SEARCH · Search PubMed

Results for “sparsity”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources

PubMed1998

Pyoderma gangrenosum in a child with congenital partial deficiency of leucocyte adherence glycoproteins.

Congenital deficiency of beta 2 integrin leucocyte adhesion molecules is a rare immunodeficiency and is often fatal. Neutrophils are unable to bind to ligands on the endothelium, and so cannot leave the circulation during inflammation or infection. When leucocyte adhesion deficiency (LAD) is caused by abnormally low expression of beta 2 integrins, it is termed LAD type 1. We describe a 5-year-old girl with a history of recurrent bacterial infections since early childhood who developed necrotic skin ulcers resembling pyoderma gangrenosum and a persistent circulating neutrophilia. Histologically, the lesions showed deep ulceration with a diffuse lymphohistiocytic infiltrate, but with a relative sparsity of neutrophils. Subsequent investigation revealed a complete absence of CD11a/CD18 beta 2 integrins on the surface of the patient's neutrophils, confirming the diagnosis of LAD type 1. The ulcers responded to treatment with oral prednisolone and colchicine.

CD11 Antigens↗

PubMed2003

Allocating resources for health and social care: the significance of rurality.

Whilst an allowance is made for sparsity in the allocation of resources for social care services in England, rurality is not a significant factor in health resource allocation. This lack of consistency in resource allocation criteria has become increasingly visible as health and social services departments are required to work in partnership across a range of areas. Differences in funding mechanisms also raise the question of why it is legitimate to make adjustments for rurality in the distribution of some public services, but not for others. Against this background, the present paper considers the case for a rural premium in health resource allocation which, it proposes, can be made on four grounds. First, there is evidence that the current National Health Service (NHS) formula introduces systematic biases in favour of urban areas in the way in which it expresses 'need' for healthcare. Secondly, the way in which the current system compensates for unavoidable variations in the costs of providing services takes insufficient account of the additional costs associated with rural service provision. Thirdly, with a growing emphasis on the need to attain national quality standards, rural primary care trusts and social services departments can no longer tolerate lower levels of services. Finally, a case for a rural premium can be made on the basis of precedent. England is the only country in the UK that does not make a major adjustment for rurality in its NHS formula. The paper concludes that the English NHS resource allocation system has done little to counter marked service deprivation in rural areas. Given evidence that rural local authorities also spend less on social care services and direct provision, this raises serious questions about the extent to which the needs of vulnerable people in English rural areas are being adequately served.

England↗

PubMed2000

Association of amino acid sequence in the PKR-eIF2 phosphorylation homology domain and response to interferon therapy.

Hepatitis C virus (HCV) genotype 1b and high pretreatment virus load are well known predictive factors of poor response to interferon (IFN) therapy. In addition, a sparsity of amino acid substitutions in the interferon sensitivity determining region (ISDR) is also predictive of a poor response to IFN in patients with genotype 1b, although this issue is still controversial. Recently, a 12 amino acid domain in the E2 protein of HCV (PKR-eIF2 alpha phosphorylation homology domain [PePHD]) has been reported to bind with and block the virus replication inhibition ability of PKR, suggesting that the interaction of E2 and PKR may be one mechanism by which HCV circumvents the antiviral effect of IFN. To clarify the significance of amino-acid sequences in this domain in predicting the effect of IFN therapy, we analyzed 82 patients with genotype 1b. Eleven patients (13.4%) responded to treatment whereas the remaining 71 patients (86.6%) were nonresponders. Multivariate analysis showed that only HCV load and amino-acid substitutions in the ISDR were predictive of sustained response to IFN. Amino-acid substitutions in the PePHD were detected in only eight of 82 patients (9.8%), and did not correlate with the therapeutic effect of IFN. However, amino-acid-sequence analyses of quasispecies before and after 1 week of IFN therapy showed elimination of clones with substitutions in this domain. Our results suggest that amino-acid sequences of the PePHD domain may be related to viral resistance to IFN but do not predict the outcome of IFN therapy as amino-acid substitutions in this domain are rare.

Adult↗

PubMed2001

Ileoanal pouch procedures in children.

PURPOSE: The aim of this study was to review the long-term experience with colectomy and the ileoanal pouch procedure (IAPP) in children from one hospital. METHODS: Between 1977 and 2001, 168 children under 18 years of age underwent colectomy and IAPP. One hundred thirty-one had ulcerative colitis (UC). Twenty-six had familial colonic polyposis (FP), 9 had Hirschsprung's disease (HD), and 2 had colonic inertia. Ninety-seven had a J-pouch, 62 had a lateral pouch, and 9 had a straight pull-through (SP). The mean age was 13.9 years. RESULTS: Complications within 2 years included pouchitis (16%), ileoanal strictures (14%), and adhesions (7%). There were no deaths. Fifty-six patients (33%) required reoperation, including 20 revisions of large pouches and 8 conversions of SP to pouches because of stool frequency. Six children (3.6%) had later pouch removal (3 had Crohn's disease). Stool frequency at 6 months was 3.8 (mean). At 6 months 5% had occasional soiling. Eighty-four percent can delay defecation over 1(1/2) hours; 82% can urinate without a bowel movement. With a mean follow-up of 11.2 years, 94.6% are functioning well. CONCLUSIONS: Colectomy with IAPP is the preferred operation for children with UC, FP, and selected HD. The J-pouch is the preferred technique because of simplicity of construction and sparsity of complications.

Adenomatous Polyposis Coli↗

PubMed1979

[Acute renal failure in alcoholic myopathy (author's transl)].

Two chronic alcoholics developed acute renal failure from alcoholic myopathy (acute alcohol-induced rhabdomyolysis). Severe muscle pain developed and was associated with transitory oligo-anuric renal failure, requiring dialysis in one patient. In addition to the typical history and clinical symptoms, excessive elevation of muscle enzymes, especially creatine-kinase, and the appearance of myoglobin in serum are characteristic. Brown discoloration of the urine and a falsely positive test for "blood" due to the presence of myoglobin in urine in the absence of red blood cells are also typical. Definite changes can be demonstrated histologically and electromyographically during the acute stage. It is likely that this condition is more frequent than the sparsity of published reports indicates.

Acute Kidney Injury↗

PubMed2006

Fast noniterative orbital localization for large molecules.

We use Cholesky decomposition of the density matrix in atomic orbital basis to define a new set of occupied molecular orbital coefficients. Analysis of the resulting orbitals ("Cholesky molecular orbitals") demonstrates their localized character inherited from the sparsity of the density matrix. Comparison with the results of traditional iterative localization schemes shows minor differences with respect to a number of suitable measures of locality, particularly the scaling with system size of orbital pair domains used in local correlation methods. The Cholesky procedure for generating orthonormal localized orbitals is noniterative and may be made linear scaling. Although our present implementation scales cubically, the algorithm is significantly faster than any of the conventional localization schemes. In addition, since this approach does not require starting orbitals, it will be useful in local correlation treatments on top of diagonalization-free Hartree-Fock optimization algorithms.

Journal Article↗

PubMed2005

Auxiliary basis expansions for large-scale electronic structure calculations.

One way to reduce the computational cost of electronic structure calculations is to use auxiliary basis expansions to approximate four-center integrals in terms of two- and three-center integrals, usually by using the variationally optimum Coulomb metric to determine the expansion coefficients. However, the long-range decay behavior of the auxiliary basis expansion coefficients has not been characterized. We find that this decay can be surprisingly slow. Numerical experiments on linear alkanes and a toy model both show that the decay can be as slow as 1/r in the distance between the auxiliary function and the fitted charge distribution. The Coulomb metric fitting equations also involve divergent matrix elements for extended systems treated with periodic boundary conditions. An attenuated Coulomb metric that is short-range can eliminate these oddities without substantially degrading calculated relative energies. The sparsity of the fit coefficients is assessed on simple hydrocarbon molecules and shows quite early onset of linear growth in the number of significant coefficients with system size using the attenuated Coulomb metric. Hence it is possible to design linear scaling auxiliary basis methods without additional approximations to treat large systems.

Alkanes↗

PubMed1998

Crystal structure of the ribosomal RNA domain essential for binding elongation factors.

The structure of a 29-nucleotide RNA containing the sarcin/ricin loop (SRL) of rat 28 S rRNA has been determined at 2.1 A resolution. Recognition of the SRL by elongation factors and by the ribotoxins, sarcin and ricin, requires a nearly universal dodecamer sequence that folds into a G-bulged cross-strand A stack and a GAGA tetraloop. The juxtaposition of these two motifs forms a distorted hairpin structure that allows direct recognition of bases in both grooves as well as recognition of nonhelical backbone geometry and two 5'-unstacked purines. Comparisons with other RNA crystal structures establish the cross-strand A stack and the GNRA tetraloop as defined and modular RNA structural elements. The conserved region at the top is connected to the base of the domain by a region presumed to be flexible because of the sparsity of stabilizing contacts. Although the conformation of the SRL RNA previously determined by NMR spectroscopy is similar to the structure determined by x-ray crystallography, significant differences are observed in the "flexible" region and to a lesser extent in the G-bulged cross-strand A stack.

Animals↗

PubMed1994

Impact of President Clinton's Health Security Act on residency programs.

The Clinton Health Security Act calls for a major shift in the emphasis of medical training. While family practice, general pediatrics, general internal medicine, and obstetrics and gynecology stand to benefit, other specialties will see decreases in their programs and their residency slots. In light of the present sparsity of programs in family practice and the prevalent student disinterest in the specialty, only heroic efforts will make possible achievement of the 55/50 ratio of primary care physicians to other specialists outlined by the Clinton plan. Problems inevitable in the transition are described and incentives for change suggested.

Education, Medical↗

PubMed1994

Oral cancer education and HIV-associated malignancies.

Interest and participation in "oral cancer" education courses has been disappointingly low, probably because of the sparsity and low impact of cases of oral cancer relative to clinical practice. Interest and participation increase as subject matter relevant to clinical practice is included to create innovative programs. Such subject matter has included more coverage of premalignant lesions (leukoplakia and erythroplakia), the role of vital staining (toluidine blue) to aid clinical judgment and biopsy, and utilization of lasers for control. A significant stimulus to encourage enrollment has been the incorporation of AIDS updating and HIV-associated malignancies, which adds identification, curiosity, and interest relative to a well-known and very current health care problem. The greater course participation presents the opportunity to emphasize the importance of oral cancer and clinician roles in prevention, early detection, and management.

Adult↗

PubMed2001

Estimation of disease progression parameters from case-control data: application to mammographic patterns and breast cancer natural history.

BACKGROUND: Estimations of mean sojourn time (MST) and sensitivity (S) in disease screening have been previously calculated from case-control data, using simple models which did not include covariates. Many studies have shown an effect of mammographic parenchymal pattern (MPP) on breast-cancer risk and tumour histology. We have expanded previous models on these to estimate MST and S with the effects of MPP as a covariate. METHODS: Data were from a nested case-control study within the East Anglian screening programme, with 875 cases and 2,601 controls. Estimates of disease progression and screening parameters were based on conditional likelihood calculation, using a Markov process model. Ninety-five per cent confidence intervals (CI) were calculated using the profile likelihood wherever possible and using a numerical estimate of the information matrix or the area under the likelihood curve where necessary. RESULTS: We obtained estimates of the incidence of preclinical disease, rate of transition from preclinical to clinical and screening sensitivity, and evaluated the association of these parameters with mammographic parenchymal pattern. A higher incidence of preclinical disease was found for high-risk MPP [relative incidence = 1.62 (95% CI: 0.89; 2.73)]. However, no difference in progression rate from preclinical to clinical disease between different MPP was found. Dense MPPs were associated with decreased sensitivity [relative sensitivity = 0.24 (95% CI: 0.06; 15)]. Wide CIs were found, probably being a consequence of the relative sparsity of interval cancer data. DISCUSSION: It is possible to estimate multiple parameters of disease progression and screening quality from case-control data. The reduction in sensitivity of the screening process associated with high-risk patterns presented here, could be of paramount interest for proposing new screening strategies, such as possible additional screening tools.

Breast Neoplasms↗

PubMed2026

The clinical promise of mass spectrometry-based single-cell proteomics: from bedside to bench.

INTRODUCTION: Single-cell proteomics (SCP) is entering into a transformative phase, moving beyond technically demanding benchmarking studies toward robust and reproducible workflows capable of quantifying thousands of proteins per cell. These advances highlight SCP's potential to address clinically relevant questions by resolving cellular and pathological heterogeneity that remains obscured in bulk proteomics. AREAS COVERED: This review discusses current advances, challenges, and clinical applications of SCP based on literature identified through searches in major scientific databases. Many clinically relevant samples remain underexplored in SCP studies, in part because their application requires careful evaluation of pre-analytical variables that can strongly influence proteomic readouts. Current SCP methodologies vary according to sample type, experimental conditions, and available resources. Compared with single-cell RNA sequencing, SCP remains limited in cellular throughput, making it challenging to define optimal sample sizes and to reliably detect both abundant and rare cell populations. These limitations also make dataset integration difficult, as reduced cellular coverage and sampling depth increase data sparsity. Moreover, implementing quality control strategies across sequential SCP experiments is essential to ensure data robustness, comparability, and accurate biological interpretation. EXPERT OPINION: Applying SCP to clinical samples advances our understanding of biological complexity and holds potential to drive progress in translational and precision medicine.

Humans↗

PubMed1970

Transitional cardiac cells of the conductive system of the dog heart. Distinguishing morphological and electrophysiological features.

Cardiac cells with distinctive electrophysiological and morphological features were found at the junctional region between Purkinje and ventricular cells of the dog heart. The electrophysiological exploration of these "transitional" cells revealed action potentials markedly different in configuration from those generated by Purkinje or by ventricular cells. The impaled cardiac cells which generated transitional action potentials were identified in serial sections and studied with the light and the electron microscopes. The transitional cells were found to be characterized cytologically by: (a) their subendocardial location, (b) their small diameter, (c) the absence of T system and sarcoplasmic reticulum, and (d) the lack of intercalated discs under the light microscope and the sparsity of specialized intercellular junctions under the electron microscope. Purkinje, transitional, and ventricular cells were found to be joined by gap junctions permeable to lanthanum. A quantitative difference in the extent and distribution of specialized intercellular junctions may be one of the factors responsible for the slow velocity of conduction characteristic of the Purkinje-ventricular junctional region.

Action Potentials↗

PubMed1982

Influence of neostigmine treatment on embryonic development of acetylcholine receptors and neuromuscular junctions.

The postulated role of the acetylcholine receptor in the formation of neuromuscular synapses during the course of embryonic development was investigated in the superior oblique muscle of white Peking duck embryos. The possibility that the number of receptors could be experimentally lowered by chronic injections of the anticholinesterase agent, neostigmine methylsulfate, was determined using 125I-alpha-bungarotoxin. The total number of acetylcholine receptors on incubation day 12, 2 d subsequent to the onset of treatment, was reducted 45% as compared to saline-treated controls. A similar reduction in total receptor content (49%) was also observed on day 19. Radioautographic preparations showed that clusters of acetylcholine receptors were rare and that the grain density of extrajunctional receptors was also reduced. Hence, chronic treatment with neostigimine during development was observed to exert an effect on both the number and distribution of receptors in the developing superior oblique muscle. These changes occurred in the absence of any apparent effect on muscle differentiation in general. Myoblasts and myotubes were present on day 14 and further differentiated into myofibers by day 18 in both neostigmine and saline-treated muscles. The cytology of the develop;ing muscle cells also appeared normal. This is in contradistinction to the striking morphological changes that take place in adult mammalian and avian muscle after anticholinesterase treatment. More significantly, the decreased total receptor content and sparsity of clusters had no apparent effect on the formation of developing neuromuscular junctions at the electron microscopic level. The frequency of neuromuscular junctions in neostigmine-treated muscles was similar to that of the controls. It is concluded that acetylcholine receptor clusters are not required for the events leading to the morphological formation of neuromuscular junctions during in vivo development.

Animals↗

PubMed2001

Reduction of computational dimensionality in inverse radiotherapy planning using sparse matrix operations.

For dynamic multileaf collimator-based intensity modulated radiotherapy in which small beam elements are used to generate continuous modulation, the sheer size of the dose calculation matrix could pose serious computational challenges. In order to circumvent this problem, the dose calculation matrix was reduced to a sparse matrix by truncating the weakly contributing entries below a certain cutoff to zero. Subsequently, the sparse matrix was compressed and matrix indexing vectors were generated to facilitate matrix-vector and matrix-matrix operations used in inverse planning. The application of sparsity permitted the reduction of overall memory requirement by an order of magnitude. In addition, the effect of disregarding the small scatter components on the quality of optimization was investigated by repeating the inverse planning using the dense dose calculation matrix. Comparison of dense and sparse matrix-based plans revealed an insignificant difference in optimization outcome, thus demonstrating the feasibility and usefulness of the sparse method in inverse planning. Furthermore, two additional methods of memory minimization are suggested, namely hexagonal dose sampling and limited normal tissue sampling.

Humans↗

PubMed2006

A high-throughput approach for associating MicroRNAs with their activity conditions.

Plant microRNAs (miRNAs) are short RNA sequences that bind to target mRNAs and change their expression levels by redirecting their stabilities and marking them for cleavage. In Arabidopsis thaliana, microRNAs have been shown to regulate development and are believed to impact expression both under various conditions, such as stress and stimuli, as well as in specific tissue types. We present a high throughput approach for associating between microRNAs and conditions in which they act, using novel statistical and algorithmic techniques. Our new tool, miRNAXpress, at first computes a (binary) matrix T denoting the potential targets of microRNAs. Then, using T and an additional predefined matrix X indicating expression of genes under various conditions, it produces a new matrix that predicts associations between microRNAs and the conditions in which they act. Thus, the program comprises two main modules that work in tandem to compute the desired output. The first is an efficient target prediction engine that predicts mRNA targets of query microRNAs by evaluating the optimal duplex that could be formed between the two: given a short query RNA, a long target RNA, and a predefined energy cut-off threshold, the program finds and reports all putative binding sites of the query RNA in the target RNA with hybridization energy bounded by the predefined threshold. The second module realizes an association operation that is computed by a method which relies on an efficient t-test to compute the associations. The calculation of the matrix of microRNAs and their potential targets is the computationally intensive part of the work done by miRNAXpress, and therefore an efficient algorithm for this portion facilitates the entire process. Thus, the target prediction engine is based on an efficient approximate hybridization search algorithm whose efficiency is the result of utilizing the sparsity of the search space without sacrificing the optimality of the results. The time complexity of this algorithm is almost linear in the size of a sparse set of locations where base-pairs are stacked at a height of three or more. Thus miRNAXpress is a novel tool for associating between microRNAs and the conditions in which they act. We employed it to conduct a study, using the plant Arabidopsis thaliana as our model organism. By applying miRNAXpress to 98 microRNAs and 380 conditions, some biologically interesting and statistically strong relations were discovered. For example, mir159C activity is possibly a factor in the misresponse of nph4 mutants to phototropic stimulations.

Arabidopsis↗

PubMed2004

Spatial patterns of infant mortality in Mali: the effect of malaria endemicity.

A spatial analysis was carried out to identify factors related to geographic differences in infant mortality risk in Mali by linking data from two spatially structured databases: the Demographic and Health Surveys of 1995-1996 and the Mapping Malaria Risk in Africa database for Mali. Socioeconomic factors measured directly at the individual level and site-specific malaria prevalence predicted for the Demographic and Health Surveys' locations by a spatial model fitted to the Mapping Malaria Risk in Africa database were examined as possible risk factors. The analysis was carried out by fitting a Bayesian hierarchical geostatistical logistic model to infant mortality risk, by Markov chain Monte Carlo simulation. It confirmed that mother's education, birth order and interval, infant's sex, residence, and mother's age at infant's birth had a strong impact on infant mortality risk in Mali. The residual spatial pattern of infant mortality showed a clear relation to well-known foci of malaria transmission, especially the inland delta of the Niger River. No effect of estimated parasite prevalence could be demonstrated. Possible explanations include confounding by unmeasured covariates and sparsity of the source malaria data. Spatial statistical models of malaria prevalence are useful for indicating approximate levels of endemicity over wide areas and, hence, for guiding intervention strategies. However, at points very remote from those sampled, it is important to consider prediction error.

Adult↗

PubMed2026

jsPCA: fast, scalable, and interpretable identification of spatial domains and variable genes across multi-slice and multi-sample spatial transcriptomics data.

MOTIVATION: Spatial transcriptomics technologies record genome-wide measurements of gene expression with high spatial resolution. These technologies generate large and high-dimensional datasets requiring efficient automated methods for their analysis. We introduce joint spatial PCA (jsPCA), a novel, fast, scalable and interpretable method for the automatic identification of spatial domains and variable genes in multi-slice and multi-sample spatial transcriptomics data. RESULTS: jsPCA relies on a simple mathematical formulation of a spatial covariance defined as the product of the gene expression covariance with the spatial autocorrelation. The principal components of this spatial covariance yield a biologically meaningful low-dimensional representation. From this representation, spatial domains are derived by simple clustering and spatially variable genes are identified directly from the principal component coefficients. A joint representation of multiple slices and samples without spatial alignment is obtained by computing common principal components via joint diagonalization. By leveraging data sparsity and non-convex manifold optimization, jsPCA leads to computing time in the order of seconds to minutes, substantially outperforming state-of-the-art approaches. We benchmarked jsPCA against 10 state-of-the-art methods on two reference databases. Our approach demonstrated excellent performance, comparable or better than state-of-the-art methods, while being much faster, interpretable, and scalable to very large datasets.

Journal Article↗