Showing papers by "University of Michigan published in 2003"

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.

Abstract: "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" provides a new guideline for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of more than 140 mm Hg is a much more important cardiovascular disease (CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75 mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension; (3) Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80 to 89 mm Hg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, β-blockers, calcium channel blockers); (5) Most patients with hypertension will require 2 or more antihypertensive medications to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal BP, consideration should be given to initiating therapy with 2 agents, 1 of which usually should be a thiazide-type diuretic; and (7) The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated. Motivation improves when patients have positive experiences with and trust in the clinician. Empathy builds trust and is a potent motivator. Finally, in presenting these guidelines, the committee recognizes that the responsible physician's judgment remains paramount.

Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure

Abstract: The National High Blood Pressure Education Program presents the complete Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Like its predecessors, the purpose is to provide an evidence-based approach to the prevention and management of hypertension. The key messages of this report are these: in those older than age 50, systolic blood pressure (BP) of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP; beginning at 115/75 mm Hg, CVD risk doubles for each increment of 20/10 mm Hg; those who are normotensive at 55 years of age will have a 90% lifetime risk of developing hypertension; prehypertensive individuals (systolic BP 120-139 mm Hg or diastolic BP 80-89 mm Hg) require health-promoting lifestyle modifications to prevent the progressive rise in blood pressure and CVD; for uncomplicated hypertension, thiazide diuretic should be used in drug treatment for most, either alone or combined with drugs from other classes; this report delineates specific high-risk conditions that are compelling indications for the use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); two or more antihypertensive medications will be required to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg) for patients with diabetes and chronic kidney disease; for patients whose BP is more than 20 mm Hg above the systolic BP goal or more than 10 mm Hg above the diastolic BP goal, initiation of therapy using two agents, one of which usually will be a thiazide diuretic, should be considered; regardless of therapy or care, hypertension will be controlled only if patients are motivated to stay on their treatment plan. Positive experiences, trust in the clinician, and empathy improve patient motivation and satisfaction. This report serves as a guide, and the committee continues to recognize that the responsible physician's judgment remains paramount.

Prospective identification of tumorigenic breast cancer cells

Abstract: Breast cancer is the most common malignancy in United States women, accounting for >40,000 deaths each year. These breast tumors are comprised of phenotypically diverse populations of breast cancer cells. Using a model in which human breast cancer cells were grown in immunocompromised mice, we found that only a minority of breast cancer cells had the ability to form new tumors. We were able to distinguish the tumorigenic (tumor initiating) from the nontumorigenic cancer cells based on cell surface marker expression. We prospectively identified and isolated the tumorigenic cells as CD44+CD24−/lowLineage− in eight of nine patients. As few as 100 cells with this phenotype were able to form tumors in mice, whereas tens of thousands of cells with alternate phenotypes failed to form tumors. The tumorigenic subpopulation could be serially passaged: each time cells within this population generated new tumors containing additional CD44+CD24−/lowLineage− tumorigenic cells as well as the phenotypically diverse mixed populations of nontumorigenic cells present in the initial tumor. The ability to prospectively identify tumorigenic cancer cells will facilitate the elucidation of pathways that regulate their growth and survival. Furthermore, because these cells drive tumor development, strategies designed to target this population may lead to more effective therapies.

Reticular synthesis and the design of new materials

Abstract: The long-standing challenge of designing and constructing new crystalline solid-state materials from molecular building blocks is just beginning to be addressed with success. A conceptual approach that requires the use of secondary building units to direct the assembly of ordered frameworks epitomizes this process: we call this approach reticular synthesis. This chemistry has yielded materials designed to have predetermined structures, compositions and properties. In particular, highly porous frameworks held together by strong metal-oxygen-carbon bonds and with exceptionally large surface area and capacity for gas storage have been prepared and their pore metrics systematically varied and functionalized.

The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R).

Abstract: ContextUncertainties exist about prevalence and correlates of major depressive disorder (MDD).ObjectiveTo present nationally representative data on prevalence and correlates of MDD by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, and on study patterns and correlates of treatment and treatment adequacy from the recently completed National Comorbidity Survey Replication (NCS-R).DesignFace-to-face household survey conducted from February 2001 to December 2002.SettingThe 48 contiguous United States.ParticipantsHousehold residents ages 18 years or older (N = 9090) who responded to the NCS-R survey.Main Outcome MeasuresPrevalence and correlates of MDD using the World Health Organization's (WHO) Composite International Diagnostic Interview (CIDI), 12-month severity with the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR), the Sheehan Disability Scale (SDS), and the WHO disability assessment scale (WHO-DAS). Clinical reinterviews used the Structured Clinical Interview for DSM-IV.ResultsThe prevalence of CIDI MDD for lifetime was 16.2% (95% confidence interval [CI], 15.1-17.3) (32.6-35.1 million US adults) and for 12-month was 6.6% (95% CI, 5.9-7.3) (13.1-14.2 million US adults). Virtually all CIDI 12-month cases were independently classified as clinically significant using the QIDS-SR, with 10.4% mild, 38.6% moderate, 38.0% severe, and 12.9% very severe. Mean episode duration was 16 weeks (95% CI, 15.1-17.3). Role impairment as measured by SDS was substantial as indicated by 59.3% of 12-month cases with severe or very severe role impairment. Most lifetime (72.1%) and 12-month (78.5%) cases had comorbid CIDI/DSM-IV disorders, with MDD only rarely primary. Although 51.6% (95% CI, 46.1-57.2) of 12-month cases received health care treatment for MDD, treatment was adequate in only 41.9% (95% CI, 35.9-47.9) of these cases, resulting in 21.7% (95% CI, 18.1-25.2) of 12-month MDD being adequately treated. Sociodemographic correlates of treatment were far less numerous than those of prevalence.ConclusionsMajor depressive disorder is a common disorder, widely distributed in the population, and usually associated with substantial symptom severity and role impairment. While the recent increase in treatment is encouraging, inadequate treatment is a serious concern. Emphasis on screening and expansion of treatment needs to be accompanied by a parallel emphasis on treatment quality improvement.

Applied Multivariate Statistics for the Social Sciences

Abstract: (2003). Applied Multivariate Statistics for the Social Sciences. The American Statistician: Vol. 57, No. 1, pp. 68-69.

The International HapMap Project

Abstract: The goal of the International HapMap Project is to determine the common patterns of DNA sequence variation in the human genome and to make this information freely available in the public domain. An international consortium is developing a map of these patterns across the genome by determining the genotypes of one million or more sequence variants, their frequencies and the degree of association between them, in DNA samples from populations with ancestry from parts of Africa, Asia and Europe. The HapMap will allow the discovery of sequence variants that affect common disease, will facilitate development of diagnostic tools, and will enhance our ability to choose targets for therapeutic intervention.

Misery Loves Companies: Rethinking Social Initiatives by Business:

Abstract: Companies are increasingly asked to provide innovative solutions to deep-seated problems of human misery, even as economic theory instructs managers to focus on maximizing their shareholders' wealt

Eplerenone, a Selective Aldosterone Blocker, in Patients with Left Ventricular Dysfunction after Myocardial Infarction

Abstract: background Aldosterone blockade reduces mortality and morbidity among patients with severe heart failure. We conducted a double-blind, placebo-controlled study evaluating the effect of eplerenone, a selective aldosterone blocker, on morbidity and mortality among patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure. methods Patients were randomly assigned to eplerenone (25 mg per day initially, titrated to a maximum of 50 mg per day; 3313 patients) or placebo (3319 patients) in addition to optimal medical therapy. The study continued until 1012 deaths occurred. The primary end points were death from any cause and death from cardiovascular causes or hospitalization for heart failure, acute myocardial infarction, stroke, or ventricular arrhythmia. results During a mean follow-up of 16 months, there were 478 deaths in the eplerenone group and 554 deaths in the placebo group (relative risk, 0.85; 95 percent confidence interval, 0.75 to 0.96; P=0.008). Of these deaths, 407 in the eplerenone group and 483 in the placebo group were attributed to cardiovascular causes (relative risk, 0.83; 95 percent confidence interval, 0.72 to 0.94; P = 0.005). The rate of the other primary end point, death from cardiovascular causes or hospitalization for cardiovascular events, was reduced by eplerenone (relative risk, 0.87; 95 percent confidence interval, 0.79 to 0.95; P=0.002), as was the secondary end point of death from any cause or any hospitalization (relative risk, 0.92; 95 percent confidence interval, 0.86 to 0.98; P=0.02). There was also a reduction in the rate of sudden death from cardiac causes (relative risk, 0.79; 95 percent confidence interval, 0.64 to 0.97; P=0.03). The rate of serious hyperkalemia was 5.5 percent in the eplerenone group and 3.9 percent in the placebo group (P = 0.002), whereas the rate of hypokalemia was 8.4 percent in the eplerenone group and 13.1 percent in the placebo group (P<0.001). conclusions The addition of eplerenone to optimal medical therapy reduces morbidity and mortality among patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure.

Hydrogen Storage in Microporous Metal-Organic Frameworks

Abstract: Metal-organic framework-5 (MOF-5) of composition Zn4O(BDC)3 (BDC = 1,4-benzenedicarboxylate) with a cubic three-dimensional extended porous structure adsorbed hydrogen up to 4.5 weight percent (17.2 hydrogen molecules per formula unit) at 78 kelvin and 1.0 weight percent at room temperature and pressure of 20 bar. Inelastic neutron scattering spectroscopy of the rotational transitions of the adsorbed hydrogen molecules indicates the presence of two well-defined binding sites (termed I and II), which we associate with hydrogen binding to zinc and the BDC linker, respectively. Preliminary studies on topologically similar isoreticular metal-organic framework-6 and -8 (IRMOF-6 and -8) having cyclobutylbenzene and naphthalene linkers, respectively, gave approximately double and quadruple (2.0 weight percent) the uptake found for MOF-5 at room temperature and 10 bar.

Estimating production functions using inputs to control for unobservables

Abstract: Economists began relating output to inputs in the early 1800's. A large literature on estimating production functions has followed, in part because much of economic theory yields testable implications that are related to the technology and optimizing behaviour.1 Since at least as early as Marschak and Andrews (1944), applied researchers have worried about the potential correlation between input levels and the unobserved firm-specific productivity shocks in the estimation of production function parameters. The economics underlying this concern are intuitive. Firms that have a large positive productivity shock may respond by using more inputs. To the extent that this is true, ordinary least squares (OLS) estimates of production functions will yield biased parameter estimates, and, by implication, biased estimates of productivity. Many alternatives to OLS have been proposed, and we add to this set by extending Olley and Pakes (1996). They show the conditions under which an investment proxy controls for correlation between input levels and the unobserved productivity shock. Their approach has the advantage that, for many questions, it is no more difficult to implement than OLS. We show when intermediate inputs (those inputs which are typically subtracted out in a value-added production function) can also solve this simultaneity problem. We discuss some potential benefits of expanding the choice set of proxies to include these inputs.

The Logic of Political Survival

Abstract: The authors of this ambitious book address a fundamental political question: why are leaders who produce peace and prosperity turned out of office while those who preside over corruption, war, and misery endure? Considering this political puzzle, they also answer the related economic question of why some countries experience successful economic development and others do not. The authors construct a provocative theory on the selection of leaders and present specific formal models from which their central claims can be deduced. They show how political leaders allocate resources and how institutions for selecting leaders create incentives for leaders to pursue good and bad public policy. They also extend the model to explain the consequences of war on political survival. Throughout the book, they provide illustrations from history, ranging from ancient Sparta to Vichy France, and test the model against statistics gathered from cross-national data. The authors explain the political intuition underlying their theory in nontechnical language, reserving formal proofs for chapter appendixes. They conclude by presenting policy prescriptions based on what has been demonstrated theoretically and empirically.

Rumination reconsidered: A psychometric analysis.

Abstract: In an attempt to eliminate similar item content as an alternative explanation for the relation between depression and rumination, a secondary analysis was conducted using the data from S. Nolen-Hoeksema, J. Larson, and C. Grayson (1999). After constructing a measure of rumination unconfounded with depression content, support for a two factor model of rumination was found. These analyses indicate that the 2 components, reflective pondering and brooding, differentially relate to depression in terms of predictive ability and gender difference mediation. The results presented here support the general premise of Nolen-Hoeksema’s Response Styles Theory (S. Nolen-Hoeksema 1987) that rumination can contribute to more depressive symptoms and to the gender difference in depression, but suggest important refinements of the theory. Such refinements include the need to differentiate between the reflective pondering component of rumination and the brooding component in rumination research.

Nanoscale thermal transport

Abstract: Rapid progress in the synthesis and processing of materials with structure on nanometer length scales has created a demand for greater scientific understanding of thermal transport in nanoscale devices, individual nanostructures, and nanostructured materials. This review emphasizes developments in experiment, theory, and computation that have occurred in the past ten years and summarizes the present status of the field. Interfaces between materials become increasingly important on small length scales. The thermal conductance of many solid–solid interfaces have been studied experimentally but the range of observed interface properties is much smaller than predicted by simple theory. Classical molecular dynamics simulations are emerging as a powerful tool for calculations of thermal conductance and phonon scattering, and may provide for a lively interplay of experiment and theory in the near term. Fundamental issues remain concerning the correct definitions of temperature in nonequilibrium nanoscale systems. Modern Si microelectronics are now firmly in the nanoscale regime—experiments have demonstrated that the close proximity of interfaces and the extremely small volume of heat dissipation strongly modifies thermal transport, thereby aggravating problems of thermal management. Microelectronic devices are too large to yield to atomic-level simulation in the foreseeable future and, therefore, calculations of thermal transport must rely on solutions of the Boltzmann transport equation; microscopic phonon scattering rates needed for predictive models are, even for Si, poorly known. Low-dimensional nanostructures, such as carbon nanotubes, are predicted to have novel transport properties; the first quantitative experiments of the thermal conductivity of nanotubes have recently been achieved using microfabricated measurement systems. Nanoscale porosity decreases the permittivity of amorphous dielectrics but porosity also strongly decreases the thermal conductivity. The promise of improved thermoelectric materials and problems of thermal management of optoelectronic devices have stimulated extensive studies of semiconductor superlattices; agreement between experiment and theory is generally poor. Advances in measurement methods, e.g., the 3ω method, time-domain thermoreflectance, sources of coherent phonons, microfabricated test structures, and the scanning thermal microscope, are enabling new capabilities for nanoscale thermal metrology.

The mammalian unfolded protein response

Abstract: In the endoplasmic reticulum (ER), secretory and transmembrane proteins fold into their native conformation and undergo posttranslational modifications important for their activity and structure. When protein folding in the ER is inhibited, signal transduction pathways, which increase the biosynthetic capacity and decrease the biosynthetic burden of the ER to maintain the homeostasis of this organelle, are activated. These pathways are called the unfolded protein response (UPR). In this review, we briefly summarize principles of protein folding and molecular chaperone function important for a mechanistic understanding of UPR-signaling events. We then discuss mechanisms of signal transduction employed by the UPR in mammals and our current understanding of the remodeling of cellular processes by the UPR. Finally, we summarize data that demonstrate that UPR signaling feeds into decision making in other processes previously thought to be unrelated to ER function, e.g., eukaryotic starvation responses and differentiation programs.

Mixing patterns in networks.

Abstract: We study assortative mixing in networks, the tendency for vertices in networks to be connected to other vertices that are like (or unlike) them in some way. We consider mixing according to discrete characteristics such as language or race in social networks and scalar characteristics such as age. As a special example of the latter we consider mixing according to vertex degree, i.e., according to the number of connections vertices have to other vertices: do gregarious people tend to associate with other gregarious people? We propose a number of measures of assortative mixing appropriate to the various mixing types, and apply them to a variety of real-world networks, showing that assortative mixing is a pervasive phenomenon found in many networks. We also propose several models of assortatively mixed networks, both analytic ones based on generating function methods, and numerical ones based on Monte Carlo graph generation techniques. We use these models to probe the properties of networks as their level of assortativity is varied. In the particular case of mixing by degree, we find strong variation with assortativity in the connectivity of the network and in the resilience of the network to the removal of vertices.

A Motivational Science Perspective on the Role of Student Motivation in Learning and Teaching Contexts.

Abstract: A motivational science perspective on student motivation in learning and teaching contexts is developed that highlights 3 general themes for motivational research. The 3 themes include the importance of a general scientific approach for research on student motivation, the utility of multidisciplinary perspectives, and the importance of use-inspired basic research on motivation. Seven substantive questions are then suggested as important directions for current and future motivational science research efforts. They include (1) What do students want? (2) What motivates students in classrooms? (3) How do students get what they want? (4) Do students know what they want or what motivates them? (5) How does motivation lead to cognition and cognition to motivation? (6) How does motivation change and develop? and (7) What is the role of context and culture? Each of the questions is addressed in terms of current knowledge claims and future directions for research in motivational science.

Racial/ethnic discrimination and health: findings from community studies.

Abstract: The authors review the available empirical evidence from population-based studies of the association between perceptions of racial/ethnic discrimination and health. This research indicates that discrimination is associated with multiple indicators of poorer physical and, especially, mental health status. However, the extant research does not adequately address whether and how exposure to discrimination leads to increased risk of disease. Gaps in the literature include limitations linked to measurement of discrimination, research designs, and inattention to the way in which the association between discrimination and health unfolds over the life course. Research on stress points to important directions for the future assessment of discrimination and the testing of the underlying processes and mechanisms by which discrimination can lead to changes in health. (Am J Public Health. 2003;93:200-208)

Quantum dynamics of single trapped ions

Abstract: Single trapped ions represent elementary quantum systems that are well isolated from the environment. They can be brought nearly to rest by laser cooling, and both their internal electronic states and external motion can be coupled to and manipulated by light fields. This makes them ideally suited for quantum-optical and quantum-dynamical studies under well-controlled conditions. Theoretical and experimental work on these topics is reviewed in the paper, with a focus on ions trapped in radio-frequency (Paul) traps.

In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells

Abstract: Although the existence of mammary stem cells has been suggested by serial transplantation studies in mice, their identification has been hindered by the lack of specific surface markers, and by the absence of suitable in vitro assays for testing stem cell properties: self-renewal and ability to generate differentiated progeny. We have developed an in vitro cultivation system that allows for propagation of human mammary epithelial cells (HMECs) in an undifferentiated state, based on their ability to proliferate in suspension, as nonadherent mammospheres. We demonstrate that nonadherent mammospheres are enriched in early progenitor/stem cells and able to differentiate along all three mammary epithelial lineages and to clonally generate complex functional structures in reconstituted 3D culture systems. Gene expression analysis of cells isolated from nonadherent mammospheres revealed overlapping genetic programs with other stem and progenitor cells and identified new markers that may be useful in the identification of mammary stem cells. The isolation and characterization of these stem cells should help elucidate the molecular pathways that govern normal mammary development and carcinogenesis.

Evolution by gene duplication: an update

Abstract: The importance of gene duplication in supplying raw genetic material to biological evolution has been recognized since the 1930s. Recent genomic sequence data provide substantial evidence for the abundance of duplicated genes in all organisms surveyed. But how do newly duplicated genes survive and acquire novel functions, and what role does gene duplication play in the evolution of genomes and organisms? Detailed molecular characterization of individual gene families, computational analysis of genomic sequences and population genetic modeling can all be used to help us uncover the mechanisms behind the evolution by gene duplication.

Prevalence and burden of overactive bladder in the United States

Abstract: Context: the National Overactive BLadder Evaluation (NOBLE) Program was initiated to better understand the prevalence and burden of overactive bladder in a broad spectrum of the United States population. Objective: to estimate the prevalence of overactive bladder with and without urge incontinence in the US, assess variation in prevalence by sex and other factors, and measure individual burden. Design: US national telephone survey using a clinically validated interview and a follow-up nested study comparing overactive bladder cases to sex- and age-matched controls. Setting: noninstitutionalized US adult population. Participants: a sample of 5,204 adults ≥18 years of age and representative of the US population by sex, age, and geographical region. Main outcome measures: prevalence of overactive bladder with and without urge incontinence and risk factors for overactive bladder in the US. In the nested case-control study, SF-36, CES-D, and MOS sleep scores were used to assess impact. Results: the overall prevalence of overactive bladder was similar between men (16.0%) and women (16.9%), but sex-specific prevalence differed substantially by severity of symptoms. In women, prevalence of urge incontinence increased with age from 2.0% to 19% with a marked increase after 44 years of age, and in men, increased with age from 0.3% to 8.9% with a marked increase after 64 years of age. Across all age groups, overactive bladder without urge incontinence was more common in men than in women. Overactive bladder with and without urge incontinence was associated with clinically and significantly lower SF-36 quality-of-life scores, higher CES-D depression scores, and poorer quality of sleep than matched controls. Conclusions: the NOBLE studies do not support the commonly held notion that women are considerably more likely than men to have urgency-related bladder control problems. The overall prevalence of overactive bladder does not differ by sex; however, the severity and nature of symptom expression does differ. Sex-specific anatomic differences may increase the probability that overactive bladder is expressed as urge incontinence among women compared with men. Nonetheless, overactive bladder, with and without incontinence, has a clinically significant impact on quality-of-life, quality-of-sleep, and mental health, in both men and women.

Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome

Abstract: Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by features reminiscent of marked premature ageing. Here, we present evidence of mutations in lamin A (LMNA) as the cause of this disorder. The HGPS gene was initially localized to chromosome 1q by observing two cases of uniparental isodisomy of 1q-the inheritance of both copies of this material from one parent-and one case with a 6-megabase paternal interstitial deletion. Sequencing of LMNA, located in this interval and previously implicated in several other heritable disorders, revealed that 18 out of 20 classical cases of HGPS harboured an identical de novo (that is, newly arisen and not inherited) single-base substitution, G608G(GGC > GGT), within exon 11. One additional case was identified with a different substitution within the same codon. Both of these mutations result in activation of a cryptic splice site within exon 11, resulting in production of a protein product that deletes 50 amino acids near the carboxy terminus. Immunofluorescence of HGPS fibroblasts with antibodies directed against lamin A revealed that many cells show visible abnormalities of the nuclear membrane. The discovery of the molecular basis of this disease may shed light on the general phenomenon of human ageing.

Chronic renal failure after transplantation of a nonrenal organ.

Abstract: Background Transplantation of nonrenal organs is often complicated by chronic renal disease with multifactorial causes. We conducted a population-based cohort analysis to evaluate the incidence of chronic renal failure, risk factors for it, and the associated hazard of death in recipients of nonrenal transplants. Methods Pretransplantation and post-transplantation clinical variables and data from a registry of patients with end-stage renal disease (ESRD) were linked in order to estimate the cumulative incidence of chronic renal failure (defined as a glomerular filtration rate of 29 ml per minute per 1.73 m2 of body-surface area or less or the development of ESRD) and the associated risk of death among 69,321 persons who received nonrenal transplants in the United States between 1990 and 2000. Results During a median follow-up of 36 months, chronic renal failure developed in 11,426 patients (16.5 percent). Of these patients, 3297 (28.9 percent) required maintenance dialysis or renal transplantation. The five-year risk of chronic renal failure varied according to the type of organ transplanted - from 6.9 percent among recipients of heart-lung transplants to 21.3 percent among recipients of intestine transplants. Multivariate analysis indicated that an increased risk of chronic renal failure was associated with increasing age (relative risk per 10-year increment, 1.36; P Conclusions The five-year risk of chronic renal failure after transplantation of a nonrenal organ ranges from 7 to 21 percent, depending on the type of organ transplanted. The occurrence of chronic renal failure among patients with a nonrenal transplant is associated with an increase by a factor of more than four in the risk of death.

Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells.

Abstract: A central issue in stem cell biology is to understand the mechanisms that regulate the self-renewal of haematopoietic stem cells (HSCs), which are required for haematopoiesis to persist for the lifetime of the animal1. We found that adult and fetal mouse and adult human HSCs express the proto-oncogene Bmi-1. The number of HSCs in the fetal liver of Bmi-1-/- mice2 was normal. In postnatal Bmi-1-/- mice, the number of HSCs was markedly reduced. Transplanted fetal liver and bone marrow cells obtained from Bmi-1-/- mice were able to contribute only transiently to haematopoiesis. There was no detectable self-renewal of adult HSCs, indicating a cell autonomous defect in Bmi-1-/- mice. A gene expression analysis revealed that the expression of stem cell associated genes3, cell survival genes, transcription factors, and genes modulating proliferation including p16Ink4a and p19Arf was altered in bone marrow cells of the Bmi-1-/- mice. Expression of p16Ink4a and p19Arf in normal HSCs resulted in proliferative arrest and p53-dependent cell death, respectively. Our results indicate that Bmi-1 is essential for the generation of self-renewing adult HSCs.

A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema.

Abstract: Background Lung-volume-reduction surgery has been proposed as a palliative treatment for severe emphysema. Effects on mortality, the magnitude and durability of benefits, and criteria for the selection of patients have not been established. Methods A total of 1218 patients with severe emphysema underwent pulmonary rehabilitation and were randomly assigned to undergo lung-volume-reduction surgery or to receive continued medical treatment. Results Overall mortality was 0.11 death per person-year in both treatment groups (risk ratio for death in the surgery group, 1.01; P=0.90). After 24 months, exercise capacity had improved by more than 10 W in 15 percent of the patients in the surgery group, as compared with 3 percent of patients in the medical-therapy group (P Conclusions Overall, lung-volume-reduction surgery increases the chance of improved exercise capacity but does not confer a survival advantage over medical therapy. It does yield a survival advantage for patients with both predominantly upper-lobe emphysema and low base-line exercise capacity. Patients previously reported to be at high risk and those with non-upper-lobe emphysema and high base-line exercise capacity are poor candidates for lung-volume-reduction surgery, because of increased mortality and negligible functional gain.