▼ In this paper a new model giving a thorough explanation of the mechanism of formation of stratified binder phase layers is proposed. The model is basically composed of a combination of thermodynamic and kinetic considerations. It is shown that the stratified structure is a result of a slow solidification process under conditions which favour a planar solidification front parallel to the insert surface. Some examples of processes that generate such conditions and thus a stratified structure are given.

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Four alloys manufactured from different combinations of powders (TiC+TiN+WC; Ti(C,N)+WC; (Ti,W)C+TiN and (Ti,W)(C,N)) were studied using X-ray diffractometry, optical microscopy (OM), scanning electron microscopy (SEM) and analytical electron microscopy (AEM). The alloy manufactured from binary powders had a smaller grain size and a more inhomogeneous microstructure than the other alloys. The alloys manufactured with WC contained an inner rim around Ti(C,N) cores, as well as W-rich cores. Thermodynamic calculations suggest that these are formed during solid-state sintering at 900°C in a low nitrogen activity. The outer rim had a composition that is in good agreement with calculations of the equilibrium during liquid phase sintering at 1450°C.

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The microstructure of (mol%) TiC–18TiN–24Ni–(10–29)WC and TiC–18TiN–24Ni–(5–14)Mo₂C has been investigated using X-ray diffraction (XRD), optical microscopy (OM), scanning electron microscopy (SEM) and analytical electron microscopy (AEM). When the WC content in the raw materials was increased the W content in the outer rim of (Ti, W)(C, N) grains increased until it had a composition similar to that of the inner rim. If the WC content was high undissolved WC was present after sintering. When the Mo₂C content in the raw materials was increased, the volume fraction of inner rim increased and the Mo content in both inner and outer rim increased. Thermodynamical calculations on the Ti–W–C–N system suggest that the inner rim is formed during solid state sintering when there is an open porosity and thus a low nitrogen activity. The composition of the outer rim can be explained by the equilibrium at the sintering temperature if the volume fraction of undissolved Ti(C, N) cores is subtracted. Calculations on the Ti–Mo–C–N system show that (Ti, Mo)(C, N) decomposes into two phases with different Mo content and that the Ti(C, N) cores might be regarded as a stable phase.

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A major, often unstated, concern of researchers carrying out epidemiological studies of medical therapy is the potential impact on validity if estimates of treatment are biased due to unmeasured confounders. One technique for obtaining consistent estimates of treatment effects in the presence of unmeasured confounders is instrumental variables analysis (IVA). This technique has been well developed in the econometrics literature and is being increasingly used in epidemiological studies. However, the approach to IVA that is most commonly used in such studies is based on linear models, while many epidemiological applications make use of non-linear models, specifically generalized linear models (GLMs) such as logistic or Poisson regression. Here we present a simple method for applying IVA within the class of GLMs using the generalized method of moments approach. We explore some of the theoretical properties of the method and illustrate its use within both a simulation example and an epidemiological study where unmeasured confounding is suspected to be present. We estimate the effects of beta-blocker therapy on one-year all-cause mortality after an incident hospitalization for heart failure, in the absence of data describing disease severity, which is believed to be a confounder. Copyright © 2007 John Wiley & Sons, Ltd.

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Summary We examine situations where interest lies in the conditional association between outcome and exposure variables, given potential confounding variables. Concern arises that some potential confounders may not be measured accurately, whereas others may not be measured at all. Some form of sensitivity analysis might be employed, to assess how this limitation in available data impacts inference. A Bayesian approach to sensitivity analysis is straightforward in concept: a prior distribution is formed to encapsulate plausible relationships between unobserved and observed variables, and posterior inference about the conditional exposure–disease relationship then follows. In practice, though, it can be challenging to form such a prior distribution in both a realistic and simple manner. Moreover, it can be difficult to develop an attendant Markov chain Monte Carlo (MCMC) algorithm that will work effectively on a posterior distribution arising from a highly nonidentified model. In this article, a simple prior distribution for acknowledging both poorly measured and unmeasured confounding variables is developed. It requires that only a small number of hyperparameters be set by the user. Moreover, a particular computational approach for posterior inference is developed, because application of MCMC in a standard manner is seen to be ineffective in this problem.

▼ The new Trillium™ Biopassive Surface is a coating designed to minimize the adsorption of protein and the attachment of cells. In previous studies, we were able to demonstrate that, by coating the bypass circuit with small amounts of albumin, the drop in circulating platelet count seen with the newer low-prime hollow-fiber membrane oxygenators is eliminated.A study was undertaken to compare the Avecor Affinity™ oxygenator with albumin in the prime with the Trillium-coated Affinity. Fifty-six patients undergoing nonemergency open-heart surgery were randomly divided into two groups. One group (Albumin) received the Affinity oxygenator with 10 ml of 25% albumin added to the pump prime. The other group (Trillium) received the Trillium-coated Affinity oxygenator. To normalize the data for the effects of hemodilution, the mean net platelet count drop on bypass was calculated for each group. The Albumin group had a net platelet count drop of 0.81 ± 9.78%, while the Trillium group had a drop of 1.58 ± 13.0%. There was no significant statistical difference between the two groups.From our investigation, we concluded that Trillium Biopassive Surface coating affords the Affinity oxygenator the same protective effects on circulating platelet counts as adding albumin to the prime.

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A new evaluation of the thermodynamic properties of tungsten has been made. A set of parameters describing the Gibbs energy of each individual phase as a function of temperature and pressure is given. The experimental information on the P, T phase diagram and the thermodynamic data are compared with calculations made using the presented set of parameters.

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Host-related and environmental factors for tuberculosis have usually been investigated separately using different study designs. Joint investigation of the genetic, immunologic, and environmental factors at play in susceptibility to tuberculosis represents an innovative goal for obtaining a better understanding of the pathogenesis of the disease. In this paper, the authors describe methods being used to investigate these points in a West African study combining several designs. Patients with newly diagnosed smear-positive cases of tuberculosis are recruited. The effect of host-related factors is assessed by comparing each case with a healthy control from the case's household. The role of environmental factors is estimated by comparing cases with randomly selected community controls. The frequencies of candidate gene variants are compared between cases and community controls, and results are validated through family-based association studies. Members of the households of cases and community controls are being followed prospectively to determine the incidence of “secondary” tuberculosis and to evaluate the influence of geographic and genetic proximity to the index case. This type of design raises important methodological issues that may be useful to consider in studies investigating the natural history of infectious diseases and in attempts to disentangle the effects of environmental and genetic factors in response to infection.

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In an accompanying paper (Am J Epidemiol 2002;155:1066–73), the authors describe the design of a large multicenter study being carried out in three West African countries for investigation of the roles of environmental and host-related factors in the development of tuberculosis. In this paper, the authors review some evidence that host genetic factors play a role in susceptibility to tuberculosis. They describe the three components of the study that are designed to investigate the effect of host genetic factors on the development of tuberculosis: case-control and family-based association studies of candidate genes and analysis of affected relative pairs to screen the human genome for areas of linkage to the disease. The authors also address a number of methodological issues that arise, such as the effects of consanguinity, half-siblings, and nonpaternity. Lastly, they review opportunities to assess gene-environment interaction in the framework of the study, in light of current methodological knowledge. Consideration of these issues may be useful in the design of other studies of genetic susceptibility to infectious diseases, particularly those to be carried out in developing countries.

▼  Abstract

Pre-treatment serum levels of sCD163 were measured in a cohort of 236 suspected tuberculosis (TB) cases from Guinea-Bissau, with a median follow-up period of 3.3 years (range 0–6.4 years). In 113 cases, the diagnosis of TB was verified by positive sputum microscopy and/or culture. Among the verified TB cases, a decreased survival rate was found in 27 patients with sCD163 levels above the upper reference limit (3.95 µg/mL). The difference in survival was significant during TB treatment (log rank, p < 0.02) and after long-term follow-up (log rank, p < 0.001). The decrease in survival rate during TB treatment remained significant in a multivariate Cox model controlling for human immunodeficiency virus (HIV) status, age and gender, with a mortality increase of 1.19 (95% CI, 1.04–1.36) per µg of sCD163, and a hazard ratio (HR) for sCD163 levels above the upper reference limit of 4.18 (95% CI, 1.06–16.4). The difference was not significant after excluding patients with concomitant HIV-1 and HIV-2 infection in Kaplan–Meier analyses (log rank, p 0.11). In contrast, the difference in survival remained significant in Kaplan–Meier analyses after long-term follow-up, even after excluding patients with concomitant HIV-1 and HIV-2 infection (log rank, p 0.002). In the Cox model, the mortality increase per µg of sCD163 was 1.27 (95% CI, 1.14–1.40), with an HR for elevated sCD163 levels of 2.85 (95% CI, 1.44–5.63). The HRs for concomitant HIV-1 and HIV-2 infection were 6.92 (95% CI, 3.28–14.58) and 2.48 (95% CI, 1.09–5.67), respectively. Thus, sCD163 levels appeared to be an independent predictor of survival in verified TB patients.

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Abstract

Object:

To assess easily monitored predictors for tuberculosis mortality.

Design:

Risk factors for tuberculosis mortality were assessed during the 8-month treatment in 440 men and 269 women diagnosed with confirmed or presumed intrathoracic tuberculosis included prospectively in Guinea-Bissau from May 1996 to April 2001. A civil war occurred in the study area from June 1998 to May 1999.

Results:

12% were HIV-1 positive, 16% HIV-2 positive and 7% were HIV dually infected. Case fatality rates for HIV positive were higher during (35% [22/63]) and after the war (29% [27/92]) compared to before the war (17% [15/88]). The war did not have an effect on the case fatality rate in HIV negative (10% [13/135] before the war). HIV-1-infected patients had higher mortality than HIV-2 infected, mortality rate ratio (MRR) = 2.28 (95% confidence interval 1.17–4.46). Men had higher mortality than women but only among the HIV negative (MRR = 2.09 [0.95–4.59]). Hence, the negative impact of HIV infection on mortality was stronger in women (MRR = 6.51 [2.98–4.2]) than in men (MRR = 2.64 [1.67–4.17]) (test of homogeneity, p = 0.051). Anergy to tuberculin was associated with death in HIV positive (MRR = 2.77 [1.38–5.54]) but not in HIV negative (MRR = 1.14 [0.52–2.53]). Signs of immune deficiency, such as oral candida infection or leukoplakia (MRR = 4.25 [1.92–9.44]) and diarrhea (MRR = 2.15 [1.29–3.58] was associated with mortality in HIV positive. Tendencies were similar among HIV negative. HIV-positive relapse cases were at increased risk of dying (MRR = 2.42 [1.10–5.34]). Malnutrition, measured through mid-upper arm circumference (MUAC), increased the risk of death.

Conclusion:

Easily monitored predictors for mortality in tuberculosis patients include clinical signs of immune deficiency and low MUAC.

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We have earlier devised a system for soft tissue sarcoma (STS), based on three negative prognostic features: large tumour size, vascular invasion, and microscopic tumour necrosis, the SIN-system. Tumours which exhibit 2 or 3 of these features are categorised as high-risk, the others as low-risk. We have now tested this system for reproducibility both as regards recognition of its components, and as regards prognostic strength in patients from another institution. We have also compared it with the American Joint Committee on Cancer (AJCC) system. 200 patients with STS were analysed, all had been treated by surgery, in 97 patients combined with radiotherapy. The median follow-up for the 117 survivors was 10 (1.5–27) years. Without knowledge of the clinical data, three groups of pathologists independently reviewed original slides from all of the tumours. Based on the factors, the tumours were classified as high-risk or low-risk. The prognostic strength was compared using the results obtained by the different observers. Concordance in recognition of vascular invasion, tumour necrosis, and overall grading was seen in 156 (78%), 154 (77%), and 167 (84%) of the 200 tumours, respectively. Based on the different observers’ grading, the cumulative 5-year metastasis-free survival rate (MFSR) varied for patients with low-risk tumours between 0.85 and 0.80, and for patients with high-risk tumours between 0.48 and 0.43. The Kappa-value for grading between all three groups of observers was 0.77. The SIN-system gave more clinically useful prognostic information than the AJCC system. Useful prognostic information in STS can be obtained by using tumour size, vascular invasion and microscopic tumour necrosis. This system provides two distinct prognostic groups, and has a high reproducibility.

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The prognostic importance of surgical margins on local recurrence rates and metastasis-free survival (MFS) was studied in 559 patients with soft tissue sarcoma of the extremities and trunk wall. The patients were all surgically treated, but received no adjuvant treatment. The median follow-up for the survivors was 7.4 (range: 0.1–12.5) years. Independent prognostic factors for MFS were analysed by Cox models. The overall 5-year MFS was 0.72 (95% confidence intervals (CI) 0.68–0.76). High histopathological malignancy grade (relative risk (RR) 3.0; 95% CI 1.5–6.3) and an inadequate surgical margin (RR 2.9; 95% CI 1.8–4.6) were independent risk factors for local recurrence. High histopathological malignancy grade and large tumour size (>7 cm) were the most important risk factors for metastasis. Local recurrence was associated with an increased risk of metastasis (RR 4.4; 95% CI 2.9–6.8), but an inadequate surgical margin was not a risk factor for metastasis (RR 1.1; 95% CI 0.8–1.7). This study confirms that, as regards metastasis, tumour-related risk factors (malignancy grade and tumour size) are more important risk factors than treatment-related factors. Local recurrence was associated with an increased metastasis rate, whereas inadequate surgical margin was a risk factor for local recurrence but not for metastasis. Hence, the proposed causal association between local recurrence and metastasis is doubtful, and if it exists is a weak association.

▼ It is sometimes advantageous to have an expression for the Gibbs energy, G_m(T,P), from which one can analytically derive an expression for the Heimholtz energy, F_m(T, V_m). Such an expression is suggested for solid substances and it is shown how expressions for other physical properties can be derived from it.

▼ Sintering of a cemented carbide body containing nitrogen in a vacuum or in a nitrogen-free atmosphere results in the formation of a cubic-carbide-free gradient zone adjacent to the insert surface. The mechanism for the formation of the gradient zone is, despite its having been thoroughly investigated by others, not fully understood. In the present paper, a kinetic model based on thermodynamic calculations and some kinetic considerations will be presented. According to this model, gradient formation is the result of nitrogen diffusion out of the insert and the coupled diffusion of cubic-carbide-forming elements in the opposite direction, from the surface region into the interior of the insert. Based on the model, a comprehensible explanation of the influence of sharp edges on the gradient growth is given. The gradient is usually thinner close to sharp edges. The present model has been successfully used to rationalize experimental data and to explain predict the influence of variations in composition, sintering time, temperature, and atmosphere.

▼ Cr, Mo and W only have one solid phase, bcc, and they do not form any intermetallic compound. The Cr-Mo-W phase diagram is thus remarkably simple and, as a consequence, it has not attracted much attention. When the present work was started no experimental report was found but an exploratory study was initiated which is now available (1). The purpose of the present work was to combine the information on the three binary systems with the new information on the ternary in order to obtain a complete thermodynamic description.

▼ An evaluation of the Cr-Ni-W system has been made using a magnetic subregular model for the interstitial solution phases, a multi-sublattice model for the intermetallic phases and an ordinary subregular solution model for the liquid phase. A set of parameter values describing the Gibbs energy of each individual phase is given and a number of calculated sections of the Cr-Ni-W phase diagram are presented.

▼ An evaluation of the C-Fe-Ni system has been made using a two-sublattice subregular model for the interstitial solution phases taking into account the magnetic contribution, and an ordinary subregular solution model for the liquid phase. A set of parameter values describing the Gibbs energy of each individual phase is given.

▼ The lattice stability is defined as the Gibbs energy of an element in a certain structure relative to its value in another structure. It is often assumed to vary linearly with temperature, an assumption which is either limited to a narrow range of temperature or implies that C_p of the two phases are the same. A better method would be to use the information available for C_p and derive a more realistic extrapolation. However, it is demonstrated that even the best assessment available today may give absurd results for the stability of a liquid phase relative to a solid. SGTE has recommended another method which makes use of the experimental difference in C_p at the melting point. It is a simple method and guarantees that the results will be reasonable. The method should not be considered as ideal but it provides a workable framework until reliable physical models are available to represent thermodynamic data for phases outside their range of stability.

▼ A new evaluation of the Fe-W system has been made using a magnetic multi-sublattice subregular model. A set of parameter values describing the Gibbs energy of each individual phase is given. The treatment of the μ phase is based upon a three-sub-lattice model.

▼ Austenitic stainless steels are used in a wide range of applications because of their excellent corrosion resistance as well as cold formability. For many applications, however, there is a demand for increased strength and retained corrosion resistance.

▼ A new evaluation of the thermodynamic properties of carbon has been made. A set of parameter values describing the Gibbs energy of each individual phase as a function of temperature and pressure is given. The experimental information on the P, T phase diagram and the thermodynamical data are compared with calculations made using the presented set of parameters. The experimental information is well reproduced.