Laser assisted directional solidification of zirconia-based eutectics

Directionally solidified zirconia-based eutectic (DSE) fibres were obtained using the laser floating zone (LFZ) method. Two systems were investigated: zirconia-barium zirconate and zirconia-mullite. The purpose was to take advantage of zirconia properties, particularly as an ionic conductor and a mechanical rein-forcement phase. The influence of processing conditions in the structural and microstructural characteristics and their consequences on the electrical and mechanical behaviour were the focus of this thesis. The novel zirconia-barium zirconate eutectic materials were developed in order to combine oxygen ionic conduction through zirconia with protonic conduction from barium zirconate, promoting mixed ionic conduction behaviour. The mi-crostructure of the fibres comprises two alternated regions: bands having coarser zirconia-rich microstructure; and inter-band regions changing from a homogeneous coupled eutectic, at the lowest pulling rate, to columnar colony microstructure, for the faster grown fibres. The bands inter-distance increases with the growth rate and, at 300 mm/h, zirconia dendrites develop enclosed in a fine-interpenetrated network of 50 vol.% ZrO2-50 vol.% BaZrO3. Both phases display contiguity without interphase boundaries, according to impedance spec-troscopy data. Yttria-rich compositions were considered in order to promote the yttrium incorporation in both phases, as revealed by Raman spectroscopy and corroborated by the elemental chemical analysis in energy dispersive spectros-copy. This is a mandatory condition to attain simultaneous contribution to the mixed ionic conduction. Such results are supported by impedance spectrosco-py measurements, which clearly disclose an increase of total ionic conduction for lower temperatures in wet/reduction atmospheres (activation energies of 35 kJ/mol in N2+H2 and 48 kJ/mol in air, in the range of 320-500 ºC) compared to the dry/oxidizing conditions (attaining values close to 90 kJ/mol, above 500 ºC). At high temperatures, the proton incorporation into the barium zirconate is un-favourable, so oxygen ion conduction through zirconia prevails, in dry and oxi-dizing environments, reaching a maximum of 1.3x10-2 S/cm in dry air, at ~1000 ºC. The ionic conduction of zirconia was alternatively combined with another high temperature oxygen ion conductor, as mullite, in order to obtain a broad elec-trolytic domain. The growth rate has a huge influence in the amount of phases and microstructure of the directionally solidified zirconia-mullite fibres. Their microstructure changes from planar coupled eutectic to dendritic eutectic mor-phology, when the growth rate rises from 1 to 500 mm/h, along with an incre-ment of tetragonal zirconia content. Furthermore, high growth rates lead to the development of Al-Si-Y glassy phase, and thus less mullite amount, which is found to considerably reduce the total ionic conduction of as-grown fibres. The reduction of the glassy phase content after annealing (10h; 1400 ºC) promotes an increase of the total ionic conduction (≥0.01 S/cm at 1370 °C), raising the mullite and tetragonal zirconia contents and leading to microstructural differ-ences, namely the distribution and size of the zirconia constituent. This has important consequences in conductivity by improving the percolation pathways. A notable increase in hardness is observed from 11.3 GPa for the 10 mm/h pulled fibre to 21.2 GPa for the fibre grown at 500 mm/h. The ultra-fine eutectic morphology of the 500 mm/h fibres results in a maximum value of 534 MPa for room temperature bending strength, which decreases to about one-fourth of this value at high temperature testing (1400 ºC) due to the soft nature of the glassy-matrix.

Prevalence of Artemisia Species Pollinosis in Western Poland: Impact of Climate Change on Aerobiological Trends, 1995-2004

Background: Artemisia species pollen represents a major cause of allergy in Central Europe. Variations in the pollen season, the influence of climate variables and the prevalence of pollinosis to it were analyzed in Poznan, in western Poland between 1995 and 2004. Methods: A Hirst volumetric spore trap was used for atmospheric sampling. Pollination date trend analysis and Spearman correlation tests were performed. Skin prick tests (SPT) and allergen specific immunoglobulin (Ig)E antibody measurements were performed in 676 and 524 patients, respectively. Results: The Artemisia species pollen season grew longer due to a clear advance in the starting day and only a slightly earlier end point; the peak day also came slightly earlier. Rainfall in the fi rst fortnight of July highly influenced pollen season severity. Temperature was directly correlated with daily Artemisia species pollen levels; relative humidity was inversely correlated. Twelve percent of patients had a positive SPT reaction to Artemisia species. Their symptoms were rhinitis and conjunctivitis (15%), atopic dermatitis (15%), chronic urticaria (14.3%), bronchial asthma (2.4%), and facial and disseminated dermatitis (1.3%). Elevated specifi c IgE concentrations were detected in the sera of 10.1% of patients. Conclusions: Artemisia species pollen is an important cause of pollinosis in western Poland. Pollen season intensity is highly influenced by rainfall in the previous weeks. Trends towards earlier season starts and longer duration, possibly caused by climate change, may have an impact on the allergic population.

River Sediment Sampling and Environment Quality Standards: A Case Study of the Ravensbourne River

Sediment is a major sink for heavy metals in river, and poses significant risks not only to river quality but also to aquatic and benthic organisms. At present in the UK, there are no mandatory sediment quality standards. This is partly due to insufficient toxicity data but also due to problems with identification of appropriate sediment monitoring and analytical techniques. The aim of this research was to examine the sampling different river sediment compartments in order to monitor compliance with any future UK sediment environmental quality standards (EQS). The significance of sediment physical and chemical characteristics on sampling and analysis was also determined. The Ravensbourne River, a tributary of the River Thames located in the highly urbanised South Eastern area of London was used for this study. Sediment was collected from the bed using the Van Veer grab, the bank using hand trowel, and from the water column (suspended sediment) using the time integrated suspended tube sampler between the period of July 2010 and December, 2011. The result for the total metal extraction carried out using aqua regia found that there were no significant differences in the metal concentrations retained in the different compartments by the <63μm sediment fraction but there were differences between the 63μm-2mm fractions of the bed and bank. The metal concentration in the bed, bank and suspended sediment exceeded the draft UK sediment quality guidelines. Sequential extraction was also carried out to determine metal speciation in each sediment compartment using the Maiz et al. (1997) and Tessier et al. (1979) methods. The Maiz et al. (1997) found over 80% of the metals in each sediment compartment were not bioavailable, while Tessier et al. (1979) method found most of the metals to be associated with the Fe/Mn and the residual phase. The bed sediment compartment and the <2mm (<63μm + 63μm-2mm) fraction appears to be the most suitable sediment sample for sediment monitoring from this study.

Utilisation de la coronarographie en Suisse: une étude de population. [The use of coronary vessel radiography in Switzerland: a population study].

All patients having undergone a coronarography during 1984 have been surveyed in Switzerland. This retrospective study has used existing data in the 13 centers practicing this diagnostic procedure. 4921 coronarographies were carried out in 1984, amongst 4359 patients. In terms of population-based rates, the national figures are 77 procedures/100,000 residents, and 68 patients/100,000 residents. Female rates are one fourth of the male rates (27/100,000 versus 112/100,000). For both sexes, the highest utilization rates are for the age groups 60-64. Swiss figures are relatively low when compared with other developed countries. However, patterns of utilization are very different within the country: according to the Canton of residence of the patient, the utilization rates (standardized for age and sex) vary from 8/100,000 to 160/100,000. There is a distinct gradient from south-west to north-east, which closely corresponds to the distribution of centers practicing the procedure. More intriguing is the fact that cardiovascular mortality shows an inverse geographical gradient, with the highest mortality in Cantons having the lowest rate of coronarography. Various reasons for the observed variations are discussed, in relation with differences in supply of diagnostic and therapeutic equipments, but also in relation with various patterns of demand related to differential morbidity rates and/or differential patterns of clinical decision.

Letter - American soldier's account of battles at Chippewa, Lundy's Lane and Fort Erie, 1814

Transcript (original grammar and spelling retained): My dear wife I take this time to inform you that I am well hoping that these few lines will Reach you and find you the same I shall in form you of all our Battles that we have had sence I left home we crossed in to Canada the 2 day of July and took fort Erie on the 3 day of July without loss of one man. We then marched down to Chipway eighteen miles below the Fort Erie we got there on the forth day and had our first battle on the 5 day our loss was not jistly known But the inemy loss was double to ours. The 6 day we started with the 2 Brigade to make a bridge a crost the crick two miles a bove the fort in Building the Bridge the inemy Brought up their Canon and playd upon us with their artiliery a bout two hours We drove them from the fort our loss was none the inemy loss was nineteen ciled dead on the ground we then marched to Queenston when we got thare our inemy had fledfrom the fort we then remained thair to Queenston ten days then we marched down to Fort George But that caurdly Chaney did not a rive with the fleet so we had to return back to Queenston thare was a bout six hundred militia formed on the heights of land thay fired up on us from their pickets and retreated to the mane body our flankers ciled and wounded and took about twenty before they got to the Maine body we then marched up the hill they gave us two firs but did not damage and then retreated from the field we stayed there one knight and then marched to Chipway and stayed there one night and the next day just as the sun set the first Brigade marched up in order to give them Battle a bout two miles from the Crick and began the Battle the 2 Brigade has to March up to the Niagara path and ingaged them we charged up on their artlery and took all their Canon Miller commanded the four companys that charged....the battles lasted three hours and forty minutes our loss was about 8 hundred cild and wounded our inemies loss was a bout fourteen hundred cild and wounded the next morning we Marched up in order to give them Battle a gin but thay was afraid to ingage us we then marched to Fort Erie and went to fortiffing and made a strong place the inemy folered us up and Began to cananade and held it fifty three days thay a tacked the fort the fifteenth of august thay atacked a bout one hiour be fore day Light we saw them and Blue up our maggerzean & two hundred of our inemy our loss wasa bout forty cild and wounded and our inemy loss was a bout one thousand on the 7 Day of September we atacked them and took their batteries and Broke all their canon and drove them from the field our loss was a Bout two hundred cild and wounded our inemy loss was a Bout 8 hundred cild and wounded...we crossed in to Canada with five thousand and came out with fifteen hundred we then Marched to Sackett’s harbor....am well and harty for the present....a bout comming home it uncarting for there is not any....given this winter as yet But I shall try to Come home if I Can But if I Cant I want you should take good car of the Phiddness[?] I have not Received any Money as yet But soon as I do receive some I send some home. I want you should write to me as soon as you receive this and and how Much Stock you wintor I Received your Letter with Great pleasure I feel uneasy a bout you I am a frade that you are sick or dead this is from your husband Chase Clough

Grant of Permission for lease of military lands from Sir Robert Prescott to Thomas Clark, 1798-1801.

Transcript (original spelling and grammar retained): By His Excellency Robert Prescott Esquire, Captain General and Governor in Chief in and over His Majestys Provinces of Upper and Lower Canada, General and Commander in Chief of all His Majesty’s forces in the Provinces of Upper and Lower Canada, Nova Scotia, New Brunswick and their several Dependencies and in the Island of Newfoundland &ca. &ca. &ca. I do hereby authorise and permit Thomas Clark of Queenstown in the County of Lincoln in the Province of Upper Canada merchant to take possession of all that Lot, piece and parcel of Land (being part of the land reserved by his Majesty for Military purposes) situate, lying and being at Queenstown in the Township of Newark, in the Home District in the said Province of Upper Canada, bounded and abutted as follows, that is to say beginning at the Distance of two Chains and ninety links from the South East End of his Majesty’s Store House, the said distance being measured along the Bank up Stream, thence South thirty nine degrees and an half West one Chain and fifty links thence south fifty degrees and an half East one Chain and thirty links thence North thirty nine degrees and an half East to the Edge of the Bank and from thence along the Bank to the place of beginning, containing thirty one perches and one hundred and twenty five square links and to occupy and hold the said Lot, piece and parcel of Land during pleasure subject nevertheless to the provisoes and Conditions herein after contained, that is to say. First on condition that it shall and may be lawful to and for His Majesty his Heirs and Successors and to and for the Commander in Chief of His Majesty Forces for the time being and to and for the Officer commanding his Majesty’s Forces in Upper Canada for the time being and to and for either of them to determine and make void this present permission to occupy during pleasure the said Lot, Piece or Parcel of Land above described at any time hereafter whenever he or they shall see fit so to do without any compensation or indemnification to the said Thomas Clark or any other Person or Persons whosoever for any Loss Injury or Damage which he the said Thomas Clark or any other Person or Persons whosoever may thereby sustain. Secondly on this further Condition that it shall and may be lawful to and for His Majesty his Heirs and Successors and to and for his and their Officers, Soldiers and Servants at any time hereafter by order of the Commander in Chief of His Majesty’s Forces for the time being or by order of the Officer commanding his Majesty’s forces in Upper Canada for the time being or by order of the Officer of His Majesty’s Corps of Royal Engineers commanding in the said Province of Upper Canada for the time being to enter upon the said Lot Piece and parcel of Land which the said Thomas Clark is hereby permitted to occupy during pleasure or upon any part thereof and to take down and from the said Lot piece and parcel of Land or from any part thereof to remove any dwelling House Store or other Buildings on the said Lot, piece or Parcel of Land or any part thereof erected and to remove any goods or Chattels on the said Lot piece and parcel of Land or on any part thereof or on any such dwelling House Store or other building found or being and that His Majesty his Heirs and Successors or any other Person or Persons whosoever shall not be liable or responsible to the said Thomas Clark or to any other Person or Persons whosoever for any Loss, Injury or Damage which he or they shall or may in such case sustain. Thirdly on this further Condition that the said Thomas Clark shall not erect on the said Lot Piece or Parcel of Land which the said Thomas Clark is hereby permitted to occupy during pleasure or upon any part thereof at any time or times hereafter any dwelling House store or other Building whatsoever of Stone or brick or of any other materials wood only exccepted and that if any dwelling House or Store or other building of Stone or brick or of any other materials except wood shall at any time be erected on the said Lot, piece or parcel of Land or upon any part thereof, then and in such case, this present permission and every Clause and Article thereof shall from thenceforth cease and determine and be absolutely and entirely null and void. And lastly on this further Condition that the said Thomas Clark or any other Person whosoever shall not assign this permission to occupy the said Lot, Piece or Parcel of Land above described to any Person of Persons whosoever, and if any such assignment shall be made by the said Thomas Clark or by any other Person in his right, or on his behalf, that then and in such case such assignment and this permission to occupy during pleasure the said Lot piece and parcel of Land above described, and every Clause and Article thereof shall from thenceforth cease and determine and be absolutely and entirely null and void. Given under my hand at the Castle of St. Lewis in the City of Quebec in the Province of Lower Canada this Ninth day of July in the year of our Lord one thousand seven hundred and ninety eight and in the thirty eighth year of His Majesty’s Reign. [Signed here by Robert Prescott] By Order of the Commander in Chief [Signed here by James Green (Illegible signature)] I the said Thomas Clark above named do hereby accept the above written Permission to occupy during pleasure the said Lot piece and parcel of Land above described upon and subject to the several Provisioes and Conditions above written and each and every of them severally and respectively. In witness whereof I have hereunto set my hand the Sixteenth day of August in the year of our Lord one thousand seven hundred and ninety eight and in the thirty eighth year of His Majesty’s Reign. [Signed here by Thomas Clark] Signed in the presence of [Illegible signature – looks like J. M Donell Lt. Col.] [Illegible – looks like 2d. Battn R. C. Sm?] [Signed here by C. Anderson] Whereas Inconveniences did arise from the peculiar situation of the Ground contiguous to the above described Lot of Land and the occupation thereof, if estimated by the above Limits would prove highly disadvantageous to Mr. Thomas Clark be it known that in consideration thereof we do permit the above Lot to extend one half Chain more in length up stream so as to comprehend the space allowed for the Road between Lots Two + Three, and we do hereby appropriate the said additional space wholly to the use of the said Thomas Clark. In witness whereof we have hereunto subscribed this Thirteenth Day of October in the Year of our Lord one thousand Eight Hundred and one. [Signed here by J. M’Donell Lt. Col] 2d. Battn. R. C. [in?] Com of Fort George + Dependencies Robt. Pilkington Captain Royal Engineers

Certificate of Acceptance and Initiation to Canadian Order Chosen Friends - Thomas Cowan

A certificate of initiation and acceptance to the Canadian Order Chosen Friends, Thomas Cowan. The certificate reads "This certifies that evidence has been received that Thomas Cowan has been accepted and initiated by the Council name below, and has thus become a member of the Canadian Order of Chosen Friends, and entitled to all the rights and privileges of membership and a benefit of not exceeding one thousand dollars from the relief fund of said order, which shall in case of death be paid to Annie Cowan his wife in the manner and subject to the conditions set forth in the laws governing said relief fund and in the application for membership. This certificate to be in force and binding when accepted in writing by the said member, with the acceptance attested by the Councilor and Recorder and the seal of the Subordinate Council affixed, so long as said member shall comply with the requirements of the Constitution, Laws and Regulations now in force or hereafter adopted for the government of the Order: otherwise, and also in the case of granting of a new certificate, to be null and void. In witness whereof, we have hereunto attached our signatures, and affixed the seal of the Grand Council of the Canadian Order of Chosen Friends. Dated the Twenty Seventh day of July, A.D. 1891." The front and back of the certificate are available for viewing.

Photograph - Glen Bernard Camp July 1946

A photograph of the female campers of July 1946 at Glen Bernard Camp on Lake Bernard. The group includes a wide range of ages and the girls are outside among the trees. The camp was started in the 1920s and became very popular. The photograph includes Anne McCordick, daughter of E.F. McCordick.

An investigation into observational characteristics of rainfall and temperature in Central Northeast India—a historical perspective 1889–2008

Mann–Kendall non-parametric test was employed for observational trend detection of monthly, seasonal and annual precipitation of five meteorological subdivisions of Central Northeast India (CNE India) for different 30-year normal periods (NP) viz. 1889–1918 (NP1), 1919–1948 (NP2), 1949–1978 (NP3) and 1979–2008 (NP4). The trends of maximum and minimum temperatures were also investigated. The slopes of the trend lines were determined using the method of least square linear fitting. An application of Morelet wavelet analysis was done with monthly rainfall during June– September, total rainfall during monsoon season and annual rainfall to know the periodicity and to test the significance of periodicity using the power spectrum method. The inferences figure out from the analyses will be helpful to the policy managers, planners and agricultural scientists to work out irrigation and water management options under various possible climatic eventualities for the region. The long-term (1889–2008) mean annual rainfall of CNE India is 1,195.1 mm with a standard deviation of 134.1 mm and coefficient of variation of 11%. There is a significant decreasing trend of 4.6 mm/year for Jharkhand and 3.2 mm/day for CNE India. Since rice crop is the important kharif crop (May– October) in this region, the decreasing trend of rainfall during themonth of July may delay/affect the transplanting/vegetative phase of the crop, and assured irrigation is very much needed to tackle the drought situation. During themonth of December, all the meteorological subdivisions except Jharkhand show a significant decreasing trend of rainfall during recent normal period NP4. The decrease of rainfall during December may hamper sowing of wheat, which is the important rabi crop (November–March) in most parts of this region. Maximum temperature shows significant rising trend of 0.008°C/year (at 0.01 level) during monsoon season and 0.014°C/year (at 0.01 level) during post-monsoon season during the period 1914– 2003. The annual maximum temperature also shows significant increasing trend of 0.008°C/year (at 0.01 level) during the same period. Minimum temperature shows significant rising trend of 0.012°C/year (at 0.01 level) during postmonsoon season and significant falling trend of 0.002°C/year (at 0.05 level) during monsoon season. A significant 4– 8 years peak periodicity band has been noticed during September over Western UP, and 30–34 years periodicity has been observed during July over Bihar subdivision. However, as far as CNE India is concerned, no significant periodicity has been noticed in any of the time series.

Opportunities and constraints of peri-urban buffalo and dairy cattle systems in Faisalabad, Punjab, Pakistan

In the big cities of Pakistan, peri-urban dairy production plays an important role for household income generation and the supply of milk and meat to the urban population. On the other hand, milk production in general, and peri-urban dairy production in particular, faces numerous problems that have been well known for decades. Peri-urban dairy producers have been especially neglected by politicians as well as non-government-organizations (NGOs). Against this background, a study in Pakistan’s third largest city, Faisalabad (Punjab Province), was carried out with the aims of gathering basic information, determining major constraints and identifying options for improvements of the peri-urban milk production systems. For data collection, 145 peri-urban households (HH) engaged in dairy production were interviewed face to face using a structured and pretested questionnaire with an interpreter. For analyses, HH were classified into three wealth groups according to their own perception. Thus, 38 HH were poor, 95 HH well off and 12 HH rich (26.2%, 65.5% and 8.3%, respectively). The richer the respondents perceived their HH, the more frequently they were actually in possession of high value HH assets like phones, bank accounts, motorbikes, tractors and cars. Although there was no difference between the wealth groups with respect to the number of HH members (about 10, range: 1 to 23), the educational level of the HH heads differed significantly: on average, heads of poor HH had followed education for 3 years, compared to 6 years for well off HH and 8 years for rich HH. About 40% of the poor and well off HH also had off-farm incomes, while the percentage was much higher - two thirds (67%) - for the rich HH. The majority of the HH were landless (62%); the rest (55 HH) possessed agricultural land from 0.1 to 10.1 ha (average 2.8 ha), where they were growing green fodder: maize, sorghum and pearl millet in summer; berseem, sugar cane and wheat were grown in winter. Dairy animals accounted for about 60% of the herds; the number of dairy animals per HH ranged from 2 to 50 buffaloes (Nili-Ravi breed) and from 0 to 20 cows (mostly crossbred, also Sahiwal). About 37% (n=54) of the HH did not keep cattle. About three quarters of the dairy animals were lactating. The majority of the people taking care of the animals were family workers; 17.3% were hired labourers (exclusively male), employed by 11 rich and 32 well off HH; none of the poor HH employed workers, but the percentages were 33.7% for the well off and 91.7% for the rich HH. The total number of workers increased significantly with increasing wealth (poor: 2.0; well off:2.5; rich: 3.4). Overall, 69 female labourers were recorded, making up 16.8% of employed workers and one fourth of the HH’s own labourers. Apparently, their only duty was to clean the animals´ living areas; only one of them was also watering and showering the animals. Poor HH relied more on female workers than the other two groups: 27.1% of the workers of poor HH were women, but only 14.8% and 6.8% of the labour force of well off and rich HH were female. Two thirds (70%) of the HH sold milk to dhodis (middlemen) and one third (35%) to neighbours; three HH (2%) did doorstep delivery and one HH (1%) had its own shop. The 91 HH keeping both species usually sold mixed milk (97%). Clients for mixed and pure buffalo milk were dhodis (78%, respectively 59%) and neighbours (28%, respectively 47%). The highest milk prices per liter (Pakistani Rupees, 100 PKR @ 0.8 Euro) were paid by alternative clients (44 PKR; 4 HH), followed by neighbours (40 PKR, 50 HH); dhodis paid lower prices (36 PKR, 99 HH). Prices for pure buffalo and mixed milk did not differ significantly. However, HH obtaining the maximum price from the respective clients for the respective type of milk got between 20% (mixed milk, alternative clients) and 68% (mixed milk, dhodi) more than HH fetching the minimum price. Some HH (19%) reported 7% higher prices for the current summer than the preceding winter. Amount of milk sold and distance from the HH to the city center did not influence milk prices. Respondents usually named problems that directly affected their income and that were directly and constantly visible to them, such as high costs, little space and fodder shortages. Other constraints that are only influencing their income indirectly, e.g. the relatively low genetic potential of their animals due to neglected breeding as well as the short- and long-term health problems correlated with imbalanced feeding and insufficient health care, were rarely named. The same accounts for problems accompanying improper dung management (storage, disposal, burning instead of recycling) for the environment and human health. Most of the named problems are linked to each other and should be addressed within the context of the entire system. Therefore, further research should focus on systematic investigations and improvement options, taking a holistic and interdisciplinary approach instead of only working in single fields. Concerted efforts of dairy farmers, researchers, NGOs and political decision makers are necessary to create an economic, ecological and social framework that allows dairy production to serve the entire society. For this, different improvement options should be tested in terms of their impact on environment and income of the farmers, as well as feasibility and sustainability in the peri-urban zones of Faisalabad.

Using historical lesion volume data in the design of a new phase II clinical trial in acute stroke

Background and Purpose-Clinical research into the treatment of acute stroke is complicated, is costly, and has often been unsuccessful. Developments in imaging technology based on computed tomography and magnetic resonance imaging scans offer opportunities for screening experimental therapies during phase II testing so as to deliver only the most promising interventions to phase III. We discuss the design and the appropriate sample size for phase II studies in stroke based on lesion volume. Methods-Determination of the relation between analyses of lesion volumes and of neurologic outcomes is illustrated using data from placebo trial patients from the Virtual International Stroke Trials Archive. The size of an effect on lesion volume that would lead to a clinically relevant treatment effect in terms of a measure, such as modified Rankin score (mRS), is found. The sample size to detect that magnitude of effect on lesion volume is then calculated. Simulation is used to evaluate different criteria for proceeding from phase II to phase III. Results-The odds ratios for mRS correspond roughly to the square root of odds ratios for lesion volume, implying that for equivalent power specifications, sample sizes based on lesion volumes should be about one fourth of those based on mRS. Relaxation of power requirements, appropriate for phase II, lead to further sample size reductions. For example, a phase III trial comparing a novel treatment with placebo with a total sample size of 1518 patients might be motivated from a phase II trial of 126 patients comparing the same 2 treatment arms. Discussion-Definitive phase III trials in stroke should aim to demonstrate significant effects of treatment on clinical outcomes. However, more direct outcomes such as lesion volume can be useful in phase II for determining whether such phase III trials should be undertaken in the first place. (Stroke. 2009;40:1347-1352.)

Non-genomic signalling of the retinoic X receptor through inhibition of Gq signalling in human platelets

Retinoid X receptors (RXRs) are important transcriptional nuclear hormone receptors, acting as either homodimers or the binding partner for at least one fourth of all the known human nuclear receptors. Functional nongenomic effects of nuclear receptors are poorly understood; however, recently peroxisome proliferator-activated receptor (PPAR) gamma, PPARbeta, and the glucocorticoid receptor have all been found active in human platelets. Human platelets express RXRalpha and RXRbeta. RXR ligands inhibit platelet aggregation and TXA(2) release to ADP and the TXA(2) receptors, but only weakly to collagen. ADP and TXA(2) both signal via the G protein, Gq. RXR rapidly binds Gq but not Gi/z/o/t/gust in a ligand-dependent manner and inhibits Gq-induced Rac activation and intracellular calcium release. We propose that RXR ligands may have beneficial clinical actions through inhibition of platelet activation. Furthermore, our results demonstrate a novel nongenomic mode for nuclear receptor action and a functional cross-talk between G-protein and nuclear receptor signaling families.

Nongenomic signaling of the retinoid X receptor through binding and inhibiting Gq in human platelets

Retinoid X receptors (RXRs) are important transcriptional nuclear hormone receptors, acting as either homodimers or the binding partner for at least one fourth of all the known human nuclear receptors. Functional nongenomic effects of nuclear receptors are poorly understood; however, recently peroxisome proliferator-activated receptor (PPAR) gamma, PPAR beta, and the glucocorticoid receptor have all been found active in human platelets. Human platelets express RXR alpha, and RXR beta. RXR ligands inhibit platelet aggregation and TXA(2) release to ADP and the TXA(2) receptors, but only weakly to collagen. ADP and TXA(2) both signal via the G protein, Gq. RXR rapidly binds Gq but not Gi/z/o/t/gust in a ligand-dependent manner and inhibits Gq-induced Rac activation and intracellular calcium release. We propose that RXR ligands may have beneficial clinical actions through inhibition of platelet activation. Furthermore, our results demonstrate a novel nongenomic mode for nuclear receptor action and a functional cross-talk between G-protein and nuclear receptor signaling families. (C) 2007 by The American Society of Hematology.

The loss of Normandy and the invention of Terre Normannorum, 1204

The conquest of Normandy by Philip Augustus of France effectively ended the ‘Anglo-Norman’ realm created in 1066, forcing cross-Channel landholders to choose between their English and their Norman estates. The best source for the resulting tenurial upheaval in England is the Rotulus de valore terrarum Normannorum, a list of seized properties and their former holders, and this article seeks to expand our understanding of the impact of the loss of Normandy through a detailed analysis of this document. First, it demonstrates that the compilation of the roll can be divided into two distinct stages, the first containing valuations taken before royal justices in June 1204 and enrolled before the end of July, and the second consisting of returns to orders for the valuation of particular properties issued during the summer and autumn, as part of the process by which these estates were committed to new holders. Second, study of the roll and other documentary sources permits a better understanding of the order for the seizure of the lands of those who had remained in Normandy, the text of which does not survive. This establishes that this royal order was issued in late May 1204 and, further, that it enjoined the temporary seizure rather than the permanent confiscation of these lands. Moreover, the seizure was not retrospective and covers a specific window of time in 1204. On the one hand, this means that the roll is far from a comprehensive record of terre Normannorum. On the other hand, it is possible to correlate the identities of those Anglo-Norman landholders whose English estates were seized with the military progress of the French king through the duchy in May and June and thus shed new light on the campaign of 1204. Third, the article considers the initial management of the seized estates and highlights the fact that, when making arrangements for the these lands, John was primarily concerned to maintain his freedom of manoeuvre, since he was not prepared to accept that Normandy had been lost for good.

Evaluation of ice cloud representation in the ECMWF and UK Met Office models using CloudSat and CALIPSO data

Ice cloud representation in general circulation models remains a challenging task, due to the lack of accurate observations and the complexity of microphysical processes. In this article, we evaluate the ice water content (IWC) and ice cloud fraction statistical distributions from the numerical weather prediction models of the European Centre for Medium-Range Weather Forecasts (ECMWF) and the UK Met Office, exploiting the synergy between the CloudSat radar and CALIPSO lidar. Using the last three weeks of July 2006, we analyse the global ice cloud occurrence as a function of temperature and latitude and show that the models capture the main geographical and temperature-dependent distributions, but overestimate the ice cloud occurrence in the Tropics in the temperature range from −60 °C to −20 °C and in the Antarctic for temperatures higher than −20 °C, but underestimate ice cloud occurrence at very low temperatures. A global statistical comparison of the occurrence of grid-box mean IWC at different temperatures shows that both the mean and range of IWC increases with increasing temperature. Globally, the models capture most of the IWC variability in the temperature range between −60 °C and −5 °C, and also reproduce the observed latitudinal dependencies in the IWC distribution due to different meteorological regimes. Two versions of the ECMWF model are assessed. The recent operational version with a diagnostic representation of precipitating snow and mixed-phase ice cloud fails to represent the IWC distribution in the −20 °C to 0 °C range, but a new version with prognostic variables for liquid water, ice and snow is much closer to the observed distribution. The comparison of models and observations provides a much-needed analysis of the vertical distribution of IWC across the globe, highlighting the ability of the models to reproduce much of the observed variability as well as the deficiencies where further improvements are required.