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S Kramer

Publications and source records attributed to S Kramer.

At least 37 records · Page 2Linked to original sources
PubMed2001

Data quality in predictive toxicology: reproducibility of rodent carcinogenicity experiments.

We compared 121 replicate rodent carcinogenicity assays from the two parts (National Cancer Institute/National Toxicology Program and literature) of the Carcinogenic Potency Database (CPDB) to estimate the reliability of these experiments. We estimated a concordance of 57% between the overall rodent carcinogenicity classifications from both sources. This value did not improve substantially when additional biologic information (species, sex, strain, target organs) was considered. These results indicate that rodent carcinogenicity assays are much less reproducible than previously expected, an effect that should be considered in the development of structure-activity relationship models and the risk assessment process.

Animals↗
PubMed2001

Percutaneous retrieval of lost or misplaced intravascular objects.

OBJECTIVE: We report on our experience with percutaneous interventional techniques for retrieval of intravascular foreign bodies or repositioning of misplaced endovascular prostheses. MATERIALS AND METHODS: Over a period of 6 years, we attempted percutaneous treatment of intravascular foreign bodies in 45 patients. The 45 foreign objects consisted of 12 endovascular stents, 14 catheter fragments, 11 embolization coils, four guidewire fragments, three vena cava filters, and one cardiac valve fragment. Percutaneous extraction was performed using a combination of multipurpose catheters and nitinol snare loop or grasping forceps. Depending on their composition, misplaced or dislodged intravascular stents were either repositioned or percutaneously removed. RESULTS: Percutaneous intervention was successful in 41 (91.1%) of 45 patients. Of 38 patients on whom we performed percutaneous removal, the procedure was successful in 34 patients (89.5%), including 13 of the 14 patients with catheter fragments, all four of the patients with guidewire fragments, 10 of the 11 patients with misplaced or dislodged embolization coils, four of the five patients with misplaced or dislodged endovascular stents, and all three of the patients with misplaced or dislodged vena cava filters. The procedure was not successful in the one patient with a cardiac valve fragment. All seven of the percutaneous repositioning procedures we performed resulted in the endovascular stent being successfully repositioned in a stable intravascular position. Most of the retrieval procedures (77.7%) were performed using the nitinol snare as the primary instrument. No late complications were registered during the follow-up period, which ranged from 9 to 68 months (mean, 42.4 months overall). CONCLUSION: Percutaneous techniques for the extraction of intravascular foreign objects or for repositioning of dislocated endovascular stents are highly effective with a low rate of complications and should always be the primary method of choice.

Blood Vessels↗
PubMed2001

Mental illness and communication.

Historical and more recent descriptions of mental illness emphasise the prominent nature of communicative difficulties in persons with these diagnoses (Sims 1995) and a large part of psychiatric intervention is verbally-mediated. Within this study, a theoretically-driven therapy programme addressed the communication needs of two persons with schizophrenia. Significant improvements were demonstrated using valid and reliable outcome measures.

Adult↗
PubMed2000

Analysis of local strain in aluminium interconnects by energy filtered CBED

Energy filtered convergent beam electron diffraction (CBED) was used to investigate localised strain in aluminium interconnects. The quantitative analysis of the experimental patterns is based on a multi-step evaluation procedure which is the main subject of the present paper. The improvements which were made to the analysis method aim at increasing both the automation and the accuracy. The detection of the higher order Laue zone (HOLZ) line positions is performed by means of the Hough transform. The required sub-pixel resolution can be achieved routinely and the achievable accuracy is only limited by the line width and the amount of noise in the patterns. The determination of the strain state is performed via a refinement algorithm which is based on varying the strain state in the sample coordinate system and simulating the patterns for the individual grains until a best fit with the experiment is obtained. For the simulation we have developed a new correction scheme in which the dynamical effects are treated separately for each individual HOLZ line. The results show that the main source of the observed strains is the difference in thermal expansion coefficients. The strain is substantially reduced underneath a hillock in the interconnect. Asymmetries in the strain distribution around the hillock show that the unidirectional diffusion during electromigration tests causes peak strains in areas next to the hillock which may be possible failure sites.

Journal Article↗
PubMed2000

Optimal outcome measures, research priorities, and international cooperation.

The participants in the Eriksholm Workshop on "Measuring Outcomes in Audiological Rehabilitation Using Hearing Aids" debated three issues that are reported in this article. First, it was agreed that the characteristics of an optimal outcome measure vary as a function of the purpose of the measurement. Potential characteristics of outcome self-report tools for four common goals of outcome measurement are briefly presented to illustrate this point. Second, 10 important research priorities in outcome measurement were identified and ranked. They are presented with brief discussion of the top five. Third, the concept of generating a brief universally applicable outcome measure was endorsed. This brief data set is intended to supplement existing outcome measures and to promote data combination and comparison across different social, cultural, and health-care delivery systems. A set of seven core items is proposed for further study.

Correction of Hearing Impairment↗
PubMed2000

Knowledge discovery and data mining in toxicology.

Knowledge discovery and data mining tools are gaining increasing importance for the analysis of toxicological databases. This paper gives a survey of algorithms, capable to derive interpretable models from toxicological data, and presents the most important application areas. The majority of techniques in this area were derived from symbolic machine learning, one commercial product was developed especially for toxicological applications. The main application area is presently the detection of structure-activity relationships, very few authors have used these techniques to solve problems in epidemiological and clinical toxicology. Although the discussed algorithms are very flexible and powerful, further research is required to adopt the algorithms to the specific learning problems in this area, to develop improved representations of chemical and biological data and to enhance the interpretability of the derived models for toxicological experts.

Algorithms↗
PubMed2000

Data quality in predictive toxicology: identification of chemical structures and calculation of chemical properties.

Every technique for toxicity prediction and for the detection of structure-activity relationships relies on the accurate estimation and representation of chemical and toxicologic properties. In this paper we discuss the potential sources of errors associated with the identification of compounds, the representation of their structures, and the calculation of chemical descriptors. It is based on a case study where machine learning techniques were applied to data from noncongeneric compounds and a complex toxicologic end point (carcinogenicity). We propose methods applicable to the routine quality control of large chemical datasets, but our main intention is to raise awareness about this topic and to open a discussion about quality assurance in predictive toxicology. The accuracy and reproducibility of toxicity data will be reported in another paper.

Data Interpretation, Statistical↗
PubMed1999

Childhood predictors of violent behavior.

In this study, prospective childhood data from birth to 7 years of age were used to determine predictors of subsequent violent behavior. The childhood predictors found for the girls accounted for more variance in the reported later violent offenses: 24.9% compared to 3.8% for the boys. This large difference may be due partly to the fact that violent behavior is more unusual among girls; thus, those girls who are violent are more readily differentiated from the others. The only two early childhood variables that were found to predict for both genders were: (a) less normal behavior and (b) presence of deviant or stereotyped behavior. Thus, abnormal behavior in childhood can be considered to be a fairly reliable predictor to greater likelihood of later violent behavior.

Adolescent↗
PubMed1999

Amino acids of conserved kinase motifs of cytomegalovirus protein UL97 are essential for autophosphorylation.

Thirteen point mutations targeting predicted domains conserved in homologous protein kinases were introduced into the UL97 coding region of the human cytomegalovirus. All mutagenized proteins were expressed in cells infected with recombinant vaccinia viruses (rVV). Several mutations drastically reduced ganciclovir (GCV) phosphorylation. Mutations at amino acids G340, A442, L446, and F523 resulted in a complete loss of pUL97 phosphorylation, which was strictly associated with a loss of GCV phosphorylation. Our results confirm that in rVV-infected cells pUL97 phosphorylation is due to autophosphorylation and show that several amino acids conserved within domains of protein kinases are essential for this pUL97 phosphorylation. GCV phosphorylation is dependent on pUL97 phosphorylation.

Amino Acid Sequence↗
PubMed1999

Procarbazine, lomustine, and vincristine (PCV) chemotherapy for anaplastic astrocytoma: A retrospective review of radiation therapy oncology group protocols comparing survival with carmustine or PCV adjuvant chemotherapy.

PURPOSE: To determine any differences in outcome for patients with anaplastic astrocytoma (AA) treated with adjuvant carmustine (BCNU) versus procarbazine, lomustine, and vincristine (PCV) chemotherapy. MATERIALS AND METHODS: The Radiation Therapy Oncology Group (RTOG) database was reviewed for patients with newly diagnosed AA treated according to protocols that included either BCNU or PCV adjuvant chemotherapy. All patients were treated with radiation therapy. The outcome analysis included overall survival, taking into account patient age, extent of resection, Karnofsky performance status (KPS), and treatment group (BCNU v PCV). Stratified and nonstratified Cox proportional hazards models were used, as well as an analysis using matched cases between the groups. RESULTS: A total of 257 patients were treated with BCNU according to RTOG protocols 70-18, 83-02, and 90-06; 175 patients were treated with PCV according to RTOG protocol 94-04. All pretreatment characteristics except KPS were well balanced by treatment group; 61% of the BCNU group had a KPS of 90 to 100 compared with 73% of the PCV group (P =.0075). No statistically significant difference in survival was observed in any age group or by KPS or extent of surgery. The stratified analysis also showed no trends for improved survival by treatment group (P =. 40). The Cox model identified only age, KPS, and extent of surgery as important variables influencing survival, not treatment group. Matching cases between groups using age, KPS, and surgery resulted in 133 matched pairs. No difference in survival was observed (P =. 41). In a Cox model in which each matched pair is a strata, there was no difference between groups (P =.20). CONCLUSION: Using this retrospective analysis, there does not seem to be any survival benefit to PCV chemotherapy. Future phase III studies for patients with AA may need to consider whether BCNU or PCV is used in the control arm.

Adult↗
PubMed1999

Sprouty: a common antagonist of FGF and EGF signaling pathways in Drosophila.

Extracellular factors such as FGF and EGF control various aspects of morphogenesis, patterning and cellular proliferation in both invertebrates and vertebrates. In most systems, it is primarily the distribution of these factors that controls the differential behavior of the responding cells. Here we describe the role of Sprouty in eye development. Sprouty is an extracellular protein that has been shown to antagonize FGF signaling during tracheal branching in Drosophila. It is a novel type of protein with a highly conserved cysteine-rich region. In addition to the embryonic tracheal system, sprouty is also expressed in other tissues including the developing eye imaginal disc, embryonic chordotonal organ precursors and the midline glia. In each of these tissues, EGF receptor signaling is known to participate in the control of the correct number of neurons or glia. We show that, in all three tissues, the loss of sprouty results in supernumerary neurons or glia, respectively. Furthermore, overexpression of sprouty in wing veins and ovarian follicle cells, two other tissues where EGF signaling is required for patterning, results in phenotypes that resemble the loss-of-function phenotypes of Egf receptor. These results suggest that Sprouty acts as an antagonist of EGF as well as FGF signaling pathways. These receptor tyrosine kinase-mediated pathways may share not only intracellular signaling components but also extracellular factors that modulate the strength of the signal.

Animals↗
PubMed1999

Management of ectopic ureterocele associated with renal duplication: a comparison of partial nephrectomy and endoscopic decompression.

PURPOSE: We compared the efficacy of primary endoscopic decompression versus partial nephrectomy for treating ectopic duplex ureteroceles. MATERIALS AND METHODS: We retrospectively reviewed the records of patients with renal duplication and upper pole ectopic ureterocele. Patients were classified according to the initial radiological evaluation. The operation performed was arbitrarily chosen by the surgeon. RESULTS: A total of 54 patients had unilateral upper or bilateral upper pole ureterocele with no associated vesicoureteral reflux. Partial nephrectomy was performed in 26 patients, of whom 4 (15%) required additional surgery for new onset ipsilateral lower pole reflux. Endoscopic decompression was performed in 28 patients, of whom 18 (64%) required additional treatment due to reflux into the ipsilateral lower pole ureter and ureterocele in 9, reflux into the ureterocele only in 4, ipsilateral lower pole reflux only in 3 and persistent ureterocele obstruction in 2 (p<0.01). An ectopic ureterocele with vesicoureteral reflux into 1 or more moieties was identified in 111 patients, including 56 of 67 (84%) treated with partial nephrectomy and 37 of 44 (84%) treated with endoscopy who have persistent reflux or required further surgery for reflux resolution. CONCLUSIONS: In patients with an ectopic ureterocele and no vesicoureteral reflux partial nephrectomy should be considered the treatment of choice. However, when the initial cystogram reveals vesicoureteral reflux, partial nephrectomy and endoscopic ureterocele decompression have identical definitive cure rates of only 16%. The majority of the latter patients require continued observation and/or additional surgery for managing persistent reflux.

Abnormalities, Multiple↗
PubMed1998

sprouty encodes a novel antagonist of FGF signaling that patterns apical branching of the Drosophila airways.

Antagonists of several growth factor signaling pathways play important roles in developmental patterning by limiting the range of the cognate inducer. Here, we describe an antagonist of FGF signaling that patterns apical branching of the Drosophila airways. In wild-type embryos, the Branchless FGF induces secondary branching by activating the Breathless FGF receptor near the tips of growing primary branches. In sprouty mutants, the FGF pathway is overactive and ectopic branches are induced on the stalks of primary branches. We show that FGF signaling induces sprouty expression in the nearby tip cells, and sprouty acts nonautonomously and in a competitive fashion to block signaling to the more distant stalk cells. sprouty encodes a novel cysteine-rich protein that defines a new family of putative signaling molecules that may similarly function as FGF antagonists in vertebrate development.

Amino Acid Sequence↗
PubMed1998

A framework for assessing communication in mental illness.

Many studies support the notion of semantic and/or pragmatic difficulties in people with mental illness. This paper describes a framework (based on a discourse analysis model) for the assessment and reassessment of communication in mentally ill persons.

Communication Disorders↗
PubMed1998

'Confabulation' in narrative discourse by schizophrenic patients.

There are many clinical reports of confabulation by schizophrenic patients. This study provides evidence of a form of confabulation by schizophrenic patients in tasks which do not include a memory component. It uses a linguistic framework to analyse the components of this confabulation.

Cognition Disorders↗