Solar generation and storage of O2 (a 1 delta g)

An investigation was performed of the technical steps required to design a solar powered oxygen-iodine laser. Singlet delta oxygen is formed upon transfer of energy from selected photoexcited dye molecules to ground state molecular oxygen and then is concentrated and stored as an endoperoxide by reaction with an aromatic hydrocarbon. The endoperoxide, when heated, releases singlet oxygen in high yield thus providing a regenerable source of laser fuel. Energy transfer from dye molecules to molecular oxygen was investigated. When dye molecules were adsorbed to polymer substrates it was observed that the dye became embedded in the polymer matrix. Porphin dyes were incorporated into films of 1,4-dimethyl-2-poly(vinylnaphthalene), 2PVN. An endoperoxide was formed when porphin-doped 2PVN was exposed to visible radiation. This demonstrates the possibility of generating singlet oxygen using solar energy and concentrating and storing it in one simple step. Transport of energy by exciton migration in polycrystalline dye films was also investigated

The Yellowstone Hotspot, Greater Yellowstone Ecosystem, and Human Geography

Active geologic processes associated with the Yellowstone hotspot are fundamental in shaping the landscapes of the greater Yellowstone ecosystem (GYE), a high volcanic plateau flanked by a crescent of still higher mountainous terrain. The processes associated with the Yellowstone hotspot are volcanism, faulting, and uplift and are observed in the geology at the surface. We attribute the driving forces responsible for the northeastward progression of these processes to a thermal plume rising through the Earth’s mantle into the base of the southwest-moving North American plate. This progression began 16 million years ago (Ma) near the Nevada-Oregon border and arrived at Yellowstone about 2 Ma. Before arrival of the hotspot, an older landscape existed, particularly mountains created during the Laramide orogeny about 70–50 Ma and volcanic terrain formed by Absaroka andesitic volcanism mostly between 50–45 Ma. These landscapes were more muted than the present, hotspot-modified landscape because the Laramide-age mountains had worn down and an erosion surface of low relief had developed on the Absaroka volcanic terrain. The Yellowstone Plateau was built by hotspot volcanism of rhyolitic lavas and caldera-forming rhyolite tuffs (ignimbrites). Streams eroding back into the edges of this plateau have created scenic waterfalls and canyons such as the Grand Canyon of the Yellowstone and Lewis Canyon. Rhyolite is poor in plant nutrients and forms sandy, well-drained soils that support the monotonous, fire-adapted lodgepole pine forests of the Yellowstone Plateau. Non-rhyolitic rocks surround this plateau and sustain more varied vegetation, including spruce, fir, and whitebark pine forests broken by grassy meadows. Heat from the hotspot rises upward and drives Yellowstone’s famed geysers, hot springs, and mudpots. These thermal waters are home to specialized, primitive ecosystems, rich in algae and bacteria. The rock alteration associated with hydrothermal systems creates the bright colors of Yellowstone’s Grand Canyon. Basin-and-range-style faulting has accompanied migration of the hotspot to Yellowstone and formed the linear mountains and valleys that occur north and south of the hotspot track, which is the present-day eastern Snake River Plain. High rates of basin-and-range faulting occurred adjacent to the migrating Yellowstone hotspot, creating distinctive landscapes within the GYE such as the Teton Range/Jackson Hole, with characteristic rugged, forested ranges and adjacent flat-floored grassy valleys. The difference in altitude between the mountains and valleys provides a topographic gradient in which vegetation maturation advances with altitude; animal-migration patterns also follow this trend. The valleys provide natural meadows, agricultural land, town sites, and corridors for roads. Uplift of the GYE by as much as 1 km (3,000 ft) during the last 5 million years has resulted in ongoing erosion of deep, steep-walled valleys. Many prominent ecological characteristics of Yellowstone derive from this hotspot-induced uplift, including the moderate- to high- altitude terrain and associated cool temperatures and deep snowfall. Modern and Pleistocene climate and associated vegetation patterns strongly relate to the topography created by the hotspot and its track along the eastern Snake River Plain. Winter air masses from the moist northern Pacific Ocean traverse the topographic low of the Snake River Plain to where orographic rise onto the Yellowstone Plateau and adjacent mountains produces deep snow. A winter precipitation shadow forms on the lee (eastern) sides of the GYE. During Pleistocene glacial times, this moisture conduit provided by the hotspot-track-produced ice-age glaciers that covered the core of the present GYE. These glaciers sculpted bedrock and produced glacial moraines that are both forested and unforested, sand and gravel of ice-marginal streams and outwash gravels that are commonly covered with sagebrush-grassland, and silty lake sediments that are commonly covered by lush grassland such as Hayden Valley. The effects of the Yellowstone hotspot also profoundly shaped the human history in the GYE. Uplift associated with the hotspot elevates the GYE to form the Continental Divide, and streams drain radially outward like spokes from a hub. Inhabitants of the GYE 12,000–10,000 years ago, as well as more recent inhabitants, followed the seasonal green-up of plants and migrating animals up into the mountain areas. During European immigration, people settled around Yellowstone in the lower parts of the drainages and established roads, irrigation systems, and cultural associations. The core Yellowstone highland is too harsh for agriculture and inhospitable to people in the winter. Beyond this core, urban and rural communities exist in valleys and are separated by upland areas. The partitioning inhibits any physical connection of communities, which in turn complicates pursuit of common interests across the whole GYE. Settlements thus geographically isolated evolved as diverse, independent communities

The feasibility of collecting information from people with Multiple Sclerosis for the UK MS Register via a web portal: characterising a cohort of people with MS.

BACKGROUND: A UK Register of people with Multiple Sclerosis has been developed to address the need for an increased knowledge-base about MS. The Register is being populated via: a web-based portal; NHS neurology clinical systems; and administrative data sources. The data are de-identified and linked at the individual level. At the outset, it was not known whether people with MS would wish to participate in the UK MS Register by personally contributing their data to the Register via a web-based system. Therefore, the research aim of this work was to build an internet-mounted recruitment and consenting technology for people with Multiple Sclerosis, and to assess its feasibility as a questionnaire delivery platform to contribute data to the UK MS Register, by determining whether the information provided could be used to describe a cohort of people with MS. METHODS: The web portal was developed using VB.net and JQuery with a Microsoft SQL 2008 database. UK adults with MS can self-register and enter data about themselves by completing validated questionnaires. Descriptive statistics were used to characterise the respondents. RESULTS: The web portal was launched in May 2011, and in first three months 7,279 individuals registered on the portal. The ratio of men to women was 1:2.4 (n = 5,899), the mean self-reported age at first symptoms was 33.8 (SD 10.5) years, and at diagnosis 39.6 (SD 10.3) years (n = 4,401). The reported types of MS were: 15% primary progressive, 63% relapsing-remitting, 8% secondary progressive, and 14% unknown (n = 5,400). These characteristics are similar to those of the prevalent MS population. Employment rates, sickness/disability rates, ethnicity and educational qualifications were compared with the general UK population. Information about the respondents' experience of early symptoms and the process of diagnosis, plus living arrangements are also reported. CONCLUSIONS: These initial findings from the MS Register portal demonstrate the feasibility of collecting data about people with MS via a web platform, and show that sufficient information can be gathered to characterise a cohort of people with MS. The innovative design of the UK MS register, bringing together three disparate sources of data, is creating a rich resource for research into this condition

Epidemiology of Nontuberculous Mycobacteria in Patients without HIV Infection, New York City

The incidence appears to be increasing

Construction of Transgenic Plasmodium berghei as a Model for Evaluation of Blood-Stage Vaccine Candidate of Plasmodium falciparum Chimeric Protein 2.9

BACKGROUND:The function of the 19 kDa C-terminal region of the merozoite surface protein 1 (MSP1-19) expressed by Plasmodium has been demonstrated to be conserved across distantly related Plasmodium species. The green fluorescent protein (GFP) is a reporter protein that has been widely used because it can be easily detected in living organisms by fluorescence microscopy and flow cytometry. METHODOLOGY AND RESULTS:In this study, we used gene targeting to generate transgenic P. berghei (Pb) parasites (designated as PfMSP1-19Pb) that express the MSP1-19 of P. falciparum (Pf) and the GFP reporter protein simultaneously. The replacement of the PbMSP1-19 locus by PfMSP1-19 was verified by PCR and Southern analysis. The expression of the chimeric PbfMSP-1 and the GFP was verified by Western blot and fluorescence microscopy, respectively. Moreover, GFP-expressing transgenic parasites in blood stages can be readily differentiated from other blood cells using flow cytometry. A comparison of growth rates between wild-type and the PfMSP1-19Pb transgenic parasite indicated that the replacement of the MSP1-19 region and the expression of the GFP protein were not deleterious to the transgenic parasites. We used this transgenic mouse parasite as a murine model to evaluate the protective efficacy in vivo of specific IgG elicited by a PfCP-2.9 malaria vaccine that contains the PfMSP1-19. The BALB/c mice passively transferred with purified rabbit IgG to the PfCP-2.9 survived a lethal challenge of the PfMSP1-19Pb transgenic murine parasites, but not the wild-type P. berghei whereas the control mice passively transferred with purified IgG obtained from adjuvant only-immunized rabbits were vulnerable to both transgenic and wild-type infections. CONCLUSIONS:We generated a transgenic P. berghei line that expresses PfMSP1-19 and the GFP reporter gene simultaneously. The availability of this parasite line provides a murine model to evaluate the protective efficacy in vivo of anti-MSP1-19 antibodies, including, potentially, those elicited by the PfCP-2.9 malaria vaccine in human volunteers

How People with Multiple Sclerosis Rate Their Quality of Life: An EQ-5D Survey via the UK MS Register

The EQ-5D is a widely-used, standardised, quality of life measure producing health profiles, indices and states. The aims of this study were to assess the role of various factors in how people with Multiple Sclerosis rate their quality of life, based on responses to the EQ-5D received via the web portal of the UK MS Register.The 4516 responses to the EQ-5D (between May 2011 and April 2012) were collated with basic demographic and descriptive MS data and the resulting dataset was analysed in SPSS (v.20).The mean health state for people with MS was 59.73 (SD 22.4, median 61), compared to the UK population mean of 82.48 (which is approximately 1SD above the cohort mean). The characteristics of respondents with high health states (at or above +1SD) were: better health profiles (most predictive dimension: Usual Activities), higher health indices, younger age, shorter durations of MS, female gender, relapsing-remitting MS, higher educational attainment and being in paid employment (all p-values<0.001). Conversely, the characteristics of respondents with low health states (at or below -1SD) were: poorer health profiles (most predictive dimension: Mobility), lower health indices, older age, longer durations of MS, male gender, progressive MS, lower educational attainment and having an employment status of sick/disabled (p = 0.0014 for age, all other p-values<0.001). Particular living arrangements were not associated with either the high or low health status groups.This large-scale study has enabled in-depth analyses on how people with MS rate their quality of life, and it provides new knowledge on the various factors that contribute to their self-assessed health status. These findings demonstrate the impact of MS on quality of life, and they can be used to inform care provision and further research, to work towards enhancing the quality of life of people with MS

The Physical and Psychological Impact of Multiple Sclerosis Using the MSIS-29 via the Web Portal of the UK MS Register

The MSIS-29 was developed to assess the physical and psychological impact of MS. The aims of this study were to use the responses to the MSIS-29 via the web portal of the UK MS Register to: examine the internal properties of the scale delivered via the internet, profile the cohort, and assess how well the scale measures impact of disability on the potential workforce.Between May 2011 and April 2012, 4558 people with MS completed the MSIS-29(v.1). The responses were collated with basic demographic and descriptive MS data and the resulting dataset was analysed in SPSS(v.20).Internal consistency was high (Cronbach's alpha 0.97 MSIS-29-PHYS, 0.92 MSIS-29-PSYCH). The mean MSIS-29-PHYS score was 60.5 (50.6%) with a median of 62 and the mean MSIS-29-PSYCH score was 24.8 (43.8%) with a median of 24. Physical scores increased with age and disease duration (p<0.001, p<0.001), but there was a weak negative relationship between psychological scores and age (p<0.001). The odds of people having an employment status of sick/disabled were 7.2 (CI 5.5, 9.4, p<0.001) for people with a moderate physical score, and 22.3 (CI 17.0, 29.3, p<0.001) for people with a high physical score (relative to having a low physical score).This largest known study of its kind has demonstrated how the MSIS-29 can be administered via the internet to characterise a cohort, and to predict the likely impact of disability on taking an active part in the workforce, as a reasonable proxy for the effects of MS on general activities. The findings examining MSIS-29-PHYS and MSIS-29-PSYCH scores against age support the use of two sub-scales, not a combined score. These results underline the importance of using a scale such as this to monitor disability levels regularly in guiding MS care to enable people to be as active as possible

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001). Interpretation: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice

Human malarial disease: a consequence of inflammatory cytokine release

Malaria causes an acute systemic human disease that bears many similarities, both clinically and mechanistically, to those caused by bacteria, rickettsia, and viruses. Over the past few decades, a literature has emerged that argues for most of the pathology seen in all of these infectious diseases being explained by activation of the inflammatory system, with the balance between the pro and anti-inflammatory cytokines being tipped towards the onset of systemic inflammation. Although not often expressed in energy terms, there is, when reduced to biochemical essentials, wide agreement that infection with falciparum malaria is often fatal because mitochondria are unable to generate enough ATP to maintain normal cellular function. Most, however, would contend that this largely occurs because sequestered parasitized red cells prevent sufficient oxygen getting to where it is needed. This review considers the evidence that an equally or more important way ATP deficency arises in malaria, as well as these other infectious diseases, is an inability of mitochondria, through the effects of inflammatory cytokines on their function, to utilise available oxygen. This activity of these cytokines, plus their capacity to control the pathways through which oxygen supply to mitochondria are restricted (particularly through directing sequestration and driving anaemia), combine to make falciparum malaria primarily an inflammatory cytokine-driven disease