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Biomedical subjects

Peter M Brown

Publications and source records attributed to Peter M Brown.

13 recordsLinked to original sources

Contingent Pacific-Atlantic Ocean influence on multicentury wildfire synchrony over western North America.

Widespread synchronous wildfires driven by climatic variation, such as those that swept western North America during 1996, 2000, and 2002, can result in major environmental and societal impacts. Understanding relationships between continental-scale patterns of drought and modes of sea surface temperatures (SSTs) such as El Niño-Southern Oscillation (ENSO), Pacific Decadal Oscillation (PDO), and Atlantic Multidecadal Oscillation (AMO) may explain how interannual to multidecadal variability in SSTs drives fire at continental scales. We used local wildfire chronologies reconstructed from fire scars on tree rings across western North America and independent reconstructions of SST developed from tree-ring widths at other sites to examine the relationships of multicentury patterns of climate and fire synchrony. From 33,039 annually resolved fire-scar dates at 238 sites (the largest paleofire record yet assembled), we examined forest fires at regional and subcontinental scales. Since 1550 CE, drought and forest fires covaried across the West, but in a manner contingent on SST modes. During certain phases of ENSO and PDO, fire was synchronous within broad subregions and sometimes asynchronous among those regions. In contrast, fires were most commonly synchronous across the West during warm phases of the AMO. ENSO and PDO were the main drivers of high-frequency variation in fire (interannual to decadal), whereas the AMO conditionally changed the strength and spatial influence of ENSO and PDO on wildfire occurrence at multidecadal scales. A current warming trend in AMO suggests that we may expect an increase in widespread, synchronous fires across the western U.S. in coming decades.

Journal Article↗

Crystal structure of a substrate complex of myo-inositol oxygenase, a di-iron oxygenase with a key role in inositol metabolism.

Altered metabolism of the inositol sugars myo-inositol (MI) and d-chiro-inositol is implicated in diabetic complications. In animals, catabolism of MI and D-chiro-inositol depends on the enzyme MI oxygenase (MIOX), which catalyzes the first committed step of the glucuronate-xylulose pathway, and is found almost exclusively in the kidneys. The crystal structure of MIOX, in complex with MI, has been determined by multiwavelength anomalous diffraction methods and refined at 2.0-A resolution (R=0.206, Rfree=0.253). The structure reveals a monomeric, single-domain protein with a mostly helical fold that is distantly related to the diverse HD domain superfamily. Five helices form the structural core and provide six ligands (four His and two Asp) for the di-iron center, in which the two iron atoms are bridged by a putative hydroxide ion and one of the Asp ligands, Asp-124. A key loop forms a lid over the MI substrate, which is coordinated in bidentate mode to one iron atom. It is proposed that this mode of iron coordination, and interaction with a key Lys residue, activate MI for bond cleavage. The structure also reveals the basis of substrate specificity and suggests routes for the development of specific MIOX inhibitors.

Animals↗

Purification, crystallization and preliminary crystallographic analysis of mouse myo-inositol oxygenase.

Myo-inositol oxygenase (MIOX) catalyzes the novel oxidative cleavage of myo-inositol (MI) and its epimer D-chiro inositol (DCI) to D-glucuronate. MIOX utilizes an Fe(II)/Fe(III) binuclear iron centre for the dioxygen-dependent cleavage of the C1-C6 bond in MI. Despite its key role in inositol metabolism, the structural basis of its unique four-electron oxidation mechanism and its substrate specificity remain unknown. In order to answer these questions and to facilitate the use of this key enzyme for the development of new therapeutic strategies for diabetes, the mouse enzyme has been cloned, expressed in Escherichia coli, purified and crystallized from 4.4 M sodium formate. The crystals belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 44.87, b = 77.26, c = 84.84 angstroms, and diffract to 2.8 angstroms resolution.

Animals↗

Development of a cell culture/ELISA assay to detect anticoagulant rodenticides and its application to analysis of rodenticide treated grain.

This study describes a generic biological screening assay designed to detect anticoagulant rodenticides based on their inhibitory action on the vitamin K epoxide reductase protein complex, resulting in an accumulation of under-carboxylated prothrombin or proteins induced by vitamin K antagonism (PIVKA-II). A combined cell culture/ELISA assay was optimized to measure PIVKA-II production by the human hepatoma HepG2 cell line cultured in the presence of anticoagulant rodenticides. The specificity and sensitivity of the assay was validated using 41 grain extracts containing representative concentrations of rodenticide or appropriate nonrodenticide control compounds. In all cases, PIVKA-II produced by HepG2 cells in response to grain extracts spiked with rodenticides was detected by ELISA, while PIVKA-II was not detected in supernatants collected from cells exposed to nonrodenticide controls. This represents a novel, class-specific biological assay for the detection of anticoagulant rodenticides present in contaminated grain.

Anticoagulants↗

Climate effects on fire regimes and tree recruitment in Black Hills ponderosa pine forests.

Climate influences forest structure through effects on both species demography (recruitment and mortality) and disturbance regimes. Here, I compare multi-century chronologies of regional fire years and tree recruitment from ponderosa pine forests in the Black Hills of southwestern South Dakota and northeastern Wyoming to reconstructions of precipitation and global circulation indices. Regional fire years were affected by droughts and variations in both Pacific and Atlantic sea surface temperatures. Fires were synchronous with La Niñas, cool phases of the Pacific Decadal Oscillation (PDO), and warm phases of the Atlantic Multidecadal Oscillation (AMO). These quasi-periodic circulation features are associated with drought conditions over much of the western United States. The opposite pattern (El Niño, warm PDO, cool AMO) was associated with fewer fires than expected. Regional tree recruitment largely occurred during wet periods in precipitation reconstructions, with the most abundant recruitment coeval with an extended pluvial from the late 1700s to early 1800s. Widespread even-aged cohorts likely were not the result of large crown fires causing overstory mortality, but rather were caused by optimal climate conditions that contributed to synchronous regional recruitment and longer intervals between surface fires. Synchronous recruitment driven by climate is an example of the Moran effect. The presence of abundant fire-scarred trees in multi-aged stands supports a prevailing historical model for ponderosa pine forests in which recurrent surface fires affected heterogenous forest structure, although the Black Hills apparently had a greater range of fire behavior and resulting forest structure over multi-decadal time scales than ponderosa pine forests of the Southwest that burned more often.

Chronology as Topic↗

Selective management of abdominal aortic aneurysms smaller than 5.0 cm in a prospective sizing program with gender-specific analysis.

PURPOSE: We present extended follow-up findings of the Kingston prospective sizing program for patients with abdominal aortic aneurysm (AAA) smaller than 5.0 cm in diameter, with gender-specific analysis. METHODS: From 1976 to 2001, 895 patients (688 men, 207 women) with AAA smaller than 5.0 cm were entered, regardless of fitness, in a prospective sizing program in which computed tomography scans were obtained every 6 months. Operations were performed in fit patients with an increase in AAA size to 5 cm (n = 190), AAA expansion greater than 0.5 cm in 6 months (n = 27), or for other reasons (n = 33). Follow-up continued until AAA rupture, surgery, death, or removal from the program. RESULTS: No AAA smaller than 5.0 cm ruptured during prospective follow-up. There was a statistically significant increase in expansion rate relative to size at entry, with the highest mean expansion rate of 0.52 cm/y for AAA 4.5 to 4.9 cm in diameter. There was no significant difference in AAA expansion rate between men and women. The frequency of surgery was inversely related to age at entry, but was positively related to AAA size at entry, with patients with AAA 4.5 to 4.9 cm at entry 6.8 times more likely (95% confidence interval, 4.3-10.7) to undergo surgery than those with AAA 3.0 to 3.4 cm at entry. Women were older than men at entry, and age at entry in those undergoing surgery was significantly greater in women. CONCLUSIONS: The study confirms the results of the United Kingdom Small Aneurysm Trial and the Aneurysm Detection and Management Study, that is, that risk for rupture is extremely unlikely with AAA smaller than 5.0 cm, which enables safe follow-up surveillance programs in both men and women with AAA smaller than 5.0 cm.

Aged↗

The risk of rupture in untreated aneurysms: the impact of size, gender, and expansion rate.

OBJECTIVE: The purpose of this study was to establish the risk of rupture as related to size of abdominal aortic aneurysm (AAA), gender, and expansion of the aneurysm. METHODS: Between 1976 and 2001, 476 patients with conditions considered unfit for surgery with AAA 5.0 cm or more were followed with computed tomographic scans every 6 months until rupture, surgery, death, or deletion from follow-up. Surgery was performed for rupture (n = 22), improved medical condition (n = 37), increase in size (n = 95), symptoms (n = 17), and other reasons (n = 24). RESULTS: Fifty ruptures occurred during the follow-up period. The average risk of rupture (and standard error) in male patients with 5.0-cm to 5.9-cm AAA was 1.0% (0.01%) per year, in female patients with 5.0-cm to 5.9-cm AAA was 3.9% (0.15%) per year, in male patients with 6.0-cm or greater AAA was 14.1% (0.18%) per year, and in female patients with 6.0-cm or greater AAA was 22.3% (0.95%) per year. CONCLUSION: The risk of rupture in male patients with AAA 5.0 to 5.9 cm is low. The four-time higher risk of rupture in female patients with AAA 5.0 to 5.9 cm suggests a lower threshold for surgery be considered in fit women. The data regarding risk of rupture in patients with AAA 6.0 cm or more may allow more appropriate decision analysis for surgery in patients with unfit conditions with large AAA.

Aged↗

The organisation of head and neck oncology services in the UK: The Royal College of Surgeons of England and British Association of Head and Neck Oncologists' preliminary multidisciplinary head and neck oncology audit.

This study was a collaboration between The Royal College of Surgeons of England Clinical Effectiveness Unit and the British Association of Head and Neck Oncologists (BAHNO). We created a multidisciplinary database through an enquiry to all 49 UK radiotherapy centres. A questionnaire audit identified teams and individuals in the UK involved with treatment of head and neck cancer. A questionnaire on their organisation, and intentions for change was sent to the 108 teams (90% response) and 11 sole practitioners (45% response) identified. Overall, 335 surgical consultants were involved in the treatment of 7500 cases per annum, with large variations in size of catchment populations served by teams. Mean length of time spent with each out-patient was 11 min. Of respondents, 58% were already using the BAHNO basic dataset and more indicated intention to use it, but only 32% could actually deliver information on their work-load. More computerisation of data collection is essential, and national audit may bridge the data gap.

Databases, Factual↗

Smoking inside Canadian acute care hospitals.

OBJECTIVE: To assess smoking policies at Canadian acute care hospitals. METHOD: A questionnaire was designed, piloted and faxed to all acute care hospitals in Canada. The questionnaire was designed to address the following: what is the current policy regarding patient smoking? Are staff and/or visitors allowed to smoke inside the hospital? Is there a separate policy for psychiatric patients? Are smoking cessation products available at the hospital pharmacy? Is the policy governed by regional or municipal legislation? RESULTS: A total of 852 hospitals were included in the study. Of these, 476 responded to the questionnaire, for an overall response rate of 56%. Twenty-seven per cent of respondents allowed patient smoking inside the hospital. While staff smoking was not allowed inside most hospitals (93%), 32% of hospitals in Quebec allowed staff to smoke inside the building. Thirty per cent of hospitals had a separate policy for psychiatric patients, and 27% of hospitals had provisions for visitor smoking. Sixty-seven per cent of hospitals were able to offer patients smoking cessation products while they were in hospital. CONCLUSIONS: Many Canadian hospitals continue to allow smoking inside their facilities. There is considerable variation in hospital smoking policies across the country.

Canada↗

Analytical methods used in the United Kingdom Wildlife Incident Investigation Scheme for the detection of animal poisoning by pesticides.

The United Kingdom Wildlife Incident Investigation Scheme (WIIS) investigates cases of suspected poisoning of wildlife, honey bees, and companion animals by pesticides. Together with field inquiries and veterinary post-mortem examinations, the analytical procedures presented here provide a comprehensive approach to the investigation of these cases. The paper covers selection of animal tissues for analysis and methods suitable for the analysis of honey bees and for various types of bait. Seven multiresidue methods cover around 130 pesticides, and methods are also described for a further 8 compounds. These methods are currently used on samples submitted to the Scheme in England and Wales.

Aluminum↗