Showing papers by "Case Western Reserve University published in 2005"

A haplotype map of the human genome

Abstract: Inherited genetic variation has a critical but as yet largely uncharacterized role in human disease. Here we report a public database of common variation in the human genome: more than one million single nucleotide polymorphisms (SNPs) for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted. These data document the generality of recombination hotspots, a block-like structure of linkage disequilibrium and low haplotype diversity, leading to substantial correlations of SNPs with many of their neighbours. We show how the HapMap resource can guide the design and analysis of genetic association studies, shed light on structural variation and recombination, and identify loci that may have been subject to natural selection during human evolution.

Learning Styles and Learning Spaces: Enhancing Experiential Learning in Higher Education

Abstract: Drawing on the foundational theories of John Dewey and Kurt Lewin, we examine recent developments in theory and research on experiential learning and explore how this work can enhance experiential ...

EGFR Mutation and Resistance of Non–Small-Cell Lung Cancer to Gefitinib

Abstract: Mutations of the epidermal growth factor receptor (EGFR) gene have been identified in specimens from patients with non-small-cell lung cancer who have a response to anilinoquinazoline EGFR inhibitors. Despite the dramatic responses to such inhibitors, most patients ultimately have a relapse. The mechanism of the drug resistance is unknown. Here we report the case of a patient with EGFR-mutant, gefitinib-responsive, advanced non-small-cell lung cancer who had a relapse after two years of complete remission during treatment with gefitinib. The DNA sequence of the EGFR gene in his tumor biopsy specimen at relapse revealed the presence of a second point mutation, resulting in threonine-to-methionine amino acid change at position 790 of EGFR. Structural modeling and biochemical studies showed that this second mutation led to gefitinib resistance.

Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy.

Abstract: background Hypothermia is protective against brain injury after asphyxiation in animal models. However, the safety and effectiveness of hypothermia in term infants with encephalopathy is uncertain. methods We conducted a randomized trial of hypothermia in infants with a gestational age of at least 36 weeks who were admitted to the hospital at or before six hours of age with either severe acidosis or perinatal complications and resuscitation at birth and who had moderate or severe encephalopathy. Infants were randomly assigned to usual care (control group) or whole-body cooling to an esophageal temperature of 33.5°C for 72 hours, followed by slow rewarming (hypothermia group). Neurodevelopmental outcome was assessed at 18 to 22 months of age. The primary outcome was a combined end point of death or moderate or severe disability. results Of 239 eligible infants, 102 were assigned to the hypothermia group and 106 to the control group. Adverse events were similar in the two groups during the 72 hours of cooling. Primary outcome data were available for 205 infants. Death or moderate or severe disability occurred in 45 of 102 infants (44 percent) in the hypothermia group and 64 of 103 infants (62 percent) in the control group (risk ratio, 0.72; 95 percent confidence interval, 0.54 to 0.95; P=0.01). Twenty-four infants (24 percent) in the hypothermia group and 38 (37 percent) in the control group died (risk ratio, 0.68; 95 percent confidence interval, 0.44 to 1.05; P=0.08). There was no increase in major disability among survivors; the rate of cerebral palsy was 15 of 77 (19 percent) in the hypothermia group as compared with 19 of 64 (30 percent) in the control group (risk ratio, 0.68; 95 percent confidence interval, 0.38 to 1.22; P=0.20). conclusions Whole-body hypothermia reduces the risk of death or disability in infants with moderate or severe hypoxic–ischemic encephalopathy.

Myocardial Substrate Metabolism in the Normal and Failing Heart

Abstract: The alterations in myocardial energy substrate metabolism that occur in heart failure, and the causes and consequences of these abnormalities, are poorly understood. There is evidence to suggest th...

The Genome of the African Trypanosome Trypanosoma brucei

Abstract: African trypanosomes cause human sleeping sickness and livestock trypanosomiasis in sub-Saharan Africa. We present the sequence and analysis of the 11 megabase-sized chromosomes of Trypanosoma brucei. The 26-megabase genome contains 9068 predicted genes, including ∼900 pseudogenes and ∼1700 T. brucei–specific genes. Large subtelomeric arrays contain an archive of 806 variant surface glycoprotein (VSG) genes used by the parasite to evade the mammalian immune system. Most VSG genes are pseudogenes, which may be used to generate expressed mosaic genes by ectopic recombination. Comparisons of the cytoskeleton and endocytic trafficking systems with those of humans and other eukaryotic organisms reveal major differences. A comparison of metabolic pathways encoded by the genomes of T. brucei, T. cruzi, and Leishmania major reveals the least overall metabolic capability in T. brucei and the greatest in L. major. Horizontal transfer of genes of bacterial origin has contributed to some of the metabolic differences in these parasites, and a number of novel potential drug targets have been identified.

Evaluation study of congestive heart failure and pulmonary artery catheterization effectiveness

Abstract: Context Pulmonary artery catheters (PACs) have been used to guide therapy in multiple settings, but recent studies have raised concerns that PACs may lead to increased mortality in hospitalized patients. Objective To determine whether PAC use is safe and improves clinical outcomes in patients hospitalized with severe symptomatic and recurrent heart failure. Design, setting, and participants The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) was a randomized controlled trial of 433 patients at 26 sites conducted from January 18, 2000, to November 17, 2003. Patients were assigned to receive therapy guided by clinical assessment and a PAC or clinical assessment alone. The target in both groups was resolution of clinical congestion, with additional PAC targets of a pulmonary capillary wedge pressure of 15 mm Hg and a right atrial pressure of 8 mm Hg. Medications were not specified, but inotrope use was explicitly discouraged. Main outcome measures The primary end point was days alive out of the hospital during the first 6 months, with secondary end points of exercise, quality of life, biochemical, and echocardiographic changes. Results Severity of illness was reflected by the following values: average left ventricular ejection fraction, 19%; systolic blood pressure, 106 mm Hg; sodium level, 137 mEq/L; urea nitrogen, 35 mg/dL (12.40 mmol/L); and creatinine, 1.5 mg/dL (132.6 micromol/L). Therapy in both groups led to substantial reduction in symptoms, jugular venous pressure, and edema. Use of the PAC did not significantly affect the primary end point of days alive and out of the hospital during the first 6 months (133 days vs 135 days; hazard ratio [HR], 1.00 [95% confidence interval {CI}, 0.82-1.21]; P = .99), mortality (43 patients [10%] vs 38 patients [9%]; odds ratio [OR], 1.26 [95% CI, 0.78-2.03]; P = .35), or the number of days hospitalized (8.7 vs 8.3; HR, 1.04 [95% CI, 0.86-1.27]; P = .67). In-hospital adverse events were more common among patients in the PAC group (47 [21.9%] vs 25 [11.5%]; P = .04). There were no deaths related to PAC use, and no difference for in-hospital plus 30-day mortality (10 [4.7%] vs 11 [5.0%]; OR, 0.97 [95% CI, 0.38-2.22]; P = .97). Exercise and quality of life end points improved in both groups with a trend toward greater improvement with the PAC, which reached significance for the time trade-off at all time points after randomization. Conclusions Therapy to reduce volume overload during hospitalization for heart failure led to marked improvement in signs and symptoms of elevated filling pressures with or without the PAC. Addition of the PAC to careful clinical assessment increased anticipated adverse events, but did not affect overall mortality and hospitalization. Future trials should test noninvasive assessments with specific treatment strategies that could be used to better tailor therapy for both survival time and survival quality as valued by patients.

Intrinsic plasticity or brittleness of metallic glasses

Abstract: The intrinsic plasticity or brittleness of crystalline metals correlates with the ratio of the elastic shear modulus μ to the bulk modulus B; when the ratio μ/B exceeds a critical value, the metal is brittle. Sufficient data on elastic moduli and toughness are now available to permit an assessment for metallic glasses. We find a similar correlation, with the critical value of μ/B for metallic glasses (0.41–0.43) more sharply defined than for crystalline metals. This critical value applies also for annealing-induced embrittlement of metallic glasses. The clear correlation between mechanical behaviour (plasticity or brittleness) and μ/B assists in understanding flow and fracture mechanisms, and in guiding alloy design to alleviate brittleness of metallic glasses.

Fine-scale structural variation of the human genome.

Abstract: Inversions, deletions and insertions are important mediators of disease and disease susceptibility. We systematically compared the human genome reference sequence with a second genome (represented by fosmid paired-end sequences) to detect intermediate-sized structural variants >8 kb in length. We identified 297 sites of structural variation: 139 insertions, 102 deletions and 56 inversion breakpoints. Using combined literature, sequence and experimental analyses, we validated 112 of the structural variants, including several that are of biomedical relevance. These data provide a fine-scale structural variation map of the human genome and the requisite sequence precision for subsequent genetic studies of human disease.

Validation of the National Institutes of Health consensus definition of bronchopulmonary dysplasia.

Abstract: Objective. A number of definitions of bronchopulmonary dysplasia (BPD), or chronic lung dis- ease, have been used. A June 2000 National Institute of Child Health and Human Development/National Heart, Lung, and Blood Institute Workshop proposed a severity- based definition of BPD for infants 28 days but not at 36 weeks' postmenstrual age (PMA) or discharge, moderate BPD as O2 for >28 days plus treatment with 28 days plus >30% O2 and/or positive pressure at 36 weeks' PMA. The objective of this study was to determine the predictive validity of the severity-based, consensus definition of BPD. Methods. Data from 4866 infants (birth weight <1000 g, GA <32 weeks, alive at 36 weeks' PMA) who were entered into the National Institute of Child Health and Human Development Neonatal Research Network Very Low Birth weight (VLBW) Infant Registry between Jan- uary 1, 1995 and December 31, 1999, were linked to data from the Network Extremely Low Birth Weight (ELBW) Follow-up Program, in which surviving ELBW infants have a neurodevelopmental and health assessment at 18 to 22 months' corrected age. Linked VLBW Registry and Follow-up data were available for 3848 (79%) infants. Selected follow-up outcomes (use of pulmonary medica- tions, rehospitalization for pulmonary causes, receipt of respiratory syncytial virus prophylaxis, and neurodevel- opmental abnormalities) were compared among infants who were identified with BPD defined as O2 for 28 days (28 days definition), as O2 at 36 weeks' PMA (36 weeks' definition), and with the consensus definition of BPD. Results. A total of 77% of the neonates met the 28- days definition, and 44% met the 36-weeks definition. Using the consensus BPD definition, 77% of the infants had BPD, similar to the cohort identified by the 28-days definition. A total of 46% of the infants met the moderate (30%) or severe (16%) consensus definition criteria, iden- tifying a similar cohort of infants as the 36-weeks defi- nition. Of infants who met the 28-days definition and 36-weeks definition and were seen at follow-up at 18 to 22 months' corrected age, 40% had been treated with pulmonary medications and 35% had been rehospital- ized for pulmonary causes. In contrast, as the severity of BPD identified by the consensus definition worsened, the incidence of those outcomes and of selected adverse neurodevelopmental outcomes increased in the infants who were seen at follow-up. Conclusion. The consensus BPD definition identifies a spectrum of risk for adverse pulmonary and neurode- velopmental outcomes in early infancy more accurately than other definitions. Pediatrics 2005;116:1353-1360; bronchopulmonary dysplasia, chronic lung disease, ex- tremely preterm infants, neurodevelopmental.

Error Measures for Generalizing About Forecasting Methods: Empirical Comparisons

Abstract: This study evaluated measures for making comparisons of errors across time series. We analyzed 90 annual and 101 quarterly economic time series. We judged error measures on reliability, construct validity, sensitivity to small changes, protection against outliers, and their relationship to decision making. The results lead us to recommend the Geometric Mean of the Relative Absolute Error (GMRAE) when the task involves calibrating a model for a set of time series. The GMRAE compares the absolute error of a given method to that from the random walk forecast. For selecting the most accurate methods, we recommend the Median RAE (MdRAE) when few series are available and the Median Absolute Percentage Error (MdAPE) otherwise. The Root Mean Square Error (RMSE) is not reliable, and is therefore inappropriate for comparing accuracy across series.

Spike and slab variable selection: Frequentist and Bayesian strategies

Abstract: Variable selection in the linear regression model takes many apparent faces from both frequentist and Bayesian standpoints. In this paper we introduce a variable selection method referred to as a rescaled spike and slab model. We study the importance of prior hierarchical specifications and draw connections to frequentist generalized ridge regression estimation. Specifically, we study the usefulness of continuous bimodal priors to model hypervariance parameters, and the effect scaling has on the posterior mean through its relationship to penalization. Several model selection strategies, some frequentist and some Bayesian in nature, are developed and studied theoretically. We demonstrate the importance of selective shrinkage for effective variable selection in terms of risk misclassification, and show this is achieved using the posterior from a rescaled spike and slab model. We also show how to verify a procedure’s ability to reduce model uncertainty in finite samples using a specialized forward selection strategy. Using this tool, we illustrate the effectiveness of rescaled spike and slab models in reducing model uncertainty.

SLC24A5, a Putative Cation Exchanger, Affects Pigmentation in Zebrafish and Humans

Abstract: Lighter variations of pigmentation in humans are associated with diminished number, size, and density of melanosomes, the pigmented organelles of melanocytes. Here we show that zebrafish golden mutants share these melanosomal changes and that golden encodes a putative cation exchanger slc24a5 (nckx5) that localizes to an intracellular membrane, likely the melanosome or its precursor. The human ortholog is highly similar in sequence and functional in zebrafish. The evolutionarily conserved ancestral allele of a human coding polymorphism predominates in African and East Asian populations. In contrast, the variant allele is nearly fixed in European populations, is associated with a substantial reduction in regional heterozygosity, and correlates with lighter skin pigmentation in admixed populations, suggesting a key role for the SLC24A5 gene in human pigmentation.

Segmental Duplications and Copy-Number Variation in the Human Genome

Abstract: The human genome contains numerous blocks of highly homologous duplicated sequence. This higher-order architecture provides a substrate for recombination and recurrent chromosomal rearrangement associated with genomic disease. However, an assessment of the role of segmental duplications in normal variation has not yet been made. On the basis of the duplication architecture of the human genome, we defined a set of 130 potential rearrangement hotspots and constructed a targeted bacterial artificial chromosome (BAC) microarray (with 2,194 BACs) to assess copy-number variation in these regions by array comparative genomic hybridization. Using our segmental duplication BAC microarray, we screened a panel of 47 normal individuals, who represented populations from four continents, and we identified 119 regions of copy-number polymorphism (CNP), 73 of which were previously unreported. We observed an equal frequency of duplications and deletions, as well as a 4-fold enrichment of CNPs within hotspot regions, compared with control BACs (P 4-fold within regions of CNP. Almost without exception, CNPs were not confined to a single population, suggesting that these either are recurrent events, having occurred independently in multiple founders, or were present in early human populations. Our study demonstrates that segmental duplications define hotspots of chromosomal rearrangement, likely acting as mediators of normal variation as well as genomic disease, and it suggests that the consideration of genomic architecture can significantly improve the ascertainment of large-scale rearrangements. Our specialized segmental duplication BAC microarray and associated database of structural polymorphisms will provide an important resource for the future characterization of human genomic disorders.

Randomized Trial of Prolonged Exposure for Posttraumatic Stress Disorder with and without Cognitive Restructuring: Outcome at Academic and Community Clinics.

Abstract: Female assault survivors (N=171) with chronic posttraumatic stress disorder (PTSD) were randomly assigned to prolonged exposure (PE) alone, PE plus cognitive restructuring (PE/CR), or wait-list (WL). Treatment, which consisted of 9-12 sessions, was conducted at an academic treatment center or at a community clinic for rape survivors. Evaluations were conducted before and after therapy and at 3-, 6-, and 12-month follow-ups. Both treatments reduced PTSD and depression in intent-to-treat and completer samples compared with the WL condition; social functioning improved in the completer sample. The addition of CR did not enhance treatment outcome. No site differences were found: Treatment in the hands of counselors with minimal cognitive- behavioral therapy (CBT) experience was as efficacious as that of CBT experts. Treatment gains were maintained at follow-up, although a minority of patients received additional treatment.

Copper oxide nanocrystals.

Abstract: It is well-known that inorganic nanocrystals are a benchmark model for nanotechnology, given that the tunability of optical properties and the stabilization of specific phases are uniquely possible at the nanoscale. Copper (I) oxide (Cu(2)O) is a metal oxide semiconductor with promising applications in solar energy conversion and catalysis. To understand the Cu/Cu(2)O/CuO system at the nanoscale, we have developed a method for preparing highly uniform monodisperse nanocrystals of Cu(2)O. The procedure also serves to demonstrate our development of a generalized method for the synthesis of transition metal oxide nanocrystals. Cu nanocrystals are initially formed and subsequently oxidized to form highly crystalline Cu(2)O. The volume change during phase transformation can induce crystal twinning. Absorption in the visible region of the spectrum gave evidence for the presence of a thin, epitaxial layer of CuO, which is blue-shifted, and appears to increase in energy as a function of decreasing particle size. XPS confirmed the thin layer of CuO, calculated to have a thickness of approximately 5 A. We note that the copper (I) oxide phase is surprisingly well-stabilized at this length scale.

Natural selection on protein-coding genes in the human genome

Abstract: Comparisons of DNA polymorphism within species to divergence between species enables the discovery of molecular adaptation in evolutionarily constrained genes as well as the differentiation of weak from strong purifying selection. The extent to which weak negative and positive darwinian selection have driven the molecular evolution of different species varies greatly, with some species, such as Drosophila melanogaster, showing strong evidence of pervasive positive selection, and others, such as the selfing weed Arabidopsis thaliana, showing an excess of deleterious variation within local populations. Here we contrast patterns of coding sequence polymorphism identified by direct sequencing of 39 humans for over 11,000 genes to divergence between humans and chimpanzees, and find strong evidence that natural selection has shaped the recent molecular evolution of our species. Our analysis discovered 304 (9.0%) out of 3,377 potentially informative loci showing evidence of rapid amino acid evolution. Furthermore, 813 (13.5%) out of 6,033 potentially informative loci show a paucity of amino acid differences between humans and chimpanzees, indicating weak negative selection and/or balancing selection operating on mutations at these loci. We find that the distribution of negatively and positively selected genes varies greatly among biological processes and molecular functions, and that some classes, such as transcription factors, show an excess of rapidly evolving genes, whereas others, such as cytoskeletal proteins, show an excess of genes with extensive amino acid polymorphism within humans and yet little amino acid divergence between humans and chimpanzees.

Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways

Abstract: Cystic renal diseases are caused by mutations of proteins that share a unique subcellular localization: the primary cilium of tubular epithelial cells1. Mutations of the ciliary protein inversin cause nephronophthisis type II, an autosomal recessive cystic kidney disease characterized by extensive renal cysts, situs inversus and renal failure2. Here we report that inversin acts as a molecular switch between different Wnt signaling cascades. Inversin inhibits the canonical Wnt pathway by targeting cytoplasmic dishevelled (Dsh or Dvl1) for degradation; concomitantly, it is required for convergent extension movements in gastrulating Xenopus laevis embryos and elongation of animal cap explants, both regulated by noncanonical Wnt signaling. In zebrafish, the structurally related switch molecule diversin ameliorates renal cysts caused by the depletion of inversin, implying that an inhibition of canonical Wnt signaling is required for normal renal development. Fluid flow increases inversin levels in ciliated tubular epithelial cells and seems to regulate this crucial switch between Wnt signaling pathways during renal development.

Functional electrical stimulation for neuromuscular applications

Abstract: ▪ Abstract Paralyzed or paretic muscles can be made to contract by applying electrical currents to the intact peripheral motor nerves innervating them. When electrically elicited muscle contractions are coordinated in a manner that provides function, the technique is termed functional electrical stimulation (FES). In more than 40 years of FES research, principles for safe stimulation of neuromuscular tissue have been established, and methods for modulating the strength of electrically induced muscle contractions have been discovered. FES systems have been developed for restoring function in the upper extremity, lower extremity, bladder and bowel, and respiratory system. Some of these neuroprostheses have become commercialized products, and others are available in clinical research settings. Technological developments are expected to produce new systems that have no external components, are expandable to multiple applications, are upgradable to new advances, and are controlled by a combination of signals, ...

Review: mesenchymal stem cells: cell-based reconstructive therapy in orthopedics.

Abstract: Adult stem cells provide replacement and repair descendants for normal turnover or injured tissues. These cells have been isolated and expanded in culture, and their use for therapeutic strategies requires technologies not yet perfected. In the 1970s, the embryonic chick limb bud mesenchymal cell culture system provided data on the differentiation of cartilage, bone, and muscle. In the 1980s, we used this limb bud cell system as an assay for the purification of inductive factors in bone. In the 1990s, we used the expertise gained with embryonic mesenchymal progenitor cells in culture to develop the technology for isolating, expanding, and preserving the stem cell capacity of adult bone marrow-derived mesenchymal stem cells (MSCs). The 1990s brought us into the new field of tissue engineering, where we used MSCs with site-specific delivery vehicles to repair cartilage, bone, tendon, marrow stroma, muscle, and other connective tissues. In the beginning of the 21st century, we have made substantial advances: the most important is the development of a cell-coating technology, called painting, that allows us to introduce informational proteins to the outer surface of cells. These paints can serve as targeting addresses to specifically dock MSCs or other reparative cells to unique tissue addresses. The scientific and clinical challenge remains: to perfect cell-based tissue-engineering protocols to utilize the body's own rejuvenation capabilities by managing surgical implantations of scaffolds, bioactive factors, and reparative cells to regenerate damaged or diseased skeletal tissues.

Acute heart failure syndromes: current state and framework for future research.

Abstract: Acute heart failure syndromes (AHFS) poses unique diagnostic and management challenges. This syndrome has recently received attention from researchers, clinicians, regulatory agencies, and the pharmaceutical industry. However, there is no consensus on its definition, epidemiology, pathophysiology, appropriate therapeutic options, and directions for future research. This document is the result of the First and Second International Workshop on Acute Heart Failure Syndrome that took place in May 2004 and April 2005. At these workshops, a selected group of physician scientists, epidemiologists, clinicians, regulatory and governmental funding agencies, and industry representatives from North and South America and Europe convened to develop a platform for future investigative approaches and management of AHFS. Subsequently, emergency physicians, who play a pivotal role in the early management of AHFS, contributed to this document. AHFS is defined as gradual or rapid change in heart failure (HF) signs and symptoms resulting in a need for urgent therapy. These symptoms are primarily the result of severe pulmonary congestion due to elevated left ventricular (LV) filling pressures (with or without low cardiac output). AHFS can occur in patients with preserved or reduced ejection fraction (EF). Concurrent cardiovascular conditions such as coronary heart disease (CHD), hypertension, valvular heart disease, atrial arrhythmias, and/or noncardiac conditions (including renal dysfunction, diabetes, anemia) are often present and may precipitate or contribute to the pathophysiology of this syndrome.1–3 HF hospitalizations have risen steadily, with >1 million in 2004 in the United States4; a similar number has been reported in Europe. In the United States, it is estimated that these hospitalizations account for >75% of the 46 billion dollars spent each year on the care of HF patients.4 Although much has been accomplished in the management of chronic HF, the absence of evidence-based clinical practice guidelines for AHFS is striking in comparison to …

Evaluation of the Learning Curve in Laparoscopic Colorectal Surgery: Comparison of Right-Sided and Left-Sided Resections

Abstract: Objective: To provide a multidimensional analysis of the learning curve in major laparoscopic colonic and rectal surgery and compare outcomes between right-sided versus left-sided resections.

Improved Survival Rates With Increased Neurodevelopmental Disability for Extremely Low Birth Weight Infants in the 1990s

Abstract: Background. Advances in perinatal care have resulted in increased survival rates for extremely low birth weight children. We sought to examine the relative changes in rates of survival and neurodevelopmental impairment at 20 months of corrected age among 500- to 999-g birth weight infants born at our perinatal center during 2 periods, before and after the introduction of surfactant therapy in 1990. Methods. Four hundred ninety-six infants with birth weights of 500 to 999 g were born at our perinatal center during period I (1982–1989) (mean body weight: 762 g; mean gestational age: 25.8 weeks) and 682 during period II (1990–1998) (mean body weight: 756 g; mean gestational age: 25.5 weeks). Rates of death and survival with and without neurodevelopmental impairment at 20 months of corrected age for the 2 periods were compared with logistic regression analyses, with adjustment for gestational age. Results. Survival rates increased from 49% during period I to 67% during period II. Neonatal morbidity rates also increased during period II, including rates of sepsis (from 37% to 51%), periventricular leukomalacia (from 2% to 7%), and chronic lung disease, defined as oxygen dependence at 36 weeks of corrected age (from 32% to 43%). Rates of severe cranial ultrasound abnormalities were similar (22% vs 22%). Among children monitored, the rate of neurologic abnormalities, including cerebral palsy, increased from 16% during period I to 25% during period II and the rate of deafness increased from 3% to 7%. The overall rate of neurodevelopmental impairment (major neurosensory abnormality and/or Bayley Mental Developmental Index score of Conclusions. The improved survival rates in the 1990s occurred with an increased risk of significant neurodevelopmental impairment. Prospective parents of extremely low birth weight infants should be advised of this substantial risk, to facilitate decision-making in the delivery room.

Postoperative nomogram predicting the 10-year probability of prostate cancer recurrence after radical prostatectomy

Abstract: Purpose A postoperative nomogram for prostate cancer recurrence after radical prostatectomy (RP) has been independently validated as accurate and discriminating. We have updated the nomogram by extending the predictions to 10 years after RP and have enabled the nomogram predictions to be adjusted for the disease-free interval that a patient has maintained after RP. Methods Cox regression analysis was used to model the clinical information for 1,881 patients who underwent RP for clinically-localized prostate cancer by two high-volume surgeons. The model was externally validated separately on two independent cohorts of 1,782 patients and 1,357 patients, respectively. Disease progression was defined as a rising prostate-specific antigen (PSA) level, clinical progression, radiotherapy more than 12 months postoperatively, or initiation of systemic therapy. Results The 10-year progression-free probability for the modeling set was 79% (95% CI, 75% to 82%). Significant variables in the multivariable model include...

Curvilinear Effects of Consumer Loyalty Determinants in Relational Exchanges

Abstract: Drawing from need, motivation, and social exchange theories, this study conceptualizes and empirically examines the differential curvilinear effects of multiple determinants of loyalty intentions, including transactional satisfaction, trust, and value for relational exchanges. The authors conceptualize trust as a “motivator,” satisfaction as a “hygiene,” and value as a “bivalent” factor in consumer loyalty mechanisms. Using consumer data on relational exchanges in two different service contexts—retail clothing and nonbusiness airline travel—and accounting for different sources of error—namely, measurement, common method, and response style—the authors empirically investigate the hypothesized mechanisms. The data support the motivator, or the enhancing role of trust, and the hygiene, or the maintaining role of satisfaction, on loyalty intentions in both contexts. Although the authors also obtain consistent results for the influence of value, its role is aligned with a hygiene mechanism, not a biva...