Showing papers by "McMaster University published in 1999"

Using SeDuMi 1.02, a MATLAB toolbox for optimization over symmetric cones

Abstract: SeDuMi is an add-on for MATLAB, which lets you solve optimization problems with linear, quadratic and semidefiniteness constraints. It is possible to have complex valued data and variables in SeDuMi. Moreover, large scale optimization problems are solved efficiently, by exploiting sparsity. This paper describes how to work with this toolbox.

Intra-arterial Prourokinase for Acute Ischemic Stroke: The PROACT II Study: A Randomized Controlled Trial

Abstract: ContextIntravenous tissue-type plasminogen activator can be beneficial to some patients when given within 3 hours of stroke onset, but many patients present later after stroke onset and alternative treatments are needed.ObjectiveTo determine the clinical efficacy and safety of intra-arterial (IA) recombinant prourokinase (r-proUK) in patients with acute stroke of less than 6 hours' duration caused by middle cerebral artery (MCA) occlusion.DesignPROACT II (Prolyse in Acute Cerebral Thromboembolism II), a randomized, controlled, multicenter, open-label clinical trial with blinded follow-up conducted between February 1996 and August 1998.SettingFifty-four centers in the United States and Canada.PatientsA total of 180 patients with acute ischemic stroke of less than 6 hours' duration caused by angiographically proven occlusion of the MCA and without hemorrhage or major early infarction signs on computed tomographic scan.InterventionPatients were randomized to receive 9 mg of IA r-proUK plus heparin (n = 121) or heparin only (n = 59).Main Outcome MeasuresThe primary outcome, analyzed by intention-to-treat, was based on the proportion of patients with slight or no neurological disability at 90 days as defined by a modified Rankin score of 2 or less. Secondary outcomes included MCA recanalization, the frequency of intracranial hemorrhage with neurological deterioration, and mortality.ResultsFor the primary analysis, 40% of r-proUK patients and 25% of control patients had a modified Rankin score of 2 or less (P = .04). Mortality was 25% for the r-proUK group and 27% for the control group. The recanalization rate was 66% for the r-proUK group and 18% for the control group (P<.001). Intracranial hemorrhage with neurological deterioration within 24 hours occurred in 10% of r-proUK patients and 2% of control patients (P = .06).ConclusionDespite an increased frequency of early symptomatic intracranial hemorrhage, treatment with IA r-proUK within 6 hours of the onset of acute ischemic stroke caused by MCA occlusion significantly improved clinical outcome at 90 days.

Impact of formal continuing medical education: do conferences, workshops, rounds, and other traditional continuing education activities change physician behavior or health care outcomes?

Abstract: ContextAlthough physicians report spending a considerable amount of time in continuing medical education (CME) activities, studies have shown a sizable difference between real and ideal performance, suggesting a lack of effect of formal CME.ObjectiveTo review, collate, and interpret the effect of formal CME interventions on physician performance and health care outcomes.Data SourcesSources included searches of the complete Research and Development Resource Base in Continuing Medical Education and the Specialised Register of the Cochrane Effective Practice and Organisation of Care Group, supplemented by searches of MEDLINE from 1993 to January 1999.Study SelectionStudies were included in the analyses if they were randomized controlled trials of formal didactic and/or interactive CME interventions (conferences, courses, rounds, meetings, symposia, lectures, and other formats) in which at least 50% of the participants were practicing physicians. Fourteen of 64 studies identified met these criteria and were included in the analyses. Articles were reviewed independently by 3 of the authors.Data ExtractionDeterminations were made about the nature of the CME intervention (didactic, interactive, or mixed), its occurrence as a 1-time or sequenced event, and other information about its educational content and format. Two of 3 reviewers independently applied all inclusion/exclusion criteria. Data were then subjected to meta-analytic techniques.Data SynthesisThe 14 studies generated 17 interventions fitting our criteria. Nine generated positive changes in professional practice, and 3 of 4 interventions altered health care outcomes in 1 or more measures. In 7 studies, sufficient data were available for effect sizes to be calculated; overall, no significant effect of these educational methods was detected (standardized effect size, 0.34; 95% confidence interval [CI], −0.22 to 0.97). However, interactive and mixed educational sessions were associated with a significant effect on practice (standardized effect size, 0.67; 95% CI, 0.01-1.45).ConclusionsOur data show some evidence that interactive CME sessions that enhance participant activity and provide the opportunity to practice skills can effect change in professional practice and, on occasion, health care outcomes. Based on a small number of well-conducted trials, didactic sessions do not appear to be effective in changing physician performance.

Development and validation of a questionnaire to measure asthma control

Abstract: International guidelines on asthma management indicate that the primary goal of treatment should be optimum asthma control. The aim of this study was to develop and validate the Asthma Control Questionnaire (ACQ). The authors generated a list of all symptoms used to assess control and sent it to 100 asthma clinicians who were members of guidelines committees (18 countries). They scored each symptom for its importance in evaluating asthma control. From the 91 responses, the five highest scoring symptoms were selected for the ACQ. In addition, there is one question on beta2-agonist use and another on airway calibre (total questions=7). The ACQ was tested in a 9-week observational study of 50 adults with symptomatic asthma. The ACQ and other measures of asthma health status were assessed at baseline, 1, 5 and 9 weeks. In patients whose asthma was stable between clinic visits, reliability of the ACQ was high (intraclass correlation coefficient (ICC)=0.90). The questionnaire was very responsive to change in asthma control (p<0.0001). Cross-sectional and longitudinal validity were supported by correlations between the ACQ and other measures of asthma health status being close to a priori predictions. In conclusion, the Asthma Control Questionnaire has strong evaluative and discriminative properties and can be used with confidence to measure asthma control.

Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification.

Abstract: Background—Endoscopic oesophageal changes are diagnostically helpful and identify patients exposed to the risk of dis- ease chronicity. However, there is a seri- ous lack of agreement about how to describe and classify the appearance of reflux oesophagitis Aims—To examine the reliability of crite- ria that describe the circumferential ex- tent of mucosal breaks and to evaluate the functional and clinical correlates of pa- tients with reflux disease whose oesoph- agitis was graded according to the Los Angeles system. Methods—Forty six endoscopists from diVerent countries used a detailed work- sheet to evaluate endoscopic video record- ings from 22 patients with the full range of severity of reflux oesophagitis. In separate studies, Los Angeles system gradings were correlated with 24 hour oesophageal pH monitoring (178 patients), and with clini- cal trials of omeprazole treatment (277 patients). Results—Evaluation of circumferential extent of oesophagitis by the criterion of whether mucosal breaks extended be- tween the tops of mucosal folds, gave acceptable agreement (mean Œ value 0.4) among observers. This approach is used in the Los Angeles system. An alternative approach of grouping the circumferential extent of mucosal breaks as occupying 0-25%, 26-50%, 51-75%, 76-99%, or 100% of the oesophageal circumference, gave unacceptably high interobserver variation (mean Œ values 0-0.15) for all but the low- est category of extent (mean Œ value 0.4). Severity of oesophageal acid exposure was significantly (p<0.001) related to the se- verity grade of oesophagitis. Preteatment oesophagitis grades A-C were related to heartburn severity (p<0.01), outcomes of omeprazole (10 mg daily) treatment (p<0.01),and the risk for symptom relapse oV therapy over six months (p<0.05). Conclusions—Results add further support to previous studies for the clinical utility of the Los Angeles system for endoscopic grading of oesophagitis. (Gut 1999;45:172-180)

The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes

Abstract: OBJECTIVE To develop a standardized nomenclature system for the neuropsychiatric syndromes of systemic lupus erythematosus (NPSLE). METHODS An international, multidisciplinary committee representing rheumatology, neurology, psychiatry, neuropsychology, and hematology developed case definitions, reporting standards, and diagnostic testing recommendations. Before and after the meeting, clinician committee members assigned diagnoses to sets of vignettes randomly generated from a pool of 108 NPSLE patients. To assess whether the nomenclature system improved diagnostic agreement, a consensus index was developed and pre- and postmeeting scores were compared by t-tests. RESULTS Case definitions including diagnostic criteria, important exclusions, and methods of ascertainment were developed for 19 NPSLE syndromes. Recommendations for standard reporting requirements, minimum laboratory evaluation, and imaging techniques were formulated. A short neuropsychological test battery for the diagnosis of cognitive deficits was proposed. In the postmeeting exercise, a statistically significant improvement in diagnostic agreement was observed. CONCLUSION The American College of Rheumatology (ACR) Nomenclature for NPSLE provides case definitions for 19 neuropsychiatric syndromes seen in SLE, with reporting standards and recommendations for laboratory and imaging tests. It is intended to facilitate and enhance clinical research, particularly multicenter studies, and reporting. In clinical settings, consultation with other specialists may be required. It should be useful for didactic purposes but should not be used uncritically or as a substitute for a clinical diagnosis. The complete case definitions are available on the ACR World Wide Web site: http://www.rheumatology .org/ar/ar.html.

The pseudogap in high-temperature superconductors: an experimental survey

Abstract: We present an experimental review of the nature of the pseudogap in the cuprate superconductors. Evidence from various experimental techniques points to a common phenomenology. The pseudogap is seen in all high-temperature superconductors and there is general agreement on the temperature and doping range where it exists. It is also becoming clear that the superconducting gap emerges from the normal state pseudogap. The d-wave nature of the order parameter holds for both the superconducting gap and the pseudogap. Although an extensive body of evidence is reviewed, a consensus on the origin of the pseudogap is as lacking as it is for the mechanism underlying high-temperature superconductivity.

The Lower Extremity Functional Scale (LEFS): Scale Development, Measurement Properties, and Clinical Application

Abstract: Background and Purpose. The purpose of this study was to assess the reliability, construct validity, and sensitivity to change of the Lower Extremity Functional Scale (LEFS). Subjects and Methods. The LEFS was administered to 107 patients with lower-extremity musculoskeletal dysfunction referred to 12 outpatient physical therapy clinics. Methods. The LEFS was administered during the initial assessment, 24 to 48 hours following the initial assessment, and then at weekly intervals for 4 weeks. The SF-36 (acute version) was administered during the initial assessment and at weekly intervals. A type 2,1 intraclass correlation coefficient was used to estimate test-retest reliability. Pearson correlations and one-way analyses of variance were used to examine construct validity. Spearman rank-order correlation coefficients were used to examine the relationship between an independent prognostic rating of change for each patient and change in the LEFS and SF-36 scores. Results. Test-retest reliability of the LEFS scores was excellent ( R =.94 [95% lower limit confidence interval (CI)=.89]). Correlations between the LEFS and the SF-36 physical function subscale and physical component score were r =.80 (95% lower limit CI=.73) and r =.64 (95% lower limit CI=.54), respectively. There was a higher correlation between the prognostic rating of change and the LEFS than between the prognostic rating of change and the SF-36 physical function score. The potential error associated with a score on the LEFS at a given point in time is ±5.3 scale points (90% CI), the minimal detectable change is 9 scale points (90% CI), and the minimal clinically important difference is 9 scale points (90% CI). Conclusion and Discussion. The LEFS is reliable, and construct validity was supported by comparison with the SF-36. The sensitivity to change of the LEFS was superior to that of the SF-36 in this population. The LEFS is efficient to administer and score and is applicable for research purposes and clinical decision making for individual patients.

A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism.

Abstract: Background Patients who have a first episode of venous thromboembolism in the absence of known risk factors for thrombosis (idiopathic thrombosis) are often treated with anticoagulant therapy for three months. Such patients may benefit from longer treatment, however, because they appear to have an increased risk of recurrence after anticoagulant therapy is stopped. Methods In this double-blind study, we randomly assigned patients who had completed 3 months of anticoagulant therapy for a first episode of idiopathic venous thromboembolism to continue receiving warfarin, with the dose adjusted to achieve an international normalized ratio of 2.0 to 3.0, or to receive placebo for a further 24 months. Our goal was to determine the effects of extended anticoagulant therapy on rates of recurrent symptomatic venous thromboembolism and bleeding. Results A prespecified interim analysis of efficacy led to the early termination of the trial after 162 patients had been enrolled and followed for an average of 10 months....

The Lewis Model and Beyond

Abstract: The electron pair density, in conjunction with the definition of an atom in a molecule, enables one to determine the average number of electron pairs that are localized to each atom and the number that are formed between any given pair of atoms. Thus, it is through the pair density that the Lewis model of electronic structure finds physical expression. The pairing of electrons is a consequence of the Pauli principle whose effect is made manifest through the creation of the Fermi hole. The density describing the spatial distribution of the Fermi hole for an electron of given spin determines how the density of that electron is spread out in space, excluding an equivalent amount of same-spin density. The averaging of the Fermi density over single atoms or pairs of atoms determines the corresponding contributions to the total Fermi correlation. It is these terms that yield the localization and delocalization indices that determine the intra- and interatomic distribution of electron pairs that enables one to c...

Homocyst(e)ine and cardiovascular disease: a critical review of the epidemiologic evidence.

Abstract: disease. Study Selection: Prospective studies and major retrospective epidemiologic studies evaluating the association between homocyst(e)ine levels and cardiovascular disease and the association between blood levels or dietary intake of folate, vitamin B 6, and vitamin B12 and cardiovascular disease. Data Extraction: Relevant data on patient population, plasma homocyst(e)ine levels, duration of follow-up, and main results were extracted from studies that met the inclusion criteria. Data Synthesis: The designs and results of studies included in this review are summarized. A formal metaanalysis was not performed because the studies were heterogeneous in method and design. Conclusions: Results of epidemiologic studies suggest that moderately elevated plasma or serum homocyst(e)ine levels are prevalent in the general population and are associated with an increased risk for cardiovascular disease, independent of classic cardiovascular risk factors. Simple, inexpensive, nontoxic therapy with folic acid, vitamin B 6, and vitamin B12 reduces plasma homocyst(e)ine levels. Although the association between homocyst(e)ine levels and cardiovascular disease is generally strong and biologically plausible, the data from the prospective studies are less consistent. In addition, epidemiologic observations of an association between hyperhomocyst(e)inemia and cardiovascular risk do not prove the existence of a causal relation. Therefore, the effectiveness of folate, vitamin B 6, and vitamin B12 in reducing cardiovascular morbidity and mortality requires rigorous testing in randomized clinical trials. Several such trials are under way; their results may greatly affect cardiovascular morbidity and mortality, given the simplicity and low cost of vitamin therapy.

Comparison of candesartan, enalapril, and their combination in congestive heart failure: randomized evaluation of strategies for left ventricular dysfunction (RESOLVD) pilot study. The RESOLVD Pilot Study Investigators.

Abstract: Background—We investigated the effects of candesartan (an angiotensin II antagonist) alone, enalapril alone, and their combination on exercise tolerance, ventricular function, quality of life (QOL)...

Degradation Mechanism of Small Molecule-Based Organic Light-Emitting Devices

Abstract: Studies on the long-term degradation of organic light-emitting devices (OLEDs) based on tris(8-hydroxyquinoline) aluminum (AlQ 3 ), the most widely used electroluminescent molecule, reveal that injection of holes in AlQ 3 is the main cause of device degradation. The transport of holes into AlQ 3 caused a decrease in its fluorescence quantum efficiency, thus showing that cationic AlQ 3 species are unstable and that their degradation products are fluorescence quenchers. These findings explain the success of different approaches to stabilizing OLEDs, such as doping of the hole transport layer, introducing a buffer layer at the hole-injecting contact, and using mixed emitting layers of hole and electron transporting molecules.

The role of psychological and biological factors in postinfective gut dysfunction

Abstract: BACKGROUND—Both psychological and physiological disturbances have been implicated in the aetiopathogenesis of irritable bowel syndrome (IBS). AIMS—To investigate how the psychological factors act, and the involvement of infective and physiological factors. METHODS—Consecutive patients hospitalised for gastroenteritis reported life events for the previous 12 months, and past illness experiences on standardised questionnaires. They also completed psychometric questionnaires for anxiety, neuroticism, somatisation, and hypochondriasis. In some patients, rectal biopsy specimens were obtained during the acute illness and at three months postinfection. RESULTS—Ninety four patients completed all questionnaires: 22 patients were diagnosed with IBS after their gastroenteritis (IBS+), and 72 patients returned to normal bowel habits (IBS−). IBS+ patients reported more life events and had higher hypochondriasis scores than IBS− patients. The predictive value of the life event and hypochondriasis measures was highly significant and independent of anxiety, neuroticism, and somatisation scores, which were also elevated in IBS+ patients. Rectal biopsy specimens from 29 patients showed a chronic inflammatory response in both IBS+ and IBS− patients. Three months later, specimens from IBS+ patients continued to show increased chronic inflammatory cell counts but those from IBS− patients had returned to normal levels. IBS+ and IBS− patients exhibited rectal hypersensitivity and hyper-reactivity and rapid colonic transit compared with normal controls, but there were no significant differences between IBS+ and IBS− patients for these physiological measurements. CONCLUSION—Psychological factors most clearly predict the development of IBS symptoms after gastroenteritis but biological mechanisms also contribute towards the expression of symptoms. Keywords: irritable bowel syndrome; gastroenteritis; chronic inflammation; rectal sensitivity; intestinal transit; psychosomatic

Development and validation of the Mini Asthma Quality of Life Questionnaire

Abstract: The 32-item Asthma Quality of Life Questionnaire (AQLQ) has shown good responsiveness, reliability and construct validity; properties that are essential for use in clinical trials, clinical practice and surveys. However, to meet the needs of large clinical trials and long-term monitoring, where efficiency may take precedent over precision of measurement, the 15-item self-administered MiniAQLQ has been developed. The MiniAQLQ was tested in a 9-week observational study of 40 adults with symptomatic asthma. Patients completed the MiniAQLQ, the AQLQ, the Short Form (SF)-36, the Asthma Control Questionnaire and spirometry at baseline, 1, 5 and 9 weeks. In patients whose asthma was stable between clinic visits, reliability was very acceptable for the MiniAQLQ (intraclass correlation coefficient (ICC)=0.83), but not quite as good as for the AQLQ (ICC=0.95). Similarly, responsiveness in the MiniAQLQ (p=0.0007) was good but not quite so good as for the AQLQ (p<0.0001). Construct validity (correlation with other indices of health status) was strong for both the MiniAQLQ and the AQLQ. Criterion validity showed that there was no bias between the instruments (p=0.61) and the correlation between them was high (r=0.90). The Mini Asthma Quality of Life Questionnaire has good measurement properties but they are not quite as strong as those of the original Asthma Quality of Life Questionnaire. The choice of questionnaire should depend on the task at hand.

What do we mean by partnership in making decisions about treatment

Abstract: For many decades, the dominant approach to making decisions about treatment in the medical encounter has been one of paternalism.1–7 In recent years this model has been challenged by doctors, patients, medical ethicists, and researchers who advocate more of a partnership relation between doctors and patients.2 8–13 The reasons for this challenge have been described in detail elsewhere and include the rise of consumerism and the notion of consumer sovereignty in healthcare decision making; the women's movement with its emphasis on challenging medical authority; the passage of legislation focusing on patients' rights in health care; and small area variations in doctors' practice patterns that seem unrelated to differences in health status.7 Though the first three factors are seen as either contributors to or facilitators of patients' participation in making decisions about health care, the fourth highlights the imprecision or the “art” of medical care14: patients with similar clinical problems may receive different treatments from different doctors, due in part to systematic variations in practice patterns across geographical areas.14 15 The call for doctor-patient partnerships opens up options beyond paternalism for approaching the task of making decisions about treatment. But it also raises new complexities. Because a partnership between patient and doctor can take different forms, it is not intuitively apparent what this model would look like. The Oxford English Dictionary (1995) defines a partner as “a person who shares or takes part with another or others.” This definition leaves several important questions unanswered. For example, does the concept of a partnership imply that both doctor and patient need to share all parts of the decision making process? What is it that both parties are sharing, and to what degree? Who is responsible for determining if a partnership is possible and …

Crystalloids vs. colloids in fluid resuscitation: a systematic review.

Abstract: ObjectiveTo systematically review the effects of isotonic crystalloids compared with colloids in fluid resuscitation.Data SourcesComputerized bibliographic search of published research and citation review of relevant articles.Study SelectionAll randomized clinical trials of adult patients requiring

Interstitial cells of Cajal as precursors of gastrointestinal stromal tumors.

Abstract: Interstitial cells of Cajal (ICC) are implicated in the regulation of gut peristalsis and are immunostained by antibodies against Kit (CD117), a tyrosine kinase receptor. Most gastrointestinal mesenchymal tumors (GIMTs) are of uncertain histogenesis, although many are CD34-positive. CD34 was found to colocalize with vimentin (Vim) and the Kit-positive networks of cells within and around neural plexi, indicating that ICC can be Vim- and CD34-positive. ICCs appear to be the only Kit+CD34+Vim+ cell in the gut. Formalin-fixed, paraffin-embedded tissues from 43 GIMTs were immunostained for Kit, CD34, Vim, PGP 9.5 (PGP, a neural marker), muscle-specific actin (MSA), and other markers including desmin (Des). Eight tumors were myoid (MSA+Des+Vim-Kit-CD34-), and one was a schwannoma (PGP+S100+Vim+Kit-CD34-), but 34 tumors were of uncertain histogenesis (gastrointestinal stromal tumors, GIST), exhibiting neither a complete myoid nor a schwannian immunophenotype. All 34 were Vim+, and 33/34 were either Kit (n = 30) or CD34 (n = 23) immunoreactive. Of these 34 GIST, 24 were negative for all myoid and neural markers, 6 were PGP+S100-, and 4 were MSA+Des-. The Kit+CD34+Vim+ immunophenotype of GIST suggests that they originate from, or have differentiated into, ICC-like cells; the term ICC tumor (ICCT) is suggested. Kit is a more sensitive marker than CD34 for ICCT, but both are required in tumor identification. All clinically malignant GISTs were pathologically malignant (size, mitoses) but also showed loss of either CD34 or Kit. "Blind" examination of electron micrographs in 10 tumors showed them to be heterogeneous. Some had features seen in normal ICC, but cells could not be positively identified as being adult ICC. GIMT may therefore be classifiable into those with pure myoid, schwannian (or neural) differentiation, but the majority are of ICC origin or show ICC differentiation immunophenotypically (ICCT).

Development of a disease specific questionnaire to measure health related quality of life in patients with chronic liver disease.

Abstract: BACKGROUND AND AIMS To develop and assess a disease specific instrument for measuring health related quality of life (HRQL) in patients with chronic liver disease (CLD). METHODS Based on responses from 60 patients with chronic liver disease, from 20 liver experts, and from a Medline search of the literature, items potentially affecting the HRQL of these patients were identified. A separate sample of 75 patients identified which items they found problematic and rated their importance. Results were explored using factor analysis; domains were chosen and items placed within domains. Redundant questions were eliminated and the final questionnaire was pretested in 10 patients. Using this instrument, HRQL was assessed in a further 133 patients with various types and stages of liver disease. RESULTS Patients, experts, and the literature search identified 156 items of potential importance. Of these, 35 proved important to over 50% of 75 respondents in the item reduction sample. The factor analysis suggested six domains. After eliminating redundancies, the Chronic Liver Disease Questionnaire (CLDQ) included 29 items in the following domains: fatigue, activity, emotional function, abdominal symptoms, systemic symptoms, and worry. In pretesting, patients found the CLDQ clear and easy to complete in 10 minutes. In another 133 patients, the CLDQ showed a gradient between patients without cirrhosis, Child’s A cirrhosis, and those with Child’s B or C cirrhosis. CLDQ has evidence for moderate reliability at six months and seems to be responsive. CONCLUSION The CLDQ is short, easy to administer, produces both a summary score and domain scores, and correlates with the severity of liver disease.

The Human Telomerase Catalytic Subunit hTERT: Organization of the Gene and Characterization of the Promoter

Abstract: Telomerase, the enzyme that synthesizes telomeric DNA, is not expressed in most human somatic cells but is activated with in vitro immortalization and during tumorigenesis, and repressed by cell differentiation. Of the two components of the core enzyme, the catalytic protein hTERT is limiting for activity. To investigate mechanisms of hTERT gene regulation, we have cloned genomic sequences encompassing the complete hTERT transcription unit. The hTERT gene consists of 16 exons and 15 introns spanning approximately 35 kb. Transient transfections of immortal human cells with potential regulatory 5' sequences linked to a reporter, combined with deletion analysis of these sequences, indicated that elements responsible for promoter activity are contained within a region extending from 330 bp upstream of the ATG to the second exon of the gene. Assays in different cell types have shown that the hTERT promoter is inactive in normal and in transformed pre-immortal cells, but, like telomerase, it is activated with cell immortalization. Sequence analysis revealed that the hTERT promoter is GC-rich, lacks TATA and CAAT boxes but contains binding sites for several transcription factors that may be involved in its regulation. The abundance of these sites suggests the possibility that hTERT expression may be subject to multiple levels of control and be regulated by different factors in different cellular contexts.

Elevated expression of activated forms of Neu/ErbB-2 and ErbB-3 are involved in the induction of mammary tumors in transgenic mice: implications for human breast cancer.

Abstract: To assess the importance of Neu activation during mammary tumorigenesis, altered receptors harboring in-frame deletions within the extracellular domain were expressed in transgenic mice. Females from several independent lines develop multiple mammary tumors that frequently metastasize to the lung. Tumor progression in these strains was associated with elevated levels of tyrosine-phosphorylated Neu and ErbB-3. Consistent with these observations, a survey of primary human breast tumors revealed frequent co-expression of both erbB-2 and erbB-3 transcripts. The ability of altered Neu receptors to induce mammary tumorigenesis in transgenic mice prompted us to examine whether similar mutations occurred in ErbB-2 during human breast cancer progression. Interestingly, an alternatively spliced form of erbB-2, closely resembling spontaneous activated forms of neu, was detected in human breast tumors. The ErbB-2 receptor encoded by this novel transcript harbors an in-frame deletion of 16 amino acids in the extracellular domain and can transform Rat-1 fibroblasts. Together, these observations argue that co-expression of ErbB-2 and ErbB-3 may play a critical role in the induction of human breast tumors, and raise the possibility that activating mutations in the ErbB-2 receptor may also contribute to this process.

Family-centered caregiving and well-being of parents of children with disabilities:linking process with outcome

Abstract: Objective: This study examined the strength of the relationship between parents’ perceptions of familycentered, professionally provided caregiving and their emotional well-being (feelings of distress and depression). This was done in the context of other factors that might affect well-being (child behavior problems, coping strategies of parents, protective factors in the social environment, child factors related to disability, and family factors). Method: We asked 164 parents of children with nonprogressive neurodevelopmental disorders (primarily cerebral palsy, spina bifida, or hydrocephalus) to complete a series of instruments measuring the constructs of interest. Results: Structural equation modeling showed that more family-centered caregiving was a significant predictor of parents’ well-being. The most important predictors of well-being were child behavior problems and protective factors in the social environment. Conclusions: Services are most beneficial when they are delivered in a family-centered manner and address parent-identified issues such as the availability of social support, family functioning, and child behavior problems.