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Biomedical subjects

M Brady

Publications and source records attributed to M Brady.

At least 55 records · Page 3Linked to original sources
PubMed1998

A respiratory challenge model for infection with Bordetella pertussis: application in the assessment of pertussis vaccine potency and in defining the mechanism of protective immunity.

The evaluation of vaccines for human use usually requires the development of appropriate animal models and the definition of laboratory correlates of immunity. Traditionally whole cell pertussis vaccines have been controlled by using an active mouse protection test, which measures protection following intracerebral challenge with Bordetella pertussis. However, this test is unsuitable for assessing the potency of the new generation acellular pertussis vaccines. In the present study we demonstrate that a murine respiratory challenge model for infection with B. pertussis is suitable for assessing the potency of acellular and whole cell pertussis vaccines. To allow standardization of different vaccines we have expressed the area under the clearance curve for immunized mice as a ratio of that for non-immunized controls to obtain a potency index. A comparison of estimated vaccine efficacy in children with potency in the murine model results in a highly significant correlation (r = 0.976, p < 0.001). Furthermore, we have used this model to define the protective mechanism of immunity against respiratory infection with B. pertussis and demonstrate a requirement for both specific T and B cells. In accordance with studies in humans, no clear relationship was observed between monotypic serum antibody responses against the putative protective antigens of B. pertussis and protection. In contrast, the most potent protection was observed when the T cell response is polarized to the Th1 subtype.

Animals↗
PubMed1997

The forms of knowledge mobilized in some machine vision systems.

This paper describes a number of computer vision systems that we have constructed, and which are firmly based on knowledge of diverse sorts. However, that knowledge is often represented in a way that is only accessible to a limited set of processes, that make limited use of it, and though the knowledge is amenable to change, in practice it can only be changed in rather simple ways. The rest of the paper addresses the questions: (i) what knowledge is mobilized in the furtherance of a perceptual task?; (ii) how is that knowledge represented?; and (iii) how is that knowledge mobilized? First we review some cases of early visual processing where the mobilization of knowledge seems to be a key contributor to success yet where the knowledge is deliberately represented in a quite inflexible way. After considering the knowledge that is involved in overcoming the projective nature of images, we move the discussion to the knowledge that was required in programs to match, register, and recognize shapes in a range of applications. Finally, we discuss the current state of process architectures for knowledge mobilization.

Humans↗
PubMed1997

Analysis of dynamic MR breast images using a model of contrast enhancement.

We describe a model of dynamic contrast enhancement in breast MRI designed to aid the radiologist in cases for which X-ray mammography is ineffective. The breasts are segmented from the image slices by a dynamic programming algorithm after morphological opening. A pharmacokinetic model has been derived to fit the rise in intensities after injection of a contrast agent, in a way that facilitates investigation of the effects of different models of bolus injection. The pharmacokinetic model is used in a modified Horn-Schunck algorithm to correct for motion effects during the seven minute acquisition period. The results show significant localization of tumours and enable discrimination of cancerous tissue. In particular, we illustrate the approach with an image that shows a carcinoma, whose appearance and localization are greatly improved by the registration algorithm.

Algorithms↗
PubMed1997

Paradigm lost?

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Biotechnology↗
PubMed1997

Quality of life measurement in bone marrow transplantation: development of the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) scale.

We developed a 12-item bone marrow transplant subscale (BMTS) for the general Functional Assessment of Cancer Therapy (FACT) measure. The subscale combined with the FACT, (FACT-BMT) is a 47-item, valid and reliable measure of five dimensions of quality of life in bone marrow transplant patients. The three-step validation process involved the generation and selection of BMT-specific items and the testing of the overall measure. Items were selected from a list produced by seven oncology experts and 15 patients and were designed to assess content not represented in the general FACT items. A total of 182 patients completed the FACT-BMT at baseline, prior to BMT. An analysis measuring sensitivity to change was performed with 74 patients after transplantation and 60 patients over the three time-points of baseline, hospital discharge and 100 days. The FACT-BMT and all subscales were correlated, sensitivity to change was measured, and the internal consistency for each scale was calculated. Coefficients of reliability and validity ranged from 0.86 to 0.89 for the entire FACT-BMT and 0.54 to 0.63 for the BMTS. The BMTS was able to discriminate patients on the basis of performance status rating and also demonstrated sensitivity to change over time. The FACT-BMT has good psychometric properties for use in assessing quality of life in bone marrow transplant patients. The addition of the bone marrow transplant subscale to the general FACT measure makes it an excellent choice for use in BMT clinical trials.

Adolescent↗
PubMed1997

Estimating the bias field of MR images.

We propose a modification of Wells et al. technique for bias field estimation and segmentation of magnetic resonance (MR) images. We show that replacing the class other, which includes all tissue not modeled explicitly by Gaussians with small variance, by a uniform probability density, and amending the expectation-maximization (EM) algorithm appropriately, gives significantly better results. We next consider the estimation and filtering of high-frequency information in MR images, comprising noise, intertissue boundaries, and within tissue microstructures. We conclude that post-filtering is preferable to the prefiltering that has been proposed previously. We observe that the performance of any segmentation algorithm, in particular that of Wells et al. (and our refinements of it) is affected substantially by the number and selection of the tissue classes that are modeled explicitly, the corresponding defining parameters and, critically, the spatial distribution of tissues in the image. We present an initial exploration to choose automatically the number of classes and the associated parameters that give the best output. This requires us to define what is meant by "best output" and for this we propose the application of minimum entropy. The methods developed have been implemented and are illustrated throughout on simulated and real data (brain and breast MR).

Algorithms↗
PubMed1996

A representation for mammographic image processing.

Mammographic image analysis is typically performed using standard, general-purpose algorithms. We note the dangers of this approach and show that an alternative physics-model-based approach can be developed to calibrate the mammographic imaging process. This enables us to obtain, at each pixel, a quantitative measure of the breast tissue. The measure we use is h(int) and this represents the thickness of 'interesting' (non-fat) tissue between the pixel and the X-ray source. The thicknesses over the image constitute what we term the h(int) representation, and it can most usefully be regarded as a surface that conveys information about the anatomy of the breast. The representation allows image enhancement through removing the effects of degrading factors, and also effective image normalization since all changes in the image due to variations in the imaging conditions have been removed. Furthermore, the h(int) representation gives us a basis upon which to build object models and to reason about breast anatomy. We use this ability to choose features that are robust to breast compression and variations in breast composition. In this paper we describe the h(int) representation, show how it can be computed, and then illustrate how it can be applied to a variety of mammographic image processing tasks. The breast thickness turns out to be a key parameter in the computation of h(int), but it is not normally recorded. We show how the breast thickness can be estimated from an image, and examine the sensitivity of h(int) to this estimate. We then show how we can simulate any projective X-ray examination and can simulate the appearance of anatomical structures within the breast. We follow this with a comparison between the h(int) representation and conventional representations with respect to invariance to imaging conditions and the surrounding tissue. Initial results indicate that image analysis is far more robust when specific consideration is taken of the imaging process and the h(int) representation is used.

Breast Diseases↗
PubMed1995

Rat testicular carboxylesterase: cloning, cellular localization, and relationship to liver hydrolase A.

We recently purified from rat liver microsomes a carboxylesterase, designated hydrolase A, that catalyzes the hydrolysis of para-nitrophenylacetate with high affinity (Km approximately 25 microM) and is very sensitive to the inhibitory effects of phenylmethylsulfonyl fluoride (PMSF). Based on its catalytic properties, isoelectric point, and N-terminal amino acid sequence, hydrolase A corresponds to the pI 6.1 esterase cloned from a rat liver cDNA library by Robbi et al. (Biochem. J. 269, 451-458, 1990). A PMSF-sensitive esterase with high affinity toward para-nitrophenylacetate is also present in testicular microsomes at levels that slightly exceed those in liver microsomes. Antibody against purified hydrolase A recognizes a 57-kDa protein in both liver and testicular microsomes, suggesting that hydrolase A is expressed to a high degree in both tissues. To determine whether the testicular carboxylesterase is identical to hydrolase A, a rat testicular cDNA library was constructed and screened with antibody against hydrolase A. A 709-bp cDNA was isolated from immunopositive clones. Screening the same cDNA library by polymerase chain reaction (PCR) with one primer based on the sequence of the 709-bp cDNA and one primer based on the sequence of the adjoining lambda gt11 arm yielded a 1.1-kb cDNA that overlapped with the 709 bp-sequence. Together these two cDNA fragments spanned a 1792-bp sequence with an opening reading frame encoding 518 amino acids, which corresponds to approximately 95% of the C-terminal sequence of the liver pI 6.1 esterase (i.e., hydrolase A). Except for four nucleotide differences at positions 479, 855, 1335, and 1350, the sequence of the testicular cDNA was identical to the cDNA sequence of the liver pI 6.1 esterase reported by Robbi et al. None these changes results in an amino acid substitution. However, these four base substitutions were not observed when a cDNA encoding hydrolase A was isolated from a rat liver cDNA library by PCR. These results establish that the same carboxylesterase, namely, hydrolase A, is expressed in rat liver and testis. The levels of mRNA for hydrolase A in various rat tissues was estimated from Northern blots probed with the 709-bp cDNA isolated from the rat testicular cDNA library. A approximately 2-kb mRNA for hydrolase A was detected in liver, testis, lung, and prostate, which confirms the tissue distribution of hydrolase A based on catalytic activity and Western immunoblotting.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Culture in treatment, culture as treatment. A critical appraisal of developments in addictions programs for indigenous North Americans and Australians.

Indigenous people in Australia and in North America have been creating innovative interventions in the addictions field for several years now--incorporating traditional healing practices and cultural values into otherwise western programs--although this process is more developed in Canada and the U.S. than it is in Australia. Through a process of cultural diffusion, Australian Aborigines have incorporated many ideas from Native Canadian treatment models. As a result, residential treatment utilizing adapted forms of the 12 steps of Alcoholics Anonymous is being promoted by indigenous Australians. This paper examines comparative material on the uses of culture as a form of healing and traces the rationale for the argument that cultural wholeness can serve as a preventive, or even curing agent in drug and alcohol abuse. This is a qualitative leap from the now universally accepted notion that treatment and rehabilitation for native people should be culturally appropriate. There are, however, certain dilemmas confronting native treatment directors attempting these syncretic approaches, given aspects of cultural contexts which can serve to foster drug and alcohol use rather than discourage it. Additionally, North American Indians have at their disposal a rich heritage of communal healing techniques; some (such as the sweat lodge) have been adapted and incorporated into the treatment both of solvent abuse by adolescents, and alcohol abuse by adults. In Australia on the other hand, traditional healing techniques have been less amenable to adaptation. On neither continent are indigenous people attempting to adapt recent mainstream models of intervention to suit their needs (such as Brief Intervention) which is currently receiving international attention in addictions research and treatment.

Australia↗
PubMed1995

Health care policy for aboriginal Australians: the relevance of the American Indian experience.

This paper discusses and compares the systems for the delivery of health care services to indigenous peoples in the United States and Australia; both are poor minorities in wealthy countries and many live in remote locations. Three necessary conditions that have shaped the relative success of the Indian Health Service in the United States are relevant to the Australian situation: federal government administration; the separation of the Indian Health Service from other Indian affairs; and the provision of an integrated health service. Ironically, recent policy changes in the United States by the Clinton administration are reducing the federal bureaucracy, and along with it, Indian Health Service funding. In Australia, the states have had responsibility for service delivery to Aboriginal people, there have been no treaties formalising the relationship between indigenous people and the federal government, and Aboriginal health has been switched between different departments while remaining primarily within the Aboriginal affairs (rather than the health) portfolio. Since 1993, there has been pressure to return Aboriginal health to the health portfolio, and in July 1995, funding and administration of Aboriginal health services were moved from the Aboriginal and Torres Strait Islander Commission to the Department of Human Services and Health.

Australia↗