Effect of maternal and infant covariates on sibship correlation in birth weight

Birth weight on 12,644 singleton infants from 6,196 sibships born in Maryland between 1980 and 1984 were used to estimate the effects of nine maternal and infant covariates on the sibship correlation in birth weight. Assuming a homogeneous correlation across all families, the estimated intraclass correlation was 0.4664 (+/- 0.0099). This high sibship correlation makes it possible to predict, with reasonable accuracy, the birth weight of a child given information on previous sibs, as well as covariates on the mother and/or infant pertinent to a given pregnancy. The reduction in variance associated with incorporating information on the nine covariates used here was approximately equal to that obtained by conditioning on a single previous sib. Testing for heterogeneity in correlation among different groups of families showed that a crude measure of parity (first live birth vs. other), time between births, mother's marital status, and maternal age at the birth of the last child significantly influenced the sibship correlation in birth weight.     

3D FEA of cemented steel, glass and carbon posts in a maxillary incisor.

OBJECTIVES: A comparative study on the stress distribution in the dentine and cement layer of an endodontically treated maxillary incisor has been carried out by using Finite Element Analysis (FEA). The role of post and cement rigidity on reliability of endodontic restorations is discussed. METHODS: A 3D FEM model (13,272 elements and 15,152 nodes) of a central maxillary incisor is presented. A chewing static force of 10 N was applied at 125 degree angle with the tooth longitudinal axis at the palatal surface of the crown. Steel, carbon and glass fiber posts have been considered. The differences in occlusal load transfer ability when steel, carbon and glass posts, fixed to root canal using luting cements of different elastic moduli (7.0 and 18.7 GPa) are discussed. RESULTS AND SIGNIFICANCE: The more stiff systems (steel and carbon posts) have been evaluated to work against the natural function of the tooth. Maximum Von Mises equivalent stress values ranging from 7.5 (steel) to 5.4 and 3.6 MPa (respectively, for carbon posts fixed with high and low cement moduli) and to 2.2 MPa (either for glass posts fixed with high and low cement moduli) have been observed under a static masticatory load of 10 N. A very stiff post works against the natural function of the tooth creating zones of tension and shear both in the dentine and at the interfaces of the luting cement and the post. Stresses in static loading do not reach material (dentine and cement) failure limits, however, they significantly differ leading to different abilities of the restored systems to sustain fatigue loading. The influence of the cement layer elasticity in redistributing the stresses has been observed to be less relevant as the post flexibility is increased.     

Retrospective review of pemetrexed with or without platinum in malignant mesothelioma: The Australian 'Special Access Scheme' experience

Background: Pemetrexed and cisplatin have recently been shown to significantly improve survival compared with cisplatin alone. However, there are only limited data reflecting teaching hospital experience outside a clinical trial. Pemetrexed has only been available in Australia on a restricted basis since 2002. We reviewed our experience of patients treated on the Australian ‘Special Access Scheme’ at three major thoracic oncology units. Methods: Charts were reviewed for all patients enrolled on the scheme. Data was extracted on age, World Health Organization (WHO) performance status, histology, prior therapy, time from diagnosis to starting pemetrexed, chemotherapy (pemetrexed alone or with a platinum), cycle number, response rate, actuarial progression‐free and overall survival. Doses were cisplatin 75 mg/m² or carboplatin AUC = 5 and pemetrexed 500 mg/m² every 21 days. Results: 52 patients (32 male and 20 female) were reviewed. Median age was 58 years and 88% were WHO 0–1. Histology included 54% epithelial, 17% biphasic (epithelial and sarcomatoid) and 21% undefined. The median time from diagnosis to administration of pemetrexed was 145 days. Sixty‐five percent had minimal surgical intervention with video assisted thoracoscopy, pleurodesis and biopsy, while 19% had received prior palliative radiation. Seventy‐one percent were chemotherapy naïve, the remaining 29% having received previous platinum and/or gemcitabine regimens. Twenty‐three percent had pemetrexed alone, 35% in combination with carboplatin and 42% with cisplatin. The median number of cycles was 4 (range 1–13). The response rate was 33%. No toxicity was observed in 20% grade 3–4 toxicity in 10% (majority nausea/vomiting). The median progression‐free and overall survival times from starting pemetrexed were 184 days and 298 days, respectively. Conclusions: Pemetrexed‐based regimens are safe and effective in a community setting in malignant mesothelioma.     

Gonococcal opacity: lectin-like interactions between Opa proteins and lipooligosaccharide.

Previous evidence from our laboratory suggested that the tight intercellular adhesions between the outer membranes of gonococci displaying the opacity colony phenotype occurred because Opa proteins expressed on one gonococcus adhered to the lipooligosaccharide (LOS) of the opposing bacterium (M.S. Blake, p. 51-66, in G. G. Jackson and H. Thomas, ed., The Pathogenesis of Bacterial Infections, 1985, and M. S. Blake and E. C. Gotschlich, p. 377-400, in M. Inouye, ed., Bacterial Outer Membranes as Model Systems, 1986). A noncompetitive inhibition assay used previously to determine the carbohydrate structures recognized by the major hepatic asialoglycoprotein receptor was modified to determine the gonococcal LOS structures that bind Opa proteins (R. T. Lee, Targeted Diagn. Ther. Ser. 4:65-84, 1991). The LOS carbohydrates used in these assays were LOS structures purified from pyocin LOS mutants of Neisseria gonorrhoeae 1291 described by K. C. Dudas and M. A. Apicella (Infect. Immun. 56:499-504, 1988) and further characterized by C. M. John et al. (J. Biol. Chem. 266:19303-19311, 1991). Purified gonococcal Opa proteins were incubated with each of the parent and mutant LOS, and the amount of binding of Opa proteins was measured by a direct enzyme-linked immunosorbent assay using the Opa-specific monoclonal antibody 4B12. The affinities of the Opa proteins for each of the LOS were determined indirectly by measuring the concentrations of Opa proteins that noncompetitively inhibited 50% of the binding of LOS-specific monoclonal antibodies. This concentration is inversely proportional to the affinity of the inhibitor (R. T. Lee, Targeted Diagn. Ther. Ser. 4:65-84, 1991). Our data suggest that the gonococcal Opa proteins tested had the highest affinity for the Gal beta 1-4GlcNAc residue present on the gonococcal lactoneoseries LOS. This affinity was comparable to that reported for the binding of the major hepatic asialoglycoprotein receptor to glycoconjugates containing terminal galactose and N-acetylgalactosamine (R. T. Lee, Targeted Diagn. Ther. Ser. 4:65-84, 1991). After sialylation of the lactoneoseries LOS, presumably on the terminal galactose residue, the interaction with the Opa proteins was ablated. Therefore, the gonococcal Opa-LOS and mammalian epithelial cell asialoglycoprotein receptor-carbohydrate interactions have quite similar specificities.     

FEASIBILITY OF CONDUCTING CARDIOVASCULAR OUTCOME RESEARCH IN AUSTRALIAN GENERAL PRACTICE: RESULTS FROM THE ANBP2 PILOT STUDY

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was 160 mmHg systolic or 90 mmHg diastolic if systolic BP was 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82 000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP 5=160/90 mmHg. Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.     

Responses of tonically discharging neurons in the monkey striatum to primary rewards delivered during different behavioral states

In the primate striatum, the tonically discharging neurons respond to conditioned stimuli associated with reward. We investigated whether these neurons respond to the reward itself and how changes in the behavioral context in which the reward is delivered might influence their responsiveness. A total of 286 neurons in the caudate nucleus and putamen were studied in two awake macaque monkeys while liquid reward was delivered in three behavioral situations: (1) an instrumental task, in which reward was delivered upon execution of a visually triggered arm movement; (2) a classically conditioned task, in which reward was delivered 1 s after a visual signal; (3) a free reward situation, in which reward was delivered at irregular time intervals outside of any conditioning task. The monkeys′ uncertainty about the time at which reward will be delivered was assessed by monitoring their mouth movements. A larger proportion of neurons responsive to reward was observed in the free reward situation (86%) than in the classically conditioned (57%) and instrumental tasks (37%). Among the neurons tested in all situations (n = 78), 24% responded to reward regardless of the situation and 65% in only one or two situations. Responses selective for one particular situation occurred exclusively in the free reward situation. When the reward was delivered immediately after the visual signal in the classically conditioned task, most of the neurons reduced or completely lost their responses to reward, and other neurons remained responsive. Conversely, neuronal responses invariably persisted when reward was delivered later than 1 s after the visual signal. This is the first report that tonic striatal neurons might display responses directly to primary rewards. The neuronal responses were strongly influenced by the behavioral context in which the animals received the reward. An important factor appears to be the timing of reward. These neurons might therefore contribute to a general aspect of behavioral reactivity of the subject to relevant stimuli. Received: 16 September 1996 / Accepted: 1 April 1997