bluuebunny/crossref_metadata_2025 huggingface dataset:
The Familial Cancer Program of the Vermont Cancer Center: Development of a Cancer Genetics Program in a Rural Area
Authors: McKinnon Wendy C. , Guttmacher Alan E. , Greenblatt Marc S. , Compas Bruce E. , May Sandy , Cutler Roy E. , Yandell David W.
Published: September 2003

In response to many scientific discoveries linking cancer in certain families to inherited factors, the Vermont Cancer Center established the Familial Cancer Program (FCP) in December 1993. This multifaceted program combines the expertise of clinicians and researchers in many disciplines, including genetics, oncology, psychology, and molecular biology. The program's goals are identification of families in its region with excess cancer, provision of clinical services to such families, and use of research protocols when available and appropriate. This article describes the experience of setting up a familial cancer program in a rural area and discusses both successes and challenges in such an endeavor.
Toward a Model Informed Consent Process for BRCA1 Testing: A Qualitative Assessment of Women's Attitudes
Authors: Bernhardt Barbara A. , Geller Gail , Strauss Misha , Helzlsouer Kathy J. , Stefanek Michael , Wilcox Patti M. , Holtzman Neil A.
Published: September 2003

As an initial part of a project to develop a model informed consent process for BRCA1 testing, we conducted a series of focus groups. At the groups, women initially expressed great interest in testing, but their interest diminished after learning more. If offered testing, women would most want to learn about test accuracy, practical details of testing, and management options if the result was positive. Perceived benefits of testing included gaining information leading to risk reduction, relief of uncertainty, more responsible parenting, and assisting in research. Perceived risks included the discomfort and cost of the testing process itself, and anxiety after a positive result. The risk of possible insurance discrimination was rarely mentioned spontaneously. Many women would want their providers to make recommendations, rather than be nondirective about testing. We observed that women vary greatly in their informational and counseling needs, and suggest that the informed consent process should be individualized, taking into account a woman's perception and her preferences for how testing decisions should be made.
Toward a Critical Community Psychological Perspective on Unemployment and Mental Health Research
Authors: Fryer David , Fagan Rose
Published: September 2003

Psychological research has established that unemployment causes widespread psychological distress and ill health in communities but, arguably, little of this research is truly community psychological. In this paper we sketch out a critical community psychological perspective and use it to contribute to understanding of the role of psychosocial aspects of income in the experience and mental health of employed and unemployed members of low‐income families in a severely deprived community context; to the development of innovative participatory methodology, and to promote the interests of impoverished unemployed people through the research process as well as through the research outcome.
Role of wave cyclones in transporting boundary layer air to the free troposphere during the spring 2001 NASA/TRACE‐P experiment
Authors: Hannan John R. , Fuelberg Henry E. , Crawford James H. , Sachse Glen W. , Blake Donald R.
Published: September 2003

Transport of boundary layer air to the free troposphere by cyclones during NASA's Transport and Chemical Evolution over the Pacific (TRACE‐P) experiment is investigated. Airstreams responsible for boundary layer venting are diagnosed using results from a high‐resolution meteorological model (MM5) together with in situ and remotely sensed chemical data. Hourly wind data from the MM5 are used to calculate three‐dimensional grids of backward air trajectories. A reverse domain filling (RDF) technique then is employed to examine the characteristics of airstreams over the computational domain, and to isolate airstreams ascending from the boundary layer to the free troposphere during the previous 36 hours. Two cases are examined in detail. Results show that airstreams responsible for venting the boundary layer differ considerably from those described by classic conceptual models and in the recent literature. In addition, airstreams sampled by the TRACE‐P aircraft are found to exhibit large variability in chemical concentrations. This variability is due to differences in the boundary layer histories of individual airstreams with respect to anthropogenic sources over continental Asia and Japan. Complex interactions between successive wave cyclones also are found to be important in determining the chemical composition of the airstreams. Particularly important is the process of post‐cold frontal boundary layer air being rapidly transported offshore and recirculated into ascending airstreams of upstream cyclones.
Predictors of Mortality in 2,249 Nonagenarians—The Danish 1905‐Cohort Survey
Authors: Nybo Hanne , Petersen Hans Chr. , Gaist David , Jeune Bernard , Andersen Kjeld , McGue Matt , Vaupel James W. , Christensen Kaare
Published: September 2003

Objectives: To elucidate whether well‐known predictions of mortality are reduced or even reversed, or whether mortality is a stochastic process in the oldest old.

Design: A multidimensional survey of the Danish 1905 cohort conducted in 1998 with follow‐up of vital status after 15 months.

Setting: Denmark.

Participants: All Danes born in 1905, irrespective of physical and mental status were approached. Two thousand two hundred sixty‐two persons of 3,600 participated in this survey.

Measurements: Professional interviewers collected data concerning sociodemographic factors, smoking, alcohol consumption, body mass index, physical and cognitive performance, and health during a visit at the participant's residency. Cox regression models were used to evaluate predictors of mortality.

Results: Five hundred seventy‐nine (25.7%) of the 2,249 participants eligible for the analysis died during the 15 months follow‐up. Multivariate analyses showed that marital status, education, smoking, obesity, consumption of alcohol, and number of self‐reported diseases were not associated with mortality. Disability and cognitive impairment were significant risk factors in men and women. In addition poor self‐rated health was associated with an increase in mortality in women.

Conclusion: In the oldest old, several known predictors of mortality, such as sociodemographic factors, smoking, and obesity, have lost their importance, but a high disability level, poor physical and cognitive performance, and self‐rated health (women only), predict mortality, which shows that mortality in the oldest old is not a stochastic process.
Strategies to Advance Geriatric Nursing: The John A. Hartford Foundation Initiatives
Authors: Regenstreif Donna I. , Brittis Sarajane , Fagin Claire M. , Rieder Corinne H.
Published: September 2003

This article chronicles the efforts of the John A. Hartford Foundation to improve the health care of older adults by strategically investing $34 million in geriatric nursing programs nationally. It includes a brief background of the Foundation followed by a description of the Foundation's geriatric nursing programs and the lessons learned that could be relevant to a variety of audiences.
Vision and Driving Self‐Restriction in Older Adults
Authors: West Catherine G. , Gildengorin Ginny , Haegerstrom‐Portnoy Gunilla , Lott Lori A. , Schneck Marilyn E. , Brabyn John A.
Published: September 2003

Objectives: To assess driving self‐restriction (vision related and nonvision related) in relation to vision test performance of older adults.

Design: Cross‐sectional study.

Setting: Population‐based cohort of community‐dwelling older adults.

Participants: Six hundred twenty‐nine current drivers aged 55 and older had driving behavior, health, and physical function assessed and vision function tested in 1993–95.

Measurements: Self‐report of driving restriction as vision or non‐vision related and performance on a comprehensive battery of vision tests (visual acuity; contrast sensitivity; effects of illumination level, contrast, and glare on acuity; visual fields with and without attentional load; color vision; temporal sensitivity; and the effect of dim light on walking ability).

Results: Demographic, health, and functional characteristics differed significantly between restrictors and nonrestrictors but not between vision‐ and nonvision‐related restrictors. Controlling for potential confounding, only vision‐related driving self‐restriction was significantly associated with reduced performance on nonstandard measures of acuity. Poor depth perception was significantly associated with restriction for both vision‐ and nonvision‐related reasons. Poor performance on attentional visual field tests, analyzed individually and in combination with standard field tests, was not associated with driving self‐restriction.

Conclusion: Older adults with early changes in spatial vision function and depth perception appear to recognize their limitations and restrict their driving even if they do not acknowledge the visual impairment as the cause for restriction. Poor visual attention, a risk factor for crashes, may not be recognized. Additional studies of driving self‐restriction in relation to risk factors for crashes in older adults may help refine this strategy of reducing driving‐related injury and death.
Epidemiology of Primary Hepatic Malignancies in U.S. Children
Authors: Darbari Anil , Sabin Keith M. , Shapiro Craig N. , Schwarz Kathleen B.
Published: September 2003

The epidemiology of primary hepatic malignancies in U.S. children is poorly characterized. We analyzed the incidence, mortality, and characteristics of primary hepatic malignancies in U.S. residents less than 20 years of age. Fatal primary hepatic malignancies in persons less than 20 years of age, between 1979 and 1996, were identified using the multiple–cause–of–death database (National Center for Health Statistics). Histologically confirmed primary hepatic malignancies occurring between 1973 and 1997 were identified using the Surveillance, Epidemiology, and End Results (SEER) database. Between 1979 and 1996, 918 primary hepatic malignancy deaths (average, 0.7/1,000,000/year) were reported nationally among persons less than 20 years of age; rates were higher among Asians and among foreign–born children. Between 1973 and 1997, 271 primary hepatic malignancy cases were reported to SEER among persons less than 20 years of age, of which 184 (67%) and 83 (31%) were hepatoblastoma and hepatocellular carcinoma, respectively. Among children less than 5 years of age, hepatoblastoma accounted for 91% of primary hepatic malignancy cases, whereas among those 15 to 19 years of age, hepatocellular carcinoma accounted for 87% of cases. Five–year survival for hepatoblastoma was 52%, compared with 18% for hepatocellular carcinoma. In the SEER sites, between 1973 and 1977 and 1993 and 1997, hepatoblastoma rates increased (0.6 to 1.2/1,000,000, respectively), while hepatocellular carcinoma rates decreased (0.45 to 0.29/1,000,000, respectively). In conclusion, histologically confirmed hepatocellular carcinoma was reported in children less than 5 years of age, also, where hepatoblastoma is the predominant primary hepatic malignancy. Hepatocellular carcinoma has worse survival rates than hepatoblastoma, and its incidence has not increased. Better maintenance of databases may provide information about associated factors behind this unexpected occurrence.
Cuntz-Krieger algebras of infinite graphs and matrices
Authors: Raeburn Iain , Szymański Wojciech
Published: September 2003

We show that the Cuntz-Krieger algebras of infinite graphs and infinite

{
0
,
1
}

\{0,1\}

-matrices can be approximated by those of finite graphs. We then use these approximations to deduce the main uniqueness theorems for Cuntz-Krieger algebras and to compute their

K
K

-theory. Since the finite approximating graphs have sinks, we have to calculate the

K
K

-theory of Cuntz-Krieger algebras of graphs with sinks, and the direct methods we use to do this should be of independent interest.
Gaining a competitive advantage through customer service training
Authors: Prager Howard
Published: September 2003

Research shows that when funds are tight, the most effective use of training investment is on frontline workers and frontline managers. Some of the key frontline employees are customer service representatives, since they are often the go‐between for customers and the company. One large mutlinational organization achieved a competitive edge by developing a customer service representative certificate program in cooperation with a Graduate School of Management and training management organization. Results impacted both the customer and the financial bottom line. Descriptions of this multi‐day certificate program, as well as important lessons for creating successful initiatives, are highlighted.
An economic study: should we sell human organs?
Authors: Kolnsberg Heather R.
Published: September 2003

The debate over whether or not to allow the sale of human organs is compelling enough to warrant discussion. A literature review revealed much ethical discussion, but little discussion was found on economic outcomes related to donors and selling human organs. It was demonstrated in the literature how an increased organ supply will benefit recipients. If allowing the sale of organs is the way to increase the organ supply for the benefit of recipients, then, in order to demonstrate that donors will not be exploited, it must be demonstrated how, and if, such sales would benefit those donors. This study explores whether or not one should sell human organs. Using basic models, this study develops economic scenarios and outcomes related to the selling of human organs with particular focus on pricing and profitability in relation to donor benefit. Theoretical outcomes show that the donor will not benefit in the long run.
Senior police leadership: does rank matter?
Authors: Densten Iain L.
Published: September 2003

This paper examines the leadership of police officers in the top levels or ranks of an Australian police organization. The sample consisted of 480 senior police who recorded the frequency of leadership behaviors of the person they directly report to via the Multifactor Leadership Questionnaire. Multi‐regression was used to identify predictors of the leadership outcomes of leader effectiveness and extra effort. The study found that each rank of senior officers had unique sets of leadership behaviors that influence the perception of leader effectiveness and motivation to exert extra effort. The Stratified System Theory was used to explore why each rank had unique combinations of predictors. Finally, the paper discusses the multilevel issues of leadership and the importance of considering rank in relation to leadership at the senior levels of police organizations.
The phenomenology of traumatic experiences in police work
Authors: Karlsson Ingemar , Christianson Sven‐Åke
Published: September 2003

Investigates situations that were perceived as stressful by Swedish police officers and the kind of support and help they had received in connection with that. A total of 162 respondents took part in the study. Results show that most of the traumatic experiences reported by police officers occurred early on in their careers. The traumatic experiences often remained in their memories in the form of visual, tactile, and olfactory sensations. A variety of stress reactions were described in connection with these experiences. As regards ways of working through the traumatic experiences, more than half reported that it helped them to talk about the event with their colleagues. Only a few had been offered debriefing or professional help in connection with the event. A notable finding is that the majority of the officers did not receive any support at all from their superiors in connection with the event.
Seeking tools for the war on terror
Authors: Nunn Samuel
Published: September 2003

As the war on terrorism escalates, police agencies are using technologies that electronically scan individuals, structures, and vehicles to identify things hidden from public scrutiny. These machines create new socio‐technical systems for police and citizens. Public policy gaps evolve when new systems give police sensory capabilities that fall outside existing procedural standards such as probable cause and reasonable suspicion. Mobile digital terminals are now common, but are also abused by police officers who run queries on vehicles without articulate suspicions. New technologies such as passive millimeter imaging that permit “X‐ray”‐like examination of individuals and structures create more potential for abuse. As these new technologies diffuse among police agencies, policies should be guided by questions about whether technologies work as designed, whether they are effective, and whether they accomplish anti‐terrorist and crime control objectives. Traditional rules for wiretapping can offer models for operating policies for the new scanning and imaging technologies.
A framework of dynamic CRM: linking marketing with information strategy
Authors: Park Chung‐Hoon , Kim Young‐Gul
Published: September 2003

Committed customers are profitable to an organization for the long term. Customer commitment forms when a customer's expectation is satisfied and the customer realizes fair value from his/her relationship with the organization. From an organization's perspective, this value reflects customer equity, but from a customer's perspective, it represents the customer's perceived value of the relationship. In order to manage such a relationship successfully, it is necessary to support diverse customer information – such as of‐the‐customer, for‐the‐customer, and by‐the‐customer information. A customer information system (CIS) plays the role of boundary spanning that manages and distributes customer information. But the gap between marketing and IT strategy is a barrier in implementing a successful CIS. The CIS, which includes the database, communication channel, and decision model for relationship management, should be designed to facilitate the two‐way customer relationship exchanges. This paper develops a framework of dynamic customer relationship management, suggests the information technology strategy to support the framework, and illustrates the applicability of such framework and strategy through a real business case.
Direct Similarity Analysis of Generalized Burgers Equations and Perturbation Solutions of Euler–Painlevé Transcendents
Authors: Mayil Vaganan B. , Asokan R.
Published: September 2003

Similarity reductions of the generalized Burgers equation , where α, β, and γ are non‐negative constants, n a positive integer and j= 0, 1, 2, are obtained by the direct method of Clarkson and Kruskal [1]. This is the first work to report the similarity variables as an incomplete gamma function and also as a power of , and to provide a perturbation solution of an Euler–Painlevé transcedent.
Miniature synaptic transmission and BDNF modulate dendritic spine growth and form in rat CA1 neurones
Authors: Tyler William J. , Pozzo‐Miller Lucas
Published: September 2003

The refinement and plasticity of neuronal connections require synaptic activity and neurotrophin signalling; their specific contributions and interplay are, however, poorly understood. We show here that brain‐derived neurotrophic factor (BDNF) increased spine density in apical dendrites of CA1 pyramidal neurones in organotypic slice cultures prepared from postnatal rat hippocampal slices. This effect was observed also in the absence of action potentials, and even when miniature synaptic transmission was inhibited with botulinum neurotoxin C (BoNT/C). There were, however, marked differences in the morphology of individual spines induced by BDNF across these different levels of spontaneous ongoing synaptic activity. During both normal synaptic transmission, and when action potentials were blocked with TTX, BDNF increased the proportion of stubby, type‐I spines. However, when SNARE‐dependent vesicular release was inhibited with BoNT/C, BDNF increased the proportion of thin, type‐III spines. Our results indicate that BDNF increases spine density irrespective of the levels of synaptic transmission. In addition, miniature synaptic transmission provides sufficient activity for the functional translation of BDNF‐triggered spinogenesis into clearly defined morphological spine types, favouring those spines potentially responsible for coordinated Ca2+ transients thought to mediate synaptic plasticity. We propose that BDNF/TrkB signalling represents a mechanism of expression of both morphological and physiological homeostatic plasticity in the hippocampus, leading to a more efficient synaptic information transfer across widespread levels of synaptic activity.
Meeting Summary--Cell Biology of Parkinson's Disease and Related Neurodegenerative Disorders
Authors: Trojanowski John Q. , Lee Virginia M.-Y.
Published: September 2003

Parkinsonian disorders (idiopathic Parkinson's disease and clinically similar disorders) are characterized by impaired movements caused by the degeneration of brain centers involved in regulating normal and smooth movements of the body and its extremities. The mechanisms that cause such degeneration are unknown. This Perspective summarizes research described at a meeting held in June 2003, which was organized by the
National Institute of Neurological Disorders and Stroke
and the
National Institute on Aging
to provide an update on recent advances in the cell biology of parkinsonian disorders.
Raise a Glass to Long Life
Authors: Leslie Mitch
Published: September 2003

Vintners and researchers who tout wine's health benefits now have another reason to toast the beverage: A molecule in red wine boosts survival of yeast and human cells, according to new research. The findings indicate that the compound activates the same life-stretching enzyme as austere diets do and offer a possible way to slow aging.
Focusing on the Big Picture
Authors: Chen Ingfei
Published: September 2003

As a postdoc in cognitive neuroscience who's also a neurology fellow, Adam Gazzaley is a meld of basic science expertise and clinical experience: He studies brain aging in people by using functional magnetic resonance imaging at the University of California (UC), Berkeley, and he also sees patients at UC San Francisco's Memory and Aging Center. The 34-year-old native New Yorker dives with equal fervor into scientific research and nature photography, two lenses for viewing a single world of discovery. Growing up in Queens, Gazzaley knew from age 7 that he wanted to become a scientist, and as a teenager, he commuted long hours to attend the Bronx High School of Science. He earned an M.D.-Ph.D. from the Mount Sinai School of Medicine in New York City. Gazzaley's hobby as a shutterbug periodically takes him on backpacking trips to document the beauty of the great outdoors. He sells fine-art prints of his photographs to individuals, hospitals, and clinics through his company, Wanderings Inc.
Starve a Neuron, Feed Pneumonia
Authors: Davenport R. John
Published: September 2003

Strokes not only paralyze muscles, they numb the immune system too, and a new study reveals why. The research on mice suggests that strokes leave their victims vulnerable to infection because they reduce amounts of a key antibacterial molecule. The result offers the first explanation for elevated infection rates after stroke, a phenomenon that doctors have known about for decades.
Apoplectic From ApoE
Authors: Leslie Mitch
Published: September 2003

Apolipoprotein E (apoE) helps perpetrate Alzheimer's disease, and different varieties of the molecule shift the odds of developing dementia. New research adds a charge to the protein's rap sheet, indicating that it accelerates blood vessel deterioration that can result in a fatal stroke. The findings suggest that hampering apoE might forestall the sometimes deadly accumulation.
Matching Accessories
Authors: Foord Steven M.
Published: September 2003

Heterodimerization enhances the complexity of ligand recognition and diversity of signaling responses of heterotrimeric guanine nucleotide-binding protein-coupled receptors (GPCRs). Many accessory proteins (for ion channels or GPCRs) appear to associate with their partners relatively early in the process whereby proteins are transported to the cell surface; their roles in modulating function may have evolved out of simple proximity to a protein that once upon a time they either facilitated or accompanied through the maturation process. The receptor activity-modifying proteins (RAMPs) are a family of single-transmembrane accessory proteins that heterodimerize with GPCRs and, thereby, allow individual GPCRs to recognize multiple ligands and to activate various signaling pathways in response to ligand binding. The M10 family of major histocompatibility complex (MHC) class 1b proteins has recently been shown to associate with murine vomeronasal V2R receptors, as well as to escort them to the cell surface. The exact role of M10 in modulating V2R function (or vice versa) remains to be determined.
Dictyostelium discoideum
cAMP Chemotaxis Pathway
Authors: Kimmel Alan R. , Parent Carole A.
Published: September 2003

Cells migrating directionally toward a chemoattractant display highly polarized cytoskeletal organizations, with F-actin predominantly at the anterior and myosin II localized laterally and posteriorly.
Dictyostelium discoideum
has proven a remarkable model system for elucidating signaling pathways that regulate this chemotactic response. During development, extracellular adenosine 3′,5′-monophosphate (cAMP) functions as a primary signal to activate a specific family of heterotrimeric guanosine triphosphate-binding protein (G protein)-coupled, seven-transmembrane receptors and their downstream effectors, phospholipase C (PLC), adenylyl cyclase (AC), phosphatidylinositol 3-kinase (PI3K), the lipid phosphatase PTEN, and guanylyl cyclase (GC). The PI3K-PTEN and GC pathways interact to establish polarity in chemotaxing
D. discoideum
. Receptor-mediated signaling spatially restricts PI3K and PTEN localization; this directs phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P
3
] to the anterior of the cell, thus recruiting a family of pleckstrin homology (PH) domain-containing proteins. These and other signaling components ultimately localize F-actin. Data suggest that guanosine 3′,5′-monophosphate (cGMP) target proteins and p21-activated kinase (PAKa) cooperate to regulate the phosphorylation state and assembly of myosin II. Many of the molecular interactions described in the Connections Map are fundamental to regulating chemotaxis in all eukaryotic cells.

Science Viewpoint

A. R. Kimmel, C. A. Parent, The signal to move:
D. discoideum
go orienteering.
Science
300
, 1525-1527 (2003). [
Abstract
] [
Full Text
]
Dictyostelium discoideum
cAMP Receptor, G Protein-Independent Pathways
Authors: Kimmel Alan R. , Parent Carole A.
Published: September 2003

Seven-transmembrane receptors can transduce signals in the absence of productive heterotrimeric guanosine triphosphate-binding protein (G protein) interaction. In
Dictyostelium discoideum
, these signals activate transcriptional, mitogen-activated protein kinase (MAPK), and Ca
2+
influx pathways, as well as ligand-stimulated phosphorylation of the receptors themselves. This Connections Map illustrates the pathways that remain active in
D. discoideum
carrying mutations in various G protein genes.

Science Viewpoint

A. R. Kimmel, C. A. Parent, The signal to move:
D. discoideum
go orienteering.
Science
300
, 1525-1527 (2003). [
Abstract
] [
Full Text
]
Trans-Endocytosis of Notch Receptors into Ligand-Expressing Cells
Authors: Krämer Helmut , Gough Nancy R.
Published: September 2003

The animation shows a schematic representation of how trans-endocytosis of Notch into Delta-expressing cells contributes to Notch activation. Notch proteins are receptors that mediate several developmental processes. Notch receptors are activated upon binding transmembrane ligands of the DSL family, such as Delta (δ). Following ligand binding, Notch is cleaved twice. First, Notch is cleaved in its extracellular domain at the S2 site. The subsequent cleavage within Notch's transmembrane domain at the S3 site releases an intracellular domain (N-ICD), which translocates into the nucleus and regulates the transcription of target genes. The cleavage and trans-endocytosis of the Notch extracellular domain (N-ECD) into the ligand-expressing cell facilitates release of the N-ICD.

[
Resource Details
]
Linezolid Compared with Eperezolid, Vancomycin, and Gentamicin in an In Vitro Model of Antimicrobial Lock Therapy for
Staphylococcus epidermidis
Central Venous Catheter-Related Biofilm Infections
Authors: Curtin John , Cormican Martin , Fleming Gerard , Keelehan John , Colleran Emer
Published: September 2003

Central venous catheter (CVC)-related infection (CVC-RI) is a common complication of CVC use. The most common etiological agents of CVC-RI are gram-positive organisms, in particular, staphylococci. An in vitro model for the formation of biofilms by
Staphylococcus epidermidis
ATCC 35984 on polyurethane coupons in a modified Robbins device was established. Biofilm formation was confirmed by electron microscopy and was quantified by determination of viable counts. Mueller-Hinton broth was replaced with sterile physiological saline (control) or a solution of vancomycin (10 mg/ml), gentamicin (10 mg/ml), linezolid (2 mg/ml), or eperezolid (4 mg/ml). Viable counts were performed with the coupons after exposure to antimicrobials for periods of 24, 72, 168, and 240 h. The mean viable count per coupon following establishment of the biofilm was 4.6 × 10
8
CFU/coupon, and that after 14 days of exposure to physiological saline was 2.5 × 10
7
CFU/coupon. On exposure to vancomycin (10 mg/ml), the mean counts were 2.5 × 10
7
CFU/coupon at 24 h, 4.3 × 10
6
CFU/coupon at 72 h, 1.4 × 10
5
CFU/coupon at 168 h, and undetectable at 240 h. With gentamicin (10 mg/ml) the mean counts were 2.7 × 10
7
CFU/coupon at 24 h, 3.7 × 10
6
CFU/coupon at 72 h, 8.4 × 10
6
CFU/coupon at 168 h, and 6.5 × 10
6
CFU/coupon at 240 h. With linezolid at 2 mg/ml the mean counts were 7.1 × 10
5
CFU/coupon at 24 h and not detectable at 72, 168, and 240 h. With eperezolid (4 mg/ml) no viable cells were recovered after 168 h. These data suggest that linezolid (2 mg/ml) and eperezolid (4 mg/ml) achieve eradication of
S. epidermidis
biofilms more rapidly than vancomycin (10 mg/ml) and gentamicin (10 mg/ml).
In Vivo Pharmacokinetics and Pharmacodynamics of a New Triazole, Voriconazole, in a Murine Candidiasis Model
Authors: Andes D. , Marchillo K. , Stamstad T. , Conklin R.
Published: September 2003

In vivo studies have described the pharmacodynamic (PD) characteristics of several triazoles. These investigations have demonstrated that the 24-h area under the concentration-time curve (AUC)/MIC ratio is the critical pharmacokinetic (PK)-PD parameter associated with treatment efficacy. Further analyses from these in vivo studies have demonstrated that a triazole free drug 24-h AUC/MIC of 20 to 25 is predictive of treatment success. We used a neutropenic murine model of disseminated
Candida albicans
infection to similarly characterize the PK-PD of the new triazole voriconazole. PK and PD parameters (percentage of time that the concentration remains above the MIC [
T
> MIC], AUC/MIC ratio, and peak level in serum/MIC ratio) were correlated with in vivo efficacy, as measured by the organism number in kidney cultures after 24 h of therapy. Voriconazole kinetics and protein binding were studied in infected neutropenic mice. Peak level/dose and AUC/dose values ranged from 0.1 to 0.2 and 0.1 to 0.7, respectively. The serum elimination half-life ranged from 0.7 to 2.9 h. The level of protein binding in mouse serum was 78%. Treatment efficacy with the four dosing intervals studied was similar, supporting the AUC/MIC ratio as the PK-PD parameter predictive of efficacy. Nonlinear regression analysis also suggested that the AUC/MIC ratio was strongly predictive of treatment outcomes (
R
2
for AUC/MIC ratio = 82%,
R
2
for peak level/MIC ratio = 63%,
R
2
for
T
> MIC = 75%). Similar studies were conducted with nine additional
C. albicans
isolates with various voriconazole susceptibilities (MICs, 0.007 to 0.25 μg/ml) to determine if a similar 24-h AUC/MIC ratio was associated with efficacy. The voriconazole free drug AUC/MIC ratios were similar for all of the organisms studied (range, 11 to 58; mean ± standard deviation, 24 ± 17 [
P
= 0.45]). These AUC/MIC ratios observed for free drug are similar to those observed for other triazoles in this model.
Sensitive Assay for Antifungal Activity of Glucan Synthase Inhibitors That Uses Germ Tube Formation in
Candida albicans
as an End Point
Authors: Brayman Timothy G. , Wilks John W.
Published: September 2003

We implemented a simple, sensitive, objective, and rapid cellular assay to reveal the antifungal activity of a novel class of glucan synthase inhibitors. The assay, especially useful for early drug discovery, measures the transformation of
Candida albicans
from the yeast form to the hyphal form. Test compounds were ranked by potency (50% inhibitory concentration) and efficacy (percent inhibition of germ tube formation); the intra-assay coefficients of variation for these parameters were 17 and 5%, respectively. The germ tube formation assay proved useful for the early-stage antifungal characterization of a novel class of glucan synthase inhibitors discovered at Pharmacia. Drug concentrations required in this assay to inhibit germ tube formation were lower for 90% of the novel compounds than the concentrations required to determine MICs. The method may have utility for other mechanistic classes of antifungal compounds during the hit-to-lead transition of drug discovery.
Virucidal Efficacy of Soap and Water against Human Immunodeficiency Virus in Genital Secretions
Authors: Li Jonathan Z. , Mack Elizabeth C. , Levy Jay A.
Published: September 2003

A common bar soap and tap water solution was able to demonstrate a 30-fold human immunodeficiency virus (HIV) inactivation and a 57 to 87% reduction in viable peripheral blood mononuclear cells in a mixture of cervicovaginal lavage fluid and seminal fluid. These observations indicate that soap and water might be used to inactivate HIV and HIV-infected cells in genital secretions.
Oral Synthetic Phospholipid (DMPC) Raises High-Density Lipoprotein Cholesterol Levels, Improves High-Density Lipoprotein Function, and Markedly Reduces Atherosclerosis in Apolipoprotein E–Null Mice
Authors: Navab Mohamad , Hama Susan , Hough Greg , Fogelman Alan M.
Published: September 2003

Background—

Lecithin has been widely sold as a dietary supplement. 1,2-Dimyristoyl-
sn
-glycero-3-phosphocholine (DMPC) is a phospholipid that does not exist in nature and has been used in vitro to study lipid binding. We tested DMPC in vivo in apolipoprotein (apo) E–null mice.

Methods and Results—

DMPC or soy or egg lecithin at 1.0 mg/mL was added to the drinking water of 4-week-old apoE-null female mice. Eight weeks later, HDL cholesterol levels and apoA-I levels were markedly increased in the mice that received DMPC. HDL function was also dramatically improved in the mice receiving DMPC, and there was a significant reduction in aortic lesions (
P
=0.021) in the DMPC mice but not in those receiving lecithin. Adding 1.0 mg/mL of DMPC to the drinking water of 10-month-old apoE-null female mice for 5 weeks caused regression of aortic sinus lesions (
P
=0.003). Adding 1.0 mg/mL DMPC to the drinking water of 6-month-old apoE-null male mice for 8 weeks significantly reduced aortic sinus lesion area (
P
=0.0031) and en face whole aorta lesion area (
P
=0.001), whereas adding the same concentrations of soy or egg lecithin did not significantly alter lesion area. Jejunal apoA-I synthesis and plasma apoA-I levels were increased 2- to 3-fold in mice receiving DMPC but not soy or egg lecithin.

Conclusions—

DMPC (but not lecithin) raises HDL cholesterol and apoA-I, improves HDL function, and prevents lesions or causes their regression in apoE-null mice.
Cell Coupling Between Ventricular Myocyte Pairs From Connexin43-Deficient Murine Hearts
Authors: Yao Jian-An , Gutstein David E. , Liu Fangyu , Fishman Glenn I. , Wit Andrew L.
Published: September 2003

Mice with cardiac-restricted inactivation of the connexin43 gene (CKO mice) have moderate slowing of ventricular conduction and lethal arrhythmias. Mechanisms through which propagation is maintained in the absence of Cx43 are unknown. We evaluated gap junctional conductance in CKO ventricular pairs using dual patch clamp methods. Junctional coupling was reduced to 4±2 nS (side-to-side) and 11±2 nS (end-to-end), including 21% of cell-pairs with no detectable coupling, compared with 588±104 nS (side-to-side) and 558±92 nS (end-to-end) in control cell-pairs. Voltage dependence of control gap junctions was characteristic of Cx43. CKO conductance showed increased voltage dependence, suggesting low-level expression of other connexin isoforms. From theoretical models, this degree of CKO coupling is not expected to support levels of conduction persisting in vivo, suggesting the possibility that there are additional mechanisms for maintained propagation when gap junctional conductance is severely reduced.
Book Review: International Criminal Law, Ilias Bantekas/Susan Nash and Mark Mackarel.
Authors: Bohlander
Published: September 2003

No Abstract
Blood plasmacytoid dendritic cell responses to CpG oligodeoxynucleotides are impaired in human newborns
Authors: De Wit Dominique , Olislagers Véronique , Goriely Stanislas , Vermeulen Françoise , Wagner Hermann , Goldman Michel , Willems Fabienne
Published: September 2003

Plasmacytoid dendritic cells (pDCs) respond to unmethylated cytosine-phosphate-guanosine (CpG) motifs present in bacterial DNA or unmethylated synthetic oligodeoxynucleotides (CpG). In order to assess the function of pDCs in human newborns, interferon-α (IFN-α) production induced by CpG 2216 and phenotypic maturation of pDCs in response to CpG 2006 were compared in cord blood and adult blood. We first observed that neonatal pDCs displayed decreased up-regulation of CD80, CD83, CD86, and CD40, whereas HLA-DR and CD54 up-regulation did not differ significantly between adults and neonates. We then found that the production of IFN-α in response to CpG was dramatically impaired in cord blood. This neonatal defect was detected both at protein and mRNA levels and was still present in blood of 4-day-old babies. Further experiments on enriched pDCs confirmed that these cells are intrinsically deficient in CpG-induced IFN-α production at birth. These findings might be relevant to the increased susceptibility of human newborns to infections as well as to the use of CpG oligodeoxynucleotides as vaccine adjuvants in the neonatal period. (Blood. 2004;103:1030-1032)
Chronic obstructive pulmonary disease as a systemic disease: an epidemiological perspective: Fig. 1.—
Authors: Andreassen H. , Vestbo J.
Published: September 2003

Chronic obstructive pulmonary disease (COPD) has been increasingly recognised as a systemic disease. The hormonal, metabolic and musculoskeletal implications of the generalised processes involving oxidative stress, inflammatory mediators, cytokines, and endocrine hormones have only begun to be understood.

Only a few studies have looked into the epidemiology of inflammatory markers in patients with chronic obstructive pulmonary disease. Common extrapulmonary effects of chronic obstructive pulmonary disease include skeletal muscle dysfunction, wasting and osteoporosis. The resulting effects of a systemic inflammation can be measured at specific extrapulmonary organs such as skeletal muscle or in more general terms using body composition, body weight or derived measures, and only a few studies have set the parameters in an epidemiological context. Nevertheless, these studies indicate an association between inflammatory markers and forced expiratory volume in one second not only in subjects with severe chronic obstructive pulmonary disease. Also, it is increasingly clear that systemic markers in chronic obstructive pulmonary disease have important effects on prognosis.
The Thyroid Hormone Receptor-Associated Protein TRAP220 Is Required at Distinct Embryonic Stages in Placental, Cardiac, and Hepatic Development
Authors: Landles Christian , Chalk Sara , Steel Jennifer H. , Rosewell Ian , Spencer-Dene Bradley , Lalani El-Nasir , Parker Malcolm G.
Published: September 2003

Recent work indicates that thyroid hormone receptor-associated protein 220 (TRAP220), a subunit of the multiprotein TRAP coactivator complex, is essential for embryonic survival. We have generated TRAP220 conditional null mice that are hypomorphic and express the gene at reduced levels. In contrast to TRAP220 null mice, which die at embryonic d 11.5 (E11.5), hypomorphic mice survive until E13.5. The reduced expression in hypomorphs results in hepatic necrosis, defects in hematopoiesis, and hypoplasia of the ventricular myocardium, similar to that observed in TRAP220 null embryos at an earlier stage. The embryonic lethality of null embryos at E11.5 is due to placental insufficiency. Tetraploid aggregation assays partially rescues embryonic development until E13.5, when embryonic loss occurs due to hepatic necrosis coupled with poor myocardial development as observed in hypomorphs. These findings demonstrate that, for normal placental function, there is an absolute requirement for TRAP220 in extraembryonic tissues at E11.5, with an additional requirement in embryonic tissues for hepatic and cardiovascular development thereafter.
Phylogeny and cloning of ion transporters in mosquitoes
Authors: Pullikuth Ashok K. , Filippov Valeri , Gill Sarjeet S.
Published: September 2003

Membrane transport in insect epithelia appears to be energized through proton-motive force generated by the vacuolar type proton ATPase (V-ATPase). However, secondary transport mechanisms that are coupled to V-ATPase activity have not been fully elucidated. Following a blood meal, the female mosquito regulates fluid and ion homeostasis through a series of characteristic behaviors that require brain-derived factors to regulate ion secretion. Despite the knowledge on the behaviors of the mosquito, little is known of the targets of several factors that have been implicated in cellular changes following a blood meal. This review discusses current models of membrane transport in insects and specific data on mosquito ion regulation together with the molecular aspects of membrane transport systems that are potentially linked to V-ATPase activity, which collectively determine the functioning of mosquito midgut and Malpighian tubules. Ion transport mechanisms will be discussed from a comparative physiology perspective to gain appreciation of the exquisite mechanisms of mosquito ion regulation.
Cage versus tricortical graft for cervical interbody fusion
Authors: Siddiqui A. A. , Jackowski A.
Published: September 2003

We conducted a prospective, randomised study of 42 cervical interbody fusions undertaken with either an autologous tricortical graft or a cage. The factors assessed in the two groups were: (1) time taken to achieve fusion; (2) neck disability index; (3) pain score; (4) interbody height ratio; (5) interbody angle and (6) the influence of smoking on fusion.

No statistical difference was seen in the time taken to achieve fusion, neck disability index, interbody height ratio, or interbody angles. Smoking did not have any effect on the fusion process. The pain score was significantly lower in the tricortical graft group at six months. We conclude that both methods of fusion give similar results, although tricortical graft fusion is cheaper than cage fusion, and is more effective in reducing the pain score.
A population-based study of surgery for spinal metastases
Authors: Finkelstein J. , Zaveri G. , Wai E. , Vidmar M. , Kreder H. , Chow E.
Published: September 2003

The management of spinal metastases is palliative and aimed at improving quality of life at an acceptable risk. This population study uses administrative databases and measures survivorship and complication rates after surgery for spinal metastases. The effects of various potential predictor variables were evaluated. We identified 987 patients with a median survival for all types of cancer of 227 days. The one and three-month mortality was 9% and 29%, respectively. Increasing age, male gender and primary lung cancer were significant risk factors for death within 30 days of surgery. A preoperative neurological deficit contributed a 19% increase in mortality and a 71% increase in the risk of postoperative wound infection. We found an overall major complication rate of 27%. This information will provide patients, families and clinicians with objective data which will help in the choice of treatment and the understanding of the surgical risk and outcome.
Incidence of clostridial contamination in donors’ musculoskeletal tissue
Authors: Malinin T. I. , Buck B. E. , Temple H. T. , Martinez O. V. , Fox W. P.
Published: September 2003

Reports of infection by Clostridium sordellii associated with allograft transplantation have generated considerable interest. We report our experience in recognising clostridial contamination in cadaver donors of musculoskeletal tissue. Tissues obtained from 795 consecutive donors were excised using standard surgical techniques. Samples of blood and bone marrow were also obtained. Donors with clostridia recovered from any site were matched with the preceding donor without clostridia as a procedural and environmental control. The histories of the donors were analysed to determine which variables had a relationship to contamination by running a contingency table and chi-squared test on the variables against the event of a donor being contaminated.

Sixty-four donors (8.1%) had clostridia, most commonly C. sordellii. Clostridia were grown from the blood, marrow and tissue samples of 52, 37 and 30 donors, respectively. In eight cases, they were cultured from the tissue samples alone. There was no significant difference in age or gender between the contaminated donors and the control group. Open wounds were more common in control than in contaminated subjects, but only death by drowning in the contaminated group was statistically significant (p = 0.02). The time between death and the excision of tissue which was contaminated (16 hrs 10 mins) compared with control (11 hrs 10 mins) donors was also significant (p < 10−6).

We conclude that there is clostridial contamination in a significant number of tissue donors, particularly with increasing time between death and tissue excision. Among the most commonly encountered species is C. sordellii. Multiple microbiological cultures, including blood, are necessary in order to identify clostridial contamination.
Mathematical model for the pultrusion of blocked PU–UP matrix composites
Authors: Chen Chin‐Hsing , Yen Chih‐Chao
Published: September 2003

The thermokinetic behavior of blocked polyurethane (PU)–unsaturated polyester (UP)–based composites during the pultrusion of glass‐fiber‐reinforced composites was investigated utilizing a mathematical model that accounted for the heat transfer and heat generation during curing. The equations of continuity and energy balance, coupled with a kinetic expression for the curing system, were solved using a finite difference method to calculate the temperature profiles and conversion profiles in the thickness direction in a rectangular pultrusion die. A kinetic model, dP/dt = A exp(−E/RT)Pm(1 − P)n, was proposed to describe the curing behavior of a blocked PU–UP resin. Kinetic parameters for the model were obtained from dynamic differential scanning calorimetry scans using a multiple regression technique, which was able to predict the effects of processing parameters on the pultrusion. The effects of processing parameters including pulling speed, die wall temperature, and die thickness on the performance of the pultrusion also were evaluated. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1996–2002, 2003