An americium‐fueled gas core nuclear rocket

A gas core fission reactor that utilizes americium in place of uranium is examined for potential utilization as a nuclear rocket for space propulsion. The isomer 242mAm with a half life of 141 years is obtained from an (n, γ) capture reaction with 241Am, and has the highest known thermal fission cross section. We consider a 7500 MW reactor, whose propulsion characteristics with 235U have already been established, and re‐examine it using americium. We find that the same performance can be achieved at a comparable fuel density, and a radial size reduction (of both core and moderator/reflector) of about 70%.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87734/2/585_1.pd

Mass spectrometry detection of inhaled drug in distal fibrotic lung

BACKGROUND: Currently the only available therapies for fibrotic Interstitial Lung Disease are administered systemically, often causing significant side effects. Inhaled therapy could avoid these but to date there is no evidence that drug can be effectively delivered to distal, fibrosed lung. We set out to combine mass spectrometry and histopathology with rapid sample acquisition using transbronchial cryobiopsy to determine whether an inhaled drug can be delivered to fibrotic, distal lung parenchyma in participants with Interstitial Lung Disease. METHODS: Patients with radiologically and multidisciplinary team confirmed fibrotic Interstitial Lung Disease were eligible for this study. Transbronchial cryobiopsies and endobronchial biopsies were taken from five participants, with Interstitial Lung Disease, within 70 min of administration of a single dose of nebulised ipratropium bromide. Thin tissue cryosections were analysed by Matrix Assisted Laser Desorption/Ionization-Mass Spectrometry imaging and correlated with histopathology. The remainder of the cryobiopsies were homogenised and analysed by Liquid Chromatography—tandem Mass Spectrometry. RESULTS: Drug was detected in proximal and distal lung samples from all participants. Fibrotic regions were identified in research samples of four of the five participants. Matrix Assisted Laser Desorption/Ionization-Mass Spectrometry imaging showed co-location of ipratropium with fibrotic regions in samples from three participants. CONCLUSIONS: In this proof of concept study, using mass spectrometry, we demonstrate for the first-time that an inhaled drug can deposit in distal fibrotic lung parenchyma in patients with Interstitial Lung Disease. This suggests that drugs to treat pulmonary fibrosis could potentially be administered by the inhaled route

A descriptive analysis of child-relevant systematic reviews in the Cochrane Database of Systematic Reviews

<p>Abstract</p> <p>Background</p> <p>Systematic reviews (SRs) are considered an important tool for decision-making. There has been no recent comprehensive identification or description of child-relevant SRs. A description of existing child-relevant SRs would help to identify the extent of available child-relevant evidence available in SRs and gaps in the evidence base where SRs are required. The objective of this study was to describe child-relevant SRs from the Cochrane Database of Systematic Reviews (CDSR, Issue 2, 2009).</p> <p>Methods</p> <p>SRs were assessed for relevance using pre-defined criteria. Data were extracted and entered into an electronic form. Univariate analyses were performed to describe the SRs overall and by topic area.</p> <p>Results</p> <p>The search yielded 1666 SRs; 793 met the inclusion criteria. 38% of SRs were last assessed as up-to-date prior to 2007. Corresponding authors were most often from the UK (41%). Most SRs (59%) examined pharmacological interventions. 53% had at least one external source of funding. SRs included a median of 7 studies (IQR 3, 15) and 679 participants (IQR 179, 2833). Of all studies, 48% included only children, and 27% only adults. 94% of studies were published in peer-reviewed journals. Primary outcomes were specified in 72% of SRs. Allocation concealment and the Jadad scale were used in 97% and 25% of SRs, respectively. Adults and children were analyzed separately in 12% of SRs and as a subgroup analysis in 14%. Publication bias was assessed in only 14% of SRs. A meta-analysis was conducted in 68% of SRs with a median of 5 trials (IQR 3, 9) each. Variations in these characteristics were observed across topic areas.</p> <p>Conclusions</p> <p>We described the methodological characteristics and rigour of child-relevant reviews in the CDSR. Many SRs are not up-to-date according to Cochrane criteria. Our study describes variation in conduct and reporting across SRs and reveals clinicians' ability to access child-specific data.</p

Incorporating statistical uncertainty in the use of physician cost profiles

<p>Abstract</p> <p>Background</p> <p>Physician cost profiles (also called efficiency or economic profiles) compare the costs of care provided by a physician to his or her peers. These profiles are increasingly being used as the basis for policy applications such as tiered physician networks. Tiers (low, average, high cost) are currently defined by health plans based on percentile cut-offs which do not account for statistical uncertainty. In this paper we compare the percentile cut-off method to another method, using statistical testing, for identifying high-cost or low-cost physicians.</p> <p>Methods</p> <p>We created a claims dataset of 2004-2005 data from four Massachusetts health plans. We employed commercial software to create episodes of care and assigned responsibility for each episode to the physician with the highest proportion of professional costs. A physicians' cost profile was the ratio of the sum of observed costs divided by the sum of expected costs across all assigned episodes. We discuss a new method of measuring standard errors of physician cost profiles which can be used in statistical testing. We then assigned each physician to one of three cost categories (low, average, or high cost) using two methods, percentile cut-offs and a t-test (p-value ≤ 0.05), and assessed the level of disagreement between the two methods.</p> <p>Results</p> <p>Across the 8689 physicians in our sample, 29.5% of physicians were assigned a different cost category when comparing the percentile cut-off method and the t-test. This level of disagreement varied across specialties (17.4% gastroenterology to 45.8% vascular surgery).</p> <p>Conclusions</p> <p>Health plans and other payers should incorporate statistical uncertainty when they use physician cost-profiles to categorize physicians into low or high-cost tiers.</p

Prolonged In Vivo Retention of a Cathepsin D Targeted Optical Contrast Agent in a Mouse Model of Alzheimer\u27s Disease.

BACKGROUND: Cathepsin D (CatD) is a lysosomal protease that is elevated early in Alzheimer\u27s disease (AD). We have previously developed a Targeted contrast agent (CA) to detect CatD activity in vivo, consisting of a magnetic resonance imaging/fluorescent moiety linked to a cell penetrating peptide (CPP) by means of a CatD cleavage site and have demonstrated its uptake in the brain of an AD mouse model. OBJECTIVE: The purpose of this study was to characterize the in vivo retention of a near infra-red fluorescent dye labeled version of this CA. METHODS: Six adult C57Bl/6 wild-type mice and six adult 5XFAD transgenic AD mice were studied using a small animal imaging system at five and twelve months of age using our novel Targeted CA, or two different control CAs; a Non-Targeted (lacking the CatD cleavage site) and a Non-Penetrating (lacking the CPP). Following intravenous CA administration, the optical signal was recorded within the brain and uptake and washout curves were measured and fitted to a one-phase exponential decay curve. RESULTS: In all wild-type and 5XFAD mice, the washout of the Targeted CA that included a CPP domain was significantly slower than the washout of the Non-Penetrating and Non-Targeted CA. Furthermore, the washout of the CatD Targeted CA was significantly slower in the 5XFAD mice compared to the age matched wild-type controls (p \u3c  0.05) at 5 and 12 months of age. Control CAs showed no differences in washout. CONCLUSIONS: The prolonged retention of the CatD targeted CA in 5XFAD mice suggests this agent may be useful for AD detection

Species composition, larval habitats, seasonal occurrence and distribution of potential malaria vectors and associated species of Anopheles (Diptera: Culicidae) from the Republic of Korea

<p>Abstract</p> <p>Background</p> <p>Larval mosquito habitats of potential malaria vectors and related species of <it>Anopheles </it>from three provinces (Gyeonggi, Gyeongsangbuk, Chungcheongbuk Provinces) of the Republic of Korea were surveyed in 2007. This study aimed to determine the species composition, seasonal occurrence and distributions of <it>Anopheles </it>mosquitoes. Satellite derived normalized difference vegetation index data (NDVI) was also used to study the seasonal abundance patterns of <it>Anopheles </it>mosquitoes.</p> <p>Methods</p> <p>Mosquito larvae from various habitats were collected using a standard larval dipper or a white plastic larval tray, placed in plastic bags, and were preserved in 100% ethyl alcohol for species identification by PCR and DNA sequencing. The habitats in the monthly larval surveys included artificial containers, ground depressions, irrigation ditches, drainage ditches, ground pools, ponds, rice paddies, stream margins, inlets and pools, swamps, and uncultivated fields. All field-collected specimens were identified to species, and relationships among habitats and locations based on species composition were determined using cluster statistical analysis.</p> <p>Results</p> <p>In about 10,000 specimens collected, eight species of <it>Anopheles </it>belonging to three groups were identified: Hyrcanus Group - <it>Anopheles sinensis</it>, <it>Anopheles kleini</it>, <it>Anopheles belenrae</it>, <it>Anopheles pullus</it>, <it>Anopheles lesteri</it>, <it>Anopheles sineroides</it>; Barbirostris Group - <it>Anopheles koreicus</it>; and Lindesayi Group - <it>Anopheles lindesayi japonicus</it>. Only <it>An. sinensis </it>was collected from all habitats groups, while <it>An. kleini, An. pullus </it>and <it>An. sineroides </it>were sampled from all, except artificial containers. The highest number of <it>Anopheles </it>larvae was found in the rice paddies (34.8%), followed by irrigation ditches (23.4%), ponds (17.0%), and stream margins, inlets and pools (12.0%). <it>Anopheles sinensis </it>was the dominant species, followed by <it>An. kleini, An. pullus </it>and <it>An. sineroides</it>. The monthly abundance data of the <it>Anopheles </it>species from three locations (Munsan, Jinbo and Hayang) were compared against NDVI and NDVI anomalies.</p> <p>Conclusion</p> <p>The species composition of <it>Anopheles </it>larvae varied in different habitats at various locations. <it>Anopheles </it>populations fluctuated with the seasonal dynamics of vegetation for 2007. Multi-year data of mosquito collections are required to provide a better characterization of the abundance of these insects from year to year, which can potentially provide predictive capability of their population density based on remotely sensed ecological measurements.</p

Ghosts of Yellowstone: Multi-Decadal Histories of Wildlife Populations Captured by Bones on a Modern Landscape

Natural accumulations of skeletal material (death assemblages) have the potential to provide historical data on species diversity and population structure for regions lacking decades of wildlife monitoring, thereby contributing valuable baseline data for conservation and management strategies. Previous studies of the ecological and temporal resolutions of death assemblages from terrestrial large-mammal communities, however, have largely focused on broad patterns of community composition in tropical settings. Here, I expand the environmental sampling of large-mammal death assemblages into a temperate biome and explore more demanding assessments of ecological fidelity by testing their capacity to record past population fluctuations of individual species in the well-studied ungulate community of Yellowstone National Park (Yellowstone). Despite dramatic ecological changes following the 1988 wildfires and 1995 wolf re-introduction, the Yellowstone death assemblage is highly faithful to the living community in species richness and community structure. These results agree with studies of tropical death assemblages and establish the broad capability of vertebrate remains to provide high-quality ecological data from disparate ecosystems and biomes. Importantly, the Yellowstone death assemblage also correctly identifies species that changed significantly in abundance over the last 20 to ∼80 years and the directions of those shifts (including local invasions and extinctions). The relative frequency of fresh versus weathered bones for individual species is also consistent with documented trends in living population sizes. Radiocarbon dating verifies the historical source of bones from Equus caballus (horse): a functionally extinct species. Bone surveys are a broadly valuable tool for obtaining population trends and baseline shifts over decadal-to-centennial timescales