In this paper we discuss the non-parametric estimation of a distribution function based on incomplete data for which the measurement origin of a survival time or the date of enrollment in a study is known only to belong to an interval. Also the survival time of interest itself is observed from a truncated distribution and is known only to lie in an interval. To estimate the distribution function, a simple self-consistency algorithm, a generalization of Turnbull's (1976, Journal of the Royal Statistical Association, Series B 38, 290-295) self-consistency algorithm, is proposed. This method is then used to analyze two AIDS cohort studies, for which direct use of the EM algorithm (Dempster, Laird and Rubin, 1976, Journal of the Royal Statistical Association, Series B 39, 1-38), which is computationally complicated, has previously been the usual method of the analysis.
Clinical trials indicate that mammography provides a substantial breast cancer survival benefit; however, there is a need to demonstrate that this benefit extends to clinical practice and to determine the extent that current reductions in mortality are attributable to regular screening or adjuvant systemic therapy. Mammography was used routinely at our institution across a broad age range, in an era when most patients received no adjuvant systemic therapy. We examined breast cancer survival for a cohort of 678 stage I-III primary invasive breast cancer patients accrued from 1971 to 1990, and followed to 1996; 18% received adjuvant hormonal therapy and 15% received adjuvant chemotherapy. There were 61 women less than 40 years old; 136, 40-49 years; 341, 50-69 years; 140, > or =70 years. Factors available for multivariate investigations were age (years), tumor size (cm), nodal status (N-, Nx, N+), ER (fmol/mg protein), PgR (fmol/mg protein), adjuvant radiotherapy (no, yes), adjuvant hormonal therapy (no, yes), and adjuvant chemotherapy (no, yes). Forward stepwise multivariate regression with log-normal survival analysis was used to examine the effects of these factors on disease-specific survival. Ten-year survival by tumor size was adjusted for the effects of other significant factors. For women less than 40 years of age, 10-year survival at the T1a, T1b, T1c, and T2 cut-points for tumor size is, respectively, 0.77, 0.74, 0.67, 0.44; for 40-49 years it is 0.92, 0.90, 0.85, 0.62; for 50-69 years it is 0.81, 0.79, 0.75, 0.62; for > or =70 years it is 0.84, 0.81, 0.73, 0.44. With routine use of clinical mammography and up to 26 years of follow-up, we found breast cancer survival to be significantly better (p
Comment In: Breast J. 2002 Jul-Aug;8(4):185-612100108
T lymphocytes may play a regulatory role in the development of allergic airway hyperresponsiveness (AHR). We have studied the relationship between airway responsiveness and a number of immunological changes in Brown-Norway rats sensitized intraperitoneally and repeatedly exposed to ovalbumin (OVA) aerosol. Acetylcholine provocation concentration (PC)150 (the concentration of acetylcholine causing a 150% increase of base-line lung resistance) was measured and peripheral blood and bronchoalveolar lavage (BAL) cells were collected 18-24hr after the final exposure. Total and OVA-specific IgE in serum was measured by enzyme-linked immunosorbent assay (ELISA). Mononuclear cells were analysed by flow cytometry after labelling with monoclonal antibodies against CD2 (pan T-cell marker), CD4, CD8 (T-cell subsets) or CD25 (interleukin-2 receptor). There were significant differences in PC150 (P
We investigated the potential role of intercellular-adhesion molecule-1 (ICAM-1) in allergen-induced bronchial hyperresponsiveness (BHR) and inflammation in sensitised Brown-Norway rats. Rats were sensitised with ovalbumin (OA) intraperitoneally and 21 days later they were either exposed to 0.9% NaCl or 1% OA aerosol for 15 min. Rats exposed to OA aerosol were pretreated either with ICAM-1 antibody (3 mg/kg i.p. and i.v., 45 min prior to OA exposure) or with the diluent for the antibody. Eighteen to twenty-four hours after OA or 0.9% NaCl exposure, rats were anaesthetised, tracheostomised and mechanically ventilated, and airway responsiveness to acetylcholine (ACh) aerosol was measured as the provocative concentration of ACh needed to increase pulmorary resistance by 100% (PC100). Mean -log PC100 was increased in rats exposed to OA but pretreated with diluent (2.75 +/- 0.06) compared to rats treated with ICAM-1 antibody (2.51 +/- 0.08;
Anti-PF4/heparin antibodies are frequently generated after coronary artery bypass grafting (CABG) surgery, with platelet-activating IgG implicated in heparin-induced thrombocytopenia (HIT). It is controversial whether non-platelet-activating antibodies are associated with thrombosis.
To determine in post-CABG patients whether thromboprophylaxis using fondaparinux vs. unfractionated heparin (UFH) reduces the frequency of anti-PF4/heparin antibodies, and whether anti-PF4/heparin antibodies are associated with early graft occlusion.
In a pre-planned secondary analysis of a randomized control trial (RCT) comparing fondaparinux vs. UFH thromboprophylaxis post-CABG, we determined the frequency of anti-PF4/heparin antibody formation by solid-phase enzyme-immunoassay (EIA) and of platelet-activating antibodies by serotonin-release assay (SRA); the SRA and fluid-phase EIA were used to assess fondaparinux cross-reactivity. We also examined whether anti-PF4/heparin antibodies were associated with early arterial or venous graft occlusion (6-week CT angiography).
We found no significant difference in the frequency of antibody formation between patients who received fondaparinux vs. UFH (65.3% vs. 46.0%; P = 0.069), and no significant fondaparinux cross-reactivity. Venous graft occlusion(s) occurred in 6/26 patients who formed 'strong' IgG antibodies (= 1.0 optical density [OD] units and = 2? baseline) vs. 3/66 who did not (P = 0.0139). In both unadjusted and adjusted analyses, strong postoperative (but not pre-operative) anti-PF4/heparin IgG responses were associated with a markedly increased risk of early venous (but not arterial) graft occlusion (adjusted OR, 9.25 [95% CI, 1.73, 49.43]; P = 0.0093); notably, none of the three SRA-positive patients developed a venous graft occlusion.
Fondaparinux vs. UFH thromboprophylaxis postCABG does not reduce anti-PF4/heparin antibody formation. Non-platelet-activating anti-PF4/heparin IgG antibodies generated post operatively are associated with early venous graft occlusion.
Clonotypic heterogeneity in experimental interstitial nephritis. Restricted specificity of the anti-tubular basement membrane B cell repertoire is associated with a disease-modifying crossreactive idiotype.
Experimental anti-tubular basement membrane (anti-TBM) disease is an autoimmune interstitial nephritis elicited in susceptible rodents after immunization with renal tubular antigen. The nephritogenic antigen in the immunizing preparation is 3M-1, a 48,000 Mr noncollagenous glycoprotein. The hallmarks of the renal lesion are the presence of anti-TBM antibodies (anti-TBM-Ab) and a dense mononuclear cell infiltrate. The anti-TBM B cell repertoire in this disease was analyzed using a library of 22 anti-TBM mAbs generated in a prototypically susceptible Brown Norway rat. These anti-TBM mAbs were all demonstrated to be 3M-1 specific and their characterization formed the basis for the following observations: (a) The size of the anti-TBM B cell population is estimated at 58 distinct clones; (b) by competitive inhibition criteria, all anti-TBM mAbs recognize the same (or spatially close) epitope(s) on 3M-1. This focused recognition was maintained in spite of considerable variability in affinity. Epitopic dominance could also be demonstrated in human polyclonal anti-TBM antisera from a patient with anti-TBM disease; and (c) a crossreactive idiotype was documented, and antisera directed toward this set of variable region determinants was shown to be effective as a prophylactic regimen to abrogate disease, and as a therapeutic modality to arrest the progression of disease; (d) analysis of VH gene families suggested biased usage of Q52- and 7183-like families, although at least three gene families are used in the anti-TBM-Ab response. Thus, the anti-TBM B cell compartment in BN rats is moderately large, but is primarily focused to a single epitope on the nephritogenic antigen and is associated with a disease-modifying crossreactive idiotype.
We investigated the effects of genetic down- and up-regulation of sac1 expression on Aß42 accumulation and the associated neural deficits in flies with direct expression of arctic mutant Aß42 (Aßarc) in the neurons of GF pathway.
We genetically down-regulated and up-regulated the level of sac1, encoding a major phosphoinositide phosphatases in a disease model, in which arctic mutant Aß42 is directly expressed in the neurons of a neural pathway of adult fruit flies.
We conducted a time-course analysis of Aß42 level in the model and found an age-dependent elevation of Aß42 accumulation, closely correlated to the age-dependent decline of climbing ability in the model flies. Neither sac1 insufficiency nor sac1 over-expression significantly changed the three phenotypes.
We found that the alterations of sac1 expression did not change Aß42 accumulation and neural deficits in the model.
The ability to function as an effective member of a dental care team is a highly desirable--frequently mandated--attribute of dental technology (DT) graduates. Currently, there is little rigorous examination of how the learning of team-working skills might best be structured in a DT curriculum. This research compares DT curricula, and students' attitudes and perceptions regarding collaboration in practice, from four countries. Students (n=376) were invited to complete an education profile questionnaire, and the standardised measure--the shared learning scale. There were 196 (52%) responses. Students given opportunities to engage with others had better perceptions of inter-professional learning (IPL). Most believed that team-work and collaborative skills were best acquired by learning together with other dental care professionals, preferably sharing cases for real patients. Curricula should maximise opportunities for dental technology students to experience authentic IPL. Collaboration and team-work needs to be embedded through the whole undergraduate programme.
Randomized trials have demonstrated risks and failed to establish a clear benefit for the use of the pulmonary artery catheter. We assessed rates of pulmonary artery catheter use in multiple centers over 5 yrs, variables associated with their use, and how these variables changed over time (2002-2006).
A multicenter longitudinal study using the Hamilton Regional Critical Care Database. A two-level multiple logistic regression analysis was used to determine significant variables associated with pulmonary artery catheter use and whether these varied over time.
Academic intensive care units in Hamilton, Canada.
We identified patients from five intensive care units who received a pulmonary artery catheter within the first 2 days of intensive care unit admission.
Pulmonary artery catheter use over a 5-yr period.
Among 15,006 patients, 1,921 (12.8%) had a pulmonary artery catheter. Adjusted rates of pulmonary artery catheter use decreased from 16.4% to 6.5% over 5 yrs. Determinants of pulmonary artery catheter use included Acute Physiology and Chronic Health Evaluation II score (odds ratio [OR], 1.05; confidence interval [CI], 1.04-1.06; p 50% reduction in the rate of pulmonary artery catheter use over 5 yrs. Patient factors predicting pulmonary artery catheter use were illness severity, specific diagnoses, and the need for advanced life support. Nonpatient factors predicting pulmonary artery catheter use were intensive care unit and the attending physician's base specialty.
Comment In: Crit Care Med. 2011 Jul;39(7):1820-221685743
Social network analysis (SNA) is an innovative approach to the collection and analysis of infectious disease transmission data. We studied whether this approach can detect patterns of Mycobacterium tuberculosis transmission and play a helpful role in the complex process of prioritizing tuberculosis (TB) contact investigations.
We abstracted routine demographic and clinical variables from patient medical records and contact interview forms. We also administered a structured questionnaire about places of social aggregation to TB patients and their contacts. All case-contact, contact-contact, case-place, and contact-place dyads (pairs and links) were considered in order to analyze the structure of a social network of TB transmission. Molecular genotyping was used to confirm SNA-detected clusters of TB.
TB patients not linked through conventional contact-investigation data were connected through mutual contacts or places of social aggregation, using SNA methods. In some instances, SNA detected connected groups prior to the availability of genotyping results. A positive correlation between positive results of contacts' tuberculin skin test (TST) and location in denser portions of the person-place network was observed (P