bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating Allele Age
Authors: Slatkin Montgomery , Rannala Bruce
Published: July 2002

The age of an allele can be estimated both from genetic variation among different copies (intra-allelic variation) and from its frequency. Estimates based on intra-allelic variation follow from the exponential decay of linkage disequilibrium because of recombination and mutation. The confidence interval depends both on the uncertainty in recombination and mutation rates and on randomness of the genealogy of chromosomes that carry the allele (the intra-allelic genealogy). Several approximate methods to account for variation in the intra-allelic genealogy have been derived. Allele frequency alone also provides an estimate of age. Estimates based on frequency and on intra-allelic variability can be combined to provide a more accurate estimate or can be contrasted to show that an allele has been subject to natural selection. These methods have been applied to numerous cases, including alleles associated with cystic fibrosis, idiopathic torsion dystonia, and resistance to infection by HIV. We emphasize that estimates of allele age depend on assumptions about demographic history and natural selection.
USHERSYNDROME: From Genetics to Pathogenesis
Authors: Petit Christine
Published: July 2002

▪ Abstract  Usher syndrome (USH) is defined by the association of sensorineural deafness and visual impairment due to retinitis pigmentosa. The syndrome has three distinct clinical subtypes, referred to as USH1, USH2, and USH3. Each subtype is genetically heterogeneous, and 12 loci have been detected so far. Four genes have been identified, namely, USH1B, USH1C, USH1D, and USH2A. USH1B, USH1C, and USH1D encode an unconventional myosin (myosin VIIA), a PDZ domain–containing protein (harmonin), and a cadherin-like protein (cadherin-23), respectively. Mutations of these genes cause primary defects of the sensory cells in the inner ear, and probably also in the retina. In the inner ear, the USH1 genes, I propose, are involved in the same signaling pathway, which may control development and/or maintenance of the hair bundles of sensory cells via an adhesion force (a) at the junctions between these cells and supporting cells and (b) at the level of the lateral links that interconnect the stereocilia. In contrast, the molecular pathogenesis of USH2A, which is owing to a defect of a novel extracellular matrix protein, is likely to be different from that of USH1.
MINIMALLY INVASIVE SURGERY
Authors: Vierra, M.D Mark
Published: July 2002

▪ Abstract  With the widespread introduction of laparoscopic cholecystectomy in late 1989, the practice and expectations of general surgery were changed forever. The techniques of laparoscopy were not new—they had been adopted by gynecologists and orthopedic surgeons at least a decade before—but it was laparoscopic cholecystectomy that captured the attention of the surgical profession and the public and spawned the tremendous growth in what has come to be called minimally invasive surgery. Although this surgery has tremendous appeal, offering quicker recovery, less pain, and possibly greater safety, it presents new challenges in the areas of training, credentialing, and quality assessment and raises serious questions about the real benefits of new technology at a time when the political and economic sensitivity of these issues is greater than ever.

In this chapter I limit myself to a discussion of laparoscopy in general surgery, with a focus on what we have learned from laparoscopic cholecystectomy and on what this knowledge suggests for the future of other laparoscopic general surgical procedures.
Inferior Vena Cava Interruption: How and When?
Authors: Girard Philippe , Tardy Bernard , Decousus Hervé
Published: July 2002

Interruption of the inferior vena cava (IVC) to prevent pulmonary embolism arising from venous thrombi in the lower extremities has become widely used since IVC filters became available about 30 years ago. However, reliable data regarding efficacy and safety of IVC filters are still lacking. The first controlled clinical trial of IVC filters demonstrated their effectiveness, but filters had no detectable impact on mortality and were associated with an increased risk of recurrent deep venous thrombosis. On the basis of the literature, indications for IVC interruption can be classified as accepted, debated, and debatable. The relevance of debated indications, more accurate identification of patients who remain “very high-risk” despite preventive or curative anticoagulant treatment, and selection of the most appropriate filter should be looked at in prospective clinical studies.
Prevention of Uremic Bone Disease Using Calcimimetic Compounds
Authors: Olgaard Klaus , Lewin Ewa
Published: July 2002

▪ Abstract  The discovery, characterization, and cloning of the calcium-sensing receptor (CaR) in 1993 was soon followed by the creation of a new type of drug, the calcimimetics—NPS R-568 and NPS R-467—which are small phenylalkylamine derivative compounds that act as CaR agonists and increase the sensitivity of the CaR to activation by extracellular calcium (Ca2+). As expected, these compounds turned out to have a significant effect on the Ca2+/parathyroid hormone (PTH) relationship, resulting in a dramatically greater suppression of the PTH level than would otherwise occur at the actual extracellular Ca2+ levels. Renal osteodystrophy (RO) due to secondary hyperparathyroidism (HPT) in chronic renal failure was an obvious target for studying the effects of NPS R-568. In a study on experimental animals, the results clearly showed that this first generation of calcimimetics, NPS R-568, had an acute dose-dependent and short-lived suppressive effect on PTH secretion from the parathyroid glands. A similar effect was found in patients with chronic renal failure and secondary HPT. At the same time, the calcimimetics induced a slight degree of hypocalcemia. Such a significant suppressive effect on PTH secretion would be expected to result in therapeutic potential for a preventive or therapeutic effect on the RO accompanying chronic uremia. Administration would probably be in close concert with present strategies, phosphate binders and vitamin D analogs. A wide distribution of CaRs have now been demonstrated in the body, and an important question is how calcimimetics will affect the function of different tissues and organs when used for long-term treatment or prevention of secondary HPT and RO. Although relatively few experimental and clinical investigations have been completed, they clearly confirm the suppressive effect of calcimimetics on PTH secretion. In rats with experimental chronic renal failure, a significant and beneficial effect on the prevention of RO has been demonstrated. The effect of calcimimetic compounds is presently being evaluated in humans. Besides induction of hypocalcemia, the adverse effects in these mainly short-term studies have been few. Future studies with calcimimetics will further define the physiology and pathophysiology of the CaR and the long-term benefit of calcimimetic compounds in patients with chronic renal failure.
CELL BIOLOGY OF THE PRIMITIVE EUKARYOTE GIARDIA LAMBLIA
Authors: Gillin Frances D. , Reiner David S. , McCaffery J. Michael
Published: July 2002

Giardia lamblia is an extremely primitive or early-diverging eukaryote that has been considered to have no typical ER or Golgi apparatus, although it is a complex and highly developed cell. Both the trophozoite and cyst have unusual surface proteins that enable these stages to survive in very different and hostile environments. We found that G. lamblia forms novel encystation-specific secretory vesicles and can sort cyst wall proteins to a regulated secretory pathway distinct from the constitutive pathway used to transport the variable cysteine-rich protein to the trophozoite surface. Our studies, utilizing novel ultrastructural methods that preserve the endomembranes, as well as IEM, support the idea that G. lamblia has many of the endomembrane protein transport elements and sorting functions of higher cells and that these appeared very early in the evolution of eukaryotic cells.
SULFUR TUFT AND TURKEY TAIL: Biosynthesis and Biodegradation of Organohalogens by Basidiomycetes
Authors: de Jong Ed , Field Jim A.
Published: July 2002

▪ Abstract  Chlorinated aliphatic and aromatic compounds are generally considered to be undesirable xenobiotic pollutants. However, the higher fungi, Basidiomycetes, have a widespread capacity for organohalogen biosynthesis. Adsorbable organic halogens (AOX) and/or low-molecular-weight halogenated compounds are produced by Basidiomycetes of 68 genera from 20 different families. Most of the 81 halogenated metabolites identified from Basidiomycetes to date are chlorinated, although brominated and iodated metabolites have also been described. Two broad categories of Basidiomycete organohalogen metabolites are the halogenated aromatic compounds and the haloaliphatic compounds. Some of these organohalogen metabolites have demonstrable physiological roles as antibiotics and as metabolites involved in lignin degradation. Basidiomycetes produce large amounts of low-molecular-weight organohalogens or adsorbable organic halogens (AOX) when grown on lignocellulosic substrates. In our view, Basidiomycetes, as decomposers of forest litter, are a major source of natural organohalogens in terrestrial environments.

Basidiomycetes are also potent degraders of a wide range of chlorinated pollutants, such as bleachery effluent from kraft mills and pentachlorophenol, polychlorinated dioxins, and polychlorinated biphenyls. The extracellular, lignin-degrading enzymes of the Basidiomycetes are involved in the oxidative degradation of chlorophenols and dioxin and can cause reductive dechlorination of halomethanes.

There is no clear-cut separation between “polluters” and “clean-uppers” within the Basidiomycetes. Several genera, e.g. Bjerkandera, Hericium, Phlebia, and Trametes, produce significant amounts of chlorinated compounds but are also highly effective in metabolizing or biotransforming chlorinated pollutants.
PARTON-MODEL SUM RULES
Authors: Hinchliffe Ian , Kwiatkowski Axel
Published: July 2002

▪ Abstract  This review discusses the experimental and theoretical status of various parton-model sum rules. The basis of the sum rules in perturbative quantum chromodynamics is discussed. Their use in extracting the value of the strong coupling constant is evaluated, and the failure of the naive version of some of these sum rules is assessed.
EVALUATION OF METHODOLOGY FOR NUTRITIONAL ASSESSMENT IN CHILDREN: Anthropometry, Body Composition, and Energy Expenditure
Authors: Zemel Babette S. , Riley Elizabeth M. , Stallings Virginia A.
Published: July 2002

▪ Abstract  Nutritional status in children is an indicator of health and well-being at both the individual and the population level. Screening for malnutrition should be an integral part of pediatric care universally. Nutritional intervention requires repeated measurement of nutritional status to assess severity and to track progress over time. Methodological issues in the assessment of nutritional status are reviewed with emphasis on anthropometric measurement, body composition, and energy expenditure of children at risk for malnutrition. Use of reference data, measurement error, maturational effects, and hereditary factors are among the issues reviewed and serve as guidelines in the interpretation of measurement of nutritional status.
MECHANISMS BY WHICH CARBOHYDRATES REGULATE EXPRESSION OF GENES FOR GLYCOLYTIC AND LIPOGENIC ENZYMES
Authors: Girard Jean , Ferré Pascal , Foufelle Fabienne
Published: July 2002

▪ Abstract  Regulation of gene expression by nutrients is an important mechanism in the adaptation of mammals to their nutritional environment. This is especially true for enzymes involved in the storage of energy, such as the lipogenic and glycolytic enzymes in liver and adipose tissue. Transcription of the genes for lipogenic and glycolytic enzymes is stimulated by glucose in adipose tissue, liver, and pancreatic β-cells. Several lines of evidence suggest that glucose must be metabolized to glucose-6-phosphate to stimulate gene transcription. In adipose tissue, insulin increases the expression of lipogenic enzymes indirectly by stimulating glucose uptake. In the liver, insulin also acts indirectly by stimulating the expression of glucokinase and, hence, by increasing glucose metabolism. Glucose response elements have been characterized for the l-pyruvate kinase and S14 genes. They have in common the presence of a sequence 5′-CACGTG-3′, which binds a transcription factor called USF (upstream stimulatory factor). Another glucose response element, which uses a transcription factor named Sp1, has been characterized in the gene for the acetyl-coenzyme A carboxylase. The mechanisms linking glucose-6-phosphate to the glucose-responsive transcription complex are largely unknown.
MOLECULAR MECHANISMS OF GENETIC POLYMORPHISMS OF DRUG METABOLISM
Authors: Meyer Urs A. , Zanger Ulrich M.
Published: July 2002

▪ Abstract  One of the major causes of interindividual variation of drug effects is genetic variation of drug metabolism. Genetic polymorphisms of drug-metabolizing enzymes give rise to distinct subgroups in the population that differ in their ability to perform certain drug biotransformation reactions. Polymorphisms are generated by mutations in the genes for these enzymes, which cause decreased, increased, or absent enzyme expression or activity by multiple molecular mechanisms. Moreover, the variant alleles exist in the population at relatively high frequency. Genetic polymorphisms have been described for most drug metabolizing enzymes. The molecular mechanisms of three polymorphisms are reviewed here.

The acetylation polymorphism concerns the metabolism of a variety of arylamine and hydrazine drugs, as well as carcinogens by the cytosolic N-acetyltransferase NAT2. Seven mutations of the NAT2 gene that occur singly or in combination define numerous alleles associated with decreased function.

The debrisoquine-sparteine polymorphism of drug oxidation affects the metabolism of more than 40 drugs. The poor metabolizer phenotype is caused by several “loss of function” alleles of the cytochrome P450 CYP2D6 gene. On the other hand, “ultrarapid” metabolizers are caused by duplication or amplification of an active CYP2D6 gene. Intermediate metabolizers are often heterozygotes or carry alleles with mutations that decrease enzyme activity only moderately.

The mephenytoin polymorphism affects the metabolism of mephenytoin and several other drugs. Two mutant alleles of CYP2C19 have so far been identified to cause this polymorphism.

These polymorphisms show recessive transmission of the poor or slow metabolizer phenotype, i.e. two mutant alleles define the genotype in these individuals. Simple DNA tests based on the primary mutations have been developed to predict the phenotype. Analysis of allele frequencies in different populations revealed major differences, thereby tracing the molecular history and evolution of these polymorphisms.
Pharmacogenetics of Sulfotransferase
Authors: Nagata K. , Yamazoe Y.
Published: July 2002

Cytosolic sulfotransferase catalyzes sulfoconjugation of relatively small lipophilic endobiotics and xenobiotics. At least 44 cytosolic sulfotransferases have been identified from mammals, and based on their amino acid sequences, these forms are shown to constitute five different families. In humans, 10 sulfotransferase genes have been identified and shown to localize on at least five different chromosomes. The enzymatic properties characterized in the recombinant forms indicate the association of their substrate specificity with metabolisms of such nonpeptide hormones as estrogen, corticoid, and thyroxine, although most forms are also active on the sulfation of various xenobiotics. Genetic polymorphisms are observed on such human sulfotransferases as ST1A2, ST1A3, and ST2A3.
Simulation of Clinical Trials
Authors: Holford N. H. G. , Kimko H. C. , Monteleone J. P. R. , Peck C. C.
Published: July 2002

Computer simulation of clinical trials has evolved over the past two decades from a simple instructive game to “full” simulation models yielding pharmacologically sound, realistic trial outcomes. The need to make drug development more efficient and informative and the awareness that many industries make extensive use of simulation in product development have advanced considerably the use of simulation of clinical trials in pharmaceutical product development over the past decade. The structural and stochastic components of trial simulation models are explained as a prelude to a listing of representative simulation projects, reflecting investigative applications of statistical methods, trial design comparisons, and full simulation of new drugs being developed. Lessons learned from these projects are reviewed in the context of their current impact and potential for influencing the future of drug development.
Neurotrophic and Neuroprotective Actions of Estrogens and Their Therapeutic Implications
Authors: Lee Susan J , McEwen Bruce S
Published: July 2002

Originally known for its regulation of reproductive functions, estradiol, a lipophilic hormone that can easily cross plasma membranes as well as the blood-brain barrier, maintains brain systems subserving arousal, attention, mood, and cognition. In addition, both synthetic and natural estrogens exert neurotrophic and neuroprotective effects. There is increasing evidence that estrogen actions are mediated by nongenomic as well as direct and indirect genomic pathways. Although in vitro models have provided the most extensive evidence for neurotrophic and neuroprotective actions to date, there are also in vivo studies that support these actions.
Prostanoid Receptors: Subtypes and Signaling
Authors: Breyer Richard M , Bagdassarian Carey K , Myers Scott A , Breyer Matthew D
Published: July 2002

Cyclooxygenases metabolize arachidonate to five primary prostanoids: PGE2, PGF2α, PGI2, TxA2, and PGD2. These autacrine lipid mediators interact with specific members of a family of distinct G-protein-coupled prostanoid receptors, designated EP, FP, IP, TP, and DP, respectively. Each of these receptors has been cloned, expressed, and characterized. This family of eight prostanoid receptor complementary DNAs encodes seven transmembrane proteins which are typical of G-protein-coupled receptors and these receptors are distinguished by their ligand-binding profiles and the signal transduction pathways activated on ligand binding. Ligand-binding selectivity of these receptors is determined by both the transmembrane sequences and amino acid residues in the putative extracellular-loop regions. The selectivity of interaction between the receptors and G proteins appears to be mediated at least in part by the C-terminal tail region. Each of the EP1, EP3, FP, and TP receptors has alternative splice variants described that alter the coding sequence in the C-terminal intracellular tail region. The C-terminal variants modulate signal transduction, phosphorylation, and desensitization of these receptors, as well as altering agonist-independent constitutive activity.
Human and Murine Phenotypes Associated with Defects in Cation-Chloride Cotransport
Authors: Delpire Eric , Mount David B.
Published: July 2002

▪ Abstract  The diuretic-sensitive cotransport of cations with chloride is mediated by the cation-chloride cotransporters, a large gene family encompassing a total of seven Na-Cl, Na-K-2Cl, and K-Cl cotransporters, in addition to two related transporters of unknown function. The cation-chloride cotransporters perform a wide variety of physiological roles and differ dramatically in patterns of tissue expression and cellular localization. The renal-specific Na-Cl cotransporter (NCC) and Na-K-2Cl cotransporter (NKCC2) are involved in Gitelman and Bartter syndrome, respectively, autosomal recessive forms of metabolic alkalosis. The associated phenotypes due to loss-of-function mutations in NCC and NKCC2 are consistent, in part, with their functional roles in the distal convoluted tubule and thick ascending limb, respectively. Other cation-chloride cotransporters are positional candidates for Mendelian human disorders, and the K-Cl cotransporter KCC3, in particular, may be involved in degenerative peripheral neuropathies linked to chromosome 15q14. The characterization of mice with both spontaneous and targeted mutations of several cation-chloride cotransporters has also yielded significant insight into the physiological and pathophysiological roles of several members of the gene family. These studies implicate the Na-K-2Cl cotransporter NKCC1 in hearing, salivation, pain perception, spermatogenesis, and the control of extracellular fluid volume. Targeted deletion of the neuronal-specific K-Cl cotransporter KCC2 generates mice with a profound seizure disorder and confirms the central role of this transporter in modulating neuronal excitability. Finally, the comparison of human and murine phenotypes associated with loss-of-function mutations in cation-chloride cotransporters indicates important differences in physiology of the two species and provides an important opportunity for detailed physiological and morphological analysis of the tissues involved.
Regulation of Endothelial Nitric Oxide Synthase: Location, Location, Location
Authors: Shaul Philip W.
Published: July 2002

▪ Abstract  Endothelial nitric oxide synthase (eNOS) is expressed in vascular endothelium, airway epithelium, and certain other cell types where it generates the key signaling molecule nitric oxide (NO). Diminished NO availability contributes to systemic and pulmonary hypertension, atherosclerosis, and airway dysfunction. Complex mechanisms underly the cell specificity of eNOS expression, and co- and post-translational processing leads to trafficking of the enzyme to plasma membrane caveolae. Within caveolae, eNOS is the downstream target member of a signaling complex in which it is functionally linked to both typical G protein-coupled receptors and less typical receptors such as estrogen receptor (ER) α and the high-density lipoprotein receptor SR-BI displaying novel actions. This compartmentalization facilitates dynamic protein-protein interactions and calcium- and phosphorylation-dependent signal transduction events that modify eNOS activity. Further understanding of these mechanisms will enable us to take preventive and therapeutic advantage of the powerful actions of NO in multiple cell types.
PSYCHOBIOLOGICAL MODELS OF HIPPOCAMPAL FUNCTION IN LEARNING AND MEMORY
Authors: Gluck Mark A. , Myers Catherine E.
Published: July 2002

▪ Abstract  We review current computational models of hippocampal function in learning and memory, concentrating on those that make strongest contact with psychological issues and behavioral data. Some models build upon Marr's early theories for modeling hippocampal field CA3's putative role in the fast, temporary storage of episodic memories. Other models focus on hippocampal involvement in incrementally learned associations, such as classical conditioning. More recent efforts have attempted to bring functional interpretations of the hippocampal region in closer contact with underlying anatomy and physiology. In reviewing these psychobiological models, three major themes emerge. First, computational models provide the conceptual glue to bind together data from multiple levels of analysis. Second, models serve as important tools to integrate data from both animal and human studies. Third, previous psychological models that capture important behavioral principles of memory provide an important top-down constraint for developing computational models of the neural bases of these behaviors.
EARLY AND PERIODIC SCREENING, DIAGNOSIS, AND TREATMENT AND MANAGED CARE
Authors: Rosenbach Margo L. , Gavin Norma I.
Published: July 2002

▪ Abstract  This paper presents evidence on the performance of Medicaid managed care organizations (MCOs) in providing Early and Periodic Screening, Diagnosis, and Treatment (EPSDT) services to children under age 21. States face considerable challenges in integrating EPSDT into managed care. For example, MCOs rarely offer all services required under federal law. Also, MCOs often are unable to meet state reporting requirements. On the other hand, MCOs offer children a medical home, often for the first time, that may encourage timely preventive care. The literature generally shows no differences in the performance of MCOs relative to traditional FFS providers in the EPSDT participation rate. Future needs include improving the specificity of contract language, more precisely defining the EPSDT benefit package, evaluating the adequacy of EPSDT payments, monitoring the capacity of MCO provider networks, establishing the effectiveness of outreach and enabling services, developing standardized MCO reporting requirements, documenting program outcomes, and assessing benchmarks for accountability.
Graduate Medical Education: The Policy Debate
Authors: Anderson Gerard F , Greenberg George D , Wynn Barbara O
Published: July 2002

▪ Abstract  The cost of providing graduate medical education to the approximately 100,000 medical residents in the United States is approximately $18 billion. The government, primarily through the Medicare program, funds almost two thirds of the cost. Unfortunately, the federal government lacks a coherent policy with respect to what objectives it wants to achieve for this expenditure. This article traces (a) the evolution of graduate medical education funding; (b) current proposals to reform the funding mechanism; (c) how the Medicare program currently funds graduate medical education; (d) how funds are allocated to specific institutions; and (e) specific policy objectives that academic medical centers should be held accountable for achieving in return for receiving public funds.
Consumer Reports in Health Care: Do They Make a Difference?
Authors: Schauffler Helen Halpin , Mordavsky Jennifer K
Published: July 2002

▪ Abstract  The public release of health care–quality data into more formalized consumer health report cards is intended to educate consumers, improve quality of care, and increase competition in the marketplace The purpose of this review is to evaluate the evidence on the impact of consumer report cards on the behavior of consumers, providers, and purchasers. Studies were selected by conducting database searches in Medline and Healthstar to identify papers published since 1995 in peer-review journals pertaining to consumer report cards on health care. The evidence indicates that consumer report cards do not make a difference in decision making, improvement of quality, or competition. The research to date suggests that perhaps we need to rethink the entire endeavor of consumer report cards. Consumers desire information that is provider specific and may be more likely to use information on rates of errors and adverse outcomes. Purchasers may be in a better position to understand and use information about health plan quality to select high-quality plans to offer consumers and to design premium contributions to steer consumers, through price, to the highest-quality plans.
Public Health Quality Measurement: Concepts and Challenges
Authors: Derose Stephen F. , Schuster Mark A. , Fielding Jonathan E. , Asch Steven M.
Published: July 2002

▪ Abstract  Public health agencies increasingly are recognizing the need to formally and quantitatively assess and improve the quality of their programs, information, and policies. Measuring quality can help organizations monitor their progress toward public health goals and become more accountable to both the populations they serve and policy makers. Yet quality assessment is a complex task that involves precise determination and specification of useful measures. We discuss a well-established conceptual framework for organizing quality assessment in the context of planning and delivery of programs and services by local health departments, and consider the strengths and limitations of this approach for guiding quality improvement. We review several past and present quality measurement–related initiatives designed for public health department use, and discuss current and future challenges in this evolving area of public health practice.
Anthropometric Indices and Metabolic Dysfunction–Associated Fatty Liver Disease in Males and Females Living With Severe Obesity
Authors: Lajeunesse-Trempe Fannie , Dugas Selena , Maltais-Payette Ina , Tremblay Ève-Julie , Piché Marie-Eve , K. Dimitriadis Georgios , Lafortune Annie , Marceau Simon , Biertho Laurent , Tchernof André
Published: February 2025

Introduction: Metabolic dysfunction–associated fatty liver disease (MAFLD) is highly prevalent among people living with severe obesity (body mass index [BMI] ≥ 35 kg/m2). However, it remains unknown how sex and adipose tissue distribution are related to MAFLD onset and progression into metabolic dysfunction–associated steatohepatitis (MASH) or advanced stages of fibrosis.

Methodology: We retrospectively studied patients with severe obesity who were eligible for bariatric surgery. Demographic characteristics, biomarkers, and cardiometabolic comorbidities were reported. Anthropometric indices such as BMI, waist circumference (WC), waist‐to‐hip ratio (WHR), waist‐to‐height ratio (WHtR), neck circumference (NC), lipid accumulation product (LAP), visceral adiposity index (VAI), body adiposity index (BAI), abdominal volume index (AVI), and body roundness index (BRI) were measured or calculated. MAFLD, MASH, and stages of fibrosis (F1‐F4) were established from perioperative liver biopsies. Standardized univariate and multivariate logistic regression analyses were used to examine the association between demographic variables, anthropometric indices, cardiometabolic conditions, and the risk of MASH or severe fibrosis (F2‐F4).

Results: A total of 2091 participants with severe obesity were included in the analyses; BMI 47.9 ± 7.3 kg/m2, age 46.2 ± 11.2 years, and 68.4% females. Overall, MAFLD prevalence was 79.5%, with 44.5% having MASH and 24.4% having severe fibrosis (Stage 2 or higher). No anthropometric indices of adiposity were associated with MASH or fibrosis severity. In this population, female sex was a risk factor for severe fibrosis (OR: 1.27, 95% CI 1.01–1.59, p < 0.05).

Conclusions: MAFLD and MASH are highly prevalent in individuals living with severe obesity, but no anthropometric indices or laboratory tests are good predictors of MAFLD or MASH in this population. When MAFLD is diagnosed, our results suggest that females with severe obesity might be at higher risk of advanced stages of fibrosis.
Effects of the Spin Trap Agent Disodium- [tert-butylimino)methyl]benzene-1,3-disulfonate
N
-Oxide (Generic NXY-059) on Intracerebral Hemorrhage in a Rabbit Large Clot Embolic Stroke Model
Authors: Lapchak Paul A. , Araujo Dalia M. , Song Donghuan , Wei Jiandong , Purdy Robert , Zivin Justin A.
Published: July 2002

Background and Purpose

—

It has been proposed that the novel spin trap agent disodium-[(tert-butylimino)methyl]benzene-1,3-disulfonate
N
-oxide (NXY-059) may be useful in the treatment of ischemia and stroke. To date, there is little information concerning the safety of NXY-059 when administered in combination with the only Food and Drug Administration–approved pharmacological agent for the treatment of stroke, the thrombolytic tissue plasminogen activator (tPA). Thus, we determined the effects of NXY-059G, a generic form of NXY-059, on hemorrhage and infarct rate and volume when administered alone or in combination with tPA. In addition, we determined whether NXY-059G affected 2 physiological variables, blood glucose levels and body temperature.

Methods

—

Male New Zealand White rabbits were embolized by injecting a large blood clot into the middle cerebral artery via a catheter. Five minutes after embolization, NXY-059G (100 mg/kg) was infused intravenously; control rabbits received infusions of saline, the vehicle required to solubilize NXY-059G. In tPA studies, the thrombolytic was administered intravenously starting 60 minutes after embolization (20% bolus injection/80% infusion over 30 minutes). Body temperature and blood glucose levels were measured throughout the study. Postmortem analysis included assessment of hemorrhage and infarct rate, size, and location.

Results

—

In the vehicle control group, the hemorrhage rate after a thromboembolic stroke was 52% (n=23), and this was increased by 67% if tPA was administered (n=15). The rabbits treated with NXY-059G in the absence of tPA had a 79% incidence of hemorrhage (n=19), an increase of 52% over the control group. In the combination drug–treated groups, the NXY-059G/tPA group had a 47% incidence of hemorrhage (n=15). There was a decrease of hemorrhage volume in the NXY-059G+tPA group compared with the other 3 groups included in the study. There was no significant effect of NXY-059G either alone or in combination with tPA on infarct rate or volume. NXY-059G did not significantly alter the physiological variables that were measured.

Conclusions

—

This study suggests that NXY-059G may affect the integrity of the cerebral vasculature when administered immediately after an embolic stroke, as evidenced by an increase in hemorrhage rate. However, when NXY-059G is administered in combination with tPA, it may improve the safety of tPA by reducing the incidence of tPA-induced hemorrhage. The mechanism(s) involved in the NXY-059G–induced increase in hemorrhage rate and reduction of tPA-induced hemorrhage rate remains to be elucidated.
Use of Intravenous Heparin by North American Neurologists
Authors: Al-Sadat Ahmad , Sunbulli Mohammad , Chaturvedi Seemant
Published: July 2002

Background and Purpose

—

Our aim was to determine current usage patterns of intravenous heparin for patients with acute ischemic stroke.

Methods

—

A survey was undertaken of 280 neurologists from the United States and 270 neurologists from Canada. Brief vignettes were presented for the following 5 scenarios: stroke in evolution, atrial fibrillation-related stroke (A FIB), vertebrobasilar stroke, carotid territory stroke, and multiple transient ischemic attacks. The effect of medicolegal factors was also ascertained. Statistical comparisons were done with chi-squared testing.

Results

—

US neurologists were significantly more likely than Canadian neurologists to use intravenous heparin for patients with stroke in evolution (51% versus 33%,
P
<0.001), vertebrobasilar stroke (30% versus 8%,
P
<0.001), carotid territory stroke (31% versus 4%,
P
<0.001), and multiple transient ischemic attacks (47% versus 9%,
P
<0.001). The vast majority of US and Canadian neurologists would use intravenous heparin for acute stroke patients with A FIB (88% and 84%, respectively). US neurologists more often cited medicolegal factors as a potential influence on the decision-making process than Canadian neurologists (33% versus 10%,
P
<0.001).

Conclusions

—

In several clinical scenarios, US neurologists were significantly more likely than Canadian neurologists to use intravenous heparin. Fears regarding medicolegal consequences may partially explain the treatment disparity. Despite the publication of 4 clinical trials, which have not shown any long-term benefit for patients with acute stroke and A FIB (International Stroke Trial, Heparin in Acute Embolic Stroke Trial) or cardioembolic stroke (Trial of Org 10172 in Acute Stroke Treatment, the Tinzaparin in Acute Ischemic Stroke Trial), both US and Canadian neurologists would use intravenous heparin in large numbers for this condition. Further studies are warranted to investigate the lack of impact of “negative” studies on clinician behavior.
Defending International Norms: The Role of Obligation, Material Interest, and Perception in Decision Making
Authors: Herrmann Richard K. , Shannon Vaughn P.
Published: July 2002

States defend norms in some cases but not in others. Understanding this variation sheds light on both U.S. foreign policy and the role of normative reasoning. We report the results of four experiments embedded in a survey of U.S. elites. The experiments identified the effects of felt normative obligation (that is, the logic of what is appropriate) and concern for U.S. economic and security interests (that is, the logic of utilitarian consequence) as well as the role played by individual perceptions. We find that perceptions of another actor's motivation, of conflicts as civil or cross-border wars, and of the democratic nature of victims affect decisions to defend a prescriptive norm. This finding means that theories of international relations that feature norms as structural concepts need to consider actor-level cognition when examining the operation of norms. Moreover, we find that when U.S. economic and security interests are at stake there is a much greater inclination to defend norms than when simply normative obligation is present. Most U.S. elites appear to treat the presence or absence of U.S. material interests as a legitimate criterion for deciding whether or not to defend an international prescriptive norm.
Checking Economy
Authors: Ndayiragije Juvénal
Published: July 2002

This article argues for a restrictive asymmetric checking theory according to which only formal features of functional heads need to be checked for convergence. This theory enables us to dispense with several economy conditions assumed within Chomsky's (1995) checking theory: the Equidistance Condition, Last Resort (Greed), the multiple-Spec hypothesis, and the assumed null cost of Merge as a feature-checking operation. Empirical data supporting these arguments come mainly from Kirundi (Bantu) subject-object reversal and transitive expletive constructions.
Public Policy, Private Preferences, and the Japanese Trade Pattern
Authors: Noland Marcus
Published: July 2002

As nontariff forms of trade protection proliferate it has become more difficult to analyze the impact of trade policy on trade flows. In a number of well-known papers researchers have attempted to infer the impact of trade policy indirectly by ascribing to trade policy the differences between actual and predicted trade flows. Much of the work has been applied to analysis of Japanese trade policy, and the conclusions of these studies have differed widely. Some previous research has also ascribed a role to the keiretsu, or networks of affiliated firms, in explaining Japan's apparently distinctive trade performance.

This paper presents a model that integrates data on factor endowments, observable protection in traditional and nontraditional forms, and the keiretsu. It extends existing research in two principal ways. First, alternative cross-national models of comparative advantage are nested to permit the identification of critical modeling assumptions underlying the divergent conclusions of the previous studies. Second, the results of the indirect method are externally validated by confronting these inferences with data on trade policy and the keiretsu. The results indicate that trade policy and the keiretsu have an important impact on Japanese trade performance.
Functional Anatomical Correlates of Controlled and Automatic Processing
Authors: Jansma Johan Martijn , Ramsey Nick F. , Slagter Heleen A. , Kahn Rene S.
Published: July 2002

Behavioral studies have shown that consistent practice of a cognitive task can increase the speed of performance and reduce variability of responses and error rate, reflecting a shift from controlled to automatic processing. This study examines how the shift from controlled to automatic processing changes brain activity. A verbal Sternberg task was used with continuously changing targets (novel task, NT) and with constant, practiced targets (practiced task, PT). NT and PT were presented in a blocked design and contrasted to a choice reaction time (RT) control task (CT) to isolate working memory (WM)-related activity. The three-dimensional (3-D) PRESTO functional magnetic resonance imaging (fMRI) sequence was used to measure hemodynamic responses. Behavioral data revealed that task processing became automated after practice, as responses were faster, less variable, and more accurate. This was accompanied specifically by a decrease in activation in regions related to WM (bilateral but predominantly left dorsolateral prefrontal cortex (DLPFC), right superior frontal cortex (SFC), and right frontopolar area) and the supplementary motor area. Results showed no evidence for a shift of foci of activity within or across regions of the brain. The findings have theoretical implications for understanding the functional anatomical substrates of automatic and controlled processing, indicating that these types of information processing have the same functional anatomical substrate, but differ in efficiency. In addition, there are practical implications for interpreting activity as a measure for task performance, such as in patient studies. Whereas reduced activity can reflect poor performance if a task is not sensitive to practice effects, it can reflect good performance if a task is sensitive to practice effects.
Striatal Contribution to Cognition: Working Memory and Executive Function in Parkinson's Disease before and after Unilateral Posteroventral Pallidotomy
Authors: Jahanshahi M. , Rowe J. , Saleem T. , Brown R. G. , Limousin-Dowsey P. , Rothwell J. C. , Thomas D. G. T. , Quinn N. P.
Published: July 2002

The basal ganglia are intimately connected to the frontal cortex via five fronto-striatal circuits. While the role of the frontal cortex in cognition has been extensively studied, the contribution of the basal ganglia to cognition has remained less clear. In Parkinson's disease, posteroventral pallidotomy (PVP) involves surgical lesioning of the internal section of the globus pallidus (GPi, the final output pathway from the basal ganglia) to relieve the motor symptoms of the disorder. PVP in Parkinson's disease provides a unique opportunity to investigate the impact of disruption of striatal outflow to the frontal cortex on cognition. We assessed executive function and working memory after withdrawal of medication in 13 patients with Parkinson's disease before and 3 months after unilateral PVP compared to 12 age-and IQ-matched normals assessed twice with an interval of 3 months. The tests used were: Wisconsin Card Sorting (WCST), Self-Ordered Random Number Sequences, Missing Digit Test, Paced Visual Serial Addition Test (PVSAT), and Visual Conditional Associative Learning Test (VCALT). After PVP, the patients performed significantly better on the Self-Ordered Random Number Sequences and the WCST, an improvement that was also observed in the normals across the two assessment and is therefore likely to reflect practice effects. Relative to the normals, the patients showed significant differential change following PVP on the Missing Digit Test and PVSAT, on which they performed worse after compared to before surgery, while the controls performed better on the second assessment. For the patients, performance on the VCALT also indicated deterioration after PVP, but the changes approached significance. The side of PVP had no effect on the results. The pattern of change observed 3 months after PVP was maintained at 15-month follow-up. The results suggest that striatal outflow to the frontal cortex may be essential for those aspects of executive function that showed deterioration after PVP. &
Why Faces May Be Special: Evidence of the Inversion Effect in Chimpanzees
Authors: Parr Lisa A. , Dove Tara , Hopkins William D.
Published: July 2002

Five chimpanzees were tested on their ability to discriminate faces and automobiles presented in both their upright and inverted orientations. The face stimuli consisted of 30 black and white photographs, 10 each of unfamiliar chimpanzees (Pan troglodytes), brown capuchins (Cebus apella), and humans (Homo sapiens). Ten black and white photographs of automobiles were also used. The stimuli were presented in a sequential matching-to-sample (SMTS) format using a computerized joystick-testing apparatus. Subjects performed better on upright than inverted stimuli in all classes. Performance was significantly better on upright than inverted presentations of chimpanzee and human faces but not on capuchin monkey faces or automobiles. These data support previous studies in humans that suggest the inversion effect occurs for stimuli for which subjects have developed an expertise. Alternative explanations for the inversion effect based on the type of spatial frequency contained in the stimuli are also discussed. These data are the first to provide evidence for the inversion effect using several classes of face stimuli in a great ape species.
Choice and Value Flexibility Jointly Contribute to the Capacity of a Subsampled Quadratic Classifier
Authors: Poirazi Panayiota , Mel Bartlett W.
Published: July 2002

Biophysical modeling studies have suggested that neurons with active dendrites can be viewed as linear units augmented by product terms that arise from interactions between synaptic inputs within the same dendritic subregions. However, the degree to which local nonlinear synaptic interactions could augment the memory capacity of a neuron is not known in a quantitative sense. To approach this question, we have studied the family of subsampled quadratic classifiers: linear classifiers augmented by the best k terms from the set of K = (d2 + d)/2 second-order product terms available in d dimensions. We developed an expression for the total parameter entropy, whose form shows that the capacity of an SQ classifier does not reside solely in its conventional weight values—the explicit memory used to store constant, linear, and higher-order coefficients. Rather, we identify a second type of parameter flexibility that jointly contributes to an SQ classifier's capacity: the choice as to which product terms are included in the model and which are not. We validate the form of the entropy expression using empirical studies of relative capacity within families of geometrically isomorphic SQ classifiers. Our results have direct implications for neurobiological (and other hardware) learning systems, where in the limit of high-dimensional input spaces and low-resolution synaptic weight values, this relatively little explored form of choice flexibility could constitute a major source of trainable model capacity.
The Effects of Pair-wise and Higher-order Correlations on the Firing Rate of a Postsynaptic Neuron
Authors: Bohte S. M. , Spekreijse H. , Roelfsema P. R.
Published: July 2002

Coincident firing of neurons projecting to a common target cell is likely to raise the probability of firing of this postsynaptic cell. Therefore, synchronized firing constitutes a significant event for postsynaptic neurons and is likely to play a role in neuronal information processing. Physiological data on synchronized firing in cortical networks are based primarily on paired recordings and cross-correlation analysis. However, pair-wise correlations among all inputs onto a postsynaptic neuron do not uniquely determine the distribution of simultaneous postsynaptic events. We develop a framework in order to calculate the amount of synchronous firing that, based on maximum entropy, should exist in a homogeneous neural network in which the neurons have known pair-wise correlations and higher-order structure is absent. According to the distribution of maximal entropy, synchronous events in which a large proportion of the neurons participates should exist even in the case of weak pair-wise correlations. Network simulations also exhibit these highly synchronous events in the case of weak pair-wise correlations. If such a group of neurons provides input to a common postsynaptic target, these network bursts may enhance the impact of this input, especially in the case of a high postsynaptic threshold. The proportion of neurons participating in synchronous bursts can be approximated by our method under restricted conditions. When these conditions are not fulfilled, the spike trains have less than maximal entropy, which is indicative of the presence of higher-order structure. In this situation, the degree of synchronicity cannot be derived from the pair-wise correlations.