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1.  Groupwise Registration by Hierarchical Anatomical Correspondence Detection 
We present a novel feature-based groupwise registration method to simultaneously warp the subjects towards the common space. Due to the complexity of the groupwise registration, we resort to decoupling it into two easy-to-solve tasks, i.e., alternatively establishing the robust correspondences across different subjects and interpolating the dense deformation fields based on the detected sparse correspondences. Specifically, several novel strategies are proposed in the correspondence detection step. First, attribute vector, instead of intensity only, is used as a morphological signature to guide the anatomical correspondence detection among all subjects. Second, we detect correspondence only on the driving voxels with distinctive attribute vectors for avoiding the ambiguity in detecting correspondences for non-distinctive voxels. Third, soft correspondence assignment (allowing for adaptive detection of multiple correspondences in each subject) is also presented to help establish reliable correspondences across all subjects, which is particularly necessary in the beginning of groupwise registration. Based on the sparse correspondences detected on the driving voxels of each subject, thin-plate splines (TPS) are then used to propagate the correspondences on the driving voxels to the entire brain image for estimating the dense transformation for each subject. By iteratively repeating correspondence detection and dense transformation estimation, all the subjects will be aligned onto a common space simultaneously. Our groupwise registration algorithm has been extensively evaluated by 18 elderly brains, 16 NIREP, and 40 LONI data. In all experiments, our algorithm achieves more robust and accurate registration results, compared to a groupwise registration method and a pairwise registration method, respectively.
PMCID: PMC3018804  PMID: 20879375
2.  Robust Anatomical Correspondence Detection by Hierarchical Sparse Graph Matching 
Robust anatomical correspondence detection is a key step in many medical image applications such as image registration and motion correction. In the computer vision field, graph matching techniques have emerged as a powerful approach for correspondence detection. By considering potential correspondences as graph nodes, graph edges can be used to measure the pairwise agreement between possible correspondences. In this paper, we present a novel, hierarchical graph matching method with sparsity constraint to further augment the power of conventional graph matching methods in establishing anatomical correspondences, especially for the cases of large inter-subject variations in medical applications. Specifically, we first propose to measure the pairwise agreement between potential correspondences along a sequence of intensity profiles which reduces the ambiguity in correspondence matching. We next introduce the concept of sparsity on the fuzziness of correspondences to suppress the distraction from misleading matches, which is very important for achieving the accurate, one-to-one correspondences. Finally, we integrate our graph matching method into a hierarchical correspondence matching framework, where we use multiple models to deal with the large inter-subject anatomical variations and gradually refine the correspondence matching results between the tentatively deformed model images and the underlying subject image. Evaluations on both synthetic data and public hand X-ray images indicate that the proposed hierarchical sparse graph matching method yields the best correspondence matching performance in terms of both accuracy and robustness when compared with several conventional graph matching methods.
doi:10.1109/TMI.2012.2223710
PMCID: PMC3767391  PMID: 23070298
Graph matching; hierarchical correspondence detection; line patch; multi-models; sparsity
3.  Correspondence as conditional stimulus control: insights from experiments with pigeons. 
Correspondence between saying and doing, typically studied in young children and individuals with developmental disabilities, was examined as an instance of conditional stimulus control. In Experiment 1, 3 pigeons were exposed to a two-component repeated-trials procedure. In the first-sample or say-component, two response keys transilluminated by different colored lights were presented and the pigeon pecked one of the keys. After 1 s of darkness in the chamber, the second-choice or do-component was presented, in which the two keys again were transilluminated, one by the color selected in the first component and the second by another color. Selecting the color that matched that selected in the say component resulted in access to food. Selecting the other color produced a blackout of the chamber. After an intertrial interval (ITI), the next say component was programmed, and the procedure was repeated. Correspondence remained at chance levels through several manipulations of ITI duration and sample response requirement. When a correction procedure was added such that only the originally selected sample stimulus was re-presented until a correct choice response occurred, reliable correspondence developed in 2 pigeons. This correspondence was eliminated by making reinforcement independent of correspondence and subsequently was reestablished when reinforcement again depended on correspondence. In Experiment 2, 3 other pigeons rapidly acquired correspondence under the final procedure used in Experiment 1. Increasing the time interval between the say and do components diminished correspondence. The results of the two experiments suggest how correspondence may be considered an instance of conditional stimulus control and that it is possible to construct a homologue of human say-do correspondence with pigeons.
doi:10.1901/jaba.2001.34-127
PMCID: PMC1284307  PMID: 11421307
4.  Wild plant folk nomenclature of the Mongol herdsmen in the Arhorchin national nature reserve, Inner Mongolia, PR China 
Background
Folk names of plants are the root of traditional plant biodiversity knowledge. In pace with social change and economic development, Mongolian knowledge concerning plant diversity is gradually vanishing. Collection and analysis of Mongolian folk names of plants is extremely important. During 2008 to 2012, the authors have been to the Arhorchin National Nature Reserve area 5 times. Fieldwork was done in 13 villages, with 56 local Mongol herdsmen being interviewed. This report documents plant folk names, analyzes the relationship between folk names and scientific names, looks at the structure and special characteristics of folk names, plant use information, and comparative analysis were also improved.
Methods
Ethnobotanical interviewing methods of free-listing and open-ended questionnaires were used. Ethnobotanical interview and voucher specimen collection were carried out in two ways as local plant specimens were collected beforehand and then used in interviews, and local Mongol herdsmen were invited to the field and interviewed while collecting voucher specimens. Mongolian oral language was used as the working language and findings were originally recorded in Mongolian written language. Scientific names of plants are defined through collection and identification of voucher specimens by the methods of plant taxonomy.
Results
A total of 146 folk names of local plants are recorded. Plant folk names corresponded with 111 species, 1 subspecies, 7 varieties, 1 form, which belong to 42 families and 88 genera. The correspondence between plant folk names and scientific names may be classified as one to one correspondence, two or three to one correspondence, and one to multitude correspondence. The structure of folk names were classified as primary names, secondary names and borrowed names. There were 12 folk names that contain animal names and they have correspondence with 15 species. There are nine folk names that contain usage information and they have correspondence with 10 species in which five species and one variety of plant are still used by the local people. The results of comparative analysis on the Mongol herdsmen in the Arhorchin National Nature Reserve and the Mongolians in the Ejina desert area shows that there are some similarities, as well as many differences whether in language or in the structure.
Conclusion
In the corresponding rate between plant folk names and scientific names yielded a computational correspondence of 82.19%, which can be considered as a high level of consistency between scientific knowledge and traditional knowledge in botanical nomenclature. Primary names have most cultural significance in the plant folk names. Special characteristic of plant folk names were focused on the physical characteristics of animals which were closely related to their traditional animal husbandry and environment. Plant folk names are not only a code to distinguish between different plant species, but also a kind of culture rich in a deep knowledge concerning nature. The results of comparative analysis shows that Mongolian culture in terms of plant nomenclature have characteristics of diversity between the different regions and different tribes.
doi:10.1186/1746-4269-9-30
PMCID: PMC3649933  PMID: 23628479
Wild plants; The Mongol herdsmen; Folk nomenclature; Arhorchin National Nature Reserve; Inner Mongolia
5.  Timing and Completeness of Trial Results Posted at ClinicalTrials.gov and Published in Journals 
PLoS Medicine  2013;10(12):e1001566.
Agnes Dechartres and colleagues searched ClinicalTrials.gov for completed drug RCTs with results reported and then searched for corresponding studies in PubMed to evaluate timeliness and completeness of reporting.
Please see later in the article for the Editors' Summary
Background
The US Food and Drug Administration Amendments Act requires results from clinical trials of Food and Drug Administration–approved drugs to be posted at ClinicalTrials.gov within 1 y after trial completion. We compared the timing and completeness of results of drug trials posted at ClinicalTrials.gov and published in journals.
Methods and Findings
We searched ClinicalTrials.gov on March 27, 2012, for randomized controlled trials of drugs with posted results. For a random sample of these trials, we searched PubMed for corresponding publications. Data were extracted independently from ClinicalTrials.gov and from the published articles for trials with results both posted and published. We assessed the time to first public posting or publishing of results and compared the completeness of results posted at ClinicalTrials.gov versus published in journal articles. Completeness was defined as the reporting of all key elements, according to three experts, for the flow of participants, efficacy results, adverse events, and serious adverse events (e.g., for adverse events, reporting of the number of adverse events per arm, without restriction to statistically significant differences between arms for all randomized patients or for those who received at least one treatment dose).
From the 600 trials with results posted at ClinicalTrials.gov, we randomly sampled 50% (n = 297) had no corresponding published article. For trials with both posted and published results (n = 202), the median time between primary completion date and first results publicly posted was 19 mo (first quartile = 14, third quartile = 30 mo), and the median time between primary completion date and journal publication was 21 mo (first quartile = 14, third quartile = 28 mo). Reporting was significantly more complete at ClinicalTrials.gov than in the published article for the flow of participants (64% versus 48% of trials, p<0.001), efficacy results (79% versus 69%, p = 0.02), adverse events (73% versus 45%, p<0.001), and serious adverse events (99% versus 63%, p<0.001).
The main study limitation was that we considered only the publication describing the results for the primary outcomes.
Conclusions
Our results highlight the need to search ClinicalTrials.gov for both unpublished and published trials. Trial results, especially serious adverse events, are more completely reported at ClinicalTrials.gov than in the published article.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
When patients consult a doctor, they expect to be recommended what their doctor believes is the most effective treatment with the fewest adverse effects. To determine which treatment to recommend, clinicians rely on sources that include research studies. Among studies, the best evidence is generally agreed to come from systematic reviews and randomized controlled clinical trials (RCTs), studies that test the efficacy and safety of medical interventions by comparing clinical outcomes in groups of patients randomly chosen to receive different interventions. Decision-making based on the best available evidence is called evidence-based medicine. However, evidence-based medicine can only guide clinicians if trial results are published in a timely and complete manner. Unfortunately, underreporting of trials is common. For example, an RCT in which a new drug performs better than existing drugs is more likely to be published than one in which the new drug performs badly or has unwanted adverse effects (publication bias). There can also be a delay in publishing the results of negative trials (time-lag bias) or a failure to publish complete results for all the prespecified outcomes of a trial (reporting bias). All three types of bias threaten informed medical decision-making and the health of patients.
Why Was This Study Done?
One initiative that aims to prevent these biases was included in the 2007 US Food and Drug Administration Amendments Act (FDAAA). The Food and Drug Administration (FDA) is responsible for approving drugs and devices that are marketed in the US. The FDAAA requires that results from clinical trials of FDA-approved drugs and devices conducted in the United States be made publicly available at ClinicalTrials.gov within one year of trial completion. ClinicalTrials.gov—a web-based registry that includes US and international clinical trials—was established in 2000 in response to the 1997 FDA Modernization Act, which required mandatory registration of trial titles and designs and of the conditions and interventions under study. The FDAAA expanded these mandatory requirements by requiring researchers studying FDA-approved drugs and devices to report additional information such as the baseline characteristics of the participants in each arm of the trial and the results of primary and secondary outcome measures (the effects of the intervention on predefined clinical measurements) and their statistical significance (an indication of whether differences in outcomes might have happened by chance). Researchers of other trials registered in ClinicalTrials.gov are welcome to post trial results as well. Here, the researchers compare the timing and completeness (i.e., whether all relevant information was fully reported) of results of drug trials posted at ClinicalTrials.gov with those published in medical journals.
What Did the Researchers Do and Find?
The researchers searched ClinicalTrials.gov for reports of completed phase III and IV (late-stage) RCTs of drugs with posted results. For a random sample of 600 eligible trials, they searched PubMed (a database of biomedical publications) for corresponding publications. Only 50% of trials with results posted at ClinicalTrials.gov had a matching published article. For 202 trials with both posted and published results, the researchers compared the timing and completeness of the results posted at ClinicalTrials.gov and of results reported in the corresponding journal publication. The median time between the study completion date and the first results being publicly posted at ClinicalTrials.gov was 19 months, whereas the time between completion and publication in a journal was 21 months. The flow of participants through trials was completely reported in 64% of the ClinicalTrials.gov postings but in only 48% of the corresponding publications. Results for the primary outcome measure were completely reported in 79% and 69% of the ClinicalTrials.gov postings and corresponding publications, respectively. Finally, adverse events were completely reported in 73% of the ClinicalTrials.gov postings but in only 45% of the corresponding publications, and serious adverse events were reported in 99% and 63% of the ClinicalTrials.gov postings and corresponding publications, respectively.
What Do These Findings Mean?
These findings suggest that the reporting of trial results is significantly more complete at ClinicalTrials.gov than in published journal articles reporting the main trial results. Certain aspects of this study may affect the accuracy of this conclusion. For example, the researchers compared the results posted at ClinicalTrials.gov only with the results in the publication that described the primary outcome of each trial, even though some trials had multiple publications. Importantly, these findings suggest that, to enable patients and physicians to make informed treatment decisions, experts undertaking assessments of drugs should consider seeking efficacy and safety data posted at ClinicalTrials.gov, both for trials whose results are not published yet and for trials whose results are published. Moreover, they suggest that the use of templates to guide standardized reporting of trial results in journals and broader mandatory posting of results may help to improve the reporting and transparency of clinical trials and, consequently, the evidence available to inform treatment of patients.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001566.
Wikipedia has pages on evidence-based medicine and on publication bias (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
The US Food and Drug Administration provides information about drug approval in the US for consumers and health-care professionals, plus detailed information on the 2007 Food and Drug Administration Amendments Act
ClinicalTrials.gov provides information about the US National Institutes of Health clinical trial registry, including background information about clinical trials, and a fact sheet detailing the requirements of the 2007 Food and Drug Administration Amendments Act
PLOS Medicine recently launched a Reporting Guidelines Collection, an open access collection of reporting guidelines, commentary, and related research on guidelines from across PLOS journals that aims to help advance the efficiency, effectiveness, and equitability of the dissemination of biomedical information; a 2008 PLOS Medicine editorial discusses the 2007 Food and Drug Administration Amendments Act
doi:10.1371/journal.pmed.1001566
PMCID: PMC3849189  PMID: 24311990
6.  X-RAY DIFFRACTION STUDIES ON FROG MUSCLES 
The Journal of General Physiology  1944;28(2):151-178.
1. X-ray diffraction studies of sartorius muscles of Rana pipiens were made in a new x-ray diffraction camera which permits exposures of 3 to 6 minutes. The object-film distance can be varied from 20 to 80 mm; the muscle inside the camera can be electrically stimulated while contracting isotonically or isometrically, and can be observed by a special device. After exposures up to 30 minutes (approximately 40,830 r) muscles are still alive and responsive. 2. Contrary to the x-ray diffraction pattern of powdered dry muscle, which pattern consists of two rings corresponding to spacings of 4.46 Å.u. and 9.66 Å.u., both moist and dried whole sartorius muscle show signs of orientation in both rings, consisting of two equatorial streaks (wet) or points (dry) and meridional sickles. The moist muscle shows in addition a diffuse water ring. The spacings corresponding to the orientation points and elliptical structure show only slight differences in moist and dried samples. Through statistical computations based on two different series consisting of thirteen moist and twenty-eight dried samples, and nine muscles before and after drying, it was shown that only the divergence in the smaller spacing has some real significance, which indicates that most water of the moist muscle is bound intermolecularly. Upon resoaking of dried muscle the x-ray diffraction pattern of the moist muscle is restored. 3. Stretching of muscle by weights below the breaking point produces an additional well defined diffraction line, corresponding to a spacing of 4.32 Å.u. A similar diffraction line can be produced in frog tendon upon stretching. 4. The influence of heat on the x-ray diffraction pattern of muscle depends upon the maximum temperature and the length of action; 5 minutes at 50° C. markedly reduces the orientation of the sample; 5 minutes' immersion in boiling Ringer's solution destroys the orientation and produces a ring corresponding to a spacing of 5.3 to 5.5 Å.u. in the moist and sharpening of the backbone reflection in the dried specimen. 5. Ultraviolet light brings forth changes in the x-ray diffraction pattern varying with the intensity of the irradiation. Ultimately a disappearance of the equatorial points and of the outside sickles is achieved while the elliptical shape of the outside ring and its diffuseness persist. In addition two salt rings characteristic of NaCl indicate that the irradiated muscles have become permeable to the surrounding medium (Ringer's solution). 6. Both faradic and single shock electrical stimulation were tried on muscles. If shortening of the muscle is prevented either by sufficient weight or by tying the muscle in a frame, no changes in the x-ray diffraction pattern occur; if the muscle is allowed to shorten without weights or by using insufficient weights, then the orientation either disappears completely or partially. When the muscle is stretched while contracted by electrical stimulation the orientation of the x-ray diffraction pattern reappears. 7. A number of salts with uni- and bivalent ions in concentrations corresponding osmotically to 0.73 per cent NaCl and 10 per cent NH4Cl were studied in their effects upon the x-ray diffraction of muscles. Of the salts with univalent ions in the lower concentration only KCl causes a marked decrease of orientation and an increase in the permeability of the fiber membranes. Similar effects on the orientation seem to be produced by CaCl2 while MgCl2 causes rather a more pronounced orientation. At hypertonic salt concentrations the orientation disappears completely and the corresponding salt rings become visible. Besides, NaCNS seems to have a specific effect on the outside ring and LiCl produces a ring at 21.3 Å.u. and a splitting of the outside ring. 8. Strong mineral and lactic acids in concentrations up to 0.005 N have little if any influence upon the x-ray diffraction of muscles. A further increase in acidity to 0.01 N and above destroys the orientation completely, causes sharpening of the backbone reflection, and increased membrane permeability. These changes are irreversible upon neutralization. Also the effects of swelling upon the water ring of fresh muscle become manifest. Weak acids at higher concentrations show an effect similar to that of strong acids. 9. Rigor mortis produces a more or less complete loss of orientation. The muscles show signs of increased permeability. 10. Alkalies destroy the orientation of the x-ray diffraction pattern. The effective concentration is higher than the corresponding amount of acid. 11. Formaldehyde produces only minor changes in the x-ray diffraction patterns of muscles. 12. The effects of alcohol depend primarily upon the concentration applied. Low concentrations (5 per cent) seem to have a passing stimulating effect, at concentrations of 15 per cent, the anesthetizing effect becomes manifest in well defined orientation. The diameter of the water ring is reduced. If 95 per cent alcohol is allowed to act upon muscle for more than 12 minutes, then the orientation disappears completely and the backbone spacing becomes as sharp as in boiled muscle. 13. The effects of chloroform depend upon whether the muscle is allowed to contract or not. Only if the muscle is allowed to contract in chloroform-saturated Ringer's solution is the orientation lost and salt rings appear as well as a ring corresponding to a spacing of 22 Å.u,, which has been observed in other changes in muscles. 14. In muscles allowed to shorten in a caffeine-Ringer's solution the orientation disappears, salt rings become visible as well as a decrease in size of the water ring; a new arc corresponding to a spacing of 4.18 Å.u. was observed in one case.
PMCID: PMC2142657  PMID: 19873411
7.  SCFIA: a statistical corresponding feature identification algorithm for LC/MS 
BMC Bioinformatics  2011;12:439.
Background
Identifying corresponding features (LC peaks registered by identical peptides) in multiple Liquid Chromatography/Mass Spectrometry (LC-MS) datasets plays a crucial role in the analysis of complex peptide or protein mixtures. Warping functions are commonly used to correct the mean of elution time shifts among LC-MS datasets, which cannot resolve the ambiguity of corresponding feature identification since elution time shifts are random. We propose a Statistical Corresponding Feature Identification Algorithm(SCFIA) based on both elution time shifts and peak shape correlations between corresponding features. SCFIA first trains a set of statistical models, and then, all candidate corresponding features are scored by the statistical models to find the maximum likelihood solution.
Results
We test SCFIA on publicly available datasets. We first compare its performance with that of warping function based methods, and the results show significant improvements. The performance of SCFIA on replicates datasets and fractionated datasets is also evaluated. In both cases, the accuracy is above 90%, which is near optimal. Finally the coverage of SCFIA is evaluated, and it is shown that SCFIA can find corresponding features in multiple datasets for over 90% peptides identified by Tandem MS.
Conclusions
SCFIA can be used for accurate corresponding feature identification in LC-MS. We have shown that peak shape correlation can be used effectively for improving the accuracy. SCFIA provides high coverage in corresponding feature identification in multiple datasets, which serves the basis for integrating multiple LC-MS measurements for accurate peptide quantification.
doi:10.1186/1471-2105-12-439
PMCID: PMC3233610  PMID: 22078262
8.  Combined SPHARM-PDM and entropy-based particle systems shape analysis framework 
Proceedings of SPIE  2012;8317:83170L-.
Description of purpose
The NA-MIC SPHARM-PDM Toolbox represents an automated set of tools for the computation of 3D structural statistical shape analysis. SPHARM-PDM solves the correspondence problem by defining a first order ellipsoid aligned, uniform spherical parameterization for each object with correspondence established at equivalently parameterized points. However, SPHARM correspondence has shown to be inadequate for some biological shapes that are not well described by a uniform spherical parameterization. Entropy-based particle systems compute correspondence by representing surfaces as discrete point sets that does not rely on any inherent parameterization. However, they are sensitive to initialization and have little ability to recover from initial errors. By combining both methodologies we compute reliable correspondences in topologically challenging biological shapes.
Data
Diverse subcortical structures cohorts were used, obtained from MR brain images.
Method(s)
The SPHARM-PDM shape analysis toolbox was used to compute point based correspondent models that were then used as initializing particles for the entropy-based particle systems. The combined framework was implemented as a stand-alone Slicer3 module, which works as an end-to-end shape analysis module.
Results
The combined SPHARM-PDM-Particle framework has demonstrated to improve correspondence in the example dataset over the conventional SPHARM-PDM toolbox.
Conclusions
The work presented in this paper demonstrates a two-sided improvement for the scientific community, being able to 1) find good correspondences among spherically topological shapes, that can be used in many morphometry studies 2) offer an end-to-end solution that will facilitate the access to shape analysis framework to users without computer expertise.
doi:10.1117/12.911228
PMCID: PMC3766973  PMID: 24027625
Spherical harmonic representation; entropy-based particle systems; statistical shape analysis; shape analysis framework; 3DSlicer
9.  A Mixture Model for Robust Point Matching under Multi-Layer Motion 
PLoS ONE  2014;9(3):e92282.
This paper proposes an efficient mixture model for establishing robust point correspondences between two sets of points under multi-layer motion. Our algorithm starts by creating a set of putative correspondences which can contain a number of false correspondences, or outliers, in addition to the true correspondences (inliers). Next we solve for correspondence by interpolating a set of spatial transformations on the putative correspondence set based on a mixture model, which involves estimating a consensus of inlier points whose matching follows a non-parametric geometrical constraint. We formulate this as a maximum a posteriori (MAP) estimation of a Bayesian model with hidden/latent variables indicating whether matches in the putative set are outliers or inliers. We impose non-parametric geometrical constraints on the correspondence, as a prior distribution, in a reproducing kernel Hilbert space (RKHS). MAP estimation is performed by the EM algorithm which by also estimating the variance of the prior model (initialized to a large value) is able to obtain good estimates very quickly (e.g., avoiding many of the local minima inherent in this formulation). We further provide a fast implementation based on sparse approximation which can achieve a significant speed-up without much performance degradation. We illustrate the proposed method on 2D and 3D real images for sparse feature correspondence, as well as a public available dataset for shape matching. The quantitative results demonstrate that our method is robust to non-rigid deformation and multi-layer/large discontinuous motion.
doi:10.1371/journal.pone.0092282
PMCID: PMC3962380  PMID: 24658087
10.  Antibiotics Modulate Vaccine-Induced Humoral Immune Response 
The effects of antibiotics on the antigen-specific humoral immune response are not known. Macrolides, tetracyclines, and beta-lactams are commonly prescribed antibiotics. The first two are known to have immunomodulatory activities. The effects of clarithromycin, doxycycline, and ampicillin on the primary and secondary antibody responses to tetanus toxoid, a pneumococcal polysaccharide vaccine, a hepatitis B virus surface antigen (HBsAg) vaccine, and live attenuated Salmonella typhi (Ty21a) were investigated using a mouse model. For the mice receiving the tetanus toxoid, the immunoglobulin M (IgM) level of the clarithromycin group at day 7 was significantly lower than the corresponding antibody level of the normal saline (NS) group. For the mice receiving the pneumococcal polysaccharide vaccine, the total antibody and IgM levels of the clarithromycin group and the IgM level of the doxycycline group at day 7 were significantly lower than the corresponding antibody levels of the ampicillin and NS groups. For the mice receiving the HBsAg vaccine, the IgM level of the doxycycline group at day 7 was significantly lower than the corresponding antibody levels of the clarithromycin and NS groups, while the IgM level of the clarithromycin group at day 28 was significantly lower than the corresponding antibody levels of the doxycycline, ampicillin, and NS groups. For the mice receiving all three vaccines, there were no statistically significant differences between any of the antibody levels of the ampicillin group and the corresponding antibody levels of the NS group. For the mice receiving Ty21a, the total antibody levels of the ampicillin group at days 7 and 21 were significantly higher than the corresponding antibody levels of the NS group. Moreover, the IgM levels of the clarithromycin, doxycycline, and ampicillin groups at days 7 and 21 were significantly higher than the corresponding antibody levels of the NS group. Furthermore, the total antibody level of the ampicillin group at day 21 was significantly higher than the corresponding antibody level of the doxycycline group. For all four vaccines, there were no statistically significant differences among the serum levels of interleukin-10 and gamma interferon for the mice treated with the various antibiotics. We conclude that clarithromycin and doxycycline, but not ampicillin, suppress the antibody responses of mice to T-cell-dependent and T-cell-independent antigens, whereas all three antibiotics enhance the antibody response to live attenuated mucosal bacterial vaccines.
PMCID: PMC95784  PMID: 10548572
11.  Cortical Correspondence with Probabilistic Fiber Connectivity 
This paper presents a novel method of optimizing point-based correspondence among populations of human cortical surfaces by combining structural cues with probabilistic connectivity maps. The proposed method establishes a tradeoff between an even sampling of the cortical surfaces (a low surface entropy) and the similarity of corresponding points across the population (a low ensemble entropy). The similarity metric, however, isn’t constrained to be just spatial proximity, but uses local sulcal depth measurements as well as probabilistic connectivity maps, computed from DWI scans via a stochastic tractography algorithm, to enhance the correspondence definition. We propose a novel method for projecting this fiber connectivity information on the cortical surface, using a surface evolution technique. Our cortical correspondence method does not require a spherical parameterization. Experimental results are presented, showing improved correspondence quality demonstrated by a cortical thickness analysis, as compared to correspondence methods using spatial metrics as the sole correspondence criterion.
PMCID: PMC2751643  PMID: 19694301
12.  Object Correspondence across Brief Occlusion Is Established on the Basis of both Spatiotemporal and Surface Feature Cues 
Cognition  2009;113(2):150-166.
The correspondence problem is a classic issue in vision and cognition. Frequent perceptual disruptions, such as saccades and brief occlusion, create gaps in perceptual input. How does the visual system establish correspondence between objects visible before and after the disruption? Current theories hold that object correspondence is established solely on the basis of an object's spatiotemporal properties and that an object's surface feature properties (such as color or shape) are not consulted in correspondence operations. In five experiments, we tested the relative contributions of spatiotemporal and surface feature properties to establishing object correspondence across brief occlusion. Correspondence operations were strongly influenced both by the consistency of an object's spatiotemporal properties across occlusion and by the consistency of an object's surface feature properties across occlusion. These data argue against the claim that spatiotemporal cues dominate the computation of object correspondence. Instead, the visual system consults multiple sources of relevant information to establish continuity across perceptual disruption.
doi:10.1016/j.cognition.2009.08.004
PMCID: PMC2764005  PMID: 19729155
13.  Species Richness and Range Size of the Terrestrial Mammals of the World: Biological Signal within Mathematical Constraints 
PLoS ONE  2011;6(5):e19359.
We explore global spatial diversity patterns for terrestrial mammals using as a tool range-diversity plots. These plots display simultaneously information about the number of species in localities and their spatial covariance in composition. These are highly informative, as we show by linking range-diversity plots with maps and by highlighting the correspondences between well defined regions of the plots with geographical regions or with taxonomic groups. Range-diversity plots are mathematically constrained by the lines of maximum and minimum mean covariance in species composition. We show how regions in the range-diversity plot corresponding to the line of maximum covariance correspond to large continental masses, and regions near the lower limit of the range-diversity plot correspond to archipelagos and mountain ranges. We show how curves of constant covariance correspond to nested faunas. Finally, we show that the observed distribution of the covariance range has significantly longer tails than random, with clear geographic correspondences. At the scale of our data we found that range-diversity plots reveal biodiversity patterns that cannot be replicated by null models, and correspond to conspicuous terrain features and taxonomic groupings.
doi:10.1371/journal.pone.0019359
PMCID: PMC3089617  PMID: 21573112
14.  Group-wise Cortical Correspondence via Sulcal Curve-Constrained Entropy Minimization 
We present a novel cortical correspondence method employing group-wise registration in a spherical parametrization space for the use in local cortical thickness analysis in human and non-human primate neuroimaging studies. The proposed method is unbiased registration that estimates a continuous smooth deformation field into an unbiased average space via sulcal curve-constrained entropy minimization using spherical harmonic decomposition of the spherical deformation field. We initialize a correspondence by our pair-wise method that establishes a surface correspondence with a prior template. Since this pair-wise correspondence is biased to the choice of a template, we further improve the correspondence by employing unbiased ensemble entropy minimization across all surfaces, which yields a deformation field onto the iteratively updated unbiased average. The specific entropy metric incorporates two terms: the first focused on optimizing the correspondence of automatically extracted sulcal landmarks and the second on that of sulcal depth maps. We also propose an encoding scheme for spherical deformation via spherical harmonics as well as a novel method to choose an optimal spherical polar coordinate system for the most efficient deformation field estimation. The experimental results show evidence that the proposed method improves the correspondence quality in non-human primate and human subjects as compared to the pair-wise method.
PMCID: PMC4003502  PMID: 24683983
Group-wise correspondence; Sulcal curves; Spherical harmonics; Entropy minimization; Cortical thickness
15.  Restriction Fragment Length Polymorphisms and Sequence Analysis: an Approach for Genotyping Infectious Pancreatic Necrosis Virus Reference Strains and Other Aquabirnaviruses Isolated from Northwestern Spain†  
Reference strains of infectious pancreatic necrosis virus resembling the 10 recognized serotypes and local isolates of aquabirnaviruses isolated in northwestern Spain from reservoirs (mollusks) and from asymptomatic and carrier cultured fish were genotyped by restriction fragment length polymorphism (RFLP) and nucleic acid sequence analyses. The RFLP analysis yielded seven genogroups, each of which was clearly correlated with a serotype. Sequence analysis of the three open reading frames provided quite similar results in terms of genogrouping. Based on the results of this study and in order to unify the two types of assays, we propose placing aquabirnaviruses into six genogroups, four of which can be subdivided into two genotypes based on a two-step restriction analysis. The genotyping corresponds with serotyping as follows: genogroup I includes two genotypes corresponding to serotypes A9 (genotype I.1) and A1 (genotype I.2); genogroup II corresponds to serotype A3; genogroup III includes genotypes III.1 (serotype A2) and III.2 (serotype B1); genogroups IV and V include two genotypes, each corresponding to serotypes A5, A6, A7, and A8 (genotypes IV.1, IV.2, V.1, and V.2, respectively);and genogroup VI corresponds to serotype A4. As expected, most local isolates belonged to genotype III.1 and genogroup II. However, a few local isolates corresponded to the American types of genogroup I. Finally, based on the results of this study and due to its simplicity, the two-step restriction analysis assay is proposed as a method for typing new isolates of aquabirnaviruses, and the results correspond to the results of conventional serotyping.
doi:10.1128/AEM.70.2.1059-1067.2004
PMCID: PMC348913  PMID: 14766589
16.  Geometric visual hallucinations, Euclidean symmetry and the functional architecture of striate cortex. 
This paper is concerned with a striking visual experience: that of seeing geometric visual hallucinations. Hallucinatory images were classified by Klüver into four groups called form constants comprising (i) gratings, lattices, fretworks, filigrees, honeycombs and chequer-boards, (ii) cobwebs, (iii) tunnels, funnels, alleys, cones and vessels, and (iv) spirals. This paper describes a mathematical investigation of their origin based on the assumption that the patterns of connection between retina and striate cortex (henceforth referred to as V1)-the retinocortical map-and of neuronal circuits in V1, both local and lateral, determine their geometry. In the first part of the paper we show that form constants, when viewed in V1 coordinates, essentially correspond to combinations of plane waves, the wavelengths of which are integral multiples of the width of a human Hubel-Wiesel hypercolumn, ca. 1.33-2 mm. We next introduce a mathematical description of the large-scale dynamics of V1 in terms of the continuum limit of a lattice of interconnected hypercolumns, each of which itself comprises a number of interconnected iso-orientation columns. We then show that the patterns of interconnection in V1 exhibit a very interesting symmetry, i.e. they are invariant under the action of the planar Euclidean group E(2)-the group of rigid motions in the plane-rotations, reflections and translations. What is novel is that the lateral connectivity of V1 is such that a new group action is needed to represent its properties: by virtue of its anisotropy it is invariant with respect to certain shifts and twists of the plane. It is this shift-twist invariance that generates new representations of E(2). Assuming that the strength of lateral connections is weak compared with that of local connections, we next calculate the eigenvalues and eigenfunctions of the cortical dynamics, using Rayleigh-Schrödinger perturbation theory. The result is that in the absence of lateral connections, the eigenfunctions are degenerate, comprising both even and odd combinations of sinusoids in straight phi, the cortical label for orientation preference, and plane waves in r, the cortical position coordinate. 'Switching-on' the lateral interactions breaks the degeneracy and either even or else odd eigenfunctions are selected. These results can be shown to follow directly from the Euclidean symmetry we have imposed. In the second part of the paper we study the nature of various even and odd combinations of eigenfunctions or planforms, the symmetries of which are such that they remain invariant under the particular action of E(2) we have imposed. These symmetries correspond to certain subgroups of E(2), the so-called axial subgroups. Axial subgroups are important in that the equivariant branching lemma indicates that when a symmetrical dynamical system becomes unstable, new solutions emerge which have symmetries corresponding to the axial subgroups of the underlying symmetry group. This is precisely the case studied in this paper. Thus we study the various planforms that emerge when our model V1 dynamics become unstable under the presumed action of hallucinogens or flickering lights. We show that the planforms correspond to the axial subgroups of E(2), under the shift-twist action. We then compute what such planforms would look like in the visual field, given an extension of the retinocortical map to include its action on local edges and contours. What is most interesting is that, given our interpretation of the correspondence between V1 planforms and perceived patterns, the set of planforms generates representatives of all the form constants. It is also noteworthy that the planforms derived from our continuum model naturally divide V1 into what are called linear regions, in which the pattern has a near constant orientation, reminiscent of the iso-orientation patches constructed via optical imaging. The boundaries of such regions form fractures whose points of intersection correspond to the well-known 'pinwheels'. To complete the study we then investigate the stability of the planforms, using methods of nonlinear stability analysis, including Liapunov-Schmidt reduction and Poincaré-Lindstedt perturbation theory. We find a close correspondence between stable planforms and form constants. The results are sensitive to the detailed specification of the lateral connectivity and suggest an interesting possibility, that the cortical mechanisms by which geometric visual hallucinations are generated, if sited mainly in V1, are closely related to those involved in the processing of edges and contours.
doi:10.1098/rstb.2000.0769
PMCID: PMC1088430  PMID: 11316482
17.  Establishing Object Correspondence across Eye Movements: Flexible Use of Spatiotemporal and Surface Feature Information 
Cognition  2008;109(1):66-88.
Visual input is frequently disrupted by eye movements, blinks, and occlusion. The visual system must be able to establish correspondence between objects visible before and after a disruption. Current theories hold that correspondence is established solely on the basis of spatiotemporal information, with no contribution from surface features. In five Experiments, we tested the relative contributions of spatiotemporal and surface feature information in establishing object correspondence across saccades. Participants generated a saccade to one of two objects, and the objects were shifted during the saccade so that the eyes landed between them, requiring a corrective saccade to fixate the target. To correct gaze to the appropriate object, correspondence must be established between the remembered saccade target and the target visible after the saccade. Target position and surface feature consistency were manipulated. Contrary to existing theories, surface features and spatiotemporal information both contributed to object correspondence, and the relative weighting of the two sources of information was governed by the demands of the task. These data argue against a special role for spatiotemporal information in object correspondence, indicating instead that the visual system can flexibly use multiple sources of relevant information.
doi:10.1016/j.cognition.2008.07.004
PMCID: PMC2650243  PMID: 18760406
18.  The Use of Electronic Mail in Biomedical Communication 
Objectives: To determine whether there are statistically significant differences in the content of electronic mail (e-mail) and conventional mail sent to authors of papers published in medical journals.
Design: Prospective study by postal questionnaire. Over two one-month periods, corresponding authors of papers published in medical journals were asked to record details of the correspondence prompted by their publications.
Measurements: Conventional and e-mail correspondence received. Reprint requests. Content of correspondence. Quality of correspondence.
Results: Eighty-two of 96 authors replied. Fifty received e-mail (mean, 5.7 ± 8.8 e-mails per author) and 72 received conventional mail (15.5 ± 32.8 letters per author) (p ≪ 0.05). Seventy percent of e-mails and only 53% of correspondence sent by conventional mail (p ≪ 0.05) referred to the content of the paper.
Conclusions: Publication in general medical journals stimulates more conventional than electronic mail. However, the content of e-mail may be of greater scientific relevance. Electronic mail can be encouraged without fear of diminishing the quality of the communications received.
PMCID: PMC61459  PMID: 10641967
19.  Comparison of the epidermal growth factor receptor protein expression between primary non-small cell lung cancer and paired lymph node metastases: implications for targeted nuclide radiotherapy 
Background
The knowledge of Epidermal growth factor receptor (EGFR) expression in metastases of NSCLC was limited. In receptor-mediated targeted nuclide radiotherapy, tumor cells are killed with delivered radiation and therapeutic efficiency is mainly dependent on the receptor expression. Thus, the level and stability of receptor expression in both primary tumors and corresponding metastases is crucial in the assessment of a receptor as target. The goal of this study was to evaluate whether EGFR is suitable as target for clinical therapy.
Methods
Expression of EGFR was investigated immunohistochemically in paired samples of lymph node metastases and corresponding NSCLC primary lesions (n = 51). EGFR expression was scored as 0, 1+, 2+ or 3+.
Results
Positive (1+, 2+ or 3+) EGFR immunostaining was evident in 36 of 47 (76.6%) analysed NSCLC primary tumors, and in 78.7% of the corresponding lymph node metastases. When EGFR expression is classified as positive or negative, discordance between the primary tumors and the corresponding metastases was observed in 5 cases (10.6%). EGFR overexpression (2+ or 3+) was found in 53.2% (25/47) of the NSCLC primary tumors and 59.6% of the corresponding metastases. Nine out of the 47 paired samples (19.2%) were discordant: Only three patients who had EGFR overexpression in the primary tumors showed EGFR downregulation (0 or 1+) in lymph node metastases, while six patients changed the other way around.
Conclusions
The EGFR expression in the primary tumor and the corresponding metastasis is discordant in about 10% of the patients. When overexpression is considered, the discordance is observed in about 20% of the cases. However, concerning EGFR overexpression in the primary tumors, similar expression in the metastases could be predicted with a reasonably high probability, which is encouraging for testing of EGFR targeted nuclide radiotherapy.
doi:10.1186/1756-9966-29-7
PMCID: PMC2830952  PMID: 20096104
20.  Determining spinal level using the inferior angle of the scapula as a reference landmark: a retrospective analysis of 50 radiographs 
Objective
The purpose of this study was to determine which spinal segment most closely corresponds to the level of the inferior angle of the scapula (IAS) using measurements taken on A-P full-spine radiographs.
Methods
Fifty sequentially selected radiographs were analyzed independently by two examiners. A straight edge was used to ascertain which spinal levels corresponded with the right and left IASs. For analysis, each spinal level was subdivided into three regions: upper vertebral body, lower vertebral body, and intervertebral space.
Results
he mean spinal level corresponding to the left IAS was midway between the T8–9 interspace and the upper T9 body (range, lower T7 to upper T10). The mean spinal level corresponding to the right IAS was slightly lower, but still within the upper T9 body (range, lower T7 to lower T10). These levels correspond to the T8 spinous process.
Conclusions
There is a considerable amount of variability in where the IASs are located, but most commonly, they correspond to the level of the upper body of T9.
PMCID: PMC2258239  PMID: 18327299
scapula; inferior angle; spinal segment; radiographs
21.  Fast Image Registration by Hierarchical Soft Correspondence Detection 
Pattern recognition  2009;42(5):954-961.
A new approach, based on the hierarchical soft correspondence detection, has been presented for significantly improving the speed of our previous HAMMER image registration algorithm. Currently, HAMMER takes a relative long time, e.g., up to 80 minutes, to register two regular sized images using Linux machine (with 2.40GHz CPU and 2-Gbyte memory). This is because the results of correspondence detection, used to guide the image warping, can be ambiguous in complex structures and thus the image warping has to be conservative and accordingly takes long time to complete. In this paper, a hierarchical soft correspondence detection technique has been employed to detect correspondences more robustly, thereby allowing the image warping to be completed straightforwardly and fast. By incorporating this hierarchical soft correspondence detection technique into the HAMMER registration framework, the robustness and the accuracy of registration (in terms of low average registration error) can be both achieved. Experimental results on real and simulated data show that the new registration algorithm, based the hierarchical soft correspondence detection, can run nine times faster than HAMMER while keeping the similar registration accuracy.
doi:10.1016/j.patcog.2008.08.032
PMCID: PMC2805159  PMID: 20161554
22.  Automatic Correspondence on Medical Images: A Comparative Study of Four Methods for Allocating Corresponding Points 
Journal of Digital Imaging  2009;23(4):399-421.
The accurate estimation of point correspondences is often required in a wide variety of medical image-processing applications. Numerous point correspondence methods have been proposed in this field, each exhibiting its own characteristics, strengths, and weaknesses. This paper presents a comprehensive comparison of four automatic methods for allocating corresponding points, namely the template-matching technique, the iterative closest points approach, the correspondence by sensitivity to movement scheme, and the self-organizing maps algorithm. Initially, the four correspondence methods are described focusing on their distinct characteristics and their parameter selection for common comparisons. The performance of the four methods is then qualitatively and quantitatively compared over a total of 132 two-dimensional image pairs divided into eight sets. The sets comprise of pairs of images obtained using controlled geometry protocols (affine and sinusoidal transforms) and pairs of images subject to unknown transformations. The four methods are statistically evaluated pairwise on all image pairs and individually in terms of specific features of merit based on the correspondence accuracy as well as the registration accuracy. After assessing these evaluation criteria for each method, it was deduced that the self-organizing maps approach outperformed in most cases the other three methods in comparison.
doi:10.1007/s10278-009-9190-z
PMCID: PMC3046664  PMID: 19255808
Point extraction; automatic point correspondence; iterative closest points; template matching; correspondence by sensitivity to movement; self-organizing maps; features of merit; registration accuracy
23.  Interocular Symmetry of Abnormal Multifocal Electroretinograms in Adolescents with Diabetes and No Retinopathy 
In a group of adolescents with type 1 diabetes and no retinopathy, symmetry was found between eyes for the locations of abnormal multifocal electroretinogram delays. This symmetry could be utilized in the design of clinical trials to test the efficacy of newly developed topical drugs.
Purpose.
To investigate, in adolescents with type 1 diabetes and no retinopathy, the spatial correspondence between abnormal multifocal electroretinogram (mfERG) responses in the two eyes.
Methods.
mfERG and fundus photographs were measured in both eyes of 68 adolescents with type 1 diabetes and no retinopathy (13 to 19 years old; best corrected visual acuity ≥ 20/20), and 30 age-matched controls. The mfERG stimulus was comprised of 103 hexagons, and subtended 45°. mfERG implicit times (IT) and amplitudes (AMP) were derived. Fifteen patients for IT, and five for AMP with at least one eye defined as abnormal (six or more locations with abnormal Z-scores; P < 0.03) were analyzed.
Results.
Nasal retina had significantly more abnormal IT locations compared with temporal retina (P = 0.015), and the opposite was true with regard to abnormal AMP (P < 0.001). The proportion of abnormal responses in the superior retina was not significantly different from that in the inferior retina (P > 0.1 for IT and AMP). Interocular correspondence of locations with abnormal mfERG IT was significant for all 15 patients (P values <0.0001–0.012), and agreement between eyes was 68% to 94% (AC1 agreement coefficient: 0.48–0.94). Overall interocular correspondence was also significant (P < 0.0002), with 86% agreement (AC1 = 0.76). Overall interocular correspondence of locations with abnormal mfERG AMP was also significant (P < 0.0002).
Conclusions.
Interocular spatial correspondence of abnormal mfERG responses exists in adolescents with type 1 diabetes and no retinopathy. This is most apparent for IT abnormalities. This correspondence could be used in clinical trials, and raises the possibility of initiating treatment in both eyes at early disease stages as new topical treatments emerge.
doi:10.1167/iovs.11-8825
PMCID: PMC3292367  PMID: 22159016
24.  The vertical horopter is not adaptable, but it may be adaptive 
Journal of vision  2011;11(3):10.1167/11.3.20 20.
Depth estimates from disparity are most precise when the visual input stimulates corresponding retinal points or points close to them. Corresponding points have uncrossed disparities in the upper visual field and crossed disparities in the lower visual field. Due to these disparities, the vertical part of the horopter—the positions in space that stimulate corresponding points—is pitched top-back. Many have suggested that this pitch is advantageous for discriminating depth in the natural environment, particularly relative to the ground. We asked whether the vertical horopter is adaptive (suited for perception of the ground) and adaptable (changeable by experience). Experiment 1 measured the disparities between corresponding points in 28 observers. We confirmed that the horopter is pitched. However, it is also typically convex making it ill-suited for depth perception relative to the ground. Experiment 2 tracked locations of corresponding points while observers wore lenses for 7 days that distorted binocular disparities. We observed no change in the horopter, suggesting that it is not adaptable. We also showed that the horopter is not adaptive for long viewing distances because at such distances uncrossed disparities between corresponding points cannot be stimulated. The vertical horopter seems to be adaptive for perceiving convex, slanted surfaces at short distances.
doi:10.1167/11.3.20
PMCID: PMC3804431  PMID: 21447644
stereopsis; binocular vision; horopter; corresponding points; natural environment; depth perception; cyclovergence
25.  Data-driven analysis of analogous brain networks in monkeys and humans during natural vision 
NeuroImage  2012;63(3):1107-1118.
Inferences about functional correspondences between functional networks of human and non-human primates largely rely on proximity and anatomical expansion models. However, it has been demonstrated that topologically correspondent areas in two species can have different functional properties, suggesting that anatomy-based approaches should be complemented with alternative methods to perform functional comparisons. We have recently shown that comparative analyses based on temporal correlations of sensory-driven fMRI responses can reveal functional correspondent areas in monkeys and humans without relying on spatial assumptions. Inter-species activity correlation (ISAC) analyses require the definition of seed areas in one species to reveal functional correspondences across the cortex of the same and other species. Here we propose an extension of the ISAC method that does not rely on any seed definition, hence a method void of any spatial assumption. Specifically, we apply independent component analysis (ICA) separately to monkey and human data to define species-specific networks of areas with coherent stimulus-related activity. Then, we use a hierarchical cluster analysis to identify ICA-based ISAC clusters of monkey and human networks with similar timecourses. We implemented this approach on fMRI data collected in monkeys and humans during movie watching, a condition that evokes widespread sensory-driven activity throughout large portions of the cortex. Using ICA-based ISAC, we detected seven monkey-human clusters. The timecourses of several clusters showed significant correspondences with either the motion energy in the movie or with eye-movement parameters. Five of the clusters spanned putative homologous functional networks in either primary or extrastriate visual regions, whereas two clusters included higher-level visual areas at topological locations that are not predicted by cortical surface expansion models. Overall, our ICA-based ISAC analysis complemented the findings of our previous seed-based investigations, and suggested that functional processes can be executed by brain networks in different species that are functionally but not necessarily anatomically correspondent. Overall, our method provides a novel approach to reveal evolution-driven functional changes in the primate brain with no spatial assumptions.
doi:10.1016/j.neuroimage.2012.08.042
PMCID: PMC3472137  PMID: 22992489
cluster analysis; independent component analysis; functional magnetic resonance imaging; primate brain; evolution; functional correspondence

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