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PubMed2003

Using lowess to remove systematic trends over time in predictor variables prior to logistic regression with quantile categories.

In case-control studies one may employ logistic regression to model the relationship between binary responses and continuous predictor variables that have been categorized by the empirical quartiles of the controls. Sometimes, however, systematic trends over time (or drifts) contaminate the laboratory measurements of predictor variables. In this paper we consider the use of locally weighted robust regression (lowess) to estimate and remove these systematic trends when the trends for the cases and controls have a common shape. One can then use the lowess adjusted data in the desired logistic regression model. We illustrate these methods with a case-control study that was designed to assess the risk of oesophageal cancer as a function of the quartile categories of sphinganine levels in the blood serum. Upon examination of the data, it was discovered that the sphinganine laboratory measurements were contaminated by a systematic trend, the magnitude of which depended only on the day of analysis. This trend needed to be removed before performing further analyses of the data. In addition, we present simulations to examine the use of lowess methods to estimate and remove various shapes of trends from contaminated predictor data before constructing logistic regression models with quartile categories. We found that using the trend-contaminated data tends to give attenuated parameter estimates and hence lower significance and power levels than using the uncontaminated data. Conversely, using appropriate lowess methods to adjust the data tends to give nearly unbiased parameter estimates, near nominal significance levels, and improved power.

Adult↗

PubMed1994

Transcript map of two regions from chromosome XI of Saccharomyces cerevisiae for interpretation of systematic sequencing results.

A detailed and systematic transcript map is a first and necessary step to characterize new genes revealed by systematic sequencing. Chromosome XI of Saccharomyces cerevisiae contains 331 open reading frames (ORFs) of which 44% are of unknown function (Dujon et al., 1994). As a first study towards complete transcript analysis of chromosome XI, we have extracted RNA from three isogenic strains (a, alpha and 2n) grown in three standard laboratory media, and have analysed them using contiguous probes covering two regions of 17 and 19 kilobases, respectively. All 20 predicted ORFs in the sequences correspond to expressed genes, six of which have no predicted function. Four short ORFs which were suspected as not being real genes on the basis of their sequence are not expressed in our growth conditions. An additional transcript which does not correspond to a large ORF was found. Steady-state RNA level of most ORFs is 10 to 100 times than that of the actin gene, only three are transcribed in comparable amounts. Three ORFs show variable levels of transcripts in the different growth conditions, all patterns being different from one another. Extrapolation of these results to systematic transcript analysis of chromosome XI and other yeast chromosomes is presented.

Base Sequence↗

PubMed1999

Sedimentation equilibrium analysis of interference optical data by systematic noise decomposition.

An analytical method is described for removal of systematic signal offsets from interference optical data of sedimentation equilibrium gradients. It is demonstrated that the time-invariant signal contributions can be extracted from hydrodynamic modeling of interference profiles acquired during the approach to sedimentation equilibrium. This method is based on a technique for the explicit algebraic calculation of time-invariant noise components from sedimentation data, recently described for the direct modeling of sedimentation velocity experiments (P. Schuck and B. Demeler, Biophys. J. 76, 2288-2296, 1999). The calculated systematic signal offset is very well defined by the experimental data, stable over time, and its calculation is robust and to a large extent independent of the hydrodynamic model. The calculated time-invariant signal can be used to reduce the systematic errors in the measured sedimentation equilibrium profiles by more than an order of magnitude. It is shown that the resulting net equilibrium fringe profiles after subtraction of the time-invariant noise component allow equilibrium analyses consistent with those obtained from absorbance profiles. However, due to a higher dynamic range and the higher number of data points, the parameters derived from the net interference analysis can exhibit significantly improved precision. The presented study demonstrates the feasibility and potential of this analytical method for full exploitation of the remarkable precision of the interference optical data acquisition system, allowing sedimentation equilibrium experiments at loading concentrations below 0.05 mg/ml.

Histocompatibility Antigens Class I↗

PubMed2001

Systematic optimization of expression and refolding of the Plasmodium falciparum cysteine protease falcipain-2.

The Plasmodium falciparum cysteine protease falcipain-2 is a potential new target for antimalarial chemotherapy. In order to obtain large quantities of active falcipain-2 for biochemical and structural analysis, a systematic assessment of optimal parameters for the expression and refolding of the protease was carried out. High-yield expression was achieved using M15(pREP4) Escherichia coli transformed with the pQE-30 plasmid containing a truncated profalcipain-2 construct. Recombinant falcipain-2 was expressed as inclusion bodies, solubilized, and purified by nickel affinity chromatography. A systematic approach was then used to optimize refolding parameters. This approach utilized 100-fold dilutions of reduced and denatured falcipain-2 into 203 different buffers in a microtiter plate format. Refolding efficiency varied markedly. Optimal refolding was obtained in an alkaline buffer containing glycerol or sucrose and equal concentrations of reduced and oxidized glutathione. After optimization of the expression and refolding protocols and additional purification with anion-exchange chromatography, 12 mg of falcipain-2 was obtained from 5 liters of E. coli, and crystals of the protease were grown. The systematic approach described here allowed the rapid evaluation of a large number of expression and refolding conditions and provided milligram quantities of recombinant falcipain-2.

Animals↗

PubMed1994

Computational problems in molecular systematics.

The development of extremely powerful computer programs and the ready availability of microcomputers has revealed several computational problems with data analysis. These problems occur in the handling of systematic data in general and molecular systematic data in particular. This paper examines three areas of controversy in molecular systematics resulting from increased computer power. We start by examining the first step in DNA sequence analysis, the establishment of homology via sequence alignment. Next we examine several problems in phylogenetic analysis that have arisen in the last few years due to use of the PAUP (Swofford, 1991), HENNIG86 (Farris, 1988), and PHYLIP programs. These problems include limitations on the number of taxa examined in a given analysis and the accuracy of the parsimony trees in such analyses. The final subject is an examination of programs used for assessing tree robustness. We concentrate on certain programs (such as MALIGN (Wheeler and Gladstein, 1993), PAUP (Swofford, 1991), HENNIG86 (Farris, 1988), PHYLIP (Felsenstein, 1990), CLADOS (Nixon, 1993), MacClade (Maddison and Maddison, 1993), etc.), but similar comments about other programs could also be made.

Animals↗

PubMed2002

Higher-level systematic analysis of birds: current problems and possible solutions.

Avian systematics has a rich history, as evolutionary biologists have long been interested in this conspicuous and diverse group of vertebrates. Many prominent scientists, and evolutionary biologists in particular, have focused their efforts on birds. Perhaps no other group of vertebrates is so well studied. Yet, despite the attention paid to this group, much about the history of the class Aves remains controversial, both with respect to the origin of birds and the history since that origin. This puts avian systematists in a unique position, with so much information available and so many unanswered questions to pursue. The fact that avian ordinal relationships are still the center of much controversy speaks to the difficulty of the problem. While many prominent morphologists have worked on avian relationships, relatively few morphological studies have identified characters with informative variation for interordinal relationships. Molecular data offer the hope for phylogenetic information not present (or not discovered) in avian anatomy. Since the first study of avian proteins for the purposes of systematics (Sibley, 1960), several prominent molecular systematists have devoted tremendous time and resources to solving the problems of avian relationships using molecular characters (see Barrowclough, 1992 and Sheldon and Bledsoe, 1993 and references therein). So far, their efforts have not produced adequate resolution, at least not in the minds of most practicing systematists. Here, we first outline what we think we do know about higher order avian systematics and discuss some specific cases of molecular data applied to this question. Next, we consider some of the problems which may be blocking a clearer understanding of avian relationships. We then go on to offer some new directions for systematists working on this difficult group.

Animals↗

PubMed1995

At convenience and systematic random sampling: effects on the prognostic value of nuclear area assessments in breast cancer patients.

This study compares the influence of two different nuclear sampling methods on the prognostic value of assessments of mean and standard deviation of nuclear area (MNA, SDNA) in 191 consecutive invasive breast cancer patients with long term follow up. The first sampling method used was 'at convenience' sampling (ACS); the second, systematic random sampling (SRS). Both sampling methods were tested with a sample size of 50 nuclei (ACS-50 and SRS-50). To determine whether, besides the sampling methods, sample size had impact on prognostic value as well, the SRS method was also tested using a sample size of 100 nuclei (SRS-100). SDNA values were systematically lower for ACS, obviously due to (unconsciously) not including small and large nuclei. Testing prognostic value of a series of cut off points, MNA and SDNA values assessed by the SRS method were prognostically significantly stronger than the values obtained by the ACS method. This was confirmed in Cox regression analysis. For the MNA, the Mantel-Cox p-values from SRS-50 and SRS-100 measurements were not significantly different. However, for the SDNA, SRS-100 yielded significantly lower p-values than SRS-50. In conclusion, compared with the 'at convenience' nuclear sampling method, systematic random sampling of nuclei is not only superior with respect to reproducibility of results, but also provides a better prognostic value in patients with invasive breast cancer.

Biopsy↗

PubMed2002

Systematic overview of quality of life studies for breast cancer.

BACKGROUND: The concept of quality of life (QOL) is essentially subjective, determined from the patient's point of view. Thus, an appropriate investigation and analysis of QOL as an indicator of medical treatment outcome is a task of some difficulty. The physician-led QOL assessment studies to date in Japan have suffered from insufficient knowledge and understanding of the diverse factors contributing to QOL, thereby contributing to a dearth of quality studies. Given this background, the Japanese Breast Cancer Society has established a Task Force for the development of guidelines to properly conduct QOL assessment studies. The present article reports the results of a large-scale systematic overview of QOL assessment studies for breast cancer patients that was undertaken as one part of this project. METHODS: Six databases were used in this overview: MEDLINE, CINAHL, CANCERLIT, EMBASE, PsychINFO, and Japan Centra Revuo Medicina. The search period was 1982-1999 for CINAHL, and 1990-1999 for the others. Following a check of the titles, important information was recorded on relevance and data collection forms. RESULTS: A systematic search was conducted of the literature on QOL assessment studies for breast cancer patients, and 1,954 articles were extracted from a check of titles. Using the relevance and data collection forms, the number of articles was further narrowed to 126. These articles were then classified according to the type and design of the study, the number of QOL and psychological measures used, frequency of use of each measure, and study focus and type of intervention. The results were then compiled. CONCLUSION: To date there have been almost no appropriate systematic overviews or guidelines issued for QOL assessment studies related to breast cancer, even on the international level. The results of the present study may contribute high-quality QOL information for evidence-based medicine, as it continues to gain global prevalence.

Adaptation, Physiological↗

PubMed2000

Improving diagnostic accuracy of prostate carcinoma by systematic random map-biopsy.

Systematic random rectal ultrasound directed map-biopsy of the prostate was performed in 77 RDE (rectal digital examination) positive and 25 RDE negative cases, if applicable. Hypoechoic areas were found in 30% of RDE positive and in 16% of RDE negative cases. The score for carcinoma in the hypoechoic areas was 6.5% in RDE positive and 0% in RDE negative cases, whereas systematic map biopsy detected 62% carcinomas in RDE positive, and 16% carcinomas in RDE negative patients. The probability of positive diagnosis of prostate carcinoma increased in parallel with the number of biopsy samples/case. The importance of systematic map biopsy is emphasized.

Aged↗

PubMed1996

[Principles and results of systematic lymph node dissection in surgically treated bronchial carcinoma].

Lymphatic spread of bronchial carcinoma can reach any part of the mediastinum, irrespective of the localisation of the primary tumor. Metastatic spread may not affect all topographical lymph node positions, but this is unpredictable. The number of lymph nodes in each position varies. Therefore, systematic mediastinal lymph node dissection includes all ipsilateral compartments of the mediastinum. It is also possible to reach contralateral sites. In right-sided thoracotomies the lymph node dissection is standardized. Mobilizing the aortic arch and the large vessels also allows complete mediastinal dissection by a left-sided approach. The surgical technique is described. Perioperative morbidity does not increase. Systematic mediastinal lymph node dissection is the gold standard for evaluation of an exact pN stage. The stage-related survival rate is significantly improved. Therefore, it should be required that systematic mediastinal lymph node dissection be standard in the surgical treatment of bronchial carcinoma.

Carcinoma, Bronchogenic↗

PubMed2001

Genetic predisposition and environmental causes in periodic and systematic catatonia.

The nosological heterogeneity of catatonic schizophrenia was the focus of a family study involving 139 catatonic patients. The clinical dichotomization of catatonia into periodic catatonia and systematic catatonia revealed good inter-rater reliability and stability of the diagnoses at follow-up. Analysis of the cumulative morbidity risk among first-degree relatives gave an excessive familial aggregation of homogenous psychoses in periodic catatonia with a risk of 26.9%. The mode of inheritance was consistent with an autosomal dominant model. In contrast, first-degree relatives of probands with systematic catatonia had a morbidity risk of 4.6%. Subsequent investigations pointed to a potential association of systematic catatonia to exposure to midgestational infections in the index cases and linked these sporadic disorders to disturbances of fetal neurodevelopment. The periodic catatonia, an unequivocally genetically transmitted illness, is at present under investigation in a genome-wide linkage analysis.

Catatonia↗

PubMed2006

Adrenal axis function does not appear to be associated with hemodynamic improvement in septic shock patients systematically receiving glucocorticoid therapy.

OBJECTIVE: There is mounting evidence showing the value of low-dose corticosteroids in patients with septic shock requiring vasopressor therapy. It remains unclear whether adrenal function tests should be carried out systematically to guide the decision on glucocorticoid therapy. METHODS: The retrospective study was conducted in 52 patients in three university hospital ICUs. We included consecutive patients with catecholamine-dependent septic shock who had not received ketoconazole, glucocorticoids, or etomidate in the 24 h before the ACTH test, and who had survived to day 3 after the shock onset. All patients had a 250-microg ACTH test before systematic glucocorticoid therapy was started. Various definitions of relative adrenal insufficiency were used (based on cortisol basal level and/or change in cortisol level after ACTH stimulation). We defined hemodynamic improvement as a 50% reduction in the vasoactive agent dose in the 3 days following the initiation of glucocorticoid treatment. The relationship between the hemodynamic improvement and the results of the adrenal function tests was analyzed. RESULTS: Hemodynamic improvement occurred in 29 patients (55.8%). Baseline characteristics, sites of infection, types of micro-organisms and antibiotic management did not differ between patients with and those without hemodynamic improvement. Relative adrenal insufficiency whatever the definition was not associated with hemodynamic improvement. CONCLUSION: In catecholamine-dependent septic shock patients managed with systematic glucocorticoid therapy the results of ACTH stimulation do not predict hemodynamic improvement.

Adrenal Glands↗

PubMed2003

An unusual systematic behaviour of detection limits for elements from 55Cs to 73Ta.

A representative database for detection limits for all elements from (55)Cs to (73)Ta reveals that these limits are governed by a systematic zigzag pattern, according to which the odd atomic number elements have systematically lower detection limits than the even atomic number neighbour elements. This is true even when the actual detection limits vary by several orders of magnitude. We propose that such a systematic pattern be used as a requisite analytical criterion to evaluate the detection limit data, and any departure from this pattern be looked on with caution to check the analytical technique for any interference or matrix effect problems.

Journal Article↗

PubMed1998

Systematic lymph node dissection for clinically diagnosed peripheral non-small-cell lung cancer less than 2 cm in diameter.

The value of radical systematic lymphadenectomy for treatment of early-stage bronchial carcinoma is controversial. We performed a prospective randomized study to address this question. Altogether 115 patients with peripheral non-small-cell lung cancers smaller than 2 cm in diameter were enrolled in this study. They were randomly assigned into a lobectomy with lymph node sampling group (sampling group, n = 56) or a lobectomy with radical systematic lymph node dissection group (dissection group, n = 59). Inclusion criteria were based only on preoperative clinical studies. Four tumors were larger than 2 cm postoperatively. One patient had disseminated disease, and two had intrapulmonary metastases discovered at surgery. Two patients had small-cell carcinoma. There were four with pathologic N1 disease and seven with N2 disease in the dissection group and three with N1 and eight with N2 disease in the sampling group. The numbers of local and distant recurrences were two and six, respectively, in the dissection group and two and five in the sampling group. The overall 5-year survival was 81% in the dissection group and 84% in the sampling group. No significant differences in the recurrence rate or survival was seen between the groups. Our results demonstrate that clinically evaluated peripheral non-small-cell carcinomas smaller than 2 cm in diameter do not require radical systematic mediastinal and hilar lymph node dissection.

Aged↗

PubMed2006

A comparison of the diagnostic performance of systematic versus ultrasound-guided biopsies of prostate cancer.

Transrectal ultrasound (TRUS) is an important tool for urologists and radiologists in the detection of prostate cancer. Various TRUS-guided biopsy techniques are applied in clinical practice. Frequently, only the detection rates achieved with these methods are compared. Other diagnostic performance parameters, particularly the specificity and negative predictive value, are seldom compared. After extensive assessment of the available literature, this review describes the methods of TRUS-guided biopsy for prostate cancer detection. A distinction was made between systematic biopsies and biopsies that target a perceived (hypoechoic or Doppler-enhancing) lesion on imaging. Subsequently, the diagnostic performance (sensitivity, specificity, positive and negative predictive values, accuracies) was compared between these techniques. Imaging-guided biopsy showed better diagnostic performance than systematic biopsy with higher sensitivity. The combinations of sensitivity and specificity were highest for colour Doppler and contrast-enhanced targeted biopsy. Studies targeting hypoechoic lesions had relatively high sensitivity, but specificity was low. Presently however, with widespread prostate-specific antigen screening, fewer prostate cancers are hypoechoic, and the value of targeting hypoechoic lesions has diminished. Performing colour or contrast-enhanced Doppler biopsy or adding these techniques to systematic biopsies improves diagnostic performance, particularly by increasing sensitivity.

Biopsy↗

PubMed1997

[Systematic reviews in cardiology: approaches to evidence-based medicine and the Cochrane Collaboration].

The ever growing tide of results from great numbers of clinical studies clearly outweighs the abilities of the individual clinician to keep abreast of the actual state of scientific evidence and to apply it in his clinical decision-making in a timely and valid manner. Evidence-based medicine, with its central demand to link best individual clinical knowledge with best available external, scientific evidence to achieve optimal patient care, has clearly identified the urgent need for scientific techniques which allow the synthesis of scientific evidence, as collected in numerous singular studies, in an explicit, reproducible, and critically appraisable report format, and to update these reports regularly. The methods of Systematic Reviews, encompassing the techniques of meta-analysis, were developed for this purpose. They are explained and presented here in detail as they relate to the field of cardiology. Various problematic aspects have recently dominated cardiologists' discussion of meta-analyses. We point out that the techniques of Systematic Reviews hold promising solutions for many of them and that work on technical improvements is ongoing. The International Cochrane Collaboration is introduced as a global network of scientists and experts from varying fields of medicine with the aim of producing highest quality Systematic Reviews on a wide scope of topics. However, to date only few cardiologists have joined the rapidly rising numbers of Cochrane collaborators.

Cardiology↗

PubMed2005

Transperineal ultrasound-guided 12-core systematic biopsy of the prostate for patients with a prostate-specific antigen level of 2.5-20 ng/ml in Japan.

BACKGROUND: The aim of this study was to investigate the cancer detection rate in patients with a prostate-specific antigen (PSA) level of 2.5 to 20 ng/ml, using transperineal ultrasound-guided systematic biopsy of the prostate. METHODS: Three hundred consecutive patients with PSA levels of 2.5 to 20 ng/ml underwent transperineal ultrasound-guided 12-core systematic biopsy of the prostate. RESULTS: Prostate cancer was detected in 108 of the 300 patients (36.0%). The cancer detection rates in patients with total PSA levels of 2.5-4.0, 4.01-10.0 and 10.01-20.0 ng/ml were 18.2%, 31.0%, and 50.0%, respectively. The cancer detection rates in patients with prostate volumes of less than 30 cc and over 50 cc were almost 50%, and 13.3%, respectively. The cancer detection rate in patients with a PSA density (PSAD) of less than 0.10 ng/ml per cc was only 5.6%, and no prostate cancer was detected in patients with a free-to-total PSA ratio (% f PSA) over 40%. CONCLUSION: We demonstrated a high prostate cancer detection rate by the transperineal ultrasound-guided 12-core systematic biopsy method in patients with PSA levels of 2.5 to 20 ng/ml. Accordingly, if the number of core biopsies is further increased overall, except in patients with a large prostate volume, and if the indication for biopsy is decided based on the PSAD and %f PSA, then the cancer detection rate by the present method may be further improved, with fewer unnecessary biopsies.

Adult↗

PubMed2006

Cestode systematics and phylogeny move forward.

This paper represents a meeting report for the Fifth International Workshop on Cestode Systematics and Phylogeny held at the Institute of Parasitology, Academy of Sciences of the Czech Republic, Ceské Budejovice, 18-22 July 2005. The major topics discussed included (i) the progress in cestode systematics during 2002-2005, (ii) the use of the life-cycle data in phylogenetic studies, (iii) the utilisation of new morphological and molecular characters in cestode systematics and phylogeny, and (iv) the ongoing work on the completion of the Global Cestode Database.

Animals↗