Biomedical subjects
Publications and source records attributed to Stephen Smith.
Clinical information systems are proven to enhance workflow and outcomes, and yet hospitals often face staff resistance when systems are installed. This roundtable discussion explores how nurses and physicians can collaborate on developing IT systems.
Both logographic characters and alphabetic pinyins can be used to write words in Chinese. Here we use fMRI to address the question of whether the written form affects brain processing of a word. Fifteen healthy, right-handed, native Chinese-reading volunteers participated in our study and were asked to read silently either Chinese characters (8 subjects) or pinyins (7 subjects). The stimulus presentation rate was varied for both tasks to allow us to identify brain regions with word-load-dependent activation. Rate effects (fast minus slow presentations) for Chinese character reading were observed in striate and extrastriate visual cortex, superior parietal lobule, left posterior middle temporal gyrus, bilateral inferior temporal gyri, and bilateral superior frontal gyri. Rate effects for pinyin reading were observed in bilateral fusiform, lingual, and middle occipital gyri, bilateral superior parietal lobule/precuneus, left inferior parietal lobule, bilateral inferior temporal gyrus, left middle temporal gyrus, and left superior temporal gyrus. These results demonstrate that common regions of the brain are involved in reading both Chinese characters and pinyins, activated apparently independently of the surface form of the word. There also appear to be brain regions in which activation is dependent on word form. However, it is unlikely that these are entirely specific for a given word form; their activation more likely reflects relative functional specializations within broader networks for processing written language.
Recently, there has been considerable debate regarding the involvement of the left and right prefrontal cortices in the encoding and retrieval of episodic memory. In a previous PET study, we found that the use of easily verbalisable material may lead to activation predominantly in the left lateral frontal cortex whilst the use of non-easily verbalisable material may lead to activation predominantly in the right lateral frontal cortex, in both cases irrespective of encoding and retrieval processes. In order to replicate and extend these findings, the same task was modified for use with fMRI. Six healthy volunteers were scanned while encoding and then recalling stimuli that either emphasised visual or verbal processes. It was found that, in comparison to a baseline condition, the encoding of visual stimuli led to a bilateral activation of the prefrontal cortex whilst the encoding of verbal stimuli led to a preferential activation of the left prefrontal cortex. An effect of stimulus type was less evident during retrieval, with both visual and verbal stimuli leading to bilateral prefrontal cortex activation. Overall, encoding and retrieval activated similar regions of the prefrontal cortex suggesting that these areas mediate processes that are fundamental to both aspects of memory. To extend these findings further, the tasks used in the fMRI study were used to assess a group of patients with unilateral frontal lesions and a group of healthy control volunteers. The patients were significantly impaired compared to the healthy volunteers, although no significant differences were found in performance between the right- and left-sided lesioned patients. This result suggests that the memory-related asymmetries observed during functional neuroimaging studies may not be critical for task performance.
Linear registration and motion correction are important components of structural and functional brain image analysis. Most modern methods optimize some intensity-based cost function to determine the best registration. To date, little attention has been focused on the optimization method itself, even though the success of most registration methods hinges on the quality of this optimization. This paper examines the optimization process in detail and demonstrates that the commonly used multiresolution local optimization methods can, and do, get trapped in local minima. To address this problem, two approaches are taken: (1) to apodize the cost function and (2) to employ a novel hybrid global-local optimization method. This new optimization method is specifically designed for registering whole brain images. It substantially reduces the likelihood of producing misregistrations due to being trapped by local minima. The increased robustness of the method, compared to other commonly used methods, is demonstrated by a consistency test. In addition, the accuracy of the registration is demonstrated by a series of experiments with motion correction. These motion correction experiments also investigate how the results are affected by different cost functions and interpolation methods.
Triple A (Allgrove) syndrome is characterized by achalasia, alacrima, adrenal abnormalities and a progressive neurological syndrome. Affected individuals have between two and four of these relatively common clinical problems; hence the diagnosis is often difficult in all but the classical presentation. The inheritance is autosomal recessive, and most cases of triple A have no family history. Using genetic linkage analysis in a small number of families, a locus on chromosome 12q13 was identified. The triple A gene was identified recently at this locus and called ALADIN (alacrima, achalasia, adrenal insufficiency neurologic disorder). Mutations in this gene were reported in families from North Africa and Europe. The majority of mutations were homozygous. We have identified 20 families with between two and four of the clinical features associated with the triple A syndrome. Sequencing of the triple A gene revealed five families that had a total of nine compound heterozygous mutations, and one Portuguese family (previously published) had two homozygous mutations; these changes were spread throughout the triple A gene in exons 1, 2, 7, 8, 10, 11, 12, 13 and 16, and the poly(A) tract. Those bearing mutations had the classical triple A syndrome of achalasia, alacrima, adrenal abnormalities and a progressive neurological syndrome. We identified a spectrum of associated neurological abnormalities in these cases, including pupil and cranial nerve abnormalities, frequent optic atrophy, autonomic neuropathy and upper and lower motor neurone signs including distal motor neuropathy and amyotrophy with severe selective ulnar nerve involvement. In these families, we have made genotype-phenotype correlations. Mutations in the triple A gene are thus an important cause of this clinically heterogeneous syndrome, and sequencing represents an important diagnostic investigation. Identifying further mutations and defining their phenotype along with functional protein analysis will help to characterize this neuroendocrine gene.
Information on the establishment of immunodeficiency virus infection through transmission of infected cells is sparse. Dendritic cells (DCs) and T cells may be central to the onset and subsequent spread of infection following mucosal exposure. To directly investigate the consequences of virus being introduced by DCs or T cells, we reinjected ex vivo simian immunodeficiency virus (SIV)-loaded autologous immature DCs and T cells subcutaneously (s.c.) into healthy macaques. s.c. injection of cell-bound virus was used to mirror what may happen if virus-loaded cells pass through an epithelium or perhaps DCs and T cells that immediately entrap cell-free virus, having just crossed an epithelial barrier. Virus load in the plasma was monitored along with combined in situ hybridization and immunohistochemistry to identify the cells replicating virus in the lymphoid tissues. Both DCs and T cells transmitted infection after being pulsed with either wild-type or nef-defective (delta nef) SIVmac239. As seen in animals infected intravenously, replication of delta nef was attenuated compared to that of wild-type virus when introduced in either cell-bound form. Upon examination of the draining lymph nodes (LNs) during the first days of infection, virus-producing CD4(+) T cells predominated in control animals that received s.c. cell-free virus. In dramatic contrast, both SIV-positive macrophages and T cells were detected in the LNs of monkeys infected with cell-associated SIV. Therefore, although both cell-free and cell-associated viruses are infectious, the initial cells amplifying the virus differ. This may have important implications for the subsequent dissemination of infection and/or induction of antiretroviral immunity.
Left ventricular geometry is an important parameter of its function; however, left ventricular function has been conventionally quantified through measurements of volume, ejection fraction, and mass. Left ventricular global shape has been quantified previously using methods that are based on assumptions of idealized cavity shape. Although these indices have been applied to various disease states of the left ventricle, the underlying assumption of an ideal left ventricular geometry is inherently flawed. Regional left ventricular shape using echocardiography has not been previously evaluated, principally because of the difficulty in quantitative regional geometry. Alterations in left ventricular geometry have a direct impact on wall stress and thus the diastolic performance of the left ventricle. We developed an algorithm based on Fourier transformation of traced endocardial borders from two-dimensional echocardiograms that allowed global shape of the left ventricular to be quantified without assumptions of any ideal left ventricular shape. This method is an adaptation of an algorithm defined for cineventriculograms by Marino and colleagues (Am J Physiol 1988;254:H547-H557). We further described a method to quantify regional endocardial curvature as an index of regional shape. In this preliminary validation study, we primarily tested the reproducibility of these two parameters.
In 2002, Utah became the first state to reduce benefits and increase cost sharing for existing Medicaid beneficiaries, to finance a primary care benefit expansion for previously ineligible, low-income adults. Through a 2004 survey of beneficiaries, we found that expansion enrollees were predominantly poor and that most suffered from chronic conditions or disabilities, or both. Parents whose coverage was reduced to finance the expansion were extremely poor, were in poor health, and faced major financial challenges. Findings suggest that a coverage expansion approach that relies on savings from reducing coverage for current beneficiaries and solely covers primary care has important limitations.