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Tests of rRNA hybridization to microarrays suggest that hybridization characteristics of oligonucleotide probes for species discrimination cannot be predicted.

Hybridization of rRNAs to microarrays is a promising approach for prokaryotic and eukaryotic species identification. Typically, the amount of bound target is measured by fluorescent intensity and it is assumed that the signal intensity is directly related to the target concentration. Using thirteen different eukaryotic LSU rRNA target sequences and 7693 short perfect match oligonucleotide probes, we have assessed current approaches for predicting signal intensities by comparing Gibbs free energy (DeltaG degrees) calculations to experimental results. Our evaluation revealed a poor statistical relationship between predicted and actual intensities. Although signal intensities for a given target varied up to 70-fold, none of the predictors were able to fully explain this variation. Also, no combination of different free energy terms, as assessed by principal component and neural network analyses, provided a reliable predictor of hybridization efficiency. We also examined the effects of single-base pair mismatch (MM) (all possible types and positions) on signal intensities of duplexes. We found that the MM effects differ from those that were predicted from solution-based hybridizations. These results recommend against the application of probe design software tools that use thermodynamic parameters to assess probe quality for species identification. Our results imply that the thermodynamic properties of oligonucleotide hybridization are by far not yet understood.

Animals↗

Log-linear models for the analysis of matched cohort studies.

The application of conditional logistic regression to the analysis of matched case-control studies has now become quite customary. In addition, it is well known that software designed to fit linear logistic and log-linear models can be used in these analyses. The application of conditional logistic regression to cohort designs is described, and an approach is developed that adapts the linear logistic and log-linear models for the analysis of prospectively collected data. Specific situations discussed include matched pairs, 2:1 matching, and studies in which some subjects are pair matched and others matched 2:1. The methods are illustrated with numeric examples.

Case-Control Studies↗

Aircrew dosimetry using the Predictive Code for Aircrew Radiation Exposure (PCAIRE).

During 2003, a portable instrument suite was used to conduct cosmic radiation measurements on 49 jet-altitude flights, which brings the total number of in-flight measurements by this research group to over 160 flights since 1999. From previous measurements, correlations have been developed to allow for the interpolation of the dose-equivalent rate for any global position, altitude and date. The result was a Predictive Code for Aircrew Radiation Exposure (PCAIRE), which has since been improved. This version of the PCAIRE has been validated against the integral route dose measurements made at commercial aircraft altitudes during the 49 flights. On most flights, the code gave predictions that agreed to the measured data (within +/- 25%), providing confidence in the use of PCAIRE to predict aircrew exposure to galactic cosmic radiation. An empirical correlation, based on ground-level neutron monitoring data, has also been developed for the estimation of aircrew exposure from solar energetic particle (SEP) events. This model has been used to determine the significance of SEP exposure on a theoretical jet altitude flight during GLE 42.

Aerospace Medicine↗

Meeting the educational needs of clinical equipment users.

Training equipment users to operate medical equipment effectively and safely is one of the most important and difficult tasks of clinical engineers. As medical equipment proliferates and becomes more complex, the task of education also becomes more difficult. The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) requires that all equipment users be trained annually in proper operating procedures for the equipment they use and that the training be documented. Therefore, each hospital must develop educational programs to meet those needs. This paper illustrates the use of an interactive computer-assisted instruction (CAI) program, entitled EquipTeach, to provide an effective, standardized and cost-effective method of training equipment users at the John Dempsey Hospital of The University of Connecticut Health Center in Farmington, Connecticut.

Computer-Assisted Instruction↗

The incudostapedial joint angle: implications for stapes surgery prosthesis selection and crimping.

OBJECTIVE: To evaluate the role of the incudostapedial joint (ISJ) angle in stapes prosthesis size selection and crimping. METHODS: The ISJ of 13 cadaveric human temporal bones were photographed, then measured using computer-aided design software. The relationship of ISJ angle to prosthesis length was modeled. A literature review evaluated factors contributing to stapedectomy failure. RESULTS: The mean ISJ angle was 93.0 degrees (SD = 8.3 degrees ) (range, 75.0 degrees -104.0 degrees ). The mean ISJ angle deviation from 90 degrees was 7.35 degrees (SD = 4.45 degrees ) (range, 0.3 degrees -15.0 degrees ). The mean distance along the incus accessible for prosthesis placement was 3.21 mm (SD = 0.55 mm) (range, 2.00-4.00 mm). CONCLUSIONS: Significant deviation of the ISJ angle from 90 degrees was found (P <.0001). The length along the incus accessible for prosthesis placement was sufficient to result in errors in prosthesis size selection and crimping with only small variations in the ISJ angle. Incorrect prosthesis sizing and crimping are frequently associated with stapedectomy failure. Variations in ISJ anatomy should be considered when selecting stapes prostheses lengths and may affect crimping technique.

Culture Techniques↗

Vaginal or cesarean birth? Application of an advocacy organization-driven research translation model.

BACKGROUND: Research translation models are needed to demonstrate a process for identifying and communicating high-quality scientific evidence that enables informed involvement of relevant stakeholders, including informed consumer participation in healthcare decision making. PURPOSE: To describe the rationale for, and elements of, a research translation model, as it is being applied to inform and support diverse end users with respect to decisions relating to vaginal versus cesarean birth. METHODS: The Maternity Center Association (MCA), the oldest national United States organization advocating on behalf of mothers and babies, identified the need to clarify and translate into practice best evidence about relative harms of cesarean and vaginal birth. MCA developed a model that included engaging leading stakeholder groups, conducting a systematic review to fill research gaps, and initiating an education and advocacy campaign to reach consumers, health professionals, and the general public with review results and related information and guidance. International standards for systematic reviews and evidence about effective professional practice, use of decision aids, and risk communication were used. RESULTS: Dozens of harms that differ by mode of delivery, with nearly all favoring vaginal birth, were found during review. Without clear, compelling, and well-supported justification for cesarean section, vaginal birth is the safest way for women to give birth and babies to be born. Despite modest resource expenditure, the implemented model is bringing review results to many individuals and organizations, incorporating elements that have been shown to be effective. The next step is to formally evaluate the decision aid in clinical settings. DISCUSSION: Advocacy organizations are uniquely positioned to carry out research translation. Given the importance of research translation and the challenges of carrying out this work, programs and policies should be established to support and evaluate advocacy organizations in this role.

Cesarean Section↗

Dural ectasia is associated with back pain in Marfan syndrome.

STUDY DESIGN: A cross-sectional age- and sex-matched study comparing the prevalence and size of dural ectasia in two groups of patients with Marfan syndrome. Group I comprised patients with moderate to severe back pain and Group II comprised patients without back pain. OBJECTIVES: To determine whether the presence and size of dural ectasia is associated with back pain in patients with Marfan syndrome. SUMMARY OF BACKGROUND DATA: Dural ectasia is present in more than 60% of patients with Marfan syndrome. Moderate to severe back pain is present in more than 50% of patients with Marfan syndrome. Most cases of significant low back pain in patients with Marfan syndrome do not have a clear cause. It would be useful for the clinician to know whether dural ectasia may be a cause of back pain in patients with Marfan syndrome with no other source. METHODS: Thirty two volunteers aged 30-50 with Marfan syndrome were enrolled as age- and sex-matched pairs with significant back pain (Group I) and without back pain (Group II). A completed questionnaire, physical examination, and magnetic resonance image of the lumbosacral spine were obtained. Dural volume caudal to L5 was calculated from the magnetic resonance data by specially designed software. RESULTS: Dural ectasia was present in 76% of the patients in Group I, and 41% of the patients in Group II. The proportion of patients with dural ectasia was significantly higher in Group I. Furthermore, the mean dural volume was significantly higher in Group I, and a significant correlation between dural volume and Oswestry pain score was noted. CONCLUSIONS: The presence and size of dural ectasia are associated with back pain in the Marfan syndrome. However, a high prevalence of dural ectasia (41%) exists even in patients with Marfan syndrome without back pain. The mere presence of dural ectasia therefore does not necessarily mean the patient will be symptomatic even though the two are associated.

Adult↗

Intraobserver reproducibility of a two-dimensional mapping of the optic nerve head perfusion.

PURPOSE: To evaluate the intraobserver reproducibility of a software designed to assess retinal blood flow with the Heidelberg Retina Flowmeter (HRF). METHODS: Ten subjects were consecutively recruited, and one eye of each patient was randomly selected for study. Blood flow measurements were analyzed by using an automatic full field perfusion image analysis (AFFPIA) program, which calculates the Doppler frequency shift and hemodynamic variables (flow, volume, and velocity) for each pixel. The resulting perfusion image is processed with respect to underexposed and overexposed pixels, saccades, and retinal vessel tree. Intraobserver reproducibility was calculated for the AFFPIA program. All the optic nerve heads were horizontally divided into three sections (superior, central, and inferior). The retinal blood flow was calculated in the superior and inferior section, and each section was further divided into three areas (temporal, nasal, and rim). The blood flow was evaluated for each area. RESULTS: When the same observer analyzed the same image five times (intraobserver intraimage reproducibility), the AFFPIA coefficient of variation ranged from 0.5% to 5% in the temporal area, from 0.1% to 5.3% in the nasal area, and from 0.5 to 28% in the rim area. When the same observer analyzed three different images of the same section once (intraobserver interimage reproducibility), the AFFPIA coefficient of variation of flow measurements ranged from 1% to 7.3% in the temporal area, from 1.5% to 10% in the nasal area, and from 2 to 30% in the rim area. CONCLUSION: Retinal blood flow measured by HRF and analyzed by AFFPIA had good intraobserver reproducibility. The reproducibility was significantly better in the temporal and nasal areas than in the rim area.

Aged↗

Opposed effects of hypertonic saline on contusions and noncontused brain tissue in patients with severe traumatic brain injury.

OBJECTIVE: The aim of this study was to quantify the effect of hypertonic saline solution on contused and noncontused brain tissue in patients with traumatic brain injury. We hypothesize that hypertonic saline would increase the volume of brain contusion while decreasing the volume of noncontused hemispheric areas. DESIGN: Prospective observational study. SETTING: Neurosciences critical care unit of a university hospital. PATIENTS: Fourteen traumatic brain injury patients with increased intracranial pressure. INTERVENTIONS: A computed tomography scan was performed before and after a 20-min infusion of 40 mL of 20% saline. MEASUREMENTS AND MAIN RESULTS: The volume, weight, and specific gravity of contused and noncontused hemispheric areas were assessed from computed tomography DICOM images by using a custom-designed software (BrainView). Physiologic variables and natremia were measured before and after infusion. Hypertonic saline significantly increased natremia from 143 +/- 5 to 146 +/- 5 mmol/L and decreased intracranial pressure from 23 +/- 3 to 17 +/- 5 mm Hg. The volume of the noncontused hemispheric areas decreased by 13 +/- 8 mL whereas the specific gravity increased by 0.029 +/- 0.027%. The volume of contused hemispheric tissue increased by 5 +/- 5 mL without any con-comitant change in density. There was a wide interindividual variability in the response of the noncontused hemispheric tissue with changes in specific gravity varying between -0.0124% and 0.0998%. CONCLUSIONS: Three days after traumatic brain injury, the blood- brain barrier remains semipermeable in noncontused areas but not in contusions. Further studies are needed to tailor the use of hypertonic saline in patients with traumatic brain injury according to the volume of contusions assessed on computed tomography.

Adolescent↗

A revolution in liver ultrasound.

Liver ultrasound has been revolutionized by the development of microbubble contrast agents and multipulse software designed to detect their nonlinear resonances. The ability to visualize all parts of the liver's vasculature, including the sinusoids, at high spatial and temporal resolution gives unique insights into the haemodynamics of focal liver lesions. It has enabled ultrasound to detect and, as described by Celli N, et al.Eur J Gastroenterol Hepatol 2007; 3-14, to characterize such lesions with an accuracy comparable to multidetector computed tomography with consequent improvements in patient handling.

Contrast Media↗

Building messaging substrates for Web and Grid applications.

Grid application frameworks have increasingly aligned themselves with the developments in Web services. Web services are currently the most popular infrastructure based on service-oriented architecture (SOA) paradigm. There are three core areas within the SOA framework: (i) a set of capabilities that are remotely accessible, (ii) communications using messages and (iii) metadata pertaining to the aforementioned capabilities. In this paper, we focus on issues related to the messaging substrate hosting these services; we base these discussions on the NARADABROKERING system. We outline strategies to leverage capabilities available within the substrate without the need to make any changes to the service implementations themselves. We also identify the set of services needed to build Grids of Grids. Finally, we discuss another technology, HPSEARCH, which facilitates the administration of the substrate and the deployment of applications via a scripting interface. These issues have direct relevance to scientific Grid applications, which need to go beyond remote procedure calls in client-server interactions to support integrated distributed applications that couple databases, high performance computing codes and visualization codes.

Computer Simulation↗

Biopipe: a flexible framework for protocol-based bioinformatics analysis.

We identify several challenges facing bioinformatics analysis today. Firstly, to fulfill the promise of comparative studies, bioinformatics analysis will need to accommodate different sources of data residing in a federation of databases that, in turn, come in different formats and modes of accessibility. Secondly, the tsunami of data to be handled will require robust systems that enable bioinformatics analysis to be carried out in a parallel fashion. Thirdly, the ever-evolving state of bioinformatics presents new algorithms and paradigms in conducting analysis. This means that any bioinformatics framework must be flexible and generic enough to accommodate such changes. In addition, we identify the need for introducing an explicit protocol-based approach to bioinformatics analysis that will lend rigorousness to the analysis. This makes it easier for experimentation and replication of results by external parties. Biopipe is designed in an effort to meet these goals. It aims to allow researchers to focus on protocol design. At the same time, it is designed to work over a compute farm and thus provides high-throughput performance. A common exchange format that encapsulates the entire protocol in terms of the analysis modules, parameters, and data versions has been developed to provide a powerful way in which to distribute and reproduce results. This will enable researchers to discuss and interpret the data better as the once implicit assumptions are now explicitly defined within the Biopipe framework.

Amino Acid Sequence↗

Mauve: multiple alignment of conserved genomic sequence with rearrangements.

As genomes evolve, they undergo large-scale evolutionary processes that present a challenge to sequence comparison not posed by short sequences. Recombination causes frequent genome rearrangements, horizontal transfer introduces new sequences into bacterial chromosomes, and deletions remove segments of the genome. Consequently, each genome is a mosaic of unique lineage-specific segments, regions shared with a subset of other genomes and segments conserved among all the genomes under consideration. Furthermore, the linear order of these segments may be shuffled among genomes. We present methods for identification and alignment of conserved genomic DNA in the presence of rearrangements and horizontal transfer. Our methods have been implemented in a software package called Mauve. Mauve has been applied to align nine enterobacterial genomes and to determine global rearrangement structure in three mammalian genomes. We have evaluated the quality of Mauve alignments and drawn comparison to other methods through extensive simulations of genome evolution.

Chromosomes, Bacterial↗

Use of software to search for higher symmetry: space group C2.

From a search of the October 2000 release of the Cambridge Structural Database we find coordinate data for approximately 1500 entries under space group No. 5: C2 or, occasionally, A2, I2 or B112. Software designed to detect cases of missed higher symmetry identified 144 entries for detailed inspection. Of these, 50 should, we believe, be revised to space groups of higher symmetry. The most common revision is to space group C2/m, which entails adding a center of inversion and usually results in important changes in bond lengths and angles.

Journal Article↗

A new algorithm for autoreconstruction of catheters in computed tomography-based brachytherapy treatment planning.

This paper describes innovative software for automatic reconstruction, which we term autoreconstruction, of plastic and metallic brachytherapy catheters using computed tomography (CT) data. No such automatic facility has previously existed in any treatment planning software. The patient data consists of a set of post-implantation CT images with the catheters in situ in their final positions. This new software solves those difficulties which arise when the catheters are intersecting or when loop techniques are used. With the software algorithms, catheter reconstruction time is significantly reduced and accuracy is also improved when compared with that achieved using the classical manual method of CT-slice-by-CT-slice reconstruction.

Algorithms↗

Virtual surgery in a (tele-)radiology framework.

This paper presents telemedicine as an extension of a teleradiology framework through tools for virtual surgery. To classify the described methods and applications, the research field of virtual reality (VR) is broadly reviewed. Differences with respect to technical equipment, methodological requirements and areas of application are pointed out. Desktop VR, augmented reality, and virtual reality are differentiated and discussed in some typical contexts of diagnostic support, surgical planning, therapeutic procedures, simulation and training. Visualization techniques are compared as a prerequisite for virtual reality and assigned to distinct levels of immersion. The advantage of a hybrid visualization kernel is emphasized with respect to the desktop VR applications that are subsequently shown. Moreover, software design aspects are considered by outlining functional openness in the architecture of the host system. Here, a teleradiology workstation was extended by dedicated tools for surgical planning through a plug-in mechanism. Examples of recent areas of application are introduced such as liver tumor resection planning, diagnostic support in heart surgery, and craniofacial surgery planning. In the future, surgical planning systems will become more important. They will benefit from improvements in image acquisition and communication, new image processing approaches, and techniques for data presentation. This will facilitate preoperative planning and intraoperative applications.

Surgical Procedures, Operative↗