To assess the gait variability in patients with Parkinson's disease (PD), we first used the nonparametric Parzen-window method to estimate the probability density functions (PDFs) of stride interval and its two subphases (i.e., swing interval and stance interval). The gait rhythm standard deviation (sigma) parameters computed with the PDFs indicated that the gait variability is significantly increased in PD. Signal turns count (STC) was also derived from each outlier-processed gait rhythm time series to serve as a dominant feature, which could be used to characterize the gait variability in PD. Since it was observed that the statistical parameters of swing interval or stance interval were highly correlated with those of stride interval, this article only used the stride interval parameters, i.e., sigma(r) and STC(r) , to form the feature vector in the pattern classification experiments. The results evaluated with the leave-one-out cross-validation method demonstrated that the least squares support vector machine with polynomial kernels was able to provide a classification accurate rate of 90.32% and an area (Az) of 0.952 under the receiver operating characteristic curve, both of which were better than the results obtained with the linear discriminant analysis (accuracy: 67.74%, Az: 0.917). The features and the classifiers used in the present study could be useful for monitoring of the gait in PD.

Evidence syntheses, and in particular systematic reviews (SRs), have become one of the cornerstones of evidence-based health care. The Assessment of Multiple Systematic Reviews (AMSTAR) tool has become the most widely used tool for investigating the methodological quality of SRs and is currently undergoing revision. The objective of this paper is to present insights, challenges and potential solutions from the point of view of a group of assessors, while referring to earlier methodological discussions and debates with respect to AMSTAR.

One major drawback of AMSTAR is that it relies heavily on reporting quality rather than on methodological quality. This can be found in several items. Furthermore, it should be acknowledged that there are now new methods and procedures that did not exist when AMSTAR was developed. For example, the note to item 1 should now refer to the International Prospective Register of Ongoing Systematic Reviews (PROSPERO). Furthermore, item 3 should consider the definition of hand-searching, as the process of reviewing conference proceedings using the search function (e.g. in Microsoft Word or in a PDF file) does not meet the definition set out by the Cochrane Collaboration. Moreover, methods for assessing the quality of the body of evidence have evolved since AMSTAR was developed and should be incorporated into a revised AMSTAR tool. Potential solutions are presented for each AMSTAR item with the aim of allowing a more thorough assessment of SRs. As the AMSTAR tool is currently undergoing further development, our paper hopes to add to preceding discussions and papers regarding this tool and stimulate further discussion.

BACKGROUND

Epithelial-mesenchymal transition (EMT) is important in the development of peritoneal fibrosis. Glucose degradation products (GDPs) may induce EMT in human peritoneal mesothelial cells (HPMCs).

METHODS

The effects of individual GDPs and GDPs derived from peritoneal dialysis fluid (PDF) in both HPMCs and peritoneal membranes were evaluated. EMT was assessed with alpha-smooth muscle actin (alpha-SMA) and E-cadherin.

RESULTS

In vitro, alpha-SMA protein and mRNA levels increased in the presence of the GDPs (formaldehyde, glyoxal, methylglyoxal, and 3-deoxyglucosone), and E-cadherin decreased. Changes in the EMT markers were most prominent after exposure to 3-deoxyglucosone. Changes in both alpha-SMA and E-cadherin protein levels were less with low (L)-GDP bicarbonate/lactate-buffered PDF compared to high (H)-GDP PDF. In the rat model after 8 weeks' PDF infusion, the alpha-SMA/E-cadherin mRNA ratio increased in the H-GDP group compared with the L-GDP group (p < 0.05). The peritoneum in the H-GDP group tended to be thicker (p = 0.052) and had more blood vessels than that in the L-GDP group (p < 0.05). Tissue staining for TGF-beta1 decreased in the L-GDP group. Dual-stained cytokeratin and alpha-SMA-positive myofibroblasts in the submesothelial layer were more prominent in the H-GDP group.

CONCLUSIONS

GDPs found in PDF induce EMT of HPMCs, which is associated with peritoneal fibrosis and vascularization. Conversely, L-GDP PDF reduces EMT and peritoneal fibrosis.

Opisthorchis viverrini infection induces chronic inflammation in the bile ducts, leading to periductal fibrosis (PDF), which possibly associates to cholangiocarcinoma (CCA). Patients with CCA have a poor prognosis, which is linked to asymptomatic disease and late diagnosis. Hence, detecting early stage CCA is essential. Secretory miRNAs have been promoted as biomarkers for pathological changes associated with parasitic infections, fibrosis and/or cancer. We aimed to determine levels of miR-192 and miR-21 in the urine of O. viverrini infected, periductal fibrosis (PDF) and CCA groups using qRT-PCR. We found that miR-192 was significantly higher in O. viverrini infected, PDF and also CCA groups (p<0.05) than in healthy controls. By utilizing the Receiver Operation Characteristics (ROC) analysis, miR-192 differentiated patients with opisthorchiasis (the area under the curve; AUC=0.766), PDF subjects (AUC=0.781) and CCA patients (AUC=0.682) from healthy controls. MiR-21 was significantly higher in PDF and CCA groups (p<0.05) than in healthy controls. MiR-21 discriminated PDF subjects (AUC=0.735) and CCA patients (AUC=0.682) from healthy controls. Combined levels of these two miRNAs revealed an increased AUC of 0.812 for separating opisthorchiasis, AUC of 0.815 in discriminating PDF subjects, and AUC of 0.849 in differentiating CCA from healthy controls. Odds ratios (OR) indicated high levels of miR-192/miR-21 as risk predictors for opisthorchiasis, PDF and CCA. Levels of these miRNAs declined significantly for patients following praziquantel treatment. In conclusion, urinary miR-192/miR-21 have potential as risk indicators for opisthorchiasis and PDF-associated CCA in the endemic region.

With the establishment of high-throughput (HT) screening methods there is an increasing need for automatic analysis methods. Here we present RReportGenerator, a user-friendly portal for automatic routine analysis using the statistical platform R and Bioconductor. RReportGenerator is designed to analyze data using predefined analysis scenarios via a graphical user interface (GUI). A report in pdf format combining text, figures and tables is automatically generated and results may be exported. To demonstrate suitable analysis tasks we provide direct web access to a collection of analysis scenarios for summarizing data from transfected cell arrays (TCA), segmentation of CGH data, and microarray quality control and normalization.

BACKGROUND

RReportGenerator, a user manual and a collection of analysis scenarios are available under a GNU public license on http://www-bio3d-igbmc.u-strasbg.fr/~wraff

While circadian dysfunction and neurodegeneration are correlated, the mechanism for this is not understood. It is not known if age-dependent circadian dysfunction leads to neurodegeneration or vice-versa, and the proteins that mediate the effect remain unidentified. Here, we show that the knock-down of a regulator (spag) of the circadian kinase Dbt in circadian cells lowers Dbt levels abnormally, lengthens circadian rhythms and causes expression of activated initiator caspase (Dronc) in the optic lobes during the middle of the day or after light pulses at night. Likewise, reduced Dbt activity lengthens circadian period and causes expression of activated Dronc, and a loss-of-function mutation in Clk also leads to expression of activated Dronc in a light-dependent manner. Genetic epistasis experiments place Dbt downstream of Spag in the pathway, and Spag-dependent reductions of Dbt are shown to require the proteasome. Importantly, activated Dronc expression due to reduced Spag or Dbt activity occurs in cells that do not express the spag RNAi or dominant negative Dbt and requires PDF neuropeptide signaling from the same neurons that support behavioral rhythms. Furthermore, reduction of Dbt or Spag activity leads to Dronc-dependent Drosophila Tau cleavage and enhanced neurodegeneration produced by human Tau in a fly eye model for tauopathy. Aging flies with lowered Dbt or Spag function show markers of cell death as well as behavioral deficits and shortened lifespans, and even old wild type flies exhibit Dbt modification and activated caspase at particular times of day. These results suggest that Dbt suppresses expression of activated Dronc to prevent Tau cleavage, and that the circadian clock defects confer sensitivity to expression of activated Dronc in response to prolonged light. They establish a link between the circadian clock factors, light, cell death pathways and Tau toxicity, potentially via dysregulation of circadian neuronal remodeling in the optic lobes.

Ecdysone is the key hormone regulating insect growth and development. Ecdysone synthesis occurs in the prothoracic glands (PGs) and is regulated by several neuropeptides. Four prothoracicotropic and three prothoracicostatic factors have been identified to date, suggesting that ecdysone biosynthesis is intricately regulated. Here, we demonstrate that the neuropeptide pigment dispersing factor (PDF) stimulates ecdysone biosynthesis and that this novel signaling pathway partially overlaps with the prothoracicotropic hormone (PTTH) signaling pathway. We performed transcriptome analysis and focused on receptors predominantly expressed in the PGs. From this screen, we identified a candidate orphan G protein coupled receptor (GPCR), Bombyx neuropeptide GPCR-B2 (BNGR-B2). BNGR-B2 was predominantly expressed in ecdysteroidogenic tissues, and the expression pattern in the PGs corresponded to the ecdysteroid titer in the hemolymph. Furthermore, we identified PDF as a ligand for BNGR-B2. PDF stimulated ecdysone biosynthesis in the PGs, but the stimulation was only observed in the PGs during a specific larval stage. PDF did not affect the transcript level of known ecdysone biosynthetic enzymes, and inhibiting transcription did not suppress ecdysone biosynthesis, suggesting that the effects of PDF might be mediated by translational regulation and/or post-translational modification. In addition, the participation of protein kinase A (PKA), phosphatidylinositol 3-kinase (PI3K), target of rapamycin (TOR) and eukaryotic translation initiation factor 4E (eIF4E)-binding protein (4E-BP) in the PDF signaling pathway was discovered.

BACKGROUND

Exercise has positive psychophysical effects on dialysis patients, thus effective programs should be identified. We evaluated the effects of an original 6-month walking program on physical capacity, health-related quality of life (HRQL) and postdialysis fatigue (PDF).

METHODS

Thirty-one dialysis patients (19 male, mean age 65 -/+ 11 years) were divided into exercise (group E; n=17) and control (group C; n=14) groups, and evaluated upon entry, after the 6-month program and 19 -/+ 3 months later. Outcome measures were 6-minute walking distance (6MWD), SF-36 scale scores, self-reported PDF and recovery time. E group was assigned 2 daily 10-minute home walking sessions on the nondialysis day at a speed 50% below maximal treadmill speed as determined and updated monthly at the hospital. C group: no exercise.

RESULTS

Twenty patients (13 from E, 7 from C) completed the study. The E group, unlike the C group, increased 6MWD (308 -/+ 105 m, to 351 -/+ 118 m, p=0.0007), and HRQL, significantly for bodily pain, physical role and mental health (p<0.05), decreased PDF and recovery time (p<0.05). At the follow-up, 15 patients were reevaluated (9 from E, 6 from C). The E group was still active and showed 6MWD similar to baseline, with a decline of 0.13 -/+ 1.72 m/mo. The C group decreased 6MWD (p=0.026) with a decline of 3.43 -/+ 3.2 m/mo. For both groups, HRQL, PDF and recovery time showed slight variations from baseline.

CONCLUSIONS

In dialysis patients, a 6-month exercise program prescribed at the hospital and performed at home improved physical capacity, HRQL and PDF symptoms. Patients maintained an active lifestyle after discharge and showed a slow functional decline over a 2-year period.

OBJECTIVE

To quantitatively evaluate the pulse waveform changes in macular choroidal blood flow by using laser speckle flowgraphy (LSFG) with regression of acute central serous chorioretinopathy (CSC).

METHODS

This retrospective observational case series included 20 eyes of 20 patients with acute CSC. Laser speckle flowgraphy was performed at baseline and after 6 months. On the LSFG monochrome map, automatically divided 5 × 5 grid segments within the macula were classified into predominantly delayed filling (PDF) or minimally or no delayed filling (MDF) areas according to the degree of choroidal filling delay on early-phase indocyanine green angiography. The average mean blur rate (MBR) and the pulse waveform parameters, including the skew and blowout time (BOT), were compared between the total PDF and MDF areas during follow-up.

RESULTS

The average MBR significantly decreased in both PDF (P = 0.005) and MDF (P < 0.001) areas during follow-up; in both areas, the skew decreased (P < 0.001 and P = 0.006, respectively) and BOT increased (P < 0.001 for each), showing significant reduction in vascular resistance at 6 months. The degree of the changes in the skew and BOT was significantly larger (P = 0.02 and P < 0.001, respectively) in the PDF area than in the MDF area.

CONCLUSIONS

Changes in the skew and BOT, indices for vascular resistance, confirmed the involvement of circulatory disturbance at the acute stage of CSC. The present findings suggested that the pathogenesis of CSC stems from imbalanced distribution of choroidal blood flow due to augmented vascular resistance.

This SnapShot summarizes current knowledge about the key features in mutational landscape, major pathways, and tumor evolution and heterogeneity in renal cell carcinoma, as well as the most recent advances in therapeutic development. To view this SnapShot, open or download the PDF.

OBJECTIVE

To develop and assess the diagnostic performance of a three-dimensional (3D) whole-body T1-weighted magnetic resonance (MR) imaging pulse sequence at 3.0 T for bone and node staging in patients with prostate cancer. MATERIALS AND METHODS This prospective study was approved by the institutional ethics committee; informed consent was obtained from all patients. Thirty patients with prostate cancer at high risk for metastases underwent whole-body 3D T1-weighted imaging in addition to the routine MR imaging protocol for node and/or bone metastasis screening, which included coronal two-dimensional (2D) whole-body T1-weighted MR imaging, sagittal proton-density fat-saturated (PDFS) imaging of the spine, and whole-body diffusion-weighted MR imaging. Two observers read the 2D and 3D images separately in a blinded manner for bone and node screening. Images were read in random order. The consensus review of MR images and the findings at prospective clinical and MR imaging follow-up at 6 months were used as the standard of reference. The interobserver agreement and diagnostic performance of each sequence were assessed on per-patient and per-lesion bases.

RESULTS

The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were significantly higher with whole-body 3D T1-weighted imaging than with whole-body 2D T1-weighted imaging regardless of the reference region (bone or fat) and lesion location (bone or node) (P < .003 for all). For node metastasis, diagnostic performance (area under the receiver operating characteristic curve) was higher for whole-body 3D T1-weighted imaging (per-patient analysis; observer 1: P < .001 for 2D T1-weighted imaging vs 3D T1-weighted imaging, P = .006 for 2D T1-weighted imaging + PDFS imaging vs 3D T1-weighted imaging; observer 2: P = .006 for 2D T1-weighted imaging vs 3D T1-weighted imaging, P = .006 for 2D T1-weighted imaging + PDFS imaging vs 3D T1-weighted imaging), as was sensitivity (per-lesion analysis; observer 1: P < .001 for 2D T1-weighted imaging vs 3D T1-weighted imaging, P < .001 for 2D T1-weighted imaging + PDFS imaging vs 3D T1-weighted imaging; observer 2: P < .001 for 2D T1-weighted imaging vs 3D T1-weighted imaging, P < .001 for 2D T1-weighted imaging + PDFS imaging vs 3D T1-weighted imaging).

CONCLUSIONS

Whole-body MR imaging is feasible with a 3D T1-weighted sequence and provides better SNR and CNR compared with 2D sequences, with a diagnostic performance that is as good or better for the detection of bone metastases and better for the detection of lymph node metastases.

Since the release of the 2008 Physical Activity Guidelines for Americans (https://health.gov/paguidelines/2008/pdf/paguide.pdf), the age-adjusted percentage of adults meeting the combined aerobic and muscle-strengthening guidelines increased from 18.2% to 24.3% in 2017 (1). Trends in urban and rural areas, across demographic subgroups, and among subgroups within urban and rural areas have not been reported. CDC analyzed 2008-2017 National Health Interview Survey (NHIS) data to examine trends in the age-standardized prevalence of meeting physical activity guidelines among adults aged ≥18 years living in urban and rural areas. Among urban and rural residents, prevalence increased from 19.4% to 25.3% and from 13.3% to 19.6%, respectively. Nationally, all demographic subgroups and regions experienced increases over this period; increases for several groups were not consistent year-to-year. Among urban residents, the prevalence was higher during 2016-2017 than during 2008-2009 for all demographic subgroups and regions. During the same period, prevalence was higher across all rural-dwelling subgroups except Hispanics, adults with a college education, and those living in the South U.S. Census region. Urban and rural communities can implement evidence-based approaches, including improved community design, improved access to indoor and outdoor recreation facilities, social support programs, and community-wide campaigns to make physical activity the safe and easy choice for persons of all ages and abilities (2-4). Incorporating culturally appropriate strategies into local programs might help address differences across subgroups.

BACKGROUND

Long non-coding RNAs (lncRNAs) resemble protein-coding mRNAs but do not encode proteins. Most lncRNAs are under lower sequence constraints than protein-coding genes and lack conserved secondary structures, making it hard to predict them computationally.

RESULTS

We introduce an approach to predict spliced lncRNAs in vertebrate genomes combining comparative genomics and machine learning. It is based on detecting signatures of characteristic splice site evolution in vertebrate whole genome alignments. First, we predict individual splice sites, then assemble compatible sites into exon candidates, and finally predict multi-exon transcripts. Using a novel method to evaluate typical splice site substitution patterns that explicitly takes the species phylogeny into account, we show that individual splice sites can be accurately predicted. Since our approach relies only on predicted splice sites, it can uncover both coding and non-coding exons. We show that our predicted exons and partial transcripts are mostly non-coding and lack conserved secondary structures. These exons are of particular interest, since existing computational approaches cannot detect them. Transcriptome sequencing data indicate tissue-specific expression patterns of predicted exons and there is evidence that increasing sequencing depth and breadth will validate additional predictions. We also found a significant enrichment of predicted exons that form multi-exon transcript parts, and we experimentally validate such a novel multi-exon gene. Overall, we obtain 336 novel multi-exon transcript predictions from human intergenic regions. Our results indicate the existence of novel human transcripts that are conserved in evolution and our approach contributes to the completion of the human transcript catalog.

METHODS

Predicted human splice sites, exons and gene structures together with a Perl implementation of the tree-based log-odds scoring and a supplementary PDF file containing additional figures and tables are available at: http://www.bioinf.uni-leipzig.de/publications/supplements/10-010. The five experimentally confirmed partial transcript isoforms have been deposited in GenBank under accession numbers HM587422-HM587426.

BACKGROUND

Photographs are important tools to record, track, and communicate clinical findings. Mobile devices with high-resolution cameras are now ubiquitous, giving clinicians the opportunity to capture and share images from the bedside. However, secure and efficient ways to manage and share digital images are lacking.

OBJECTIVE

The aim of this study is to describe the implementation of a secure application for capturing and storing clinical images in the electronic health record (EHR), and to describe initial user experiences.

METHODS

We developed CliniCam, a secure Apple iOS (iPhone, iPad) application that allows for user authentication, patient selection, image capture, image annotation, and storage of images as a Portable Document Format (PDF) file in the EHR. We leveraged our organization's enterprise service-oriented architecture to transmit the image file from CliniCam to our enterprise clinical data repository. There is no permanent storage of protected health information on the mobile device. CliniCam also required connection to our organization's secure WiFi network. Resident physicians from emergency medicine, internal medicine, and dermatology used CliniCam in clinical practice for one month. They were then asked to complete a survey on their experience. We analyzed the survey results using descriptive statistics.

RESULTS

Twenty-eight physicians participated and 19/28 (68%) completed the survey. Of the respondents who used CliniCam, 89% found it useful or very useful for clinical practice and easy to use, and wanted to continue using the app. Respondents provided constructive feedback on location of the photos in the EHR, preferring to have photos embedded in (or linked to) clinical notes instead of storing them as separate PDFs within the EHR. Some users experienced difficulty with WiFi connectivity which was addressed by enhancing CliniCam to check for connectivity on launch.

CONCLUSIONS

CliniCam was implemented successfully and found to be easy to use and useful for clinical practice. CliniCam is now available to all clinical users in our hospital, providing a secure and efficient way to capture clinical images and to insert them into the EHR. Future clinical image apps should more closely link clinical images and clinical documentation and consider enabling secure transmission over public WiFi or cellular networks.

The presence of web-based communities is a distinctive signature of Web 2.0. The web-based feature means that information propagation within each community is highly facilitated, promoting complex collective dynamics in view of information exchange. In this work, we focus on a community of scientists and study, in particular, how the awareness of a scientific paper is spread. Our work is based on the web usage statistics obtained from the PLoS Article Level Metrics dataset compiled by PLoS. The cumulative number of HTML views was found to follow a long tail distribution which is reasonably well-fitted by a lognormal one. We modeled the diffusion of information by a random multiplicative process, and thus extracted the rates of information spread at different stages after the publication of a paper. We found that the spread of information displays two distinct decay regimes: a rapid downfall in the first month after publication, and a gradual power law decay afterwards. We identified these two regimes with two distinct driving processes: a short-term behavior driven by the fame of a paper, and a long-term behavior consistent with citation statistics. The patterns of information spread were found to be remarkably similar in data from different journals, but there are intrinsic differences for different types of web usage (HTML views and PDF downloads versus XML). These similarities and differences shed light on the theoretical understanding of different complex systems, as well as a better design of the corresponding web applications that is of high potential marketing impact.

We present the first package of Java classes specifically aimed at the handling of structural and biophysical problems. To enable object-oriented programming a basis of fundamental Java classes is required which deals with basic operations of vectors, matrices, amino acid sequences, crystal symmetries and PDB files. Five classes, which carry out these basic operations, were constructed and bundled together with several utility functions in the PCSB package. Furthermore, to demonstrate their applicability and to obtain programs handling common tasks in structural laboratories, we present the first six applications of PCSB. All applications are portable to different platforms and require only the Java Runtime Environment to be installed on the system. available as PDF file.

BACKGROUND

The purpose of this study is to implement an electronic method to perform and analyze intensity-modulated radiation therapy quality assurance (IMRT QA) using an aSi megavoltage electronic portal imaging device in a network comprised of independent treatment planning, record and verify (R&V), and delivery systems.

METHODS

A verification plan was generated in the treatment planning system using the actual treatment plan of a patient. After exporting the treatment fields to the R&V system, the fields were delivered in QA mode with the aSi imager deployed. The resulting dosimetric images are automatically stored in a DICOM-RT format in the delivery system treatment console computer. The relative dose density images are subsequently pushed to the R&V system. The absolute dose images are then transferred electronically from the treatment console computer to the treatment planning system and imported into the verification plan in the dosimetry work space for further analysis. Screen shots of the gamma evaluation and isodose comparison are imported into the R&V system as an electronic file (e.g. PDF) to be reviewed prior to initiation of patient treatment. A relative dose image predicted by the treatment planning system can also be sent to the R&V system to be compared with the relative dose density image measured with the aSi imager.

RESULTS

Our department does not have integrated planning, R&V, and delivery systems. In spite of this, we are able to fully implement a paperless and filmless IMRT QA process, allowing subsequent analysis and approval to be more efficient, while the QA document is directly attached to its specific patient chart in the R&V system in electronic form. The calculated and measured relative dose images can be compared electronically within the R&V system to analyze the density differences and ensure proper dose delivery to patients.

CONCLUSIONS

In the absence of an integrated planning, verifying, and delivery system, we have shown that it is nevertheless possible to develop a completely electronic IMRT QA process.

Partial differential equations (PDE's) for the probability density function (PDF) of the position and orientation of the distal end of a stiff macromolecule relative to its proximal end are derived and solved. The Kratky-Porod wormlike chain, the Yamakawa helical wormlike chain, and the original and revised Marko-Siggia models are examples of stiffness models to which the present formulation is applied. The solution technique uses harmonic analysis on the rotation and motion groups to convert PDE's governing the PDF's of interest into linear algebraic equations which have mathematically elegant solutions.

High angular resolution diffusion imaging (HARDI) has become an important technique for imaging complex oriented structures in the brain and other anatomical tissues. This has motivated the recent development of several methods for computing the orientation probability density function (PDF) at each voxel. However, much less work has been done on developing techniques for filtering, interpolation, averaging and principal geodesic analysis of orientation PDF fields. In this paper, we present a Riemannian framework for performing such operations. The proposed framework does not require that the orientation PDFs be represented by any fixed parameterization, such as a mixture of von Mises-Fisher distributions or a spherical harmonic expansion. Instead, we use a nonparametric representation of the orientation PDF. We exploit the fact that under the square-root re-parameterization, the space of orientation PDFs forms a Riemannian manifold: the positive orthant of the unit Hilbert sphere. We show that various orientation PDF processing operations, such as filtering, interpolation, averaging and principal geodesic analysis, may be posed as optimization problems on the Hilbert sphere, and can be solved using Riemannian gradient descent. We illustrate these concepts with numerous experiments on synthetic, phantom and real datasets. We show their application to studying left/right brain asymmetries.

We determined the relationship between intra-fractional breathing motion and safety margins, using daily real-time tumour tracking data of 40 patients (43 tumour locations), treated with radiosurgery at Hokkaido University. We limited our study to the dose-blurring effect of intra-fractional breathing motion, and did not consider differences in positioning accuracy or systematic errors. The additional shift in the prescribed isodose level (e.g. 95 %) was determined by convolving a one-dimensional dose profile, having a dose gradient representing an 8 MV beam through either lung or water, with the probability density function (PDF) of breathing. This additional shift is a measure for the additional margin that should be applied in order to maintain the same probability of tumour control as without intra-fractional breathing. We show that the required safety margin is a nonlinear function of the peak-to-peak breathing motion. Only a small reduction in the shift of isodose curves was observed for breathing motion up to 10 mm. For larger motion, 20 or 30 mm, control of patient breathing during irradiation, using either gating or breath hold, can allow a substantial reduction in safety margins of about 7 or 12 mm depending on the dose gradient prior to blurring. Clinically relevant random setup uncertainties, which also have a blurring effect on the dose distribution, have only a small effect on the margin needed for intra-fractional breathing motion. Because of the one-dimensional nature of our analysis, the resulting margins are mainly applicable in the superior-inferior direction. Most measured breathing PDFs were not consistent with the PDF of a simple parametric curve such as cos4, either because of irregular breathing or base-line shifts. Instead, our analysis shows that breathing motion can be modelled as Gaussian with a standard deviation of about 0.4 times the peak-to-peak breathing motion.

Representation and reconstruction of data obtained by emission tomography scanners are challenging due to high noise levels in the data. Typically, images obtained using tomographic measurements are represented using grids. In this work, we define images as sets of origins of events detected during tomographic measurements; we call these origin ensembles (OEs). A state in the ensemble is characterized by a vector of 3N parameters Y, where the parameters are the coordinates of origins of detected events in a three-dimensional space and N is the number of detected events. The 3N-dimensional probability density function (PDF) for that ensemble is derived, and we present an algorithm for OE image estimation from tomographic measurements. A displayable image (e.g. grid based image) is derived from the OE formulation by calculating ensemble expectations based on the PDF using the Markov chain Monte Carlo method. The approach was applied to computer-simulated 3D list-mode positron emission tomography data. The reconstruction errors for a 10 000 000 event acquisition for simulated ranged from 0.1 to 34.8%, depending on object size and sampling density. The method was also applied to experimental data and the results of the OE method were consistent with those obtained by a standard maximum-likelihood approach. The method is a new approach to representation and reconstruction of data obtained by photon-limited emission tomography measurements.

The atmospheric pressure (AP) matrix-assisted laser desorption/ionization (MALDI) technique described to date has proven to be a convenient and rapid method for soft ionization of biomolecules. However, this technique, like other AP ionization methods, has so far suffered from a low efficiency in transmitting ions from atmospheric pressure into the vacuum of the mass spectrometer (MS). In this work, a novel technique we termed pulsed dynamic focusing, or PDF, which improves the ion transmission efficiency and sensitivity of AP-MALDI by over an order of magnitude, is described. Pulsed dynamic focusing operates on the basis of pulsing a high-voltage extraction field to zero, when ions are just outside of the MS entrance, to allow the intake gas flow of the MS to effectively entrain the ions into the MS. Results from application of the PDF technique to an AP-MALDI ion trap MS demonstrated that in comparison to static AP-MALDI operation (1). up to 2.1 times more ions from a given laser shot could be transferred into the MS, (2). applying higher voltages in combination with the switching scheme yielded up to 1.6-times-higher ion intensities, and (3). a 3-times-larger laser spot area could be utilized. The combination of these factors produced an enhancement in throughput and sensitivity, as measured by the ions detected per unit time, of over 12 times for a digest sample of bovine serum albumin. In addition, the PDF technique proved to make AP-MALDI less sensitive to laser positioning, creating a more robust ion source in comparison to static AP-MALDI.

The streptococcal C5a peptidase (ScpB) of group B streptococci (GBS) is found in virtually all clinical GBS isolates and is required for mucosal colonization in a neonatal mouse model. ScpB inhibits neutrophil chemotaxis by enzymatically cleaving the complement component C5a. We previously identified a second function of ScpB as a fibronectin (Fn) adhesin using phage display. However, phage display can identify low-affinity interactions. We therefore measured the affinity of both full-length recombinant ScpB (FL-ScpB) and the 110-amino-acid phage display fragment (Scp-PDF) for immobilized Fn using surface plasmon resonance. The affinity for Fn was very high for both FL-ScpB (equilibrium dissociation constant [KD] = 4.0 nM) and Scp-PDF (KD = 4.4 nM) and is consistent with a biologically significant role for the adhesin activity of ScpB. We also studied the Fn adhesin activity of a common natural variant of ScpB (ScpBDelta) that contains a 4-amino-acid deletion that eliminates peptidase activity. The integrity of scpB is otherwise maintained, suggesting that the Fn adhesin activity of ScpB may be responsible for its conservation in these strains. The affinities of both FL-ScpBDelta (KD = 2.4 nM) and ScpBDelta-PDF (KD = 1.4 nM) for Fn are unaffected by the deletion. Complementation in trans by both scpB and scpBDelta corrected the Fn-binding defect of an scpB deletion mutant GBS strain to an identical degree. The high affinity of ScpB for Fn and the maintenance of this affinity in ScpBDelta support our hypothesis that the Fn adhesin activity of scpB plays a role in virulence.

Groupwise registration has been recently introduced to simultaneously register a group of images by avoiding the selection of a particular template. To achieve this, several methods have been proposed to take advantage of information-theoretic entropy measures based on image intensity. However, simplistic utilization of voxelwise image intensity is not sufficient to establish reliable correspondences, since it lacks important contextual information. Therefore, we explore the notion of attribute vector as the voxel signature, instead of image intensity, to guide the correspondence detection in groupwise registration. In particular, for each voxel, the attribute vector is computed from its multi-scale neighborhoods, in order to capture the geometric information at different scales. The probability density function (PDF) of each element in the attribute vector is then estimated from the local neighborhood, providing a statistical summary of the underlying anatomical structure in that local pattern. Eventually, with the help of Jensen-Shannon (JS) divergence, a group of subjects can be aligned simultaneously by minimizing the sum of JS divergences across the image domain and all attributes. We have employed our groupwise registration algorithm on both real (NIREP NA0 data set) and simulated data (12 pairs of normal control and simulated atrophic data set). The experimental results demonstrate that our method yields better registration accuracy, compared with a popular groupwise registration method.