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PubMed2005

Constructing support vector machine ensembles for cancer classification based on proteomic profiling.

In this study, we present a constructive algorithm for training cooperative support vector machine ensembles (CSVMEs). CSVME combines ensemble architecture design with cooperative training for individual SVMs in ensembles. Unlike most previous studies on training ensembles, CSVME puts emphasis on both accuracy and collaboration among individual SVMs in an ensemble. A group of SVMs selected on the basis of recursive classifier elimination is used in CSVME, and the number of the individual SVMs selected to construct CSVME is determined by 10-fold cross-validation. This kind of SVME has been tested on two ovarian cancer datasets previously obtained by proteomic mass spectrometry. By combining several individual SVMs, the proposed method achieves better performance than the SVME of all base SVMs.

Algorithms↗
PubMedDate not supplied

Cellular drug resistance in acute myeloid leukemia: literature review and preliminary analysis of an ongoing collaborative study.

Cellular drug resistance is one of the main causes of the frequent ultimate failure of chemotherapy in childhood acute myeloid leukemia (AML). We here summarize the results of a literature review on in vitro drug resistance in childhood AML, focusing on studies using so-called cell culture assays. We also briefly describe some results of an ongoing collaborative study between the Research Laboratory of Pediatric Oncology in Amsterdam (University Hospital Vrije Universiteit) and the German BFM-AML Group. In general, the literature and our preliminary data on in vitro cellular drug resistance in AML are promising in terms of clinical relevance. Cell biological features and clinical response to chemotherapy are related to in vitro drug resistance. However, a large study including multivariate analysis is required to more firmly establish the clinical value of cellular drug resistance testing in childhood AML, and the collaborative study will therefore be continued. Possible applications of cell culture assays include risk-group stratification, rational improvements of current treatment protocols for subgroups of patients based on specific drug resistance profiles, individualised tailored therapy, the study of cross-resistance patterns between drugs, the study of possibilities to modulate or circumvent drug resistance, the study of drug interactions, selection of patients for clinical phase II studies and drug screening.

Acute Disease↗
PubMed2001

Doppler ultrasound velocimetry for timing the second intrauterine transfusion in fetuses with anemia from red cell alloimmunization.

OBJECTIVE: Middle cerebral artery peak systolic velocity has been successfully used for timing the first cordocentesis in fetuses who are at risk for anemia because of maternal red cell alloimmunization. The effects on Doppler velocimetry after the intrauterine transfusion of adult blood to these fetuses are unknown. The objective of this study was to assess the applicability of Doppler methods for the prediction of severe anemia in fetuses who had undergone 1 previous intrauterine transfusion. STUDY DESIGN: Doppler examination of middle cerebral artery peak systolic velocity was performed before cordocentesis in 64 fetuses who had undergone 1 previous intrauterine transfusion. Timing of the second intrauterine transfusion was based on traditional criteria. Anemia was defined as mild (hemoglobin value between 0.84 and 0.65 multiples of the median), moderate (hemoglobin value <0.65-0.55 multiples of the median), and severe (hemoglobin value <0.55 multiples of the median). Receiver operator characteristic curves were created to select threshold values to identify the 3 degrees of anemia with a sensitivity of 100%. RESULTS: Gestational age at the Doppler study ranged from 19 to 36 weeks. Forty-six fetuses (72%) were not or mildly anemic; 7 fetuses (11%) were moderately anemic, and 11 fetuses (17%) were severely anemic. Middle cerebral artery peak systolic velocity for the prediction of severe, moderate, and mild anemia at a sensitivity of 100% showed false-positive rates of 6%, 37%, and 70%, respectively. CONCLUSION: In fetuses who have undergone 1 previous intrauterine transfusion because of maternal red cell alloimmunization, timing the second intrauterine transfusion can be determined noninvasively by Doppler ultrasonography on the basis of an increase in the peak velocity of systolic blood flow in the middle cerebral artery.

Anemia↗
PubMedDate not supplied

Interdisciplinary research is key to understanding sex differences: report from the Society for Women's Health Research Meeting on understanding the biology of sex differences.

Progress in sex-based biology, the study of biological and behavioral differences between males and females, and the impact of those differences on health and disease will require collaboration across research disciplines and medical specialties and among all research approaches, from molecular biology to epidemiology. The importance of sex-based biology to healthcare necessitates a bench-to-bedside approach that is built on integration of research findings from studies at the cellular level, in animals, and in human subjects. Barriers to interdisciplinary collaborations are being addressed in a variety of ways by public and private funders. The J.D. and C.T. MacArthur Foundation supports interdisciplinary research networks that address broad questions in health and behavior. The National Institute of Mental Health supports cross-disciplinary research networks investigating the hypothalamic-pituitary-adrenal network. The National Institute of Child Health and Human Development offers grants for Building Interdisciplinary Research Careers in Women's Health. The National Science Foundation Directorate for Biological Sciences sponsors Research Coordination Networks in Biological Sciences. Among the challenges faced by interdisciplinary research programs are appropriate peer review, career advancement for young investigators with interdisciplinary training, and acceptance of interdisciplinary research reports by high-quality scientific publications.

Female↗
PubMed1993

Sibling perspectives on schizophrenia and the family.

Intensive audiotaped interviews with 14 adult siblings of schizophrenia patients were used to explore their experiences. Interviews focused on the ways adult siblings define and experience their sibling's mental illness and their participation in illness management. Cross-case analysis revealed that recognition of schizophrenia in a brother or sister was characterized by a pivotal, reorganizing event that redefined behavior previously viewed as difficult or different. Subjects' approach to the sibling's illness reflected three distinct patterns: collaborative, crisis-oriented, and detached. The impact of a mentally ill brother or sister on subjects' lives ranged from pervasive to discrete and was seen as emanating from the family and the sibling, but in different ways. These findings can help sensitize clinicians to the complex nature of sibling experiences as well as to the needs of siblings and their families.

Adult↗
PubMed2004

Multichannel calculation of D*s vector states and the D+sJ(2632) resonance.

We study bound states below threshold and resonances above threshold in the D0K+ and D(+)(s)eta systems, using a many-coupled-channel model for nonexotic meson-meson scattering applied to states with the quantum numbers of cs quark-antiquark vector mesons. We fit the ground state at 2.112 GeV, whence the lowest resonances in D0K+ come out at 2.61, 2.72, 3.03, and 3.08 GeV. The resonance at 2.61 GeV acquires a width of about 8 MeV, while its partial P wave cross section is up to 6 times larger in D(s)eta than in D0K+, provided a mechanism accounting for Okubo-Zweig-Iizuka-forbidden decays is included. The latter finding is in agreement with the observations of the SELEX Collaboration with respect to the recently reported D(+)(sJ)(2632) resonance. Therefore, we conclude that the D(+)(sJ)(2632) is probably the first recurrence of the D(*)(s)(2112) meson.

Journal Article↗
PubMed2002

Duration, frequency, recency, and type of migraine and the risk of ischaemic stroke in women of childbearing age.

BACKGROUND: Migraine is recognised increasingly as a risk factor for ischaemic stroke in women of childbearing age. Migraine with aura poses a higher risk than migraine without aura. OBJECTIVE: To investigate further the effect of duration, frequency, recency, and type of migraine on the risk of ischaemic stroke. METHODS: Additional analyses of a previously reported multicentre case-control study of the relation between stroke and migraine in women aged 20-44 years. RESULTS: Among 86 cases of ischaemic stroke and 214 controls, the adjusted risk of ischaemic stroke was significantly associated with: (1) migraine of more than 12 years duration, odds ratio (OR) 4.61 (1.27-16.8); (2) initial migraine with aura, OR 8.37 (2.33-30.1); (3) particularly if attacks were more frequent than 12 times per year, OR 10.4 (2.18-49.4). In no case did correction for oral contraception usage significantly alter these odds ratios. Increasing risk of ischaemic stroke was related to a change to increased frequency of headaches (trend p <or= 0.03). CONCLUSIONS: These data support earlier reports of a relation between ischaemic stroke and migraine with aura. The risk seems particularly high in those whose initial migraine type involved aura occurring more than 12 times per year.

Adult↗
PubMed2006

Within and between race differences in lymphocyte, CD4+, CD8+ and neutrophil levels in HIV-uninfected children with or without HIV exposure in Europe and Uganda.

BACKGROUND: Racial immuno-haematological differences have been reported in children but to date have not been well quantified. AIM: To investigate differences in haemato-immunological markers over age between children born and living in Europe and Uganda. SUBJECTS: HIV-uninfected children living in Uganda (n = 1633) with cross-sectional data. Black (n = 604) and white children (n = 1355) living in Europe, both with prospective data. The children born in Europe were HIV-uninfected but born to HIV-infected mothers and were included in the European Collaborative Study (ECS). METHODS: Patterns and levels of total lymphocyte (TLC), CD4+, CD8+ counts and CD4% were visualised by smoothers (a line representing the weighted average of all measurements over age by study group). Differences between groups were quantified using age-standardised Z-scores for individual TLC, CD4+ and CD8+ counts in uni- and multivariate regression models. RESULTS: In infancy, TLC, CD4+ and CD8+ counts were lower in Ugandan than black European children; neutrophil counts were similar. Thereafter, only neutrophil counts were lower in Ugandan children. To assess within-race differences, we compared Z-scores of ECS children born to Ugandan mothers with those of Ugandan children. Levels of all four markers were lower in Ugandan children at all ages. In Ugandan children, CD4+ counts were 0.5985 Z-score (p < 0.001) and neutrophil counts 0.3872 Z-score (p < 0.001) lower than in European children born to Ugandan mothers. CONCLUSIONS: There are differences in levels of haemato-immunological markers in children with comparable genetic backgrounds, suggesting that environmental factors such as nutrition and exposure to micro-organisms might have important effects on the developing immune system.

Aging↗
PubMed1999

Cardiovascular Risk in Young Finns Study: general outline and recent developments.

The Cardiovascular Risk in Young Finns Study is a collaborative effort of all university departments of paediatrics and several other institutions in Finland to study the risk factors of coronary heart disease (CHD) and their determinants in children and adolescents in different parts of the country. The main cross-sectional study carried out in 1980 included 3596 3-18-year-old subjects. Follow-up studies have been performed in 1983, 1986, 1989 and 1992; in the last of these studies the subjects were 15-30 years old. The findings in anthropometry, obesity and blood pressure have been rather similar to reports from other countries in Europe. However, serum cholesterol and low-density lipoprotein cholesterol concentrations were higher than in other countries, 4.83 mmol/L and 3.09 mmol/L, respectively in 1980. By 1992 a decrease of 8% took place, probably as a result of dietary changes. Apolipoprotein phenotypes E4E4 or E4E3 were relatively frequent (34%) in the sample. Tracking and clustering have also been studied. Serum insulin levels predicted the clustering of the typical risk factor profile associated with insulin resistance syndrome. The dietary polyunsaturated to saturated fat (P/S) ratio increased from 0.26 in 1980 to 0.39 in 1992, with no significant changes in the total energy derived from fat. 'Hard-driving' was found to be the psychological risk factor most consistently related to the CHD risk factor level.

Adolescent↗
PubMed2002

Using the STS and multinational cardiac surgical databases to establish risk-adjusted benchmarks for clinical outcomes.

One of the purposes of collecting data on cardiac surgical procedures, at a national level is to enable individual surgeons to improve quality and benchmark their own practice by making more accurate prospective prediction of outcome of each individual patient by using risk stratification based on previous local and national experiences. The past decade has seen a dramatic increase in the development of national cardiac surgical initiatives in many countries around the world. The size and extent of these databases has successfully allowed their use for patient risk stratification and preoperative risk modeling in four main aspects: patient selection and informed consent, coherent analysis of the determinants of patient outcomes, rationalizing unit management, and negotiations with external agencies. Approximately 610 cardiac surgical units presently contribute their patient data, containing pre-operative risk factors, to centralized national registries. There are currently nine different datasets used throughout the world to collect patient information. To harmonize the considerable diversity among these source materials, an International Dataset has been developed by a collaborative process among more than 50 cardiac surgeons around the world. Constructed around the Society of Thoracic Surgeons (STS) data format, the International Dataset brings in key elements from all the other datasets, allowing the sharing of data and cross-analysis, thus greatly expanding the pool of patients, and national sources, from which risk-stratifed outcomes can now be analyzed and unified. Unlike the STS dataset, the International Dataset incorporates EuroSCORE, a simple-to-use, validated patient risk stratification system, which has been rapidly adopted by large numbers of centers around the world for patient risk stratification, outcomes assessment, and improving patient informed consent. There are several benefits to collecting and centralizing national and international data: (1) understanding and defining basic demographics of patients undergoing cardiac surgery; (2) patient risk stratification and risk prediction at both a national and center-by-center level; (3) unit benchmarking, and development of effective nationally oriented and center-oriented quality improvement programs; (4) understanding and rationalizing resource utilization; and (5) use of data to leverage governments and other healthcare providers to affect policy. Cardiac surgical registries will soon attempt to track patients for longer follow-up periods after discharge in order to identify surgery-related deaths for more extended periods of time following surgery, thereby improving the monitoring and prediction of patient outcomes.

Benchmarking↗
PubMed2000

Enteral antibiotics for preventing necrotising enterocolitis in low birthweight or preterm infants.

BACKGROUND: Necrotising enterocolitis continues to be a problem, particularly in preterm neonates. There have been reports published suggesting that the use of enteral antibiotics may be effective as prophylaxis. This systematic review was undertaken to clarify the issue. OBJECTIVES: To evaluate the benefits and harms of enteral antibiotic prophylaxis for necrotising enterocolitis in low birth weight and preterm infants. SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal trials, MEDLINE (search terms: necrotizing enterocolitis, antibiotics; LIMITS: newborn infant), previous reviews with cross references, abstracts, conference and symposia proceedings, expert informants and journal handsearching in the fields of Neonatal Pediatrics and Microbiology. SELECTION CRITERIA: All randomized or quasi-randomized controlled trials where enteral antibiotics were used as prophylaxis against NEC in LBW (<2500g) and/or preterm (<37 weeks gestation) infants. DATA COLLECTION AND ANALYSIS: The standard method of the Cochrane Collaboration and its Neonatal Review Group was used. The methodological quality of each trial was reviewed by the second author who was blinded to the trial authors and institutions. Each author extracted data separately before comparison and resolution of differences. Relative risk (RR), risk difference (RD), and number needed to treat were used in the analysis. MAIN RESULTS: The administration of prophylactic enteral antibiotics resulted in a statistically significant reduction in NEC [RR 0.47 (0.23, 0.98); RD -0.072 (-0.136, -0.008); NNT 13.9 (7.4, 125)]. There was a reduction in NEC-related deaths which was of borderline statistical significance [RR 0.16 (0.02, 1.26); RD -0.097 (-0.183, -0.010); NNT 10.3 (5.46, 100)]. There were no significant differences in all deaths (one trial only) or in NEC-like enteropathies (one trial only). There was a statistically significant increase in the incidence of colonisation with resistant bacteria [RR 1.73 (1.00, 2. 97); RD 0.123 (0.008, 0.238); NNT 8.1 (4.2, 125)]. REVIEWER'S CONCLUSIONS: There is insufficient evidence to support the use of enteral antibiotic prophylaxis for NEC in clinical practice. To address this question further, a large trial would be required with a sample size sufficient to examine all the important benefits and harms. Adverse outcomes associated with infection, particularly with resistant bacteria, should be evaluated.

Anti-Bacterial Agents↗
PubMed2005

Nutritional status study of inpatients in hospitals of Galicia.

OBJECTIVE: To know the prevalence of malnutrition and to validate a nutritional screening protocol (SP) in patients hospitalised in Hospitals representative of inpatients admitted for acute illnesses in Galicia. DESIGN: Cross-sectional study of 376 randomised patients (189 female, 210 > or =65 y old) from 12 public hospitals admitted to hospital for acute medical, surgical or trauma illnesses. The patients elicited were evaluated by a simple SP, including variables relative to recent weight changes, serum albumin, lymphocytes, food ingestion and diagnosis at admission (Cardona's Protocol), and with a diagnostic protocol (DP, Subjective Global Assessment). Both SP and DP were performed by personnel trained in nutritional evaluation. Results of SP and DP were compared; principal factors related to malnutrition were also analysed; statistical significance was considered at P<0.05. RESULTS: From patients studied, according to DP 169/360 (46.94%), patients presented malnutrition (134 B category and 35C category). SP rate was significantly related to severity of malnutrition detected by DP (P<0.001). The principal factors related to the presence of malnutrition were older age and degree of metabolic stress. CONCLUSIONS: In adult patients admitted for acute illnesses, the prevalence of protein-energy malnutrition is high. The risk was related to age and to metabolic stress. The risk of malnutrition in a hospital setting is evaluated appropriately by a simple screening procedure that may contribute to detecting and correcting malnutrition risk.

Acute Disease↗
PubMed2007

Meta-analyses and systematic reviews of psychological treatments for chronic pain: relevance to an evidence-based practice.

As evidence-based practitioners become more reliant on systematic reviews to inform treatment, it becomes important to systematize reporting details as well as improve the quality of the primary studies that will later be incorporated into this secondary literature. In this article, the authors consider several specific factors that can serve this function in the area of chronic pain: (a) adhering to a standardized set of reporting standards; (b) measuring a standardized set of short- and long-term outcome variables; (c) providing information about individual differences; and (d) providing detailed, easily accessible documentation of the treatment program (or progams). The article also highlights ways that practitioners and researchers can collaborate on treatment outcome research, thereby improving the ability to discover and disseminate effective treatments for patients who suffer from chronic pain.

Chronic Disease↗
PubMed1995

Modulation of 5' splice site choice in pre-messenger RNA by two distinct steps.

Ser/Arg-rich proteins (SR proteins) are essential splicing factors that commit pre-messenger RNAs to splicing and also modulate 5' splice site choice in the presence or absence of functional U1 small nuclear ribonucleoproteins (snRNPs). Here, we perturbed the U1 snRNP in HeLa cell nuclear extract by detaching the U1-specific A protein using a 2'-O-methyl oligonucleotide (L2) complementary to its binding site in U1 RNA. In this extract, the standard adenovirus substrate is spliced normally, but excess amounts of SR proteins do not exclusively switch splicing from the normal 5' splice site to a proximal site (site 125 within the adenovirus intron), suggesting that modulation of 5' splice site choice exerted by SR proteins requires integrity of the U1 snRNP. The observation that splicing does not necessarily follow U1 binding indicates that interactions between the U1 snRNP and components assembled on the 3' splice site via SR proteins may also be critical for 5' splice site selection. Accordingly, we found that SR proteins promote the binding of the U2 snRNP to the branch site and stabilize the complex formed on a 3'-half substrate in the presence or absence of functional U1 snRNPs. A novel U2/U6/3'-half substrate crosslink was also detected and promoted by SR proteins. Our results suggest that SR proteins in collaboration with the U1 snRNP function in two distinct steps to modulate 5' splice site selection.

Blotting, Western↗
PubMed1988

Comparative study of affective disorders in three Asian countries. I. Differences in diagnostic classification.

A study aimed at the standardization of symptom evaluation of patients with depression was carried out as the first step in an extensive collaborative study on affective disorders between centers in Nagasaki, Shanghai and Seoul. This study was initiated in order to clarify the factors affecting the low reported prevalence rates of depressive disorders in Asia. No significant difference in evaluation of psychiatric symptoms was observed between the 3 centers. Nevertheless, the diagnoses given by ICD-9 showed very interesting differences. For any given case, Nagasaki tended to make a diagnosis of an affective psychosis depression, while Shanghai made a diagnosis of neurotic disorder. No significant tendency was observed in the Seoul center. These findings are discussed in terms of their importance for future international collaborative studies.

Affective Disorders, Psychotic↗
PubMed1999

Elevated frequency of loss of heterozygosity in mammary tumors arising in mouse mammary tumor virus/neu transgenic mice.

Loss of heterozygosity (LOH) analysis was performed on 62 mammary tumors that were induced in (BALB/c x C57BL/6)F1 mouse mammary tumor virus/neu transgenic mice. Eighty-six simple sequence length polymorphism markers were used to cover all of the somatic chromosomes. Frequency of LOH was observed to be significant for chromosomes 4 (50%), 19 (32%), and 8 (21%). On chromosome 4, at least three distinct regions of allelic deletions could be identified: one proximal to 22 cM; the second close to the p16INK4a/p15INK4b locus, which is commonly deleted in various tumors; and the third one in the proximity of Mom1. The frequency of LOH on chromosome 19 was the same for the four markers used. Our data suggested the presence of two distinct LOH loci, one proximal to 47 cM and the other at the distal region. On chromosome 8, possibly two distinct LOH loci could be recognized, one around 52 cM and the other one at 67 cM or distal to it. These regions map close to E-cadherin (Cdh1) and M-cadherin (Cdh15) loci, respectively. Because LOH sites are thought to harbor tumor suppressor genes, this allelotype screening has allowed the mapping of putative tumor suppressor genes that may be implicated, in collaboration with the erbB-2/neu oncogene, in the development of mammary tumors in these transgenic mice.

Acyltransferases↗
PubMed1996

Current estrogen-progestin and estrogen replacement therapy in elderly women: association with carotid atherosclerosis. CHS Collaborative Research Group. Cardiovascular Health Study.

The cardioprotective effects of combined estrogen/progestin replacement therapy have been questioned. Therefore, we have compared carotid arterial wall thickening and the prevalence of carotid stenosis in elderly women (> or = 65 years old) currently using replacement estrogen/progestins (E + P) with arterial pathology and its prevalence in women using unopposed estrogens (E). This cross-sectional study used baseline data from all 2962 women participating in the Cardiovascular Health Study, a population-based study of coronary heart disease and stroke in elderly adults. Users of hormone replacement therapy (HRT) were categorized as never (n = 1726), past (n = 787), current E (n = 280), or current E + P (n = 73). Maximal intimal-medial thicknesses of the internal and common carotid arteries and stenosis of the internal carotid arteries were measured by ultrasonography. Current E + P users resembled current E users in most respects, although some lifestyle factors were more favorable among E + P users. Current E + P use and current E use (as compared with no use) were associated with smaller internal carotid wall thicknesses (-0.22 mm; P = 0.003; and -0.09 mm; P = 0.05, respectively) and smaller common carotid wall thicknesses (-0.05 mm; P = 0.03; and -0.02 mm; P = 0.1, respectively) and lower odds ratios (OR) for carotid stenosis (> or = 1% vs. 0%); OR = 0.61; 95% confidence interval [CI]: 0.36 to 1.01; and OR = 0.91, 95% CI: 0.67 to 1.24, respectively), after adjustment for current lifestyle and risk factors. When both groups of current HRT users were compared, there were no significant differences in carotid wall thicknesses or prevalence of carotid stenosis. For this sample of elderly women, both current E + P therapy and current E therapy were associated with decreased measures of carotid atherosclerosis. These measures did not differ significantly between the two groups of HRT users.

Aged↗
PubMed2005

Cross-sector leadership development for preparedness.

After fall 2001, scientists and professionals recognized the importance of integrating public health with traditional first-response professions in planning and training for disasters. However, operationalizing this approach among professionals in the field confronted barriers that were both inter-cultural and jurisdictional. The Pennsylvania Preparedness Leadership Institute (PPLI) is a collaboration of the Pennsylvania Department of Health and the University of Pittsburgh Center for Public Health Preparedness. Team members are recruited from public health, emergency medicine, emergency management, hospitals, and public safety agencies from each of nine multi-county regions in Pennsylvania. Each team takes on a year-long project that addresses a strategic problem as a focus for capacity-building within its region. Unexpectedly during PPLI's first year in operation, a hepatitis-A outbreak tested whether one regional team could successfully mount the necessary integrated response. This experience, as well as the planned evaluation for PPLI, demonstrated both the successful processes and the positive impact of this integrated leadership training initiative.

Curriculum↗