bluuebunny/crossref_metadata_2025 huggingface dataset:
Atherosclerotic Lesion Development in a Novel Ovary-Intact Mouse Model of Perimenopause
Authors: Mayer Loretta P. , Dyer Cheryl A. , Eastgard Rebecca L. , Hoyer Patricia B. , Banka Carole L.
Published: July 2005

Objective—

Since the unexpected results from the Women’s Health Initiative, the possible protective role of estrogen in preventing heart disease in perimenopausal and postmenopausal women is uncertain. This study examined atherosclerotic lesion development in ovariectomized versus follicle-depleted ovary-intact cholesterol-fed female low-density lipoprotein (LDL) receptor–deficient mice.

Methods and Results—

We studied lesion development in LDL receptor–deficient mice that were ovariectomized or follicle depleted with 4-vinylcyclohexene diepoxide (VCD) to induce ovarian failure, then treated ± exogenous 17β-estradiol via pellet implant. At 120 days after start of cholesterol feeding, the extent of lesion in aorta and innominate artery was determined. Lesion area in both locations was similar in vehicle control, VCD-treated, and ovariectomized mice. Replacement with 17β-estradiol caused lesion reduction (
P
<0.05) in both arterial locations, but it was most efficacious in suppressing innominate lesion area in VCD-treated mice (12.9±5.2%) compared with ovariectomized mice (40.0±6.04%).

Conclusions—

Endocrine status associated with the follicle-depleted ovary influences exogenous estradiol effects during the development of atherosclerotic lesions and, in particular, inhibits lesion progression in the innominate artery.
Phosphatidylinositol 3-Kinase–Akt Pathway Plays a Critical Role in Early Cardiomyogenesis by Regulating Canonical Wnt Signaling
Authors: Naito Atsuhiko T. , Akazawa Hiroshi , Takano Hiroyuki , Minamino Tohru , Nagai Toshio , Aburatani Hiroyuki , Komuro Issei
Published: July 2005

We have recently reported that activation of phosphatidylinositol 3-kinase (PI3K) plays a critical role in the early stage of cardiomyocyte differentiation of P19CL6 cells. We here examined molecular mechanisms of how PI3K is involved in cardiomyocyte differentiation. DNA chip analysis revealed that expression levels of Wnt-3a were markedly increased and that the Wnt/β-catenin pathway was activated temporally during the early stage of cardiomyocyte differentiation of P19CL6 cells. Activation of the Wnt/β-catenin pathway during this period was required and sufficient for cardiomyocyte differentiation of P19CL6 cells. Inhibition of the PI3K/Akt pathway suppressed the Wnt/β-catenin pathway by activation of glycogen synthase kinase-3β (GSK-3β) and degradation of β-catenin. Suppression of cardiomyocyte differentiation by inhibiting the PI3K/Akt pathway was rescued by forced expression of a nonphosphorylated, constitutively active form of β-catenin. These results suggest that the PI3K pathway regulates cardiomyocyte differentiation through suppressing the GSK-3β activity and maintaining the Wnt/β-catenin activity.
Gene Transfer of Neuronal Nitric Oxide Synthase to Carotid Body Reverses Enhanced Chemoreceptor Function in Heart Failure Rabbits
Authors: Li Yu-Long , Li Yi-Fan , Liu Dongmei , Cornish Kurtis G. , Patel Kaushik P. , Zucker Irving H. , Channon Keith M. , Schultz Harold D.
Published: July 2005

Our previous studies showed that decreased nitric oxide (NO) production enhanced carotid body (CB) chemoreceptor activity in chronic heart failure (CHF) rabbits. In the present study, we investigated the effects of neuronal NO synthase (nNOS) gene transfer on CB chemoreceptor activity in CHF rabbits. The nNOS protein expression and NO production were suppressed in CBs (
P
<0.05) of CHF rabbits, but were increased 3 days after application of an adenovirus expressing nNOS (Ad.nNOS) to the CB. As a control, nNOS and NO levels in CHF CBs were not affected by Ad.EGFP. Baseline single-fiber discharge during normoxia and the response to hypoxia were enhanced (
P
<0.05) from CB chemoreceptors in CHF versus sham rabbits. Ad.nNOS decreased the baseline discharge (4.5±0.3 versus 7.3±0.4 imp/s at 105±1.9 mm Hg) and the response to hypoxia (18.3±1.2 imp/s versus 35.6±1.1 at 40±2.1 mm Hg) from CB chemoreceptors in CHF rabbits (Ad.nNOS CB versus contralateral noninfected CB respectively,
P
<0.05). A specific nNOS inhibitor, S-Methyl-
l
-thiocitrulline (SMTC), fully inhibited the effect of Ad.nNOS on the enhanced CB activity in CHF rabbits. In addition, nNOS gene transfer to the CBs also significantly blunted the baseline renal sympathetic nerve activity (RSNA) and the response of RSNA to hypoxia in CHF rabbits (
P
<0.05). These results indicate that decreased endogenous nNOS activity in the CB plays an important role in the enhanced activity of the CB chemoreceptors and peripheral chemoreflex function in CHF rabbits.
Correlated Firing in a Feedforward Network with Mexican-Hat-Type Connectivity
Authors: Hamaguchi Kosuke , Okada Masato , Yamana Michiko , Aihara Kazuyuki
Published: July 2005

We report on deterministic and stochastic evolutions of firing states through a feedforward neural network with Mexican-hat-type connectivity. The prevalence of columnar structures in a cortex implies spatially localized connectivity between neural pools. Although feedforward neural network models with homogeneous connectivity have been intensively studied within the context of the synfire chain, the effect of local connectivity has not yet been studied so thoroughly. When a neuron fires independently, the dynamics of macroscopic state variables (a firing rate and spatial eccentricity of a firing pattern) is deterministic from the law of large numbers. Possible stable firing states, which are derived from deterministic evolution equations, are uniform, localized, and nonfiring. The multistability of these three states is obtained where the excitatory and inhibitory interactions among neurons are balanced. When the presynapse-dependent variance in connection efficacies is incorporated into the network, the variance generates common noise. Then the evolution of the macroscopic state variables becomes stochastic, and neurons begin to fire in a correlated manner due to the common noise. The correlation structure that is generated by common noise exhibits a nontrivial bimodal distribution. The development of a firing state through neural layers does not converge to a certain fixed point but keeps on fluctuating.
Perfect Fault Tolerance of the n-k-n Network
Authors: Tchernev Elko B. , Mulvaney Rory G. , Phatak Dhananjay S.
Published: July 2005

It was shown in Phatak, Choi, and Koren (1993) that the neural network implementation of the n-k-n encoder-decoder has a minimal size of k = 2, and it was shown how to construct the network. A proof was given in Phatak and Koren (1995) that in order to achieve perfect fault tolerance by replicating the hidden layer, the required number of replications is at least three. In this note, exact lower bounds are derived for the number of replications as a function of n, for the n-2-n network and for the n-log2n-n network.
Analyzing Functional Connectivity Using a Network Likelihood Model of Ensemble Neural Spiking Activity
Authors: Okatan Murat , Wilson Matthew A. , Brown Emery N.
Published: July 2005

Analyzing the dependencies between spike trains is an important step in understanding how neurons work in concert to represent biological signals. Usually this is done for pairs of neurons at a time using correlation-based techniques. Chornoboy, Schramm, and Karr (1988) proposed maximum likelihood methods for the simultaneous analysis of multiple pair-wise interactions among an ensemble of neurons. One of these methods is an iterative, continuous-time estimation algorithm for a network likelihood model formulated in terms of multiplicative conditional intensity functions. We devised a discrete-time version of this algorithm that includes a new, efficient computational strategy, a principled method to compute starting values, and a principled stopping criterion. In an analysis of simulated neural spike trains from ensembles of interacting neurons, the algorithm recovered the correct connectivity matrices and interaction parameters. In the analysis of spike trains from an ensemble of rat hippocampal place cells, the algorithm identified a connectivity matrix and interaction parameters consistent with the pattern of conjoined firing predicted by the overlap of the neurons' spatial receptive fields. These results suggest that the network likelihood model can be an efficient tool for the analysis of ensemble spiking activity.
Fluctuation-Dissipation Theorem and Models of Learning
Authors: Nemenman Ilya
Published: July 2005

Advances in statistical learning theory have resulted in a multitude of different designs of learning machines. But which ones are implemented by brains and other biological information processors? We analyze how various abstract Bayesian learners perform on different data and argue that it is difficult to determine which learning—theoretic computation is performed by a particular organism using just its performance in learning a stationary target (learning curve). Based on the fluctuation—dissipation relation in statistical physics, we then discuss a different experimental setup that might be able to solve the problem.
On the Slow Convergence of EM and VBEM in Low-Noise Linear Models
Authors: Petersen Kaare Brandt , Winther Ole , Hansen Lars Kai
Published: July 2005

We analyze convergence of the expectation maximization (EM) and variational Bayes EM (VBEM) schemes for parameter estimation in noisy linear models. The analysis shows that both schemes are inefficient in the low-noise limit. The linear model with additive noise includes as special cases independent component analysis, probabilistic principal component analysis, factor analysis, and Kalman filtering. Hence, the results are relevant for many practical applications.
Supervised Learning in a Recurrent Network of Rate-Model Neurons Exhibiting Frequency Adaptation
Authors: Fortier Pierre A. , Guigon Emmanuel , Burnod Yves
Published: July 2005

For gradient descent learning to yield connectivity consistent with real biological networks, the simulated neurons would have to include more realistic intrinsic properties such as frequency adaptation. However, gradient descent learning cannot be used straightforwardly with adapting rate-model neurons because the derivative of the activation function depends on the activation history. The objectives of this study were to (1) develop a simple computational approach to reproduce mathematical gradient descent and (2) use this computational approach to provide supervised learning in a network formed of rate-model neurons that exhibit frequency adaptation.

The results of mathematical gradient descent were used as a reference in evaluating the performance of the computational approach. For this comparison, standard (nonadapting) rate-model neurons were used for both approaches. The only difference was the gradient calculation: the mathematical approach used the derivative at a point in weight space, while the computational approach used the slope for a step change in weight space. Theoretically, the results of the computational approach should match those of the mathematical approach, as the step size is reduced but floating-point accuracy formed a lower limit to usable step sizes. A systematic search for an optimal step size yielded a computational approach that faithfully reproduced the results of mathematical gradient descent.

The computational approach was then used for supervised learning of both connection weights and intrinsic properties of rate-model neurons to convert a tonic input into a phasic-tonic output pattern. Learning produced biologically realistic connectivity that essentially used a monosynaptic connection from the tonic input neuron to an output neuron with strong frequency adaptation as compared to a complex network when using nonadapting neurons. Thus, more biologically realistic connectivity was achieved by implementing rate-model neurons with more realistic intrinsic properties. Our computational approach could be applied to learning of other neuron properties.
Edgeworth Approximation of Multivariate Differential Entropy
Authors: Hulle Marc M. Van
Published: July 2005

We develop the general, multivariate case of the Edgeworth approximation of differential entropy and show that it can be more accurate than the nearest-neighbor method in the multivariate case and that it scales better with sample size. Furthermore, we introduce mutual information estimation as an application.
Quality assessment of microarrays: Visualization of spatial artifacts and quantitation of regional biases
Authors: Reimers Mark , Weinstein John N
Published: July 2005

Background

Quality-control is an important issue in the analysis of gene expression microarrays. One type of problem is regional bias, in which one region of a chip shows artifactually high or low intensities (or ratios in a two-channel array) relative to the majority of the chip. Current practice in quality assessment for microarrays does not address regional biases.

Results

We present methods implemented in R for visualizing regional biases and other spatial artifacts on spotted microarrays and Affymetrix chips. We also propose a statistical index to quantify regional bias and investigate its typical distribution on spotted and Affymetrix arrays.

We demonstrate that notable regional biases occur on both Affymetrix and spotted arrays and that they can make a significant difference in the case of spotted microarray results. Although strong biases are also seen at the level of individual probes on Affymetrix chips, the gene expression measures are less affected, especially when the RMA method is used to summarize intensities for the probe sets. A web application program for visualization and quantitation of regional bias is provided at http://www.discover.nci.nih.gov/affytools.

Conclusion

Researchers should visualize and measure the regional biases and should estimate their impact on gene expression measurements obtained. Here, we (i) introduce pictorial visualizations of the spatial biases; (ii) present for Affymetrix chips a useful resolution of the biases into two components, one related to background, the other to intensity scale factor; (iii) introduce a single parameter to reflect the global bias present across an array. We also examine the pattern distribution of such biases and conclude that algorithms based on smoothing are unlikely to compensate adequately for them.
A new short-term toxicity assay using Aspergillus awamori with recombinant aequorin gene
Authors: Kozlova Olga , Zwinderman Mark , Christofi Nick
Published: July 2005

Background

Most currently available short-term toxicity assays are based on bacterial cells. Therefore there is a need for novel eukaryotic microbial bioassays that will be relevant to higher eukaryotes such as animals and plants. Ca2+ is a universal intracellular signalling molecule found in all organisms from prokaryotes to highly specialized animal cells. In fungi calcium has been demonstrated to be involved in control of many important processes. The recombinant aequorin gene from the jellyfish Aequorea victoria responsible for the expression of the Ca2+-sensitive aequorin photoprotein has been cloned in the filamentous fungus Aspergillus awamori. This has allowed real life monitoring of [Ca2+]c changes in living fungal cells. When subjected to different physico-chemical stimuli fungal cells respond by transiently changing the concentration of free Ca2+ in the cytosol ([Ca2+]c) and the pattern of these changes (Ca2+ signature) is specific to each particular stimulus. Therefore it was interesting to investigate whether different environmental toxicants would be able to affect the pattern of [Ca2+]c changes in a reproducible and dose dependant manner.

Results

Toxicity bioassay has been developed to monitor changes [Ca2+]c of the recombinant fungus in the presence of toxicants representing heavy metals – Cr6+ and Zn2+ and a phenolic polar narcotic -3,5-DCP. The fungus responds to toxicants by a decrease in the amplitude of [Ca2+]c response to 5 mM external CaCl2 and an increase in Ca2+ final resting levels and recovery time.

Conclusion

A novel toxicity bioassay utilizing eukaryotic cells has been developed based on filamentous fungi transformed with the recombinant aequorin gene. A range of parameters characterising changes in [Ca2+]c has been identified, e.g. Amplitude, Length of Transient, Final Resting Level and Recovery Time. These parameters can be used to determine the toxicity of a range of chemicals to eukaryotic cells in a 96-well microtitre plate method.
A Review of Referrals of New Patients to the Paediatric Department of a Teaching Hospital during a Six-Month Period in 2004
Authors: Salam Samer , Badri Sondos Al , Lee George TR
Published: July 2005

Aims

The aims of this review were to assess the reasons why patients were referred to a specialist dental paediatric unit and the quality of the referral letters received.

Material and Method

All patients referred to the paediatric consultation clinic at the Liverpool University Dental Hospital from January 2004 to July 2004 were included in the review. The reasons for their referral, as stated by the referring practitioners, were compared with the clinical findings from initial assessments in the consultation clinic and the quality of referral letters was assessed.

Results

Ninety-nine out of a total of 102 referrals were from general dental practitioners. Sixty were girls and 42 boys. Their mean age was 9.5 years. The commonest reason (25 patients) was for treatment under general anaesthesia. In 90 (88.2%) cases the main reason for referral stated in the letters was consistent with the findings of the clinical assessment in the consultant clinic. All 102 letters included the patient's name, address, date of birth and telephone number and 89 (87.3%) were dated. However, only 25 (24.5%) included any mention of medical history and fewer than 30% included details of any treatment provided by the referring practitioner.

Conclusions

The vast majority of patients were referred for good reasons. The quality of the referral letters was generally poor. The use of a structured referral pro forma could improve the quality of the referral.
Dentists with Special Interests (DwSIs): Further Developments
Authors: Eaton Kenneth A
Published: July 2005

The Faculty of General Dental Practice (UK) (the Faculty) has been intimately involved in the plans to introduce dentists with special interests (DwSIs) into the National Health Service (NHS).1 It was therefore appropriate that the Faculty combined with the Faculty of Dental Surgery (FDS) of The Royal College of Surgeons of England to host a national event on Thursday, 21st April 2005 on the topic. The aims of this study day were to provide:

• An update on the development work to implement a scheme for DwSIs.

• Details of the clinical competency frameworks developed as guidance for practitioners and Primary Care Trusts (PCTs) in each of the four clinical areas designated as the first in which DwSIs will work.

The event was sold out with an audience of over 260 drawn from all areas of dentistry, and included clinicians from both primary and secondary care and administrators from PCTs and other NHS bodies.
Diplomates Day 2005
Authors: Narain Amrita
Published: July 2005

On Saturday, 26th February 2005 the Faculty of General Dental Practice (UK) hosted its annual Diplomates Day. A total of 163 individuals received Diplomas in one of the largest ceremonies in the Faculty's history, which took place in the grand setting of the Edward Lumley Hall at The Royal College of Surgeons of England.
A Survey of General Dental Practitioners on the Mersey Postgraduate Register regarding the National Institute for Clinical Excellence (NICE) Guidelines for the Removal of Wisdom Teeth
Authors: Rogers Simon N , Reginald Anusha , Lowe Derek , Grieveson Brian
Published: July 2005

Aim

To ascertain the awareness of and response to the National Institute for Clinical Excellence (NICE) guidelines among general dental practitioners (GDPs) in the Mersey region.

Methods

A pre-piloted postal questionnaire was sent to all GDPs (522) on the Mersey postgraduate register. Day case statistics for third molar surgery at the local hospital were reviewed.

Results

Three hundred and eighty-seven (74%) of the GDPs responded and virtually all reported seeing patients with problems arising from third molars in the previous month. Thirteen per cent claimed that they were either unaware or unsure of the NICE guidelines and 34% reported that they did not have a copy. Seventy-eight per cent reported that they either definitely or probably agreed with the NICE guidelines, 56% that the guidelines had definitely or probably changed their management of third molar problems, 64% that they considered that the guidelines had definitely or probably reduced numbers of extractions/surgical removals, and 56% that they definitely or probably referred fewer patients with third molar problems. However, 89% said they had either frequently or occasionally encountered problems when they left a wisdom tooth on review (untreated). Eighty-four respondents provided free text comments on the NICE guidelines; half were favourable and half were critical. The local hospital's day case statistics indicated that there had been a fall in the annual number of patients undergoing third molar surgery from 494 in 1998 to 287 in 2002.

Conclusions

It was concluded that the majority of respondents were aware of the guidelines and were using them. However, it was unclear whether or not the guidelines had, in themselves, led to a reduction in the number of referrals of patients with third molar problems, or that the reduction had already started, before the guidelines were published, and might have continued even if the guidelines had not been published.
Obtaining an Evidence-Base for Clinical Dentistry through Clinical Trials
Authors: Innes Nicola PT , Evans Dafydd JP , Clarkson Jan E , Foley Jennifer I
Published: July 2005

Ideally, all clinical practice should be based on the best available evidence; however, in general dental practice even a very routine issue, such as the appropriate management of the carious primary dentition, is hampered by the lack of a sound evidence-base from high quality clinical trials run in general dental practices. Furthermore, the use of the evidence that is available may be confounded by inadequate reporting. This paper reviews the difficulties reported in successfully completing such clinical trials, and reports on the authors’ own experiences. Suggestions are made for overcoming the challenge of patient recruitment in randomised controlled clinical trials in primary dental care. These include: regular contact with a principal investigator, who is viewed as a peer; ensuring the relevance of the research topic to the dentists’ daily practice; appropriate remuneration; acknowledgement of the contribution made and recognition of the contribution of research activity to continuing professional development. Use of the CONSORT statement to improve planning and reporting of clinical trials is recommended.
Paradox of choice in a mandatory pension savings system: challenges for Australian retirement income policy
Authors: Gallery Gerry , Gallery Natalie
Published: July 2005

English

As the Australian pension system has become increasingly privatised and less regulated, decisions about the quantum and nature of pension investments have progressively shifted to pension fund members. This choice environment provides members with the ability to control their own pensions, but it also creates challenges for ensuring pension assets are managed in a way that will maximise returns and, ultimately, retirement benefits. Government initiatives to address these challenges have principally focused on disclosure and education and not on the more pervasive behavioural constraints that limit the effectiveness of the existing policy. We advocate policy solutions consistent with libertarian paternalism where the government provides a competitive choice environment, but actively intervenes to set suitable pension savings and investment defaults.
Educational policy: politics, markets and the decline of ‘publicness’
Authors: Stewart Jenny
Published: July 2005

English

Educational policy represents a distinctive example of the changing public–private boundary that has characterised Australian public policy over the past 20 years. A values-based analysis is used to describe the trajectory of change, and to illuminate points of tension in governance and accountability relationships. As the values that subtend educational policy have changed, so the policy system (and in particular the governance mechanisms through which funding and regulation are dispensed) has responded in ways that have partly defused values conflict, and partly exacerbated it. It is suggested that forms of ‘frame reflection’ will be required in order to transcend traditional Australian notions of ‘publicness’ in education in ways that recognise the growing strength of the private sector in school education, and of competition between institutions in higher education.
Deliberative group dynamics: power, status and affect in interactive policy making
Authors: Stokkom Bas van
Published: July 2005

English

Many proponents of interactive policy making view citizen consultations as a ‘rational deliberation between equals’. Power, authority, rhetoric and emotions are considered to be obstructive factors. In this article it is argued that interactive policy settings are characterised by status and authority hierarchies and affect dynamics. First, two types of deliberative bodies are introduced: citizen forums and stakeholder committees. Next, eight possible power and emotion dynamics are distinguished, including problems maintaining facilitative authority, trust-building work of experts, occurrence of charisma, persisting fear and distrust, hope turning into disappointment, and increasing mutual recognition. The last sections examine in which respects these dynamics occur in the two types of deliberative organisation.
Social services policy and delivery in Australia: centre–periphery mixes
Authors: Brown Kerry , Keast Robyn
Published: July 2005

English

The development of social services policy and the delivery of those attendant services have come to occupy a core role for modern governments. The modes of policy development and service delivery and their coordination have shifted between centralised models operated by decision-making elites and a peripheral model in which government divests some level of authority and responsibility for the development and implementation of social services policy to community-based actors and organisations. Changing policy stances bring these models and their associated coordination principles into dominance at different points in history and, importantly, problematise social services policy making and delivery through the continued existence of residual aspects of these multiple approaches.
Distinctive Distribution of Pathogens Associated With Peritonitis in Neonates With Focal Intestinal Perforation Compared With Necrotizing Enterocolitis
Authors: Coates Eric W. , Karlowicz M. Gary , Croitoru Daniel P. , Buescher E. Stephen
Published: July 2005

Objective. Candida and coagulase-negative staphylococci are emerging pathogens associated with focal intestinal perforation (FIP) and necrotizing enterocolitis (NEC) in neonates. The objective of this study was to determine whether there are significant differences in the predominant pathogens in culture-positive cases of peritonitis associated with FIP compared with NEC in neonates.

Methods. A retrospective cross-sectional study was conducted of neonates with peritoneal culture-positive peritonitis associated with FIP or NEC over a 12-year study period (1989–2000). Cases with peritonitis were identified from a microbiology database. NEC was defined by radiologic evidence of pneumatosis intestinalis or portal venous gas or by pathology reports or surgical operative notes describing large areas of transmural bowel necrosis. FIP was defined as a <1-cm intestinal perforation surrounded by otherwise normal tissue in the absence of NEC.

Results. Thirty-six cases of FIP were compared with 80 cases of NEC. Birth weight and gestational age were significantly lower in infants with FIP compared with NEC. Age at intestinal perforation and case fatality rates were similar between FIP and NEC. There were striking differences in the distribution of predominant pathogens associated with peritonitis in NEC and FIP cases. Enterobacteriaceae were present in 60 (75%) of 80 NEC cases compared with 9 (25%) of 36 FIP cases. In contrast, Candida species were found in 16 (44%) of 36 FIP cases compared with 12 (15%) of 80 NEC cases, and coagulase-negative staphylococci were present in 18 (50%) of 36 FIP cases versus 11 (14%) of 80 NEC cases. There were no significant differences between FIP and NEC cases for the presence of Enterococcus species (28% vs 23%) or anaerobes (3% vs 6%). Stratified analysis for birth weight <1200 g found similar significant differences in the predominant pathogens for FIP (n = 29) and NEC (n = 38). Results from peritoneal fluid cultures resulted in changes in antimicrobial therapy in 46 (40%) of 116 cases.

Conclusions. Candida species and coagulase-negative staphylococci were the predominant pathogens in FIP peritonitis in contrast to Enterobacteriaceae in NEC peritonitis. A peritoneal fluid culture should be obtained in all neonates with intestinal perforation, regardless of cause, because it may help to direct the choice of the most effective antimicrobial.
A Vancomycin-Heparin Lock Solution for Prevention of Nosocomial Bloodstream Infection in Critically Ill Neonates With Peripherally Inserted Central Venous Catheters: A Prospective, Randomized Trial
Authors: Garland Jeffery S. , Alex Colleen P. , Henrickson Kelly J. , McAuliffe Timothy L. , Maki Dennis G.
Published: July 2005

Objective.Critically ill neonates are at high risk for vascular catheter–related bloodstream infection (CRBSI), most often caused by coagulase-negative staphylococci. Most CRBSIs with long-term devices derive from intraluminal contaminants. The objective of this study was to ascertain the safety and the efficacy of a vancomycin-heparin lock solution for prevention of CRBSI.

Methods.A prospective, randomized double-blind trial was conducted during 2000–2001 at a community hospital level III NICU. Very low birth weight and other critically ill neonates with a newly placed peripherally inserted central venous catheter were randomized to have the catheter locked 2 or 3 times daily for 20 or 60 minutes with heparinized normal saline (n = 43) or heparinized saline that contained vancomycin 25 μg/mL (n = 42). The origin of each nosocomial bloodstream infection (BSI) was studied by culturing skin, catheter hubs, and implanted catheter segments and blood cultures, demonstrating concordance by restriction-fragment DNA subtyping. Surveillance axillary and rectal cultures were performed to detect colonization by vancomycin-resistant organisms. The main outcome measures were (1) CRBSIs and (2) colonization or infection by vancomycin-resistant Gram-positive bacteria.

Results.Two (5%) of 42 infants in the vancomycin-lock group developed a CRBSI as compared with 13 (30%) of 43 in the control group (2.3 vs 17.8 per 1000 catheter days; relative risk: 0.13; 95% confidence interval: 0.01–0.57). No vancomycin-resistant enterococci or staphylococci were recovered from any cultures. Vancomycin could not be detected in the blood of infants who did not receive systemic vancomycin therapy. Twenty-six neonates (8 vancomycin-lock group, 18 control group) had at the end of a catheter-lock period asymptomatic hypoglycemia that resolved promptly when glucose-containing intravenous fluids were restarted.

Conclusions.Prophylactic use of a vancomycin-heparin lock solution markedly reduced the incidence of CRBSI in high-risk neonates with long-term central catheters and did not promote vancomycin resistance but was associated with asymptomatic hypoglycemia. The use of an anti-infective lock solution for prevention of CRBSI with long-term intravascular devices has achieved proof of principle and warrants selective application in clinical practice.
Acute Tellurium Toxicity From Ingestion of Metal-Oxidizing Solutions
Authors: Yarema Mark C. , Curry Steven C.
Published: July 2005

Tellurium is an element used in the vulcanization of rubber and in metal-oxidizing solutions to blacken or tarnish metals. Descriptions of human toxicity from tellurium ingestion are rare. We report the clinical course of 2 children who ingested metal-oxidizing solutions containing substantial concentrations of tellurium. Clinical features included vomiting, black discoloration of the oral mucosa, and a garlic odor to the breath. One patient developed corrosive injury to the esophagus secondary to the high concentration of hydrochloric acid in the solution. Both patients recovered without serious sequelae, which is typical of tellurium toxicity. An awareness of situations in which children may be exposed to tellurium and its clinical presentation may assist clinicians in the diagnosis of this rare poisoning.
Risk Assessment
Authors: Armitage Peter
Published: July 2005

The “risk” of a potentially dangerous hazard may be measured either by the probability of its occurrence (perhaps per unit time or unit of exposure), or by combining this with a measure of its severity. Risk assessment may involve estimation of these quantities, evaluation of their significance for individuals and communities, the extent to which individuals may differ in their perceptions of risks, and the measures taken by individuals and communities to reduce the impact of risks. These aspects are considered in turn.
Cluster Randomization
Authors: Klar Neil , Donner Allan
Published: July 2005

It is becoming increasingly common for health researchers to consider randomizing intact social units (e.g. families, schools, communities) rather than independent individuals in experimental trials. Reasons are diverse, but include administrative convenience, a desire to reduce the effect of treatment contamination and the need to avoid ethical issues, which might otherwise arise. Dependencies among cluster members typical of such designs must be considered when determining sample size and analyzing the resulting data. Failure to adjust standard statistical methods for within‐cluster dependencies may result in severely underpowered studies and in spuriously elevated Type I error rates. The purpose of this article is to review the key issues in the design and analysis of cluster randomization trials. These ideas will be illustrated using data from several recently completed studies.
Guidelines On Statistical Methods in Clinical Trials
Authors: Facey Karen M. , Lewis John A.
Published: July 2005

This article provides an overview of the International Conference on Harmonization (ICH) and its work in producing regulatory guidelines that are of interest to medical statisticians. The scope and key issues of the ICH E9 Guideline on Statistical Principles in Clinical Trials are outlined. This includes topics related to minimizing the bias in trial design, analysis and reporting, and includes specific issues such as multicenter trials, interim analysis, analysis sets, and subgroups. Other regulatory guidelines that include statistical issues are mentioned and the manner in which guidelines should be used is debated.
Prevention Trials
Authors: Prentice Ross L.
Published: July 2005

Randomized controlled trials provide the gold standard for assessing the health benefits and risks of preventive treatments or interventions. Such trials typically need to be very large‐scale and long‐term. Hence, cost and logistic considerations imply that few such trials can be conducted, and there is a need for careful hypothesis development and preliminary testing, prior to the initiation of a full‐scale disease prevention trial. Aspects of the design, conduct monitoring and analysis of prevention trials are reviewed, along with a discussion of differences from therapeutic trials, and of the interplay with observational studies. The National Institutes of Health‐sponsored Women's Health Initiative, which includes both a multi‐faceted prevention trial, and a large cohort study, among postmenopausal women, provides an illustration of prevention trial considerations and trade‐offs.
Software for Clinical Trials
Authors: Arena Vincent C. , Rockette Howard E.
Published: July 2005

This chapter provides a comprehensive overview of software that is relevant to the design, management, and analysis of clinical trials. Guidance is provided on selecting programs appropriate to the needs of the researcher. There are useful suggestions on keeping software up to date. An extensive table is included referencing most of the available software packages with brief descriptions of the features most relevant to clinical trials, vendor names, contact information, and web URLs.
Data Quality in Vital and Health Statistics
Authors: Swerdlow A. J.
Published: July 2005

In this chapter, the importance of data quality in the design and interpretation of analyses of routinely collected vital and health data is discussed. Issues considered include: the quality of information in underlying data sources; completeness of data collection; duplication; late registrations and alterations; validity and precision of data collection; coding, bridge‐coding, and assignment of underlying cause; data processing and editing; quality of denominators; and numerator/denominator discrepancies. Separate consideration is given to particular issues for analysis of clusters and other rare events, and record linkage. While not intrinsically interesting, data quality is worth considerable attention if analyses of routinely collected data are to be correctly interpreted.
Causation
Authors: Greenland Sander
Published: July 2005

The concepts of cause and effect are central to most areas of scientific research, so it is not surprising that the literature on them could fill a small library. What may be surprising, given their importance, is that consensus about basic definitions and methods for causal inferences (at best) limited, despite some three centuries of debate. A brief review cannot do justice to the history and details of this debate, nor to all the schools of thought on causation. This article will, therefore, focus on a few major themes that have affected modern biostatistical practice. Of necessity, some aspects of the discussion are simplified relative to the literature, and the references should be consulted for more thorough descriptions. Entries on related topics are given in the final section.
Cohort Study, Historical
Authors: Samet Jonathan M.
Published: July 2005

A historical cohort study, also called a retrospective cohort study or a nonconcurrent cohort study, refers to a cohort whose members were at risk for disease outcomes before the study was initiated. Historical cohort studies are widely used in occupational epidemiology because they allow one to take advantage of employment records to identify cohort membership and exposures, and because one does not need to wait for disease outcomes before analyzing the data. As in other cohort studies, historical cohort studies allow one to estimate disease incidence rates as well as relative risks and other measures of exposure effect. Because administrative databases are often used, however, there is a potential for inadequate data to define cohort membership (selection bias), exposure status, and covariates needed to control for confounding, such as smoking status. In addition, there may be special problems with loss to follow‐up and misclassification of health outcomes. Historical cohort studies may be supplemented with special nested case–control or case–cohort designs to obtain additional detailed information on selected cohort members.
Correlational Study
Authors: Gail Mitchell H.
Published: July 2005

This article defines correlational study as an ecologic study and refers the reader to related article in the Encyclopedia of Biostatistics.
Differential Error
Authors: Gail Mitchell H.
Published: July 2005

Differential error is defined and contrasted with nondifferential error. Differential error can lead to biases in any direction.
Dynamic Population
Authors: Gail Mitchell H.
Published: July 2005

Dynamic populations and steady state dynamic populations are defined and some properties mentioned.
Eligibility Restriction
Authors: Gail Mitchell H.
Published: July 2005

Eligibility restriction is a method to control for confounding in observational studies and to eliminate individuals who are unlikely to benefit from treatments or to be able to comply to treatment in clinical trials.
Incidence Density Ratio
Authors: Gail Mitchell H.
Published: July 2005

The incidence density ratio is the ratio of the incidence density in one group to that in another group.
Meta‐Analysis in Epidemiology
Authors: Stroup Donna F. , Thacker Stephen B.
Published: July 2005

Meta‐analysis is a quantitative approach for systematically combining the results of previous research in order to arrive at conclusions about the body of research. The pressure for timely, evidence‐based decisions, and the explosion of the information in the scientific literature have resulted in an increased number of published meta‐analysis. Statistical methods are integral to each step of a meta‐analysis. In this chapter, we define meta‐analysis in the context of scientific synthesis, illustrate uses of Meta‐analysis in epidemiology and public health, describe the steps in a meta‐analysis, and illustrate some specific statistical issues, such as bias, and heterogeneity. We illustrate these steps with a case study of the effects of duration of estrogen on breast cancer risk and discuss statistical software and related internet resources. Statistical issues are critical to properly understanding and interpreting the results from meta‐analysis.
Nondifferential Error
Authors: Gail Mitchell H.
Published: July 2005

Nondifferential error is defined and contrasted with differential error.
Observational Study
Authors: Gail Mitchell H.
Published: July 2005

An observational study is a study in which conditions are not under the control of the investigator, unlike an experimental study. Because randomization of exposure levels is not part of an observational study, associations with exposure may result from confounding by factors associated both with exposure and health outcome.
Population‐Based Study
Authors: Gail Mitchell H.
Published: July 2005

A population‐based study is a study of properties of a well‐defined population, such as individuals residing in a defined geographic area in a given time period.
Relative Hazard
Authors: Gail Mitchell H.
Published: July 2005

The relative hazard is the ratio of two hazard rate functions at a given time.
Software, Epidemiological
Authors: Goldstein Richard
Published: July 2005

This article presents an overview of epidemiologically oriented software, emphasizing software that either uses epidemiological jargon or is specifically aimed at epidemiologists. A discussion of some of the advantages and disadvantages of specialized versus general‐purpose analytic software is included.
Time Lag Effect
Authors: Gail Mitchell H.
Published: July 2005

The term
time lag effect
refers to the delay between the time of an intervention or exposure onset, such as the date on which a person begins smoking cigarettes, and the subsequent development of a health outcome, such as the diagnosis of lung cancer.
Counter‐Matching
Authors: Langholz Bryan
Published: July 2005

Counter‐matching is an exposure‐stratified nested case‐control technique used in epidemiological research. In this article, individually matched and grouped data versions of the design, and analysis methods based on conditional likelihoods, are described. Four data examples are provided, which illustrate the use of counter‐matching in practice. Finally, a general discussion about when and how to use the design, a comparison to matching, and a short comparison to other designs is provided.
Clinical Epidemiology
Authors: Meenan Robert F. , Felson David T.
Published: July 2005

Clinical epidemiology focuses on the study of subjects with disease—their diagnosis, disease course, and outcomes. Its core concerns are measurement of clinical phenomena, diagnostic reasoning, treatment selection, and outcome assessment. To address these concerns, clinical epidemiologists apply quantitative methods from a variety of disciplines, particularly those from epidemiology.
Computer‐Aided Diagnosis
Authors: Weiner M. G. , Pifer Eric , Williams Sankey V.
Published: July 2005

A provider's ability to make correct decisions regarding patient care is predicated on the correct identification of a patient's diagnoses. However, the process of developing diagnostic certainty remains a challenging task despite an increasingly sophisticated array of available diagnostic modalities and techniques. Clinicians need support to integrate a broad range of findings from these tools along with a patient's symptoms and signs. This chapter discusses the evolution and utility of computer‐aided diagnostic decision support systems including recent developments in neural networks, microarray technology, and syndromic surveillance.
Kappa and Its Dependence on Marginal Rates
Authors: Cook Richard J.
Published: July 2005

The kappa statistic is a widely used measure for quantifying agreement between raters using nominal scales. It is advocated on the grounds that it “corrects” for a level of agreement that would be expected by chance alone based on the marginal rates. The operating characteristics of kappa, however, show that it responds in a complicated and unintuitive way to subject‐specific and marginal agreement. Modifications to kappa and supplementary statistics, which have been proposed to help interpret kappa are discussed. Remarks are made as to why the kappa statistic has such problematic features.
Pharmacoepidemiology, Study Designs
Authors: Strom B. L.
Published: July 2005

Pharmacoepidemiology studies the use and effects of pharmaceuticals in populations. In general, its study designs are the same as those for other areas of clinical epidemiology. However, because of the existence of previously conducted premarketing clinical trials, and the need in pharmacoepidemiology to conduct very large studies very quickly, there are special issues that attend to the conduct of postmarketing pharmacoepidemiology studies. This chapter reviews the special data resources used to address these issues, the issues of data validity that arise from the use of these databases, and the special methodological approaches used to apply them.
Prognosis
Authors: Walter Stephen D.
Published: July 2005

This entry gives examples of predicting clinical outcomes following diagnosis of disease.
Screening Benefit, Evaluation of
Authors: Prorok Philip C.
Published: July 2005

Screening is the testing of apparently healthy individuals from a population for the purpose of separating them into groups with high and low probabilities of having a given disease such as cancer. This article examines various issues encountered in assessing the benefit of screening. The use of observational studies and possible involvement of selection bias is included, together with a discussion of lead time and length bias. Appropriate study endpoints are discussed. Various possibilities for randomized control trials are reviewed, and the use of observational designs to compare cancer incidence and mortality in a population before and after the introduction of a screening program is mentioned. The entry also lists important information requirements for the evaluation of screening programs.