Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Multivariate statistics”

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.

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

At least 1,279 records · Page 71Linked to original sources
PubMed2005

A semimechanistic-physiologic population pharmacokinetic/pharmacodynamic model for neutropenia following pemetrexed therapy.

PURPOSE: The objectives of these analyses were to (1) develop a semimechanistic-physiologic population pharmacokinetic/pharmacodynamic (PK/PD) model to describe neutropenic response to pemetrexed and to (2) identify influential covariates with respect to pharmacodynamic response. PATIENTS AND METHODS: Data from 279 patients who received 1,136 treatment cycles without folic acid or vitamin B12 supplementation during participation in one of eight phase II cancer trials were available for analysis. Starting doses were 500 or 600 mg pemetrexed per m2 body surface area (BSA), administered as 10-min intravenous infusions every 21 days (1 cycle). The primary analyses included 105 patients (279 cycles) for which selected covariates-including vitamin deficiency marker data (i.e., homocysteine, cystathionine, methylmalonic acid, and methylcitrate [I, II, and total] plasma concentrations)-were available. Classical statistical multivariate regression analyses and a semimechanistic-physiologic population PK/PD model were used to evaluate neutropenic response to single-agent pemetrexed administration. RESULTS: The timecourse of neutropenia following single-agent pemetrexed administration was adequately described by a semimechanistic-physiologic model. Population estimates for system-based model parameters (i.e., baseline neutrophil count, mean transit time, and the feedback parameter), which mathematically represent current understanding of the process and physiology of hematopoiesis, were consistent with previously reported values. The population PK/PD model included homocysteine, cystathionine, albumin, total protein, and BSA as covariates relative to neutropenic response. CONCLUSION: These results support the programmatic decision to introduce folic acid and vitamin B12 supplementation during pemetrexed clinical development as a means of normalizing patient homocysteine levels, thereby managing the risk of severe neutropenia secondary to pemetrexed administration. The current results also suggest that the addition of vitamin B6 supplementation to normalize patient cystathionine levels may further decrease the incidence of grade 4 neutropenia following pemetrexed administration. The results also suggest the use of folic acid as a means of lessening hematologic toxicity following administration of cytotoxic agents other than antifolates.

Adult↗
PubMed1993

Synonymous codon usage in Zea mays L. nuclear genes is varied by levels of C and G-ending codons.

A multivariate statistical method called correspondence analysis was used to examine the codon usage of one-hundred-and-one nuclear genes of maize (Zea mays L.). Forty percent of the variation in codon usage was due to bias toward G or C-ending versus A or U-ending codons. Differences in levels of G-ending codons showed the weakest correlation with the major codon usage bias. The bias toward C or U versus A or G in the silent third nucleotide position of synonymous codons accounted for approximately 10% of the variation in codon usage. The G+C content of the silent third nucleotide position of coding regions was not strongly correlated with G+C content of introns. Codon usage was strongly biased toward codons ending in G or C for a number of highly expressed genes including most light-regulated chloroplast proteins, ABA-induced proteins, histones, and anthocyanin biosynthetic enzymes. Codon usage of genes encoding storage proteins and regulatory proteins, such as transposases, kinases, phosphatases and transcription factors, was more random than that of genes encoding cytosolic enzymes with similar bias toward G or C-ending codons. Codon usage in maize may reflect both regional bias on nucleotide composition and selection on the silent third nucleotide position.

Base Composition↗
PubMed2005

Quantitative architectural analysis: a new approach to cortical mapping.

Recent progress in anatomical and functional MRI has revived the demand for a reliable, topographic map of the human cerebral cortex. Till date, interpretations of specific activations found in functional imaging studies and their topographical analysis in a spatial reference system are, often, still based on classical architectonic maps. The most commonly used reference atlas is that of Brodmann and his successors, despite its severe inherent drawbacks. One obvious weakness in traditional, architectural mapping is the subjective nature of localising borders between cortical areas, by means of a purely visual, microscopical examination of histological specimens. To overcome this limitation, more objective, quantitative mapping procedures have been established in the past years. The quantification of the neocortical, laminar pattern by defining intensity line profiles across the cortical layers, has a long tradition. During the last years, this method has been extended to enable a reliable, reproducible mapping of the cortex based on image analysis and multivariate statistics. Methodological approaches to such algorithm-based, cortical mapping were published for various architectural modalities. In our contribution, principles of algorithm-based mapping are described for cyto- and receptorarchitecture. In a cytoarchitectural parcellation of the human auditory cortex, using a sliding window procedure, the classical areal pattern of the human superior temporal gyrus was modified by a replacing of Brodmann's areas 41, 42, 22 and parts of area 21, with a novel, more detailed map. An extension and optimisation of the sliding window procedure to the specific requirements of receptorarchitectonic mapping, is also described using the macaque central sulcus and adjacent superior parietal lobule as a second, biologically independent example. Algorithm-based mapping procedures, however, are not limited to these two architectural modalities, but can be applied to all images in which a laminar cortical pattern can be detected and quantified, e.g. myeloarchitectonic and in vivo high resolution MR imaging. Defining cortical borders, based on changes in cortical lamination in high resolution, in vivo structural MR images will result in a rapid increase of our knowledge on the structural parcellation of the human cerebral cortex.

Algorithms↗
PubMedDate not supplied

Normalization procedures and factorial representations for classification of correlation-aligned images: a comparative study.

We have addressed the problem of optimizing procedures of multivariate statistical analysis (MSA) for identifying homogeneous sets of electron micrographs of biological macromolecules, with a view to averaging over consistent sets of images. Using pre-aligned images of negatively stained protein molecules - known a priori to fall into two subtly different classes - we compared how the capacity to discriminate between them was affected by the normalization procedure used, and by the choice of factorial representation. Specifically, these images were analyzed both after being scaled according to constant minimum and maximum (CMM) values, and after imposing constant values of image mean and variance (CMV). The factorial representations compared were correspondence analysis (CA) and the principal components (PC) formalism. When used with PC, CMM normalization was found to give rise to spurious inter-image fluctuations that were more pronounced than the genuine difference between the two kinds of images; even with CA, CMV proved to be a more satisfactory method of normalization. When CMV was used with CA or PC, both factorial representations yielded qualitatively similar results, although according to a quantitative measure of inter-set discrimination, the performance of PC was slightly superior. Even in the best case, however, the two classes of images - as mapped in factorial space - were not fully resolved. The implications of this observation are discussed with regard to potential ambiguities of image classification in practice.

Classification↗
PubMed1991

External beam irradiation versus 125 iodine implant in the definitive treatment of prostate carcinoma.

We reviewed the record of all 983 patients seen at the Hahnemann University, Department of Radiation Oncology for evaluation of prostate cancer during the megavoltage era. We compared the results of 276 patients who were treated definitively with either external beam irradiation or Iodine 125 implantation. The groups were similar in most prognostic characteristics. Where appropriate, multivariate statistical techniques were used to compensate for the effects of differences in grade and stage between the two groups. There were striking differences between implant and external beam patients in both local failure rates and disease-free survival, mostly attributable to poor local control in the implant patients. Thirty-eight percent of the Stage A and B implant patients failed locally in the first 5 years whereas only 5% of a comparable group of external beam patients did so. A2 patients, however, exhibited similar disease-free survival in both cohorts. Complication rates were 11% in the implant group and 19% in the external beam group. We conclude that there are serious doubts about the efficacy of Iodine 125 implantation in maintaining local control, and that this translates into worse relapse-free survival. By contrast, local control and relapse-free survival may be satisfactory in the A2 patients, and complication rates may be lower with implant. The above suggests that Iodine 125 interstitial implantation is well suited to only a minority of early stage prostate cancer patients and that most patients with Stage B and C prostatic carcinoma should be treated with either external beam irradiation or with radical prostatectomy.

Aged↗
PubMed1997

Mortality prediction in diabetic patients with myocardial infarction: experiences from the DIGAMI study.

OBJECTIVES: We analysed predictors of 1-year mortality following acute myocardial infarction in patients with diabetes mellitus by applying uni- and multivariate statistics on the DIGAMI cohort. BACKGROUND: Diabetic patients with acute myocardial infarction have a poor prognosis. This may depend on a poor metabolic control, a hypothesis that was tested in DIGAMI, a prospective randomised study. In this trial institution of immediate intensive insulin treatment reduced 1-year mortality by 30%. METHODS: We recruited 620 diabetic patients with acute myocardial infarction, 314 of whom served as controls, while the remaining 306 patients were treated with an acute insulin-glucose infusion followed by multidose subcutaneous insulin. RESULTS: Age, previous myocardial damage, duration of the diabetes and previous insulin therapy were significantly related to 1-year mortality, while conventional risk factors lacked independent prognostic weight. Female sex was not linked to mortality when controlling for the confounding effects of other predictors. One of the strongest predictors of a fatal outcome, in particular during the hospital phase, was blood glucose at hospital admission. Beta-blockade appeared to exert a striking, independent secondary-preventive effect. CONCLUSIONS: It seems that good metabolic control and not conventional risk factors is of major importance for diabetic patients sustaining acute myocardial infarction. Also treatment with beta-blockade seems to be of special importance in this category of patients.

Adrenergic beta-Antagonists↗
PubMed2002

Biomechanical comparison of isokinetic lifting and free lifting when applied to chronic low back pain rehabilitation.

The study compares free and isokinetic lifting using a multivariate statistical analysis. Each of the 13 male subjects performed three free lifts and three isokinetic lifts using a CYBEX LIFTASK. The measurement variables were obtained from a 3D video system, two force plates and two strain-gauge transducers. Coupling of fuzzy space-time windowing and multiple correspondence analysis was used to show the links between the variables and the differences between the experimental situations. Isokinetic lifting had almost no points in common with free-lifting, but there was a similar range of extension for the different joints. Most free-lifting strategies could not be used in isokinetic lifting, as constraints between the subject and his environment were different. The main drawback of the isokinetic lifting was due to the necessity for individuals to reach the machine speed, yielding high transient efforts. The maximum vertical effort at the L5/S1 joint was about 1600, 1500 and 1400N for low, medium and high speed, whereas it was lower than 1300N, irrespective of the load, during free lifting. In the context of chronic low back pain rehabilitation, movement strategies used in free lifting could not be relearnt using an isokinetic machine. A better understanding of the common points and differences between isokinetic movement and free movement could help rehabilitation physicians to plan rehabilitation programmes, taking advantage of each kind of movement.

Adult↗
PubMed2005

Group I and II metabotropic glutamate receptors alter brain cortical metabolic and glutamate/glutamine cycle activity: a 13C NMR spectroscopy and metabolomic study.

Metabotropic glutamate receptors (mGluR) modulate neuronal function. Here, we tested the effect on metabolism of a range of Group I and II mGluR ligands in Guinea pig brain cortical tissue slices, applying 13C NMR spectroscopy and metabolomic analysis using multivariate statistics. The effects of Group I agonists (S)-3,5-dihydroxyphenylglycine (DHPG) and (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) depended upon concentration and were mostly stimulatory, increasing both net metabolic flux through the Krebs cycle and glutamate/glutamine cycle activity. Only the higher (50 microm) concentrations of CHPG had the opposite effect. The Group I antagonist (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA), consistent with its neuroprotective role, caused significant decreases in metabolism. With principal components analysis of the metabolic profiles generated by these ligands, the effects could be separated by two principal components. Agonists at Group II mGluR [(2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG IV) and 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate (APDC)] generally stimulated metabolism, including glutamate/glutamine cycling, although this varied with concentration. The antagonist (2S)-alpha-ethylglutamic acid (EGLU) stimulated astrocyte metabolism with minimal impact on glutamate/glutamine cycling. (RS)-1-Aminophosphoindan-1-carboxylic acid (APICA) decreased metabolism at 5 microm but had a stimulatory effect at 50 microm. All ligand effects were separated from control and from each other using two principal components. The ramifications of these findings are discussed.

Animals↗
PubMed2005

Atmospheric bulk deposition to the Lagoon of Venice Part II. Source apportionment analysis near the industrial zone of Porto Marghera, Italy.

Multivariate statistical analyses were applied to measurements of atmospheric deposition of total particulate (TSP), inorganic elements (Al, Ca, Na, K, Mg, Si, Mn, Fe, Zn, Ni, Cr, Cu, Pb, Cd, As, Hg, V and S) and organic compounds (PAH, PCB, HCB and PCDD/F) collected in four stations, all located in the Lagoon of Venice. Aerosols at the scale of the basin (i.e., within a distance of 20 km) were mainly characterised by two end-members, one natural (composed of mineral particulate and marine spray) and one anthropogenic (with at least two different source components), affecting the sites in various ways. Variability at the two distant (>20 km) sites (Valle Dogà, Valle Figheri) was mainly due to natural components, whereas the other two stations (city of Venice, Dogaletto, approximately 5 km) were mainly impacted by industrial (and urban) sources. Total annual inputs were compared with the limits recently set by law (maximum allowed discharge=MAD). In the year of study, MAD values were exceeded for total As, Cd, Hg, Pb, dissolved Zn, PAH and PCDD/F. These results indicate that industrial sources gave rise to a quasi-permanent compositional (background) effect near the industrial area. The risk associated with atmospheric deposition should be quantified within the DSPIR framework to avoid future negative consequences in populations living in the vicinity of Porto Marghera.

Atmosphere↗
PubMed1996

Spectroscopic diagnosis of cervical intraepithelial neoplasia (CIN) in vivo using laser-induced fluorescence spectra at multiple excitation wavelengths.

BACKGROUND AND OBJECTIVE: The diagnostic contribution of cervical tissue fluorescence spectra acquired in vivo at 380 and 460 nm excitation were analyzed using a general multivariate statistical algorithm. MATERIALS AND METHODS: The primary steps of the algorithm are to: (1) preprocess data to reduce interpatient and intrapatient variation of tissue spectra from the same diagnostic category, without a priori information, (2) dimensionally reduce the pre-processed spectral data using Principal Component Analysis, and (3) develop a probability based classification scheme based on logistic discrimination using the diagnostically useful principal components. The algorithm was tested on cervical tissue spectra acquired from 165 sites at 380 nm excitation and from 147 sites at 460 nm excitation. A retrospective and prospective estimate of the algorithm's performance was determined. RESULTS: At 460 nm excitation, (1) SILs can be differentiated from normal squamous tissues with an average sensitivity and specificity of 91% +/- 1.3 and 75.5% +/- 1, respectively; furthermore, (2) high grade SILs can be differentiated from low grade SILs with an average sensitivity and specificity of 80% +/- 4 and 76% +/- 5, respectively. In addition, using tissue spectra at 380 nm excitation, SILs can be differentiated from normal columnar epithelia and inflammation with an average sensitivity and specificity of 77% +/- 1 and 72% +/- 9, respectively. CONCLUSIONS: Fluorescence spectra at multiple excitation wavelengths are essential for the detection and differential diagnosis of SILs at colposcopy.

Algorithms↗
PubMed1993

Proximal tibial osteotomy. A critical long-term study of eighty-seven cases.

Eighty-seven valgus osteotomies of the tibia were performed in seventy-three patients for osteoarthrosis of the medial compartment of the knee; the median follow-up was ten years (range, three to fourteen years). The data were subjected to univariate and multivariate statistical analysis and to survivorship analysis. For these calculations, the end-point of failure was defined as an arthroplasty of the knee, and additional calculations were performed with the end-point defined as the performance of an arthroplasty or moderate or severe pain in patients who had declined an arthroplasty. None of the many risk factors that were evaluated could be found to be associated with the duration of survival, except for relative weight and angular correction. The median loss of correction after the osteotomy was 1 degree. If, at one year after the operation, the valgus angulation was 8 degrees or more, or if the patient's weight was 1.32 times the ideal weight or less, the probability of survival five years thereafter was at least 90 per cent and the probability ten years thereafter was at least 65 per cent. However, when valgus angulation at one year was less than 8 degrees in a patient whose weight was more than 1.32 times the ideal weight, the rate of survival decreased to 38 per cent five years thereafter and to 19 per cent ten years thereafter. There is a considerable risk of failure of a proximal tibial osteotomy if the alignment is not overcorrected to at least 8 degrees of valgus angulation and if the patient is substantially overweight.

Adult↗
PubMed1993

Relative involvement of protein kinase C and of the estrogen receptor in the cytotoxic action of a population of triphenylethylenes on MCF7 cells as revealed by correspondence factorial (CF) analysis.

A multivariate statistical method, correspondence factorial (CF) analysis, was used to examine the correlations among the protein binding and cell proliferation effects of a series of 36 di- and triphenylethylenes (DPEs and TPEs). The analysis was applied to a study which measured their competition for estradiol binding to cytosol estrogen receptor (ER), their influence on protein kinase C (PKC) activity under different conditions of enzyme activation, their ability to promote the growth of a breast cancer cell line and to inhibit growth at high concentrations (cytotoxicity). The CF analysis revealed several levels of correlation. First, it distinguished those molecules within the population that stimulated rather than inhibited PKC activity. Second, it made apparent a strong correlation between cytotoxicity and inhibition of Ca++ and phosphatidylserine-dependent PKC activity, which was most marked when the enzyme had been activated by diacylglycerol indicating that PKC inhibition under physiological conditions might contribute to the overall cytotoxicity of these compounds. Third, a lower level of correlation was established between competition for ER binding and cytotoxicity. Taken together, the results suggest that MCF7 cells might be most sensitive to a cytotoxic effect of TPEs (via PKC and other targets) when they at the same time decrease estrogen-stimulated proliferation via an ER-mediated antiestrogenic effect.

Animals↗
PubMed1993

Cardiac arrest: prognostic factors and outcome at one year.

This study was designed to determine by multivariate statistical methods the influence of 38 variables on outcome after cardiopulmonary resuscitation (CPR) and to assess neuropsychological status in long-term survivors. The charts of 181 consecutive patients resuscitated in a 1,100-bed University Hospital over a 2-year period were analyzed retrospectively. Of the 181 resuscitated patients, 23 (13%) could be discharged. Outcome was significantly affected by the following variables: presence of shock or renal failure before cardiac arrest (CA) (odds ratio = 10.6; 95% confidence interval = 1.3-85.8 and odds ratio = 13.8; 95% confidence interval = 1.7-109.2, respectively), administration of epinephrine (odds ratio = 11.2; 95% confidence interval = 3.2-39.2) or prolonged CPR (> 15 min) (odds ratio = 4.9; 95% confidence interval = 1.7-13.7). By contrast, when CA occurred in uncomplicated acute myocardial infarction a significantly better prognosis could be demonstrated (odds ratio = 0.2; 95% confidence interval = 0.0-0.6). The 10 long-term survivors investigated lead an independent life and all returned to former occupation. The most common complaint was moderate memory disturbance (five patients). The conclusion is that this study confirms the critical influence of cellular anoxia on prognosis and allows the improved delineation of the situations in which cardiopulmonary resuscitation appears to be hopeless or likely to be successful. The follow up in a small number of survivors has shown a good quality of life and minor neuropsychological sequellae.

Cardiopulmonary Resuscitation↗
PubMed1998

Cephalometric features in the parents of children with orofacial clefting.

This nonrandomised retrospective case-comparison survey was based on the hypothesis that craniofacial morphometric features can be used to identify individuals at greater risk for having children with a cleft. The theory of aetiological heterogeneity suggests there may be differences according to gender and cleft type. From a completely ascertained sample of 286 children with cleft lip and/or palate born in the West of Scotland between 1 January 1980 and 31 December 1984, a sample of 83 parents of the children with non-syndromic clefts volunteered for lateral cephalometric examination. A comparison group was derived from the archives of Glasgow Dental Hospital. Multivariate statistical analyses were applied to identify which parental craniofacial parameters, if any, determine predisposition to orofacial clefting. Compared to the male comparison group, the fathers of children with CL(P) were shown to have reduced mandibular and symphyseal areas (P < 0.001), reduced maxillary area (P < 0.01) and a shorter palatal length (P < 0.01). The cranial base angle was more acute (P < 0.01) and the cross-sectional area of the cranium on lateral skull radiographs was significantly smaller (P < 0.001). However, the occipital subtenuce was larger in the fathers (P < 0.05). The craniofacial morphology in the mothers of children with CL(P) was characterized by a longer mandible (P = 0.011), an increase in the anterior facial height (P < 0.05) and greater facial length (P < 0.01). Anterior cranial base and the clivus length were also larger in the mothers (P < 0.05). The cranial parameters showed a similar trend to the paternal group with a reduced cranial area (P < 0.01) and an increase in the occipital subtenuce length (P < 0.001). Different cephalometric parameters distinguish fathers from a male comparison group and mothers from their female counterparts. An awareness of these parameters might be of value in the prediction of liability to clefting and may prove to be important in the quest for clues to the pathogenesis of both CP and CL(P).

Adult↗
PubMed1993

Volume of intracerebral hemorrhage. A powerful and easy-to-use predictor of 30-day mortality.

BACKGROUND AND PURPOSE: The aim of this study was to determine the 30-day mortality and morbidity of intracerebral hemorrhage in a large metropolitan population and to determine the most important predictors of 30-day outcome. METHODS: We reviewed the medical records and computed tomographic films for all cases of spontaneous intracerebral hemorrhage in Greater Cincinnati during 1988. Independent predictors of 30-day mortality were determined using univariate and multivariate statistical analyses. RESULTS: The 30-day mortality for the 188 cases of intracerebral hemorrhage was 44%, with half of deaths occurring within the first 2 days of onset. Volume of intracerebral hemorrhage was the strongest predictor of 30-day mortality for all locations of intracerebral hemorrhage. Using three categories of parenchymal hemorrhage volume (0 to 29 cm3, 30 to 60 cm3, and 61 cm3 or more), calculated by a quick and easy-to-use ellipsoid method, and two categories of the Glasgow Coma Scale (9 or more and 8 or less), 30-day mortality was predicted correctly with a sensitivity of 96% and a specificity of 98%. Patients with a parenchymal hemorrhage volume of 60 cm3 or more on their initial computed tomogram and a Glasgow Coma Scale score of 8 or less had a predicted 30-day mortality of 91%. Patients with a volume of less than 30 cm3 and a Glasgow Coma Scale score of 9 or more had a predicted 30-day mortality of 19%. Only one of the 71 patients with a volume of parenchymal hemorrhage of 30 cm3 or more could function independently at 30 days. CONCLUSIONS: Volume of intracerebral hemorrhage, in combination with the initial Glasgow Coma Scale score, is a powerful and easy-to-use predictor of 30-day mortality and morbidity in patients with spontaneous intracerebral hemorrhage.

Adult↗
PubMed2001

Comparative genomic hybridization detects genetic imbalances in primary ovarian carcinomas as correlated with grade of differentiation.

BACKGROUND: In the current study the authors attempted to evaluate genetic alterations in a large set of primary ovarian carcinomas and to compare the genetic findings with clinical parameters such as grade of tumor differentiation. This strategy was applied to identify chromosomal regions containing genes associated with tumor progression. METHODS: Genetic imbalances were assessed in 106 primary ovarian carcinomas using comparative genomic hybridization (CGH). CGH was applied because it is a powerful tool with which to screen the entire genome of a tumor for genetic changes by highlighting regions of altered DNA sequence copy numbers (deletions and amplifications). Multivariate statistical standard procedures were used to determine an association between tumor grading and genetic alterations. RESULTS: One hundred three carcinomas showed aberrant CGH profiles. The most frequent alterations were amplifications of 8q, 1q, 20q, 3q, and 19p, which occurred in 69-53% of tumors, and underrepresentations of 13q, 4q, and 18q, which occurred in 54-50% of tumors. Undifferentiated ovarian carcinomas (World Health Organization Grade 3) were found to be correlated significantly with underrepresentation of 11p and 13q as well as with overrepresentation of 8q and 7p (P = 0.001, 0.001, 0.01, and 0.027, respectively). However, 12p underrepresentation and 18p overrepresentation were significantly more frequent in well and moderately differentiated tumors (P = 0.01 and 0.004, respectively). To facilitate the interpretation and clinical application of the results of the current study, the significant aberrations were translated into a score system. This score system can be used easily for the prediction of an undifferentiated phenotype with a specificity and sensitivity of 79% and 86%, respectively. CONCLUSIONS: The current study data show that primary ovarian carcinomas are based on consistent genetic alterations that most likely are important for the development of this tumor entity. The correlation between certain aberrations and undifferentiated carcinomas may help to discriminate between primary and secondary genetic events and may indicate the location of those genes involved in cellular functions associated with tumor progression and the development of anaplastic and aggressive phenotypes.

Cell Differentiation↗
PubMed2005

Metal compartmentation and speciation in a soil sentinel: the earthworm, Dendrodrilus rubidus.

Earthworms are well-studied organisms in ecotoxicology because of their keystone ecological status and metal-accumulating capacity. However, the direct estimation of the bioreactive fractions of accumulated metal burdens remains technically elusive. In this study we exploited two physical techniques, electron probe X-ray microanalysis (EPXMA) and X-ray absorption spectroscopy (XAS), to improve understanding of the subcellular spatial distributions, ligand affinities, and coordination chemistries of Cd, Pb and Zn in a field population of the epigeic earthworm, Dendrodrilus rubidus. EPXMA and XAS analyses were performed on cryopreparations to maintain compositional fidelity; EPXMA data were analyzed by multivariate statistics. XAS provided whole-worm insights; EPXMA provided in situ, subcellular data from the major metal-sequestering tissue, the chloragog. Both techniques showed that Cd is coordinated with S; the measured Cd-S bond distance in XAS suggests a metallothionein-type ligand. The mean Cd:S molar ratio (EPXMA) of 0.36 is higher than the ratio of 0.29 estimated from published biochemical data. EPXMA and XAS data also found that Ca, Pb, and Zn are predominantly bound to one or more O-donating, probably phosphate-rich, ligands. X-ray distribution maps (EPXMA) of the hepatocyte-resembling chloragocytes revealed that the O-seeking (Ca, Pb, Zn) metals and S-seeking Cd bioaccumulate in distinct organelles. Extended X-ray absorption fine structure showed that the Pb complex is not biogenic pyromorphite, although X-ray absorption near edge structure did not eliminate the possibility. XAS provided no evidence of Pb spillage from the "sequestration compartment" within D. rubidus. However, the correspondence of Pb with Ca and P in EPXMA is not as strong as that of Zn. This is indicative either of spillover or of a second, hitherto unidentified, sequestered-Pb pool. By exploiting the complimentary techniques of EPXMA and XAS,we are closer to describing the mechanistic link between equilibrated body burdens and biomarker responses in earthworms.

Animals↗
PubMed2006

Overlap of anxiety and depression in a managed care population: Prevalence and association with resource utilization.

OBJECTIVE: To characterize the diagnosis of anxiety and depression within a large managed care population and to measure the impact of having both of these conditions on treatment patterns, health care utilization, and cost. Further, to compare the impact of having both conditions with having neither or either condition alone. METHOD: A retrospective, cross-sectional analysis of population-level anxiety-related and depression-related utilization over a 12-month study period was conducted. Data were from the PharMetrics Patient-Centric database, which is composed of medical and pharmaceutical claims for approximately 36 million patients from 61 health plans across the United States. Patients 18 years and older were included as cases in the analysis if they had a diagnosis of depression or anxiety during 2002. Four groups were identified based on the presence of anxiety and/or depression diagnosis: anxiety only, depression only, anxiety and depression, and controls. Controls were matched to the anxiety and depression cohort using a 4:1 ratio, based on patient age, gender, and similarity of health coverage. Cohorts were compared with respect to patient demographics, comorbid diagnoses, medication use, specialist care, utilization of health care services, and treatment costs, using both univariate and multivariate statistics. RESULTS: Significant differences in comorbid diagnoses, medication use, health care utilization, and treatment costs existed between the study groups. Specifically, patients with both anxiety and depression tended to have more somatic complaints such as abdominal pain, malaise, or chest pain than patients with either condition alone or the control group. Antidepressant use was highest among the anxiety and depression cohort, while anxiolytic use was as prevalent in the anxiety and depression cohort as in the anxiety only cohort. Patients in the anxiety only, depression only, or anxiety plus depression groups had a higher number of anxiety- and/or depression-related visits as well as visits not related to depression or anxiety than the control group, with the anxiety and depression cohort incurring the highest utilization of medical services. Similarly, in terms of cost, the disease cohorts incurred significantly higher cost than their control counterparts, with the anxiety and depression cohort incurring higher cost than those with either condition alone, even after accounting for differences in patient characteristics. CONCLUSIONS: Combination of anxiety and depression is fairly common in a managed care population as evidenced by diagnosis and treatment. The combination of both diagnoses appears to increase the complexity of these patients with respect to comorbid conditions as well as increases the economic cost to payers.

Adolescent↗