Metal cluster expansion by addition of low valent group 14 reagents: III. Reaction of bis[bis(trimethylsilyl)methyl]tin with M3(CO)12 or its derivatives (M = Fe, Ru, or Os): the crystal and molecular structures of M3(μ-SnR2)2(CO)10(R = CH(SiMe3)2; M = Ru or Os)

The stannylene [SnR2] (R = CH(SiMe3)2) reacts in different ways with the three dodecacarbonyls of the iron triad: [Fe3(CO)12] gives [Fe2(CO)8(μ-SnR2)], [Ru3(CO)12] gives the planar pentametallic cluster [Ru3(CO)10(μ-SnR2)2], for which a full structural analysis is reported, while [Os3(CO)12] fails to react. Different products are also obtained from three nitrile derivatives: [Fe3-(CO)11(MeCN)] gives [Fe2(CO)6(μ-SnR2)2], which has a structure significantly different from that of known Fe2Sn2 clusters, [Ru3(CO)10(MeCN)2] gives the pentametallic cluster described above, while [Os3(CO)10(MeCN)2] gives the isostructural osmium analogue, which shows the unusual feature of a CO group bridging two osmium atoms.

Clustered Fox genes in lophotrochozoans and the evolution of the bilaterian Fox gene cluster

FoxC, FoxF, FoxL1 and FoxQ1 genes have been shown to be clustered in some animal genomes, with mesendodermal expression hypothesised as a selective force maintaining cluster integrity. Hypotheses are, however, constrained by a lack of data from the Lophotrochozoa. Here we characterise members of the FoxC, FoxF, FoxL1 and FoxQ1 families from the annelid Capitella teleta and the molluscs Lottia gigantea and Patella vulgata. We cloned FoxC, FoxF, FoxL1 and FoxQ1 genes from C. teleta, and FoxC, FoxF and FoxL1 genes from P. vulgata, and established their expression during development. We also examined their genomic organisation in C. teleta and L. gigantea, and investigated local syntenic relationships. Our results show mesodermal and anterior gut expression is a common feature of these genes in lophotrochozoans. In L. gigantea FoxC, FoxF and FoxL1 are closely linked, while in C. teleta Ct-foxC and Ct-foxL1 are closely linked, with Ct-foxF and Ct-foxQ1 on different scaffolds. Adjacent to these genes there is limited evidence of local synteny. This demonstrates conservation of genomic organisation and expression of these genes can be traced in all three bilaterian Superphyla. These data are evaluated against competing theories for the long-term maintenance of gene clusters.

Metal cluster expansion by addition of low-valent group 4B reagents: crystal and molecular structure of [Os3SnH2(CO)10{CH(SiMe3)2}2]; a compound with hydrogen bridging osmium and tin

Cluster expansion of [Os3H2(CO)10] with [SnR2][R = CH(SiMe3)2] take place in high yield to give [Os3SnH2(CO)10R2], the first closed triosmium–main-group metal cluster to be structurally characterized; a novel feature is the presence of a hydrogen atom bridging the tin atom and one of the osmium atoms.

Stepwise construction of [Os6(CO)18(μ6-P)]-, a hexanuclear osmium cluster monoanion with trigonal-prismatic co-ordination for phosphorus: X-ray crystal structures of [Os6(μ-H)2(CO)20(MeCN)(μ3-PH)] and [PPh3Me][Os6(CO)18(μ6-P)]

Treatment of the labile cluster [Os3(CO)11(MeCN)] with PH3 affords the substituted product [Os3(CO)11(PH3)](1) in high yield. Subsequent reaction of (1) with Na2CO3 in MeOH, followed by acidification, gives the hydrido phosphido cluster [Os3(µ-H)(CO)10(µ-PH2)](2). When (2) is heated to 45–60 °C in the presence of [Os3(CO)11(MeCN)] a hexanuclear complex with the formulation [Os6(µ-H)2(CO)21(µ3-PH)](3) is obtained. If this reaction is repeated using [Os3(CO)10(MeCN)2] instead of [Os3(CO)11(MeCN)], an acetonitrile-containing product, [Os6(µ-H)2(CO)20(MeCN)(µ3-PH)](4), is obtained. An X-ray analysis of (4) shows that two Os3 triangular units are linked by a µ3-phosphinidene ligand, which symmetrically bridges an Os–Os edge of one triangle and is terminally co-ordinated to one Os atom of the second triangle. When (3) is treated with a weak base, such as [N(PPh3)2]Cl or [PPh3Me] Br, deprotonation to the corresponding cluster monoanion [Os6(µ-H)(CO)21(µ3-PH)]–(5) occurs. Treatment of (5) with a weak acid regenerates (3) in quantitative yield. Thermolysis of (3) leads to a closing up of the metal framework, affording the cluster [Os6(µ-H)(CO)18(µ6-P)], which readily deprotonates to give the anion [Os6(CO)18(µ6-P)]–(7) in the presence of [N(PPh3)2] Cl or [PPh3Me]Br. The same anion (7) may also be obtained by direct thermolysis of (5). An X-ray analysis of the [PPh3Me]+ salt of (7) confirms that the phosphorus occupies an interstitial site in a trigonal-prismatic hexaosmium framework, and co-ordinates to all six metal atoms with an average Os–P distance of 2.31 (1)Å. Proton and 31P n.m.r. data on all the new clusters are presented, and the position of the phosphorus resonance in the 31P n.m.r. spectrum is related to the changes in the environment of the phosphorus atom.

A closed paramagnetic electron-precise cluster

A pentametallic cluster is formed by addition of two [SnR2][R = CH(SiMe3)2] groups to [Os3(CO)8(µ-H)(C6H4PhPCH2PPh2)], in a reaction reversing the ortho-hydrogen abstraction and giving the first closed electron-precise paramagnetic cluster.

The distribution of the ring current: Cluster observations

Extending previous studies, a full-circle investigation of the ring current has been made using Cluster 4-spacecraft observations near perigee, at times when the Cluster array had relatively small separations and nearly regular tetrahedral configurations, and when the Dst index was greater than −30 nT (non-storm conditions). These observations result in direct estimations of the near equatorial current density at all magnetic local times (MLT) for the first time and with sufficient accuracy, for the following observations. The results confirm that the ring current flows westward and show that the in situ average measured current density (sampled in the radial range accessed by Cluster 4–4.5RE) is asymmetric in MLT, ranging from 9 to 27 nAm−2. The direction of current is shown to be very well ordered for the whole range of MLT. Both of these results are in line with previous studies on partial ring extent. The magnitude of the current density, however, reveals a distinct asymmetry: growing from 10 to 27 nAm−2 as azimuth reduces from about 12:00MLT to 03:00 and falling from 20 to 10 nAm−2 less steadily as azimuth reduces from 24:00 to 12:00MLT. This result has not been reported before and we suggest it could reflect a number of effects. Firstly, we argue it is consistent with the operation of region-2 field aligned-currents (FACs), which are expected to flow upward into the ring current around 09:00MLT and downward out of the ring current around 14:00MLT. Secondly, we note that it is also consistent with a possible asymmetry in the radial distribution profile of current density (resulting in higher peak at 4– 4.5RE). We note that part of the enhanced current could reflect an increase in the mean AE activity (during the periods in which Cluster samples those MLT).

Simulating the effects of grassland management and grass ensiling on methane emission from lactating cows

A dynamic, mechanistic model of enteric fermentation was used to investigate the effect of type and quality of grass forage, dry matter intake (DMI) and proportion of concentrates in dietary dry matter (DM) on variation in methane (CH(4)) emission from enteric fermentation in dairy cows. The model represents substrate degradation and microbial fermentation processes in rumen and hindgut and, in particular, the effects of type of substrate fermented and of pH oil the production of individual volatile fatty acids and CH, as end-products of fermentation. Effects of type and quality of fresh and ensiled grass were evaluated by distinguishing two N fertilization rates of grassland and two stages of grass maturity. Simulation results indicated a strong impact of the amount and type of grass consumed oil CH(4) emission, with a maximum difference (across all forage types and all levels of DM 1) of 49 and 77% in g CH(4)/kg fat and protein corrected milk (FCM) for diets with a proportion of concentrates in dietary DM of 0.1 and 0.4, respectively (values ranging from 10.2 to 19.5 g CH(4)/kg FCM). The lowest emission was established for early Cut, high fertilized grass silage (GS) and high fertilized grass herbage (GH). The highest emission was found for late cut, low-fertilized GS. The N fertilization rate had the largest impact, followed by stage of grass maturity at harvesting and by the distinction between GH and GS. Emission expressed in g CH(4)/kg FCM declined oil average 14% with an increase of DMI from 14 to 18 kg/day for grass forage diets with a proportion of concentrates of 0.1, and on average 29% with an increase of DMI from 14 to 23 kg/day for diets with a proportion of concentrates of 0.4. Simulation results indicated that a high proportion of concentrates in dietary DM may lead to a further reduction of CH, emission per kg FCM mainly as a result of a higher DM I and milk yield, in comparison to low concentrate diets. Simulation results were evaluated against independent data obtained at three different laboratories in indirect calorimetry trials with COWS consuming GH mainly. The model predicted the average of observed values reasonably, but systematic deviations remained between individual laboratories and root mean squared prediction error was a proportion of 0.12 of the observed mean. Both observed and predicted emission expressed in g CH(4)/kg DM intake decreased upon an increase in dietary N:organic matter (OM) ratio. The model reproduced reasonably well the variation in measured CH, emission in cattle sheds oil Dutch dairy farms and indicated that oil average a fraction of 0.28 of the total emissions must have originated from manure under these circumstances.

A pharmacist-led information technology intervention for medication errors (PINCER): a multicentre, cluster randomised, controlled trial and cost-effectiveness analysis

Background: Medication errors are common in primary care and are associated with considerable risk of patient harm. We tested whether a pharmacist-led, information technology-based intervention was more effective than simple feedback in reducing the number of patients at risk of measures related to hazardous prescribing and inadequate blood-test monitoring of medicines 6 months after the intervention. Methods: In this pragmatic, cluster randomised trial general practices in the UK were stratified by research site and list size, and randomly assigned by a web-based randomisation service in block sizes of two or four to one of two groups. The practices were allocated to either computer-generated simple feedback for at-risk patients (control) or a pharmacist-led information technology intervention (PINCER), composed of feedback, educational outreach, and dedicated support. The allocation was masked to general practices, patients, pharmacists, researchers, and statisticians. Primary outcomes were the proportions of patients at 6 months after the intervention who had had any of three clinically important errors: non-selective non-steroidal anti-inflammatory drugs (NSAIDs) prescribed to those with a history of peptic ulcer without co-prescription of a proton-pump inhibitor; β blockers prescribed to those with a history of asthma; long-term prescription of angiotensin converting enzyme (ACE) inhibitor or loop diuretics to those 75 years or older without assessment of urea and electrolytes in the preceding 15 months. The cost per error avoided was estimated by incremental cost-eff ectiveness analysis. This study is registered with Controlled-Trials.com, number ISRCTN21785299. Findings: 72 general practices with a combined list size of 480 942 patients were randomised. At 6 months’ follow-up, patients in the PINCER group were significantly less likely to have been prescribed a non-selective NSAID if they had a history of peptic ulcer without gastroprotection (OR 0∙58, 95% CI 0∙38–0∙89); a β blocker if they had asthma (0∙73, 0∙58–0∙91); or an ACE inhibitor or loop diuretic without appropriate monitoring (0∙51, 0∙34–0∙78). PINCER has a 95% probability of being cost eff ective if the decision-maker’s ceiling willingness to pay reaches £75 per error avoided at 6 months. Interpretation: The PINCER intervention is an effective method for reducing a range of medication errors in general practices with computerised clinical records. Funding: Patient Safety Research Portfolio, Department of Health, England.

Latitudinal variation of the effect of aviation NOx emissions on atmospheric ozone and methane and related climate metrics

We evaluate the response to regional and latitudinal changes in aircraft NOx emissions using several climate metrics (radiative forcing (RF), Global Warming Potential (GWP), Global Temperature change Potential (GTP)). Global chemistry transport model integrations were performed with sustained perturbations in regional aircraft and aircraft-like NOx emissions. The RF due to the resulting ozone and methane changes is then calculated. We investigate the impact of emission changes for specific geographical regions (approximating to USA, Europe, India and China) and cruise altitude emission changes in discrete latitude bands covering both hemispheres. We find that lower latitude emission changes (per Tg N) cause ozone and methane RFs that are about a factor of 6 larger than those from higher latitude emission changes. The net RF is positive for all experiments. The meridional extent of the RF is larger for low latitude emissions. GWPs for all emission changes are positive, with tropical emissions having the largest values; the sign of the GTP depends on the choice of time horizon.

The benefits of a compute cluster approach to high spatial resolution biodiversity richness modelling: projecting the impact of climate change on Mediterranean flora

High spatial resolution environmental data gives us a better understanding of the environmental factors affecting plant distributions at fine spatial scales. However, large environmental datasets dramatically increase compute times and output species model size stimulating the need for an alternative computing solution. Cluster computing offers such a solution, by allowing both multiple plant species Environmental Niche Models (ENMs) and individual tiles of high spatial resolution models to be computed concurrently on the same compute cluster. We apply our methodology to a case study of 4,209 species of Mediterranean flora (around 17% of species believed present in the biome). We demonstrate a 16 times speed-up of ENM computation time when 16 CPUs were used on the compute cluster. Our custom Java ‘Merge’ and ‘Downsize’ programs reduce ENM output files sizes by 94%. The median 0.98 test AUC score of species ENMs is aided by various species occurrence data filtering techniques. Finally, by calculating the percentage change of individual grid cell values, we map the projected percentages of plant species vulnerable to climate change in the Mediterranean region between 1950–2000 and 2020.

Displacement of methane by coadsorbed carbon dioxide is facilitated in narrow carbon nanopores

By using simulation methods, we studied the adsorption of binary CO2-CH4 mixtures on various CH4 preadsorbed carbonaceous materials (e.g., triply periodic carbon minimal surfaces, slit-shaped carbon micropores, and Harris's virtual porous carbons) at 293 K. Regardless of the different micropore geometry, two-stage mechanism of CH4 displacement from carbon nanospaces by coadsorbed CO2 has been proposed. In the first stage, the coadsorbed CO2 molecules induced the enhancement of CH4 adsorbed amount. In the second stage, the stronger affinity of CO2 to flat/curved graphitic surfaces as well as CO2-CO2 interactions cause the displacement of CH4 molecules from carbonaceous materials. The operating conditions of CO2-induced cleaning of the adsorbed phase from CH4 mixture component strongly depend on the size of the carbon micropores, but, in general, the enhanced adsorption field in narrow carbon ultramicropores facilitates the nonreactive displacement of CH4 by coadsorbed CO2. This is because in narrow carbon ultramicropores the equilibrium CO2/CH4 selectivity (i.e., preferential adsorption toward CO2) increased significantly. The adsorption field in wider micropores (i.e., the overall surface energy) for both CO2 and CH4 is very similar, which decreases the preferential CO2 adsorption. This suppresses the displacement of CH4 by coadsorbed CO2 and assists further adsorption of CH4 from the bulk mixture (i.e., CO2/CH4 mixing in adsorbed phase).

Description and process evaluation of pharmacists’ interventions in a pharmacist-led information technology-enabled multicentre cluster randomised controlled trial for reducing medication errors in general practice (PINCER trial)

Objective To undertake a process evaluation of pharmacists' recommendations arising in the context of a complex IT-enabled pharmacist-delivered randomised controlled trial (PINCER trial) to reduce the risk of hazardous medicines management in general practices. Methods PINCER pharmacists manually recorded patients’ demographics, details of interventions recommended, actions undertaken by practice staff and time taken to manage individual cases of hazardous medicines management. Data were coded and double entered into SPSS v15, and then summarised using percentages for categorical data (with 95% CI) and, as appropriate, means (SD) or medians (IQR) for continuous data. Key findings Pharmacists spent a median of 20 minutes (IQR 10, 30) reviewing medical records, recommending interventions and completing actions in each case of hazardous medicines management. Pharmacists judged 72% (95%CI 70, 74) (1463/2026) of cases of hazardous medicines management to be clinically relevant. Pharmacists recommended 2105 interventions in 74% (95%CI 73, 76) (1516/2038) of cases and 1685 actions were taken in 61% (95%CI 59, 63) (1246/2038) of cases; 66% (95%CI 64, 68) (1383/2105) of interventions recommended by pharmacists were completed and 5% (95%CI 4, 6) (104/2105) of recommendations were accepted by general practitioners (GPs), but not completed at the end of the pharmacists’ placement; the remaining recommendations were rejected or considered not relevant by GPs. Conclusions The outcome measures were used to target pharmacist activity in general practice towards patients at risk from hazardous medicines management. Recommendations from trained PINCER pharmacists were found to be broadly acceptable to GPs and led to ameliorative action in the majority of cases. It seems likely that the approach used by the PINCER pharmacists could be employed by other practice pharmacists following appropriate training.

Extreme wind storms over Europe in present and future climate: a cluster analysis approach

Boreal winter wind storm situations over Central Europe are investigated by means of an objective cluster analysis. Surface data from the NCEP-Reanalysis and ECHAM4/OPYC3-climate change GHG simulation (IS92a) are considered. To achieve an optimum separation of clusters of extreme storm conditions, 55 clusters of weather patterns are differentiated. To reduce the computational effort, a PCA is initially performed, leading to a data reduction of about 98 %. The clustering itself was computed on 3-day periods constructed with the first six PCs using "k-means" clustering algorithm. The applied method enables an evaluation of the time evolution of the synoptic developments. The climate change signal is constructed by a projection of the GCM simulation on the EOFs attained from the NCEP-Reanalysis. Consequently, the same clusters are obtained and frequency distributions can be compared. For Central Europe, four primary storm clusters are identified. These clusters feature almost 72 % of the historical extreme storms events and add only to 5 % of the total relative frequency. Moreover, they show a statistically significant signature in the associated wind fields over Europe. An increased frequency of Central European storm clusters is detected with enhanced GHG conditions, associated with an enhancement of the pressure gradient over Central Europe. Consequently, more intense wind events over Central Europe are expected. The presented algorithm will be highly valuable for the analysis of huge data amounts as is required for e.g. multi-model ensemble analysis, particularly because of the enormous data reduction.

Late Holocene methane rise caused by orbitally controlled increase in tropical sources

Considerable debate surrounds the source of the apparently ‘anomalous’1 increase of atmospheric methane concentrations since the mid-Holocene (5,000 years ago) compared to previous interglacial periods as recorded in polar ice core records2. Proposed mechanisms for the rise in methane concentrations relate either to methane emissions from anthropogenic early rice cultivation1, 3 or an increase in natural wetland emissions from tropical4 or boreal sources5, 6. Here we show that our climate and wetland simulations of the global methane cycle over the last glacial cycle (the past 130,000 years) recreate the ice core record and capture the late Holocene increase in methane concentrations. Our analyses indicate that the late Holocene increase results from natural changes in the Earth's orbital configuration, with enhanced emissions in the Southern Hemisphere tropics linked to precession-induced modification of seasonal precipitation. Critically, our simulations capture the declining trend in methane concentrations at the end of the last interglacial period (115,000–130,000 years ago) that was used to diagnose the Holocene methane rise as unique. The difference between the two time periods results from differences in the size and rate of regional insolation changes and the lack of glacial inception in the Holocene. Our findings also suggest that no early agricultural sources are required to account for the increase in methane concentrations in the 5,000 years before the industrial era.