily more so than average OECD investors, in spite of the U.S. Foreign Corrupt Practices Act of 1977.