Showing papers by "University of Toronto published in 1998"

Incidence of Adverse Drug Reactions in Hospitalized Patients: A Meta-analysis of Prospective Studies

Abstract: Objective.—To estimate the incidence of serious and fatal adverse drug reactions (ADR) in hospital patients.Data Sources.—Four electronic databases were searched from 1966 to 1996.Study Selection.—Of 153, we selected 39 prospective studies from US hospitals.Data Extraction.—Data extracted independently by 2 investigators were analyzed by a random-effects model. To obtain the overall incidence of ADRs in hospitalized patients, we combined the incidence of ADRs occurring while in the hospital plus the incidence of ADRs causing admission to hospital. We excluded errors in drug administration, noncompliance, overdose, drug abuse, therapeutic failures, and possible ADRs. Serious ADRs were defined as those that required hospitalization, were permanently disabling, or resulted in death.Data Synthesis.—The overall incidence of serious ADRs was 6.7% (95% confidence interval [CI], 5.2%-8.2%) and of fatal ADRs was 0.32% (95% CI, 0.23%-0.41%) of hospitalized patients. We estimated that in 1994 overall 2216000 (1721000-2711000) hospitalized patients had serious ADRs and 106000 (76000-137000) had fatal ADRs, making these reactions between the fourth and sixth leading cause of death.Conclusions.—The incidence of serious and fatal ADRs in US hospitals was found to be extremely high. While our results must be viewed with circumspection because of heterogeneity among studies and small biases in the samples, these data nevertheless suggest that ADRs represent an important clinical issue.

The Demography of massive dark objects in galaxy centers

Abstract: We construct dynamical models for a sample of 36 nearby galaxies with Hubble Space Telescope (HST) photometry and ground-based kinematics. The models assume that each galaxy is axisymmetric, with a two-integral distribution function, arbitrary inclination angle, a position-independent stellar mass-to-light ratio , and a central massive dark object (MDO) of arbitrary mass M•. They provide acceptable fits to 32 of the galaxies for some value of M• and ; the four galaxies that cannot be fitted have kinematically decoupled cores. The mass-to-light ratios inferred for the 32 well-fitted galaxies are consistent with the fundamental-plane correlation ∝ L0.2, where L is galaxy luminosity. In all but six galaxies the models require at the 95% confidence level an MDO of mass M• ~ 0.006Mbulge ≡ 0.006L. Five of the six galaxies consistent with M• = 0 are also consistent with this correlation. The other (NGC 7332) has a much stronger upper limit on M•. We predict the second-moment profiles that should be observed at HST resolution for the 32 galaxies that our models describe well. We consider various parameterizations for the probability distribution describing the correlation of the masses of these MDOs with other galaxy properties. One of the best models can be summarized thus: a fraction f 0.97 of early-type galaxies have MDOs, whose masses are well described by a Gaussian distribution in log (M•/Mbulge) of mean -2.28 and standard deviation ~0.51. There is also marginal evidence that M• is distributed differently for core and power law galaxies, with core galaxies having a somewhat steeper dependence on Mbulge.

Online Computation and Competitive Analysis

Abstract: Preface 1. Introduction to competitive analysis: the list accessing problem 2. Introduction to randomized algorithms: the list accessing problem 3. Paging: deterministic algorithms 4. Paging: randomized algorithms 5. Alternative models for paging: beyond pure competitive analysis 6. Game theoretic foundations 7. Request - answer games 8. Competitive analysis and zero-sum games 9. Metrical task systems 10. The k-server problem 11. Randomized k-server algorithms 12. Load-balancing 13. Call admission and circuit-routing 14. Search, trading and portfolio selection 15. Competitive analysis and decision making under uncertainty Appendices Bibliography Index.

A view of the EM algorithm that justifies incremental, sparse, and other variants

Abstract: The EM algorithm performs maximum likelihood estimation for data in which some variables are unobserved. We present a function that resembles negative free energy and show that the M step maximizes this function with respect to the model parameters and the E step maximizes it with respect to the distribution over the unobserved variables. From this perspective, it is easy to justify an incremental variant of the EM algorithm in which the distribution for only one of the unobserved variables is recalculated in each E step. This variant is shown empirically to give faster convergence in a mixture estimation problem. A variant of the algorithm that exploits sparse conditional distributions is also described, and a wide range of other variant algorithms are also seen to be possible.

Topological methods in hydrodynamics

Abstract: A group theoretical approach to hydrodynamics considers hydrodynamics to be the differential geometry of diffeomorphism groups. The principle of least action implies that the motion of a fluid is described by the geodesics on the group in the right-invariant Riemannian metric given by the kinetic energy. Investigation of the geometry and structure of such groups turns out to be useful for describing the global behavior of fluids for large time intervals.

EigenTracking: Robust Matching and Tracking of Articulated Objects Using a View-Based Representation

Abstract: This paper describes an approach for tracking rigid and articulated objects using a view-based representation. The approach builds on and extends work on eigenspace representations, robust estimation techniques, and parameterized optical flow estimation. First, we note that the least-squares image reconstruction of standard eigenspace techniques has a number of problems and we reformulate the reconstruction problem as one of robust estimation. Second we define a “subspace constancy assumption” that allows us to exploit techniques for parameterized optical flow estimation to simultaneously solve for the view of an object and the affine transformation between the eigenspace and the image. To account for large affine transformations between the eigenspace and the image we define a multi-scale eigenspace representation and a coarse-to-fine matching strategy. Finally, we use these techniques to track objects over long image sequences in which the objects simultaneously undergo both affine image motions and changes of view. In particular we use this “EigenTracking” technique to track and recognize the gestures of a moving hand.

Parkinson's disease. Second of two parts.

Abstract: At no time in the past have the basic and clinical sciences applied to Parkinson's disease been so active. Experimental therapies under study at present promise to improve on the limitations of existing treatments. Future progress in understanding the causation and pathogenesis of the disorder will permit the development of new treatments that will slow, halt, or even reverse the currently inexorable progressive course of Parkinson's disease.

The Knowing Organization: How Organizations Use Information to Construct Meaning, Create Knowledge, and Make Decisions

Abstract: An organization uses information strategically in three areas: to make sense of change in its environment; to create new knowledge for innovation; and to make decisions about courses of action. These apparently distinct processes are in fact complementary pieces of a larger canvas, and the information behaviors analyzed in each approach interweave into a richer explanation of information use in organizations. Through sensemaking, people in an organization give meaning to the events and actions of the organization. Through knowledge creation, the insights of individuals are converted into knowledge that can be used to design new products or improve performance. Finally, in decision making, understanding and knowledge are focused on the selection of and commitment to an appropriate course of action. By holistically managing its sensemaking, knowledge building and decision-making processes, the Knowing Organization will have the necessary understanding and knowledge to act wisely and decisively.

Episodic and declarative memory: role of the hippocampus.

Abstract: The fact that medial temporal lobe structures, including the hippocampus, are critical for declarative memory is firmly established by now. The understanding of the role that these structures play in declarative memory, however, despite great efforts spent in the quest, has eluded investigators so far. Given the existing scenario, novel ideas that hold the promise of clarifying matters should be eagerly sought. One such idea was recently proposed by Vargha-Khadem and her colleagues (Science 1997; 277:376-380) on the basis of their study of three young people suffering from anterograde amnesia caused by early-onset hippocampal pathology. The idea is that the hippocampus is necessary for remembering ongoing life's experiences (episodic memory), but not necessary for the acquisition of factual knowledge (semantic memory). We discuss the reasons why this novel proposal makes good sense and why it and its ramifications should be vigorously pursued. We review and compare declarative and episodic theories of amnesia, and argue that the findings reported by Vargha-Khadem and her colleagues fit well into an episodic theory that retains components already publicized, and adds new ones suggested by the Vargha-Khadem et al. study. Existing components of this theory include the idea that acquisition of factual knowledge can occur independently of episodic memory, and the idea that in anterograde amnesia it is quite possible for episodic memory to be more severely impaired than semantic memory. We suggest a realignment of organization of memory such that declarative memory is defined in terms of features and properties that are common to both episodic and semantic memory. The organization of memory thus modified gives greater precision to the Vargha-Khadem et al. neuroanatomical model in which declarative memory depends on perihippocampal cortical regions but not on the hippocampus, whereas episodic memory, which is separate from declarative memory, depends on the hippocampus.

The Arabidopsis gene MONOPTEROS encodes a transcription factor mediating embryo axis formation and vascular development

Abstract: The vascular tissues of flowering plants form networks of interconnected cells throughout the plant body. The molecular mechanisms directing the routes of vascular strands and ensuring tissue continuity within the vascular system are not known, but are likely to depend on general cues directing plant cell orientation along the apical–basal axis. Mutations in the Arabidopsis gene MONOPTEROS ( MP ) interfere with the formation of vascular strands at all stages and also with the initiation of the body axis in the early embryo. Here we report the isolation of the MP gene by positional cloning. The predicted protein product contains functional nuclear localization sequences and a DNA binding domain highly similar to a domain shown to bind to control elements of auxin inducible promoters. During embryogenesis, as well as organ development, MP is initially expressed in broad domains that become gradually confined towards the vascular tissues. These observations suggest that the MP gene has an early function in the establishment of vascular and body patterns in embryonic and post‐embryonic development.

Annealed Importance Sampling

Abstract: Simulated annealing—moving from a tractable distribution to a distribution of interest via a sequence of intermediate distributions—has traditionally been used as an inexact method of handling isolated modes in Markov chain samplers. Here, it is shown how one can use the Markov chain transitions for such an annealing sequence to define an importance sampler. The Markov chain aspect allows this method to perform acceptably even for high-dimensional problems, where finding good importance sampling distributions would otherwise be very difficult, while the use of importance weights ensures that the estimates found converge to the correct values as the number of annealing runs increases. This annealed importance sampling procedure resembles the second half of the previously-studied tempered transitions, and can be seen as a generalization of a recently-proposed variant of sequential importance sampling. It is also related to thermodynamic integration methods for estimating ratios of normalizing constants. Annealed importance sampling is most attractive when isolated modes are present, or when estimates of normalizing constants are required, but it may also be more generally useful, since its independent sampling allows one to bypass some of the problems of assessing convergence and autocorrelation in Markov chain samplers.

Alcohol and breast cancer in women: a pooled analysis of cohort studies.

Abstract: Objective. - To assess the risk of invasive breast cancer associated with total and beverage-specific alcohol consumption and to evaluate whether dietary and nondietary factors modify the association. Data Sources. - We included in these analyses 6 prospective studies that had at least 200 incident breast cancer cases, assessed long-term intake of food and nutrients, and used a validated diet assessment instrument. The studies were conducted in Canada, the Netherlands, Sweden, and the United States. Alcohol intake was estimated by food frequency questionnaires in each study. The studies included a total of 322 647 women evaluated for up to 11 years, including 4335 participants with a diagnosis of incident invasive breast cancer. Data Extraction. - Pooled analysis of primary data using analyses consistent with each study's original design and the random-effects model for the overall pooled analyses. Data Synthesis. - For alcohol intakes less than 60 g/d (reported by >99% of participants), risk increased linearly with increasing intake; the pooled multivariate relative risk for an increment of 10 g/d of alcohol (about 0.75-1 drink) was 1.09 (95% confidence interval [CI], 1.04-1.13; P for heterogeneity among studies, .71). The multivariate- adjusted relative risk for total alcohol intakes of 30 to less than 60 g/d (about 2-5 drinks) vs nondrinkers was 1.41 (95% CI, 1.18-1.69). Limited data suggested that alcohol intakes of at least 60 g/d were not associated with further increased risk. The specific type of alcoholic beverage did not strongly influence risk estimates. The association between alcohol intake and breast cancer was not modified by other factors. Conclusions. - Alcohol consumption is associated with a linear increase in breast cancer incidence in women over the range of consumption reported by most women. Among women who consume alcohol regularly, reducing alcohol consumption is a potential means to reduce breast cancer risk.

The Size of the Giant Component of a Random Graph with a Given Degree Sequence

Abstract: Given a sequence of nonnegative real numbers λ0, λ1, … that sum to 1, we consider a random graph having approximately λin vertices of degree i. In [12] the authors essentially show that if ∑i(i−2)λi>0 then the graph a.s. has a giant component, while if ∑i(i−2)λi<0 then a.s. all components in the graph are small. In this paper we analyse the size of the giant component in the former case, and the structure of the graph formed by deleting that component. We determine e, λ′0, λ′1 … such that a.s. the giant component, C, has en+o(n) vertices, and the structure of the graph remaining after deleting C is basically that of a random graph with n′=n−∣C∣ vertices, and with λ′in′ of them of degree i.

Multiple system organ failure. Is mechanical ventilation a contributing factor

Abstract: Few problems facing the intensivist are as frustrating or as difficult to manage as multiple system organ failure (MSOF). While the precise etiology remains unknown, an integral feature is the development of a rampant systemic inflammatory response that persists unabated by host control mechanisms. Either a single massive insult, or a series of less intense insults (i.e., “two-hits”) appear to be necessary to overwhelm the individuals innate regulatory mechanisms. Often the lung is the first organ to fail, leading to initiation (or continuation) of ventilatory support. Although in some patients a precipitating nidus of infection or inflammation is identifiable, and lung injury is simply the first clinically evident manifestation of a systemic process, there remain a large number of patients in whom the explanation for progression from respiratory failure to multiple system organ failure is unclear. In this Perspective, we explore the hypothesis that mechanical ventilation may play a pivotal (and hereto unrecognized) role in the initiation and/or propagation of a systemic inflammatory response leading to MSOF in certain patients. We address this issue by examining the following questions: Can mechanical ventilation initiate or exacerbate lung injury/inflammation? Can lung injury/inflammation lead to systemic inflammation? Is there evidence of MSOF secondary to mechanical ventilation?

Evaluation of a ventilation strategy to prevent barotrauma in patients at high risk for acute respiratory distress syndrome. Pressure- and Volume-Limited Ventilation Strategy Group.

Abstract: Background A strategy of mechanical ventilation that limits airway pressure and tidal volume while permitting hypercapnia has been recommended for patients with the acute respiratory distress syndrome. The goal is to reduce lung injury due to overdistention. However, the efficacy of this approach has not been established. Methods Within 24 hours of intubation, patients at high risk for the acute respiratory distress syndrome were randomly assigned to either pressure- and volume-limited ventilation (limited-ventilation group), with the peak inspiratory pressure maintained at 30 cm of water or less and the tidal volume at 8 ml per kilogram of body weight or less, or to conventional ventilation (control group), with the peak inspiratory pressure allowed to rise as high as 50 cm of water and the tidal volume at 10 to 15 ml per kilogram. All other ventilatory variables were similar in the two groups. Results A total of 120 patients with similar clinical features underwent randomization (60 in each group). The ...

The Gender Paradox in Suicide

Abstract: In most Western countries females have higher rates of suicidal ideation and behavior than males, yet mortality from suicide is typically lower for females than for males. This article explores the gender paradox of suicidal behavior, examines its validity, and critically examines some of the explanations, concluding that the gender paradox of suicidal behavior is a real phenomenon and not a mere artifact of data collection. At the same time, the gender paradox in suicide is a more culture-bound phenomenon than has been traditionally assumed; cultural expectations about gender and suicidal behavior strongly determine its existence. Evidence from the United States and Canada suggests that the gender gap may be more prominent in communities where different suicidal behaviors are expected of females and males. These divergent expectations may affect the scenarios chosen by females and males, once suicide becomes a possibility, as well as the interpretations of those who are charged with determining whether a particular behavior is suicidal (e.g., coroners). The realization that cultural influences play an important role in the gender paradox of suicidal behaviors holds important implications for research and for public policy.

Photonic band gap formation in certain self-organizing systems

Abstract: We present a detailed study of photonic band structure in certain self-organizing systems that self-assemble into large-scale photonic crystals with photonic band gaps (PBGs) or pseudogaps in the near-visible frequency regime. These include colloidal suspensions, inverted opals, and macroporous silicon. We show that complete three-dimensional PBGs spanning roughly 10% and 15% of the gap center frequency are attainable by incomplete infiltration of an opal with silicon and germanium, respectively. The photonic band structure of both face center cubic and hexagonal close packed photonic crystals are evaluated. We delineate how the PBG is modified by sintering the opal prior to infiltration and by applying strain along various crystallographic directions. We evaluate the total photon density of states as well as the local density of states (LDOS) projected onto various points within the photonic crystal. It is shown that the LDOS may exhibit considerable pseudogap structure even for systems that do not exhibit a complete PBG. These results are directly relevant to quantum optical experiments in which atoms, dye molecules, or other active materials are inserted into specific locations within the photonic crystal. When the resonant optical transition of these dopants is tuned close to a pseudogap or other abrupt structure in the LDOS, novel effects in radiative dynamics associated with a ``colored vacuum'' may be realized.

Zircon megacrysts from kimberlite: oxygen isotope variability among mantle melts

Abstract: The oxygen isotope ratios of Phanerozoic zircons from kimberlite pipes in the Kaapvaal Craton of southern Africa and the Siberian Platform vary from 4.7 to 5.9& VSMOW. High precision, accurate analyses by laser reveal subtle pipe-to-pipe diAerences not previously suspected. These zircons have distinctive chemical and physical characteristics identifying them as mantle-de- rived megacrysts similar to zircons found associated with diamond, coesite, MARID xenoliths, Cr-diopside, K-richterite, or Mg-rich ilmenite. Several lines of evi- dence indicate that these d 18 O values are unaltered by kimberlite magmas during eruption and represent com- positions preserved since crystallization in the mantle, including: U/Pb age, large crystal size, and the slow rate of oxygen exchange in non-metamict zircon. The aver- age d 18 O of mantle zircons is 5.3&,0:1& higher and in equilibrium with values for olivine in peridotite xenoliths and oceanic basalts. Zircon megacrysts from within 250 km of Kimberley, South Africa have average d 18 Oa 5:32 0:17&Ona 28U. Small, but significant, diAerences among other kimberlite pipes or groups of pipes may indicate isotopically distinct reservoirs in the sub-continental lithosphere or asthenosphere, some of which are anomalous with respect to normal mantle values of 5:3 0:3&. Precambrian zircons (2.1-2.7 Ga) from Jwaneng, Botswana have the lowest values yet measured in a mantle zircon, d 18 Oa 3:4 to 4.7&. These zircon megacrysts originally crystallized in mafic or ul- tramafic rocks either through melting and metasomat- ism associated with kimberlite magmatism or during metamorphism. The low d 18 O zircons are best explained by subduction of late Archean ocean crust that ex- changed with heated seawater prior to underplating as eclogite and to associated metasomatism of the mantle wedge. Smaller diAerences among other pipes and dis- tricts may result from variable temperatures of equili- bration, mafic versus ultramafic hosts, or variable un- derplating. The narrow range in zircon compositions found in most pipes suggests magmatic homogenization. If this is correct, these zircons document the existence of sig- nificant quantities of magma in the sub-continental mantle that was regionally variable in d 18 O and this information restricts theories about the nature of ancient subduction.

Explaining nursing turnover intent: job satisfaction, pay satisfaction, or organizational commitment?

Abstract: A number of models have been developed to explain nurses' turnover behavior. The common theme that emerges from these models is that turnover behavior is a multistage process that includes attitudinal, decisional, and behavioral components. The purpose of this study was to assess both the direct and indirect impact of certain pay policies upon the turnover intentions of paediatric nurses. The two major questions addressed were: What was the relative impact of job satisfaction, pay satisfaction, and organizational commitment upon the turnover intentions of paediatric nurses eligible for these pay policies? What model accurately portrays the relationship among these three independent variables and turnover intentions? Exploration of the causal pathways among these variables and demographic factors revealed complex models of association. The results suggest that job satisfaction has only an indirect influence on the intention to quit, whereas organizational commitment has the strongest and most direct impact. A further finding that pay satisfaction had both direct and indirect effects on turnover intent was consistent with administrators' assumptions underlying the pay policies. Control variables such as having a degree, having children, and working 12-hour shifts were found to have both direct and indirect influences upon pay satisfaction and turnover intent. © 1998 John Wiley & Sons, Ltd.

Optimal scaling of discrete approximations to Langevin diffusions

Abstract: We consider the optimal scaling problem for proposal distributions in Hastings–Metropolis algorithms derived from Langevin diffusions. We prove an asymptotic diffusion limit theorem and show that the relative efficiency of the algorithm can be characterized by its overall acceptance rate, independently of the target distribution. The asymptotically optimal acceptance rate is 0.574. We show that, as a function of dimension n, the complexity of the algorithm is O(n1/3), which compares favourably with the O(n) complexity of random walk Metropolis algorithms. We illustrate this comparison with some example simulations.

Mechanisms of endosseous integration.

Abstract: UNLABELLED Although the clinical term "osseointegration" describes the anchorage of endosseous implants to withstand functional loading, it provides no insight into the mechanisms of bony healing around such implants. Nevertheless, an understanding of the sequence of bone healing events around endosseous implants is believed to be critical in developing biologic design criteria for implant surfaces. RESULTS AND DISCUSSION This discussion paper shows that peri-implant bone healing, which results in contact osteogenesis (bone growth on the implant surface), can be phenomenologically subdivided into three distinct phases that can be addressed experimentally. The first, osteoconduction, relies on the migration of differentiating osteogenic cells to the implant surface, through a temporary connective tissue scaffold. Anchorage of this scaffold to the implant surface is a function of implant surface design. The second, de novo bone formation, results in a mineralized interfacial matrix, equivalent to that seen in cement lines in natural bone tissue, being laid down on the implant surface. Implant surface topography will determine if the interfacial bone formed is bonded to the implant. A third tissue response, that of bone remodeling, will also, at discrete sites, create a bone-implant interface comprising de novo bone formation. CONCLUSION Treatment outcomes in dental implantology will be critically dependent on implant surface designs that optimize the biologic response during each of these three distinct integration mechanisms.

Comparing the psychometric properties of checklists and global rating scales for assessing performance on an OSCE-format examination.

Abstract: PURPOSE: To compare the psychometric properties of checklists, global rating scales preceded by a checklist, and global rating scales alone in assessing surgery residents' performances on an OSCE-like technical skills examination. METHOD: In 1996, 53 general surgery residents with one to six years o

Defects in regulation of apoptosis in caspase-2-deficient mice

Abstract: During embryonic development, a large number of cells die naturally to shape the new organism. Members of the caspase family of proteases are essential intracellular death effectors. Herein, we generated caspase-2-deficient mice to evaluate the requirement for this enzyme in various paradigms of apoptosis. Excess numbers of germ cells were endowed in ovaries of mutant mice and the oocytes were found to be resistant to cell death following exposure to chemotherapeutic drugs. Apoptosis mediated by granzyme B and perforin was defective in caspase-2-deficient B lymphoblasts. In contrast, cell death of motor neurons during development was accelerated in caspase-2-deficient mice. In addition, caspase-2-deficient sympathetic neurons underwent apoptosis more effectively than wild-type neurons when deprived of NGF. Thus, caspase-2 acts both as a positive and negative cell death effector, depending upon cell lineage and stage of development.

Energy implications of future stabilization of atmospheric CO2 content

Abstract: The United Nations Framework Convention on Climate Change1 calls for “stabilization of greenhouse-gas concentrations in the atmosphere at a level that would prevent dangerous anthropogenic interference with the climate system ” A standard baseline scenario2,3 that assumes no policy intervention to limit greenhouse-gas emissions has 10 TW (10 × 1012 watts) of carbon-emission-free power being produced by the year 2050, equivalent to the power provided by all today's energy sources combined Here we employ a carbon-cycle/energy model to estimate the carbon-emission-free power needed for various atmospheric CO2 stabilization scenarios We find that CO2 stabilization with continued economic growth will require innovative, cost-effective and carbon-emission-free technologies that can provide additional tens of terawatts of primary power in the coming decades, and certainly by the middle of the twenty-first century, even with sustained improvement in the economic productivity of primary energy At progressively lower atmospheric CO2-stabilization targets in the 750–350 ppmv range, implementing stabilization will become even more challenging because of the increasing demand for carbon-emission-free power The magnitude of the implied infrastructure transition suggests the need for massive investments in innovative energy research

Drugs in Pregnancy

Abstract: Before marketing a new drug, the manufacturer almost never tests the product in pregnant women to determine its effects on the fetus. Consequently, most drugs are not labeled for use during pregnancy. Typically, descriptions of drugs that appear in the Physicians' Desk Reference and similar sources contain statements such as, “Use in pregnancy is not recommended unless the potential benefits justify the potential risks to the fetus.” Since the risk has been adequately established for only a few drugs, physicians caring for pregnant women have very little information to help them decide whether the potential benefits to the mother outweigh . . .

A newly discovered class of human hematopoietic cells with SCID-repopulating activity

Abstract: The detection of primitive hematopoietic cells based on repopulation of immune-deficient mice is a powerful tool to characterize the human stem-cell compartment. Here, we identify a newly discovered human repopulating cell, distinct from previously identified repopulating cells, that initiates multilineage hematopoiesis in NOD/SCID mice. We call such cells CD34neg-SCID repopulating cells, or CD34neg-SRC. CD34neg-SRC are restricted to a Lin-CD34-CD38- population without detectable surface markers for multiple lineages and CD38 or those previously associated with stem cells (HLA-DR, Thy-1 and CD34). In contrast to CD34+ subfractions, Lin-CD34-CD38- cells have low clonogenicity in short-and long-term in vitro assays. The number of CD34neg-SRC increased in short-term suspension cultures in conditions that did not maintain SRC derived from CD34+ populations, providing independent biological evidence of their distinctiveness. The identification of this newly discovered cell demonstrates complexity of the organization of the human stem-cell compartment and has important implications for clinical applications involving stem-cell transplantation.

Agglomeration in the Global Economy: A Survey of the ‘New Economic Geography’

Abstract: This review of recent contributions reveals common conclusions about the effects of integration on location. For high trade costs the need to supply markets locally encourages firms to spread across different regions. Integration weakens the incentives for self-sufficiency and for intermediate values of trade costs pecuniary externalities induce firms and workers to cluster together, turning location into a self-reinforcing process. Agglomeration raises the price of immobile local factors and goods, however, so for low transport costs, firms may spread to regions where those prices are lower.(This abstract was borrowed from another version of this item.)

Efficacy of oxycodone in neuronathic pain: A randomized trial in postherpetic neuralgia

Abstract: Objective Although opioid analgesics are used in the management of neuropathic pain syndromes, evidence of their efficacy remains to be established. We evaluated the clinical efficacy and safety of oxycodone in neuropathic pain using postherpetic neuralgia as a model. Methods Patients with postherpetic neuralgia of at least moderate intensity were randomized to controlled-release oxycodone 10 mg or placebo every 12 hours, each for 4 weeks, using a double-blind, crossover design. The dose was increased weekly up to a possible maximum of 30 mg every 12 hours. Pain intensity and pain relief were assessed daily, and steady (ongoing) pain, brief (paroxysmal) pain, skin pain (allo-dynia), and pain relief were recorded at weekly visits. Clinical effectiveness, disability, and treatment preference were also assessed. Results Fifty patients were enrolled and 38 completed the study (16 men, 22 women, age 70± 2 11 years, onset of postherpetic neuralgia 31± 2 29 months, duration of pain 18 ± 5 hours per day). The oxycodone dose during the final week was 45 ±5 17 mg per day. Compared with placebo, oxycodone resulted in pain relief (2.9±2 1.2 versus 1.8 ± 1.1, p = 0.0001) and reductions in steady pain (34 ± 26 versus 55 ± 27 mm, p = 0.0001), allodynia (32 ±2 26 versus 50 ±2 30 mm, p = 0.0004), and paroxysmal spontaneous pain (22 ± 24 versus 42 ± 32 mm, p = 0.0001). Global effectiveness, disability, and masked patient preference all showed superior scores with oxycodone relative to placebo (1.8 ±.11 versus 0.7 ± 1.0, p = 0.0001; 0.3 ± 0.8 versus 0.7 ± 1.0, p = 0.041; 67% versus 11%, p = 0.001, respectively). Conclusions Controlled-release oxycodone is an effective analgesic for the management of steady pain, paroxysmal spontaneous pain, and allodynia, which frequently characterize postherpetic neuralgia.