Clinical and cost effectiveness of a multi-professional medication reviews in care homes (CAREMED)

Objectives With 70% of care home residents experiencing a medication error every day in the UK, better multi‐professional working between medical practitioners, pharmacists and care homes was recommended. The aim of this study was to determine the effectiveness (falls reduction) and cost‐effectiveness, of a multi‐professional medication review (MPMR) service in care homes for older people. Method A total of care homes in the East of England were cluster randomised to ‘usual care’ or two multi‐professional (General practitioner, clinical pharmacist and care homes staff) medication reviews during the 12‐month trial period. Target recruitment was 900 residents with 10% assumed loss to follow‐up. Co‐primary outcome measures were number of falls and potentially inappropriate prescribing assessed by the Screening Tool of Older Persons Prescriptions. Key findings A total of 826 care home residents were recruited with 324 lost to follow‐up for at least one primary outcome measure. The mean number of falls per resident per annum was 3.3 for intervention and 3.0 for control (P = 0.947). Each resident was found to be prescribed 0.69 (intervention) and 0.85 (control) potentially inappropriate medicines after 12 months (P = 0.046). No significant difference identified in emergency hospital admissions or deaths. Estimated unadjusted incremental mean cost per resident was £374.26 higher in the intervention group. Conclusions In line with other medication review based interventions in care homes, two MPMRs improved medication appropriateness but failed to demonstrate improvements in clinical outcomes. From a health system perspective costs where estimated to increase overall and therefore a different model of medicines management is required

Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes.

Mutations in whole organisms are powerful ways of interrogating gene function in a realistic context. We describe a program, the Sanger Institute Mouse Genetics Project, that provides a step toward the aim of knocking out all genes and screening each line for a broad range of traits. We found that hitherto unpublished genes were as likely to reveal phenotypes as known genes, suggesting that novel genes represent a rich resource for investigating the molecular basis of disease. We found many unexpected phenotypes detected only because we screened for them, emphasizing the value of screening all mutants for a wide range of traits. Haploinsufficiency and pleiotropy were both surprisingly common. Forty-two percent of genes were essential for viability, and these were less likely to have a paralog and more likely to contribute to a protein complex than other genes. Phenotypic data and more than 900 mutants are openly available for further analysis. PAPERCLIP

Evaluation of the selectivity and sensitivity of isoform- and mutation-specific RAS antibodies

Researchers rely largely on antibodies to measure the abundance, activity, and localization of a protein, information that provides critical insight into both normal and pathological cellular functions. However, antibodies are not always reliable or universally valid for the methods in which they are used; in particular, the reliability of commercial antibodies against RAS is highly variable. Waters et al . rigorously assessed 22 commercially available RAS antibodies for their utility to detect the distinct RAS isoforms in various cell types and for their use in specific analytical methods. Their findings show how reliably one can interpret the data acquired from each reagent

Jellyfish Support High Energy Intake of Leatherback Sea Turtles (Dermochelys coriacea): Video Evidence from Animal-Borne Cameras

The endangered leatherback turtle is a large, highly migratory marine predator that inexplicably relies upon a diet of low-energy gelatinous zooplankton. The location of these prey may be predictable at large oceanographic scales, given that leatherback turtles perform long distance migrations (1000s of km) from nesting beaches to high latitude foraging grounds. However, little is known about the profitability of this migration and foraging strategy. We used GPS location data and video from animal-borne cameras to examine how prey characteristics (i.e., prey size, prey type, prey encounter rate) correlate with the daytime foraging behavior of leatherbacks (n = 19) in shelf waters off Cape Breton Island, NS, Canada, during August and September. Video was recorded continuously, averaged 1:53 h per turtle (range 0:08–3:38 h), and documented a total of 601 prey captures. Lion's mane jellyfish (Cyanea capillata) was the dominant prey (83–100%), but moon jellyfish (Aurelia aurita) were also consumed. Turtles approached and attacked most jellyfish within the camera's field of view and appeared to consume prey completely. There was no significant relationship between encounter rate and dive duration (p = 0.74, linear mixed-effects models). Handling time increased with prey size regardless of prey species (p = 0.0001). Estimates of energy intake averaged 66,018 kJ•d−1 but were as high as 167,797 kJ•d−1 corresponding to turtles consuming an average of 330 kg wet mass•d−1 (up to 840 kg•d−1) or approximately 261 (up to 664) jellyfish•d-1. Assuming our turtles averaged 455 kg body mass, they consumed an average of 73% of their body mass•d−1 equating to an average energy intake of 3–7 times their daily metabolic requirements, depending on estimates used. This study provides evidence that feeding tactics used by leatherbacks in Atlantic Canadian waters are highly profitable and our results are consistent with estimates of mass gain prior to southward migration

Mouse large-scale phenotyping initiatives: overview of the European Mouse Disease Clinic (EUMODIC) and of the Wellcome Trust Sanger Institute Mouse Genetics Project.

Two large-scale phenotyping efforts, the European Mouse Disease Clinic (EUMODIC) and the Wellcome Trust Sanger Institute Mouse Genetics Project (SANGER-MGP), started during the late 2000s with the aim to deliver a comprehensive assessment of phenotypes or to screen for robust indicators of diseases in mouse mutants. They both took advantage of available mouse mutant lines but predominantly of the embryonic stem (ES) cells resources derived from the European Conditional Mouse Mutagenesis programme (EUCOMM) and the Knockout Mouse Project (KOMP) to produce and study 799 mouse models that were systematically analysed with a comprehensive set of physiological and behavioural paradigms. They captured more than 400 variables and an additional panel of metadata describing the conditions of the tests. All the data are now available through EuroPhenome database (www.europhenome.org) and the WTSI mouse portal (http://www.sanger.ac.uk/mouseportal/), and the corresponding mouse lines are available through the European Mouse Mutant Archive (EMMA), the International Knockout Mouse Consortium (IKMC), or the Knockout Mouse Project (KOMP) Repository. Overall conclusions from both studies converged, with at least one phenotype scored in at least 80% of the mutant lines. In addition, 57% of the lines were viable, 13% subviable, 30% embryonic lethal, and 7% displayed fertility impairments. These efforts provide an important underpinning for a future global programme that will undertake the complete functional annotation of the mammalian genome in the mouse model

A call for new approaches to quantifying biases in observations of sea-surface temperature

Global surface-temperature changes are a fundamental expression of climate change. Recent, much-debated, variations in the observed rate of surface-temperature change have highlighted the importance of uncertainty in adjustments applied to sea-surface temperature (SST) measurements. These adjustments are applied to compensate for systematic biases and changes in observing protocol. Better quantification of the adjustments and their uncertainties would increase confidence in estimated surface-temperature change and provide higher- quality gridded SST fields for use in many applications. Bias adjustments have been based either on physical models of the observing processes or on the assumption of an unchanging relationship between SST and a reference data set such as night marine air temperature. These approaches produce similar estimates of SST bias on the largest space and timescales, but regional differences can exceed the estimated uncertainty. We describe challenges to improving our understanding of SST biases. Overcoming these will require clarification of past observational methods, improved modeling of biases associated with each observing method, and the development of statistical bias estimates that are less sensitive to the absence of metadata regarding the observing method. New approaches are required that embed bias models, specific to each type of observation, within a robust statistical framework. Mobile platforms and rapid changes in observation type require biases to be assessed for individual historic and present-day platforms (i.e., ships or buoys) or groups of platforms. Lack of observational metadata and of high-quality observations for validation and bias model development are likely to remain major challenges

Sources and cycling of dissolved and particulate organic radiocarbon in the northwest Atlantic continental margin

Continental shelves and slopes are productive and dynamic ocean margin systems that also regulate the fluxes of terrestrial, riverine, and estuarine materials between the continents and oceans. In order to evaluate the ages, potential sources, and transformations of organic matter in an ocean margin system, we measured the radiocarbon (Delta (14)C and delta (13)C distributions of total dissolved organic carbon (DOC), suspended particulate organic carbon (POC), and dissolved inorganic carbon (DIC) in waters of the Middle Atlantic Bight (MAB) continental shelf and slope in April-May 1994. The Delta (14)C of DOC was greatest (as high as -39 parts per thousand) in surface waters of the shelf, decreasing rapidly offshore and with depth, even in relatively shallow (25-50 in depth) shelf waters. The lowest Delta (14)C-DOC values were observed in deep slope waters, where they were significantly lower than values measured previously for the deep Sargasso Sea. There was a strong inverse relationship between Delta (14)C-DOC and delta (-13)C-DOC in all shelf and surface slope waters of the MAB, which is likely attributable to varying contributions of young, (14)C-enriched organic matter of terrestrial and/or riverine origin. The more highly (14)C-depleted DOC in deep : slope waters (as low as -442 parts per thousand) generally had a correspondingly lower delta (13)C (as low as -22.3 parts per thousand) component. However, this must originate from relic terrestrial material either in the MAB itself or be discharged to the MAB from rivers and estuaries. The isotopic signatures of POC were clearly differentiable from DOC and indicate that this pool also contained a broad range of both old and young material of terrestrial (delta (13)C as low as -24.9 parts per thousand) and marine (delta (13)C as high as -19.9 parts per thousand) origin throughout the MAB shelf and slope. The highest Delta (14)C-POC values (up to 78 parts per thousand) were observed in shallow shelf waters of the southern MAR Conversely, the lowest Delta (14)C-POC values (as low as -394 parts per thousand) were found in MAB deep slope waters and were also significantly more depleted in (14)C than POC from the central north Atlantic (Sargasso Sea). A multiple-source isotopic mass balance model employing both (14)C and (13)C was used to evaluate the relative contributions of both young and old terrigenous versus marine organic matter to DOC and POC in the MAR The results indicate that shelf and slope DOC is comprised of an old marine fraction (represented by offshore Sargasso Sea material) and either a young terrestrial/riverine/estuarine (TRE) component (in shelf and shallow slope waters) or a relic TRE component (in deep and some shallow slope waters). In contrast, suspended POC from the MAB appears to originate predominantly from a mixture of recent MAB primary production and an old, TRE component, similar to that observed in one of the major subestuaries of the Chesapeake Bay. These results suggest that both young and old sources of terrestrial and riverine organic matter can comprise a significant fraction of the DOC and POC in ocean margins. Preliminary calculations indicate that the export of this compositionally unique DOC and suspended POC may be significant terms in the organic carbon budgets of the MAB and other margin systems

Natural climate solutions for the United States

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Science Advances 4 (2018): eaat1869, doi:10.1126/sciadv.aat1869.Limiting climate warming to <2°C requires increased mitigation efforts, including land stewardship, whose potential in the United States is poorly understood. We quantified the potential of natural climate solutions (NCS)—21 conservation, restoration, and improved land management interventions on natural and agricultural lands—to increase carbon storage and avoid greenhouse gas emissions in the United States. We found a maximum potential of 1.2 (0.9 to 1.6) Pg CO2e year−1, the equivalent of 21% of current net annual emissions of the United States. At current carbon market prices (USD 10 per Mg CO2e), 299 Tg CO2e year−1 could be achieved. NCS would also provide air and water filtration, flood control, soil health, wildlife habitat, and climate resilience benefits.This study was made possible by funding from the Doris Duke Charitable Foundation. C.A.W. and H.G. acknowledge financial support from NASA’s Carbon Monitoring System program (NNH14ZDA001N-CMS) under award NNX14AR39G. S.D.B. acknowledges support from the DOE’s Office of Biological and Environmental Research Program under the award DE-SC0014416. J.W.F. acknowledges financial support from the Florida Coastal Everglades Long-Term Ecological Research program under National Science Foundation grant no. DEB-1237517

Contribution of ocean, fossil fuel, land biosphere, and biomass burning carbon fluxes to seasonal and interannual variability in atmospheric CO2

Author Posting. © American Geophysical Union, 2008. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 113 (2008): G01010, doi:10.1029/2007JG000408.Seasonal and interannual variability in atmospheric carbon dioxide (CO2) concentrations was simulated using fluxes from fossil fuel, ocean and terrestrial biogeochemical models, and a tracer transport model with time-varying winds. The atmospheric CO2 variability resulting from these surface fluxes was compared to observations from 89 GLOBALVIEW monitoring stations. At northern hemisphere stations, the model simulations captured most of the observed seasonal cycle in atmospheric CO2, with the land tracer accounting for the majority of the signal. The ocean tracer was 3–6 months out of phase with the observed cycle at these stations and had a seasonal amplitude only ∼10% on average of observed. Model and observed interannual CO2 growth anomalies were only moderately well correlated in the northern hemisphere (R ∼ 0.4–0.8), and more poorly correlated in the southern hemisphere (R < 0.6). Land dominated the interannual variability (IAV) in the northern hemisphere, and biomass burning in particular accounted for much of the strong positive CO2 growth anomaly observed during the 1997–1998 El Niño event. The signals in atmospheric CO2 from the terrestrial biosphere extended throughout the southern hemisphere, but oceanic fluxes also exerted a strong influence there, accounting for roughly half of the IAV at many extratropical stations. However, the modeled ocean tracer was generally uncorrelated with observations in either hemisphere from 1979–2004, except during the weak El Niño/post-Pinatubo period of the early 1990s. During that time, model results suggested that the ocean may have accounted for 20–25% of the observed slowdown in the atmospheric CO2 growth rate.We acknowledge the support of NASA grant NNG05GG30G and NSF grant ATM0628472