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PubMed1995

Multiwindow scatter correction techniques in single-photon imaging.

We studied the performance of linear scatter correction methods for single-photon imaging with Tc-99m and Tl-201, using a numerical model of the Rollo phantom and measurements with a gamma camera modified to record position and energy information in list mode form. We compared the performance of these methods to per-image optimized linear methods and to locally adaptive linear methods, and developed estimates of the limits on accuracy of scatter correction imposed by the presence of Poisson noise. For both Tc-99m and Tl-201 imaging at a fixed depth, particularly at low count rates, the performance of dual-window methods, or of adaptive methods, is near the best possible for linear methods. Smoothing of the scatter estimate results in minor improvement for Tl-201. Substantial gaps between the performance of any of these linear methods and the limits imposed by Poisson noise remain and are due primarily to bias, with the gap for Tl-201 being larger than that for Tc-99m.

Algorithms↗
PubMed1998

Automated lung segmentation in digital lateral chest radiographs.

We are developing a fully automated computerized scheme for segmenting the lung fields in digital lateral chest radiographs. Existing computer-aided diagnostic (CAD) schemes and automated lung segmentation methods have focused exclusively on the posteroanterior view, despite the diagnostic importance of the lateral view. Information from the lateral radiograph is routinely incorporated by radiologists in their decision-making process, and thus computer analysis of lateral images may potentially add another dimension to current CAD schemes. Automated analysis of the lung fields in lateral images will necessarily require accurate segmentation. Our scheme employs an initial procedure to eliminate external and subcutaneous pixels. Global gray-level histogram analysis then allows for the identification of a range of gray-level thresholds. An iterative gray-level thresholding scheme is implemented using this range of thresholds to construct a series of binary images in which contiguous regions are identified and geometrically analyzed. Regions determined to be outside the lungs are prevented from contributing to binary images at later iterations. Adaptive local gray-level thresholding is applied along the initial contour that results from the global thresholding procedure to extend the contour closer to the true lung borders. This local thresholding method uses regions of interest of various dimensions, depending on the enclosed anatomy. Smoothing and polynomial curve fitting complete the segmentation. A database of 100 normal and 100 abnormal lateral images was analyzed. Quantitative comparison of computer-segmented lung regions with lung regions manually delineated by two radiologists indicated that 83% and 84% of normal and abnormal images, respectively, displayed segmentation contours within three standard deviations of the mean inter-radiologist contour degree-of-overlap value.

Automation↗
PubMed2003

Geographic barriers isolate endemic populations of hyperthermophilic archaea.

Barriers to dispersal between populations allow them to diverge through local adaptation or random genetic drift. High-resolution multilocus sequence analysis revealed that, on a global scale, populations of hyperthermophilic microorganisms are isolated from one another by geographic barriers and have diverged over the course of their recent evolutionary history. The identification of a biogeographic pattern in the archaeon Sulfolobus challenges the current model of microbial biodiversity in which unrestricted dispersal constrains the development of global species richness.

Analysis of Variance↗
PubMed1985

Morphological novelty in the limb skeleton accompanies miniaturization in salamanders.

Salamanders of the genus Thorius (Plethodontidae) are among the smallest tetrapods. Hypotheses of limb skeletal evolution in these vertebrates were evaluated on the basis of estimates of natural variation, comparisons of skeletal homology, and analysis of molecular phylogeny. Nine carpal arrangements occur in Thorius, more than in all twelve related genera of typically larger salamanders; six of these arrangements are unique. They represent a trend toward a decrease in the number of separate cartilages that is independent of locomotor and ecological specialization. Miniaturization may be an important source of morphological novelty, distinct from local adaptation, in vertebrates.

Animals↗
PubMed2026

Multidrug resistance and genomic characteristics of nontypeable Haemophilus influenzae isolates from the respiratory tract of pediatric patients.

UNLABELLED: Nontypeable Haemophilus influenzae (NTHi) is a common colonizer of the human upper respiratory tract and one of the major pathogens responsible for pediatric respiratory tract infections. Given the increasing severity of its multidrug resistance (MDR), this study comprehensively investigated the genomic characteristics of circulating NTHi isolated from sputum and bronchoalveolar lavage fluid (BALF). A total of 104 H. influenzae isolates (69 from sputum; 35 from BALF) were collected from pediatric patients between January 2024 and January 2025. All isolates underwent whole-genome sequencing and antimicrobial susceptibility testing, followed by core/pan-genome phylogenetic analysis, multilocus sequence typing (MLST), and resistome profiling. Among them, 103 were identified as NTHi. We identified 29 known sequence types (STs) and 10 novel STs, with ST-107 (14.4%), ST-57 (10.6%), and ST-11 (8.7%) being the major circulating lineages. However, core-genome phylogenetic analysis provided a more granular view of the genetic variation within these identical STs. All the isolates showed high resistance to ampicillin (98.1%) and cefuroxime (84.6%). Genomically, the multidrug efflux pump gene hmrM was ubiquitous (100%). Ampicillin resistance was predominantly driven by blaTEM-1 carriage (77.9%), with minor contributions from chromosomal ftsI mutations. Fifteen plasmid replicons were predicted from 25 isolates, which highly coincided with the carriage of blaTEM-1 and other acquired resistance genes. This study demonstrates that MDR in pediatric NTHi is primarily driven by acquired resistance genes and chromosomal mutations, with specific resistant clones persisting and enriching under clinical antibiotic pressures. These findings underscore the importance of continuous high-resolution genomic surveillance in guiding rational antibiotic stewardship. IMPORTANCE: This study highlights the critical importance of high-resolution genomic surveillance in managing pediatric nontypeable Haemophilus influenzae (NTHi) infections. By utilizing whole-genome sequencing, we uncovered the pathogen's highly dynamic population structure and complex multidrug resistance (MDR) mechanisms. Crucially, our findings reveal a strong, non-random coupling between core genomic architectures, virulence factors, and MDR elements, driven by dual environmental and pharmacological pressures. This "virulence-MDR" co-evolutionary trend underscores the persistent clinical threat of locally adapted high-risk clones. These findings provide important insights for guiding rational clinical antibiotic stewardship, optimizing treatment strategies, and improving regional infection control.

Humans↗
PubMed1999

Automated localisation of the optic disc, fovea, and retinal blood vessels from digital colour fundus images.

AIM: To recognise automatically the main components of the fundus on digital colour images. METHODS: The main features of a fundus retinal image were defined as the optic disc, fovea, and blood vessels. Methods are described for their automatic recognition and location. 112 retinal images were preprocessed via adaptive, local, contrast enhancement. The optic discs were located by identifying the area with the highest variation in intensity of adjacent pixels. Blood vessels were identified by means of a multilayer perceptron neural net, for which the inputs were derived from a principal component analysis (PCA) of the image and edge detection of the first component of PCA. The foveas were identified using matching correlation together with characteristics typical of a fovea-for example, darkest area in the neighbourhood of the optic disc. The main components of the image were identified by an experienced ophthalmologist for comparison with computerised methods. RESULTS: The sensitivity and specificity of the recognition of each retinal main component was as follows: 99.1% and 99.1% for the optic disc; 83.3% and 91.0% for blood vessels; 80.4% and 99.1% for the fovea. CONCLUSIONS: In this study the optic disc, blood vessels, and fovea were accurately detected. The identification of the normal components of the retinal image will aid the future detection of diseases in these regions. In diabetic retinopathy, for example, an image could be analysed for retinopathy with reference to sight threatening complications such as disc neovascularisation, vascular changes, or foveal exudation.

Algorithms↗
PubMed1996

Short term effects of air pollution on health: a European approach using epidemiologic time series data: the APHEA protocol.

BACKGROUND AND OBJECTIVES: Results from several studies over the past five years have shown that the current levels of pollutants in Europe and North America have adverse short term effects on health. The APHEA project aims to quantifying these in Europe, using standardised methodology. The project protocol and analytical methodology are presented here. DESIGN: Daily time series data were gathered for several air pollutants (sulphur dioxide; particulate matter, measured as total particles or as the particle fraction with an aerodynamic diameter smaller than a certain cut off, or as black smoke; nitrogen dioxide; and ozone) and health outcomes (the total and cause specific number of deaths and emergency hospital admissions). The data included fulfilled the quality criteria set by the APHEA protocol. SETTING: Fifteen European cities from 10 different countries with a total population over 25 million. METHODOLOGY: The APHEA collaborative group decided on a specific methodological procedure to control for confounding effects and evaluate the hypothesis. At the same time there was sufficient flexibility to allow local characteristics to be taken into account. The procedure included modelling of all potential confounding factors (that is, seasonal and long term patterns, meteorological factors, day of the week, holidays, and other unusual events), choosing the "best" air pollution models, and applying diagnostic tools to check the adequacy of the models. The final analysis used autoregressive Poisson models allowing for overdispersion. Effects were reported as relative risks contrasting defined increases in the corresponding pollutant levels. Each participating group applied the analyses to their own data. CONCLUSIONS: This methodology enabled results from many different European settings to be considered collectively. It represented the best available compromise between feasibility, comparability, and local adaptibility when using aggregated time series data not originally collected for the purpose of epidemiological studies.

Air Pollutants↗
PubMed1999

Increasing prevalence of genital herpes in developing countries: implications for heterosexual HIV transmission and STI control programmes.

BACKGROUND: The recognition that sexually transmitted infections (STI) facilitate HIV transmission among heterosexuals has led to a rejuvenated focus on improving STI control as a component of HIV prevention programmes in developing countries. While efforts so far have focused mainly on all STI, there is increasing evidence that genital ulcers facilitate a considerable proportion of HIV transmission among heterosexuals and that this effect has been underestimated. This paper focuses on the epidemiology of genital herpes in developing countries past and present. OBJECTIVES: To review the scientific literature about the epidemiology of genital herpes in developing countries and discuss the implications of the findings for STI control and HIV prevention programmes. SEARCH METHODOLOGY: A Medline search for June 1966 to August 1999 using the keywords, genital herpes, STD and developing countries, and genital ulcers in MeSH and free text. Abstract books from recent international AIDS conferences and other international STD conferences were reviewed. The annual reports of the medical officers of heath for Harare 1982-1998 and Durban 1989-1997 were reviewed to detect trends in genital herpes diagnoses. FINDINGS: Genital herpes, formerly regarded as a minor STI in most developing countries, has now emerged as a leading cause of genital ulceration in many countries where syphilis and chancroid were more prevalent previously. This increased recognition of genital herpes reflects both a change in the pattern of STI epidemiology through a decline in syphilis and chancroid as a response to HIV control programmes and improved techniques for diagnosing herpetic infection. Countries with significant heterosexual HIV epidemics also appear to have rapidly increasing numbers of genital herpes cases. CONCLUSIONS: The emergence of this herpes epidemic must be addressed through innovative strategies that will be viable, sustainable, acceptable, and effective in developing countries. In countries where genital herpes is a significant problem, local adaptation of WHO treatment algorithms should be made. STI service providers should be trained about issues around the transmission of herpes and how best to advise clients about dealing with, and recognising, recurrences. The effectiveness of antiviral treatment for genital herpes should be investigated in core groups at high risk of HIV.

Developing Countries↗
PubMed2002

Donovanosis.

Donovanosis, a chronic cause of genital ulceration, has recently been the subject of renewed interest after a long period of relative obscurity. The causative organism, Calymmatobacterium granulomatis, has been cultured for the first time in many years and a polymerase chain reaction diagnostic using a colorimetric detection system has been developed. Phylogenetic analysis confirms close similarities with the genus Klebsiella and a proposal made that C granulomatis be reclassified as Klebsiella granulomatis comb nov. Azithromycin has emerged as the drug of choice and should be used if the diagnosis is confirmed or suspected. In donovanosis endemic areas, syndromic management protocols for genital ulceration may need to be adapted locally. A significant donovanosis epidemic was reported in Durban from 1988-97 but the current status of this epidemic is unclear. The donovanosis elimination programme among Aboriginals in Australia appears successful and is a model that could be adopted in other donovanosis endemic areas. Overall, the incidence of donovanosis seems to be decreasing. Increased attention would undoubtedly be paid to donovanosis if policy makers recognised more readily the importance of genital ulcers in fuelling the HIV epidemic.

Communicable Disease Control↗
PubMed2002

Effects of simulated microgravity on arterial nitric oxide synthase and nitrate and nitrite content.

The aim of the present work was to investigate the alterations in nitric oxide synthase (NOS) expression and nitrate and nitrite (NOx) content of different arteries from simulated microgravity rats. Male Wistar rats were randomly assigned to either a control group or simulated microgravity group. For simulating microgravity, animals were subjected to hindlimb unweighting (HU) for 20 days. Different arterial tissues were removed for determination of NOS expression and NOx. Western blotting was used to measure endothelial NOS (eNOS) and inducible NOS (iNOS) protein content. Total concentrations of NOx, stable metabolites of nitric oxide, were determined by the chemiluminescence method. Compared with controls, isolated vessels from simulated microgravity rats showed a significant increase in both eNOS and iNOS expression in carotid arteries and thoracic aorta and a significant decrease in eNOS and iNOS expression of mesenteric arteries. The eNOS and iNOS content of cerebral arteries, as well as that of femoral arteries, showed no differences between the two groups. Concerning NOx, vessels from HU rats showed an increase in cerebral arteries, a decrease in mesenteric arteries, and no change in carotid artery, femoral artery and thoracic aorta. These data indicated that there were differential alterations in NOS expression and NOx of different arteries after hindlimb unweighting. We suggest that these changes might represent both localized adaptations to differential body fluid redistribution and other factors independent of hemodynamic shifts during simulated microgravity.

Animals↗
PubMed2003

Mapping of ATP, glucose, glycogen, and lactate concentrations within the arterial wall.

OBJECTIVE: In large- and medium-sized arteries, the diffusion distances for oxygen and nutrients are long. This has been suggested to make these vessels prone to develop local energy metabolic deficiencies that could contribute to atherogenesis. To validate this hypothesis, we introduced a new method to measure energy metabolites within the arterial wall at high spatial resolution. METHODS AND RESULTS: Bioluminescence imaging was used to quantify local metabolite concentrations in cryosections of snap frozen (in vivo) and incubated pig carotid artery rings. Incubation at hypoxia resulted in increased lactate concentrations, whereas ATP, glucose, and glycogen concentrations were decreased, especially in the mid media, where concentrations of these metabolites were close to zero. In snap frozen arteries, glycogen concentrations were markedly higher in deep layers of the media than toward the lumen. ATP, glucose, and lactate were more homogenously distributed. CONCLUSIONS: Bioluminescence imaging is a new and powerful tool to assess arterial wall energy metabolism at high spatial resolution. Our experiments demonstrate heterogeneous distributions of energy metabolites under hypoxic in vitro conditions. Furthermore, we show that glycogen concentrations are higher in deep medial layers in vivo. This might represent a local adaptation to a low-oxygen microenvironment.

Adenosine Triphosphate↗
PubMed2003

Human nasal mucosa contains antigen-presenting cells of strikingly different functional phenotypes.

Professional antigen-presenting cells (APCs) constitute a heterogeneous leukocyte population that controls T cell induction. Experimental animal studies have delineated the principal APCs of the airway mucosa as a network of intraepithelial dendritic cells (DCs). Whether the situation is comparable in the human airways is unknown. Here we performed a detailed characterization of putative APCs residing in the normal upper airway mucosa, employing confocal microscopy of whole-mount preparations combined with immunophenotyping. A dense network of human leukocyte antigen-DR+ cells with dendritic morphology was found not only in the epithelium (median number, 573/mm2), but also in the lamina propria. In both compartments these cells could be divided into two main populations based on their phenotypic characteristics: the majority expressed a macrophage-like phenotype (CD11b+CD14+CD64+CD68+RFD7+), whereas the smaller population was predominantly constituted by CD1c+CD11c+ immature DCs intermingled with the former. These immature DCs corresponded to the lineage-negative human leukocyte antigen-DR+CD11c+ DC subset present in peripheral blood. Thus, the human upper airway mucosa, in contrast to the rodent counterpart, contains a heterogeneous dense network of dendritic APCs consisting of spatially closely related macrophages and DCs. How these two cell populations regulate the tone of the local adaptive immune system should be the focus of further studies.

Antigen-Presenting Cells↗
PubMed1994

Direct evidence to support the immunosurveillance concept in a human regressive melanoma.

The concept of immunosurveillance against cancer has been an extensively debated question over the last decades. Multiple indirect arguments have supported the view that the immune system may control, at least in certain cases, malignant cell growth while direct demonstration is still lacking in the human. In an attempt to address this issue, we have selected a study model, namely spontaneously regressive melanoma. In previous series of experiments, the variability of T cell receptors (TCRs) in the lymphocytes infiltrating a regressive tumor lesion was investigated. Results demonstrated that clonal T cell populations, precisely defined through their V-D-J junctional sequences, were amplified in situ. One clone was predominant, expressing the V beta 16 variable gene segment. A specific anti-V beta 16 TCR mAb was generated here to purify and functionally characterize the corresponding cells. A tumor-infiltrating lymphocyte-derived V beta 16+ T cell line was developed using this reagent. These in vitro cultured cells were found to express the in vivo predominant TCR sequence exclusively and to display an HLA-B14-restricted cytotoxic activity against the autologous tumor cells. Immunohistochemical experiments, performed with the anti-V beta 16 mAb, showed that the corresponding CTLs are present in the tumor area, some of them being closely opposed to the melanoma cells. Together, these studies demonstrate the existence of a local adaptive immune response clinically associated to tumor regression, thus strongly supporting the validity of the immunosurveillance concept in certain human tumors.

Aged↗
PubMed2003

Creatinine clearance versus serum creatinine as a risk factor in cardiac surgery.

BACKGROUND: Renal impairment is one of the predictors of mortality in cardiac surgery. Usually a binarized value of serum creatinine is used to assess the renal function in risk models. Creatinine clearance can be easily estimated by the Cockcroft and Gault equation from serum creatinine, gender, age and body weight. In this work we examine whether this estimation of the glomerular filtration rate can advantageously replace the serum creatinine in the EuroSCORE preoperative risk assessment. METHODS: In a group of 8138 patients out of a total of 11878 patients, who underwent cardiac surgery in our hospital between January 1996 and July 2002, the 18 standard EuroSCORE parameters could retrospectively be determined and logistic regression analysis performed. In all patients scored, creatinine clearance was calculated according to Cockcroft and Gault. The relationship between the predicted and observed 30-days mortality was evaluated in systematically selected intervals of creatinine clearance and significance values computed by employing Monte Carlo methods. Afterwards, risk scoring was performed using a continuous or a categorical value of creatinine clearance instead of serum creatinine. The predictive ability of several risk score models and the individual contribution of their predictor variables were studied using ROC curve analysis. RESULTS: The comparison between the expected and observed 30-days mortalities, which were determined in different intervals of creatinine clearance, revealed the best threshold value of 55 ml/min. A significantly higher 30-days mortality was observed below this threshold and vice versa (both with p < 0.001). The local adaptation of the EuroSCORE is better than the standard EuroSCORE and was further improved by replacing serum creatinine (SC) by creatinine clearance (CC). Differential ROC analysis revealed that CC is superior to SC in providing predictive power within the logistic regression. Variable rank comparison identified CC as the best single variable predictor, even better than the variable age, former number 1, and SC, previously number 9 in the standard set of EuroSCORE variables. CONCLUSION: The renal function is an important determinant of mortality in heart surgery. This risk factor is not well captured in the standard EuroSCORE risk evaluation system. Our study shows that creatinine clearance, calculated according to the Cockcroft and Gault equation, should be applied to estimate the preoperative renal function instead of serum creatinine. This predictor variable replacement gains a significant improvement in the predictive accuracy of the scoring model.

Adult↗
PubMed2006

Variation in recruitment across sites in a consent-based clinical data registry: lessons from the Canadian Stroke Network.

BACKGROUND: In earlier work, we found important selection biases when we tried to obtain consent for participation in a national stroke registry. Recognizing that not all registries will be exempt from requiring consent for participation, we examine here in greater depth the reasons for the poor accrual of patients from a systems perspective with a view to obtaining as representative sample as possible. METHODS: We determined the percent of eligible patients who were approached to participate and, among those approached, the percent who actually consented to participate. In addition we examined the reasons why people were not approached or did not consent and the variation across sites in the percent of patients approached and consented. We also considered site variation in restrictions on the accrual and data collection process imposed by either the local research ethics board or the hospital. RESULTS: Seventy percent of stroke patients were approached, with wide variations in approach rates across sites (from: 41% to 86%), and considerable inter-site variation in hospital policies governing patient accrual. Chief reasons for not approaching were discharge or death before being approached for consent. Seventeen percent of those approached refused to participate (range: 5% to 75%). Finally, 11% of those approached did not participate due to language or communication difficulties. CONCLUSION: We found wide variation in approach and agree rates across sites that were accounted for, in part, by different approaches to accrual and idiosyncratic policies of the hospitals. This wide variation in approach and agree rates raises important challenges for research ethics boards and data protection authorities in determining when to waive consent requirements, when to press for increased quality control, when to permit local adaptation of the consent process, and when to permit alternatives to individual express consent. We offer several suggestions for those registries that require consent for participation.

Canada↗
PubMed2002

A randomised controlled trial of a patient based Diabetes Recall and Management System: the DREAM trial: a study protocol [ISRCTN32042030].

BACKGROUND: Whilst there is broad agreement on what constitutes high quality health care for people with diabetes, there is little consensus on the most efficient way of delivering it. Structured recall systems can improve the quality of care but the systems evaluated to date have been of limited sophistication and the evaluations have been carried out in small numbers of relatively unrepresentative settings. Hartlepool, Easington and Stockton currently operate a computerised diabetes register which has to date produced improvements in the quality of care but performance has now plateaued leaving substantial scope for further improvement. This study will evaluate the effectiveness and efficiency of an area wide 'extended' system incorporating a full structured recall and management system, actively involving patients and including clinical management prompts to primary care clinicians based on locally-adapted evidence based guidelines. METHODS: The study design is a two-armed cluster randomised controlled trial of 61 practices incorporating evaluations of the effectiveness of the system, its economic impact and its impact on patient wellbeing and functioning.

Database Management Systems↗
PubMed2005

Genetic structure of Anopheles gambiae populations on islands in northwestern Lake Victoria, Uganda.

BACKGROUND: Alternative means of malaria control are urgently needed. Evaluating the effectiveness of measures that involve genetic manipulation of vector populations will be facilitated by identifying small, genetically isolated vector populations. The study was designed to use variation in microsatellite markers to look at genetic structure across four Lake Victoria islands and two surrounding mainland populations and for evidence of any restriction to free gene flow. METHODS: Four Islands (from 20-50 km apart) and two surrounding mainland populations (96 km apart) were studied. Samples of indoor resting adult mosquitoes, collected over two consecutive years, were genotyped at microsatellite loci distributed broadly throughout the genome and analysed for genetic structure, effective migration (Nem) and effective population size (Ne). RESULTS: Ne estimates showed island populations to consist of smaller demes compared to the mainland ones. Most populations were significantly differentiated geographically, and from one year to the other. Average geographic pair-wise FST ranged from 0.014-0.105 and several pairs of populations had Ne m < 3. The loci showed broad heterogeneity at capturing or estimating population differences. CONCLUSION: These island populations are significantly genetically differentiated. Differences reoccurred over the study period, between the two mainland populations and between each other. This appears to be the product of their separation by water, dynamics of small populations and local adaptation. With further characterisation these islands could become possible sites for applying measures evaluating effectiveness of control by genetic manipulation.

Animals↗
PubMed2005

A coarse-to-fine approach to prostate boundary segmentation in ultrasound images.

BACKGROUND: In this paper a novel method for prostate segmentation in transrectal ultrasound images is presented. METHODS: A segmentation procedure consisting of four main stages is proposed. In the first stage, a locally adaptive contrast enhancement method is used to generate a well-contrasted image. In the second stage, this enhanced image is thresholded to extract an area containing the prostate (or large portions of it). Morphological operators are then applied to obtain a point inside of this area. Afterwards, a Kalman estimator is employed to distinguish the boundary from irrelevant parts (usually caused by shadow) and generate a coarsely segmented version of the prostate. In the third stage, dilation and erosion operators are applied to extract outer and inner boundaries from the coarsely estimated version. Consequently, fuzzy membership functions describing regional and gray-level information are employed to selectively enhance the contrast within the prostate region. In the last stage, the prostate boundary is extracted using strong edges obtained from selectively enhanced image and information from the vicinity of the coarse estimation. RESULTS: A total average similarity of 98.76%(+/- 0.68) with gold standards was achieved. CONCLUSION: The proposed approach represents a robust and accurate approach to prostate segmentation.

Algorithms↗