Mathematical/computational challenges in creating deformable and probabilistic atlases of the human brain

Striking variations in brain structure, especially in the gyral patterns of the human cortex, present fundamental challenges in human brain mapping. Probabilistic brain atlases, which encode information on structural and functional variability in large human populations, are powerful research tools with broad applications. Knowledge-based imaging algorithms can also leverage atlased information on anatomic variation. Applications include automated image labeling, pathology detection in individuals or groups, and investigating how regional anatomy is altered in disease, and with age, gender, handedness and other clinical or genetic factors. In this report, we illustrate some of the mathematical challenges involved in constructing population-based brain atlases. A disease-specific atlas is constructed to represent the human brain in Alzheimer's disease (AD). Specialized strategies are developed for population-based averaging of anatomy. Sets of high-dimensional elastic mappings, based on the principles of continuum mechanics, reconfigure the anatomy of a large number of subjects in an anatomic image database. These mappings generate a local encoding of anatomic variability and are used to create a crisp anatomical image template with highly resolved structures in their mean spatial location. Specialized approaches are also developed to average cortical topography. Since cortical patterns are altered in a variety of diseases, gyral pattern matching is used to encode the magnitude and principal directions of local cortical variation. In the resulting cortical templates, subtle features emerge. Regional asymmetries appear that are not apparent in individual anatomies. Population-based maps of cortical variation reveal a mosaic of variability patterns that segregate sharply according to functional specialization and cytoarchitectonic boundaries.     

Perioperative optimisation of fluid management improves outcome

Mortality from high-risk surgery is close to 10% (20% with emergency). Poor outcome is linked to tissue hypoperfusion. Optimising fluid therapy has a good pathophysiological basis related to microvascular flow to the tissues and the risk of multiple organ failure. Metaanalysis showed the higher the risk of surgery the greater the benefit of fluid and flow optimisation. A direct technique (blood pressure is indirect) to manage fluid therapy measuring tissues perfusions has not yet fulfilled criteria (easiness, accuracy, less invasiveness). At present pulmonary artery catheter with continuous output measurement is the choice. The aim of the study is to assess the impact of fluid management to increase blood flow in high-risk surgical patient.     

Inhibition of cigarette smoke-related lipophilic DNA adducts in rat tissues by dietary oltipraz

The present study investigated the effects of dietary oltipraz on cigarette smoke-related lipophilic DNA adduct formation. Female Sprague- Dawley rats were exposed daily to sidestream cigarette smoke in a whole- body exposure chamber 6 h/day for 4 consecutive weeks. One group of rats was maintained on control diet while another group received the same diet supplemented with either a low (167 p.p.m.) or high (500 p.p.m.) dose of oltipraz, starting 1 week prior to initiation of smoke exposure until the end of the experiment. Analysis of lipophilic DNA adducts by the nuclease P1-mediated 32P-post-labeling showed up to five smoke-related adducts. Adduct no. 5 predominated in both the lung and the heart while adduct nos 3 and 2 predominated in the trachea and bladder, respectively. Quantitative analysis revealed that the total adduct level was the highest in lungs (270+/-68 adducts/10(10) nucleotides), followed by trachea (196+/-48 adducts/10(10) nucleotides), heart (141+/-22 adducts/10(10) nucleotides) and bladder (85+/-16 adducts/10(10) nucleotides). High dose oltipraz treatment reduced the adduct levels in lungs and bladder by >60%, while the reduction in lungs in the low-dose group was approximately 35%. In trachea, the effect of low and high dietary oltipraz on smoke DNA adduction was equivocal, while smoke-related DNA adducts in the heart were minimally inhibited by high-dose oltipraz. In a repeat experiment that employed a 3-fold lower dose of cigarette smoke, oltipraz (500 p.p.m.) was found to inhibit the formation of DNA adducts in rat lungs and trachea by 80 and 65%, respectively. These data clearly demonstrate a high efficacy of oltipraz in inhibiting the formation of cigarette smoke-induced DNA adducts in the target tissues.      

Mutation of the p53 tumor suppressor gene in spontaneously occurring osteosarcomas of the dog

Inactivation of the p53 tumor suppressor gene has been implicated in the pathogenesis of numerous human cancers, including osteosarcomas. Appendicular osteosarcomas of the dog appear to be a good model for their human equivalent with regard to biologic behavior, epidemiology and histopathology. We individually screened exons 5-8 of the p53 gene for mutations in 15 canine appendicular osteosarcomas using 'Cold' SSCP to compare the role of this gene in human and canine osteosarcoma tumorigenesis. Seven of the tumors (47%) exhibited point mutations, with one tumor possessing two mutations within different exons. Of these, seven were missense mutations and the eighth was a 'silent' mutation potentially affecting the exon 6-7 splicing region. Five of the missense mutations were located in highly conserved regions IV and V, while another corresponded with the highly conserved codon 220 mutational hotspot located outside the conserved domains. The locations and types of mutations were nearly identical to those reported in human cancer. These findings provide strong evidence of the involvement of p53 mutations in the development of canine appendicular osteosarcomas. Canine osteosarcomas appear to be a promising model for their human equivalent on a clinical, pathologic, and molecular level.      

Role of n-3 fatty acids in prevention of disease complications in patients with HIV.

Hypertriglyceridemia and insulin resistance have been seen in patients with HIV. Beneficial effects of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been reported for these conditions. One study of n-3 fatty acid supplementation in patients with HIV reported a decrease in serum triglyceride levels. These marine fatty acids appear to be working at a number of sites to achieve an improvement in lipid metabolism and insulin sensitivity. There is disagreement about the amount of n-3 fatty acids needed to achieve different effects and about the optimal ratio of dietary n-6 and n-3 fatty acids.     

A UK multi‐centre pilot study of speech and swallowing outcomes following head and neck cancer

Speech and swallowing are important components of health‐related quality of life following head and neck cancer treatment. The aim of this study was to demonstrate the value of prospective multi‐centre evaluation by Speech and Language Therapists and to compare health‐related quality of life with speech and swallowing impairments. The University of Washington Head and Neck questionnaire version 4 (UW‐QOL) and Therapy Outcome Measures (TOM) were rated before and 6 months after cancer treatment in 95 patients from 12 centres. There was deterioration in TOM scores at 6 months. Pretreatment UW‐QOL swallowing was ranked equal first, with speech fourth. At 6 months speech was first and swallowing second. There were positive correlations between UW‐QOL swallowing and TOM dysphagia and between UW‐QOL speech and TOM laryngectomy, voice, phonology and dysarthria disorders. Both outcome measures are suitable for routine practice. Adaptation of TOM scales for use with head and neck cancer patients may improve sensitivity, validity and therapist compliance.     

Handoff strategies in settings with high consequences for failure: lessons for health care operations.

OBJECTIVE: To describe strategies employed during handoffs in four settings with high consequences for failure. DESIGN: ANALYSIS: of observational data for evidence of use of 21 handoff strategies. SETTING: NASA Johnson Space Center in Texas, nuclear power generation plants in Canada, a railroad dispatch center in the United States, and an ambulance dispatch center in Toronto. MAIN MEASURE: Evidence of 21 handoff strategies from observations and interviews. RESULTS: Nineteen of 21 strategies were used in at least one domain, on at least an 'as needed' basis. CONCLUSIONS: An understanding of how handoffs are conducted in settings with high consequences for failure can jumpstart endeavors to modify handoffs to improve patient safety.     

The development of the emetic reflex in the house musk shrew, Suncus murinus

The emetic (retching and vomiting) reflex is an important component of the body's defence system against accidentally ingested toxins and emesis is also a common symptom of disease and a side-effect of a number of pharmacological therapies. The development of the reflex has been the subject of few systematic studies. The aim of this study was to characterise the development of the emetic reflex in Suncus murinus (the house musk shrew) using emetic stimuli acting via three different afferent pathways: motion via the vestibular system, pyrogallol via abdominal vagal afferents and resiniferatoxin (a capsaicin analog) via the brainstem. The emetic reflex was not present to any stimulus prior to postnatal day 10 but the onset of the response to motion lagged behind that to the other stimuli in not being present until postnatal day 15. Body weight was not a determinant of the presence of the reflex. It is proposed that the delayed presence of the emetic reflex in Suncus makes it an ideal species in which to investigate factors regulating its development.     

Interactions between spatial attention and global/local feature selection: an ERP study

The present study examined the interaction between spatial attention and global/local feature processing of visual hierarchical stimuli. Event-related brain potentials (ERPs) were recorded from subjects who detected global or local targets at attended locations while ignoring those at unattended locations. Spatial attention produced enhanced occipital P1 and N1 waves in both global and local conditions. Selection of local features enhanced posterior P1, N1 and N2 waves relative to selection of global features. However, the modulations of the P1 and N2 by global/local feature selection were stronger when spatial attention was directed to the left than the right visual fields. The results suggest neurophysiological bases for interactions between spatial attention and hierarchical analysis at multiple stages of visual processing.