Photoelectron diffraction: from phenomenological demonstration to practical tool

The potential of photoelectron diffraction—exploiting the coherent interference of directly-emitted and elastically scattered components of the photoelectron wavefield emitted from a core level of a surface atom to obtain structural information—was first appreciated in the 1970s. The first demonstrations of the effect were published towards the end of that decade, but the method has now entered the mainstream armoury of surface structure determination. This short review has two objectives: First, to outline the way that the idea emerged and the way this evolved in my own collaboration with Neville Smith and his colleagues at Bell Labs in the early years: Second, to provide some insight into the current state-of-the art in application of (scanned-energy mode) photoelectron diffraction to address two key issue in quantitative surface structure determination, namely, complexity and precision. In this regard a particularly powerful aspect of photoelectron diffraction is its elemental and chemical-state specificity

Simulation of tropospheric chemistry and aerosols with the climate model EC-Earth

We have integrated the atmospheric chemistry and transport model TM5 into the global climate model EC-Earth version 2.4. We present an overview of the TM5 model and the two-way data exchange between TM5 and the IFS model from the European Centre for Medium-Range Weather Forecasts (ECMWF), the atmospheric general circulation model of EC-Earth. In this paper we evaluate the simulation of tropospheric chemistry and aerosols in a one-way coupled configuration. We have carried out a decadal simulation for present-day conditions and calculated chemical budgets and climatologies of tracer concentrations and aerosol optical depth. For comparison we have also performed offline simulations driven by meteorological fields from ECMWF's ERA-Interim reanalysis and output from the EC-Earth model itself. Compared to the offline simulations, the online-coupled system produces more efficient vertical mixing in the troposphere, which reflects an improvement of the treatment of cumulus convection. The chemistry in the EC-Earth simulations is affected by the fact that the current version of EC-Earth produces a cold bias with too dry air in large parts of the troposphere. Compared to the ERA-Interim driven simulation, the oxidizing capacity in EC-Earth is lower in the tropics and higher in the extratropics. The atmospheric lifetime of methane in EC-Earth is 9.4 years, which is 7% longer than the lifetime obtained with ERA-Interim but remains well within the range reported in the literature. We further evaluate the model by comparing the simulated climatologies of surface radon-222 and carbon monoxide, tropospheric and surface ozone, and aerosol optical depth against observational data. The work presented in this study is the first step in the development of EC-Earth into an Earth system model with fully interactive atmospheric chemistry and aerosols

Variation in market access decisions for cell and gene therapies across the United States, Canada, and Europe

Transformative cell and gene therapies have now launched worldwide, and many potentially curative cell and gene therapies are in development, offering the prospect of significant health gains for patients. Access to these therapies depend on decisions made by health technology assessment (HTA) and payer organizations. We sought to describe the emerging cell and gene therapies market access landscape by analyzing 17 US commercial payer medical policies, and HTA reports from five European countries and Canada. We found that some US health plans applied coverage restrictions more often than others (four plans applied restrictions in all decisions, while four plans applied restrictions in < 30% of decisions). The European and Canadian HTA bodies recommend access to fewer therapies than US health plans, reflecting a more stringent approach in the context of limited evidence and high scientific uncertainty that is commonly associated with these treatments. Our findings suggest that patient access to approved cell and gene therapies is restricted in all regions studied, though the nature of these restrictions differs between US health plans and the European/Canada HTA recommendations. Payers, HTA groups, pharmaceutical companies, and other stakeholders should collaborate to more clearly define the “uncertainties” and develop market access policies that balance benefits of early access with ongoing data collection to close evidence gaps over time

New Agendas for Agricultural Research in Developing Countries: Policy Analysis and Institutional Implications

This article argues that the goals of agricultural research in poor countries have changed substantially over the last four decades. In particular they have broadened from the early (and narrow) emphasis on food production to a much wider agenda that includes poverty alleviation, environmental degradation, and social inclusion. Conversely, agricultural research systems have proved remarkably resistant to the concomitant need for changes in research focus. As a result many, at both the national and international level, are under great strain. In terms of public policy the article goes on to suggest that shortcomings of existing conceptual approaches to technology development could be supplemented by adopting analytical principles that view innovation in systemic terms. An approach where flows of knowledge between institutional nodes is a key to innovative performance (the “National Systems of Innovation” approach) is suggested as one such conceptual framework that might help supplement conventional policy analysis. An earlier version of this paper was presented at a workshop “New Policy Agendas for Agricultural Research: Implications for Institutional Arrangements” held on 28 March 2000 at the International Crops Research Institute for the Semi-Arid Tropics (ICRISAT), Patancheru, India. The workshop was supported by the UK Department of International Development (DFID) Crop Post-Harvest Programme as an output of the project “Optimising Institutional Arrangements.

Measurement report: Understanding the seasonal cycle of Southern Ocean aerosols

Published: 29 March 2023The remoteness and extreme conditions of the Southern Ocean and Antarctic region have meant that observations in this region are rare, and typically restricted to summertime during research or resupply voyages. Observations of aerosols outside of the summer season are typically limited to long-term stations, such as Kennaook / Cape Grim (KCG; 40.7∘ S, 144.7∘ E), which is situated in the northern latitudes of the Southern Ocean, and Antarctic research stations, such as the Japanese operated Syowa (SYO; 69.0∘ S, 39.6∘ E). Measurements in the midlatitudes of the Southern Ocean are important, particularly in light of recent observations that highlighted the latitudinal gradient that exists across the region in summertime. Here we present 2 years (March 2016–March 2018) of observations from Macquarie Island (MQI; 54.5∘ S, 159.0∘ E) of aerosol (condensation nuclei larger than 10 nm, CN10) and cloud condensation nuclei (CCN at various supersaturations) concentrations. This important multi-year data set is characterised, and its features are compared with the long-term data sets from KCG and SYO together with those from recent, regionally relevant voyages. CN10 concentrations were the highest at KCG by a factor of ∼50 % across all non-winter seasons compared to the other two stations, which were similar (summer medians of 530, 426 and 468 cm−3 at KCG, MQI and SYO, respectively). In wintertime, seasonal minima at KCG and MQI were similar (142 and 152 cm−3, respectively), with SYO being distinctly lower (87 cm−3), likely the result of the reduction in sea spray aerosol generation due to the sea ice ocean cover around the site. CN10 seasonal maxima were observed at the stations at different times of year, with KCG and MQI exhibiting January maxima and SYO having a distinct February high. Comparison of CCN0.5 data between KCG and MQI showed similar overall trends with summertime maxima and wintertime minima; however, KCG exhibited slightly (∼10 %) higher concentrations in summer (medians of 158 and 145 cm−3, respectively), whereas KCG showed ∼40 % lower concentrations than MQI in winter (medians of 57 and 92 cm−3, respectively). Spatial and temporal trends in the data were analysed further by contrasting data to coincident observations that occurred aboard several voyages of the RSV Aurora Australis and the RV Investigator. Results from this study are important for validating and improving our models and highlight the heterogeneity of this pristine region and the need for further long-term observations that capture the seasonal cycles.Ruhi S. Humphries, Melita D. Keywood, Jason P. Ward, James Harnwell, Simon P. Alexander, Andrew R. Klekociuk, Keiichiro Hara, Ian M. McRobert, Alain Protat, Joel Alroe, Luke T. Cravigan, Branka Miljevic, Zoran D. Ristovski, Robyn Schofield, Stephen R. Wilson, Connor J. Flynn, Gourihar R. Kulkarni, Gerald G. Mace, Greg M. McFarquhar, Scott D. Chambers, Alastair G. Williams, and Alan D. Griffith

Data visualization in yield component analysis: an expert study

Even though data visualization is a common analytical tool in numerous disciplines, it has rarely been used in agricultural sciences, particularly in agronomy. In this paper, we discuss a study on employing data visualization to analyze a multiplicative model. This model is often used by agronomists, for example in the so-called yield component analysis. The multiplicative model in agronomy is normally analyzed by statistical or related methods. In practice, unfortunately, usefulness of these methods is limited since they help to answer only a few questions, not allowing for a complex view of the phenomena studied. We believe that data visualization could be used for such complex analysis and presentation of the multiplicative model. To that end, we conducted an expert survey. It showed that visualization methods could indeed be useful for analysis and presentation of the multiplicative model

Can ceftazidime-avibactam and aztreonam overcome β-lactam resistance conferred by metallo-β-lactamases in Enterobacteriaceae?

Based upon knowledge of the hydrolytic profile of major β-lactamases found in Gram-negative bacteria, we tested the efficacy of the combination of ceftazidime-avibactam (CAZ-AVI) with aztreonam (ATM) against carbapenem-resistant enteric bacteria possessing metallo-β-lactamases (MBLs). Disk diffusion and agarbased antimicrobial susceptibility testing were initially performed to determine the in vitro efficacy of a unique combination of CAZ-AVI and ATM against 21 representative Enterobacteriaceae isolates with a complex molecular background that included blaIMP, blaNDM, blaOXA-48, blaCTX-M, blaAmpC, and combinations thereof. Time-kill assays were conducted, and the in vivo efficacy of this combination was assessed in a murine neutropenic thigh infection model. By disk diffusion assay, all 21 isolates were resistant to CAZ-AVI alone, and 19/21 were resistant to ATM. The in vitro activity of CAZ-AVI in combination with ATM against diverse Enterobacteriaceae possessing MBLs was demonstrated in 17/21 isolates, where the zone of inhibition was ≥21 mm. All isolates demonstrated a reduction in CAZ-AVI agar dilution MICs with the addition of ATM. At 2 h, time-kill assays demonstrated a ≥4-log10-CFU decrease for all groups that had CAZ-AVI with ATM (8 μg/ml) added, compared to the group treated with CAZ-AVI alone. In the murine neutropenic thigh infection model, an almost 4-log10-CFU reduction was noted at 24 h for CAZ-AVI (32 mg/kg every 8 h [q8h]) plus ATM (32 mg/kg q8h) versus CAZ-AVI (32 mg/kg q8h) alone. The data presented herein require us to carefully consider this new therapeutic combination to treat infections caused by MBL-producing Enterobacteriaceae

Association between Birth Defects and Cancer Risk among Children and Adolescents in a Population-Based Assessment of 10 Million Live Births

Importance: Birth defects affect approximately 1 in 33 children. Some birth defects are known to be strongly associated with childhood cancer (eg, trisomy 21 and acute leukemia). However, comprehensive evaluations of childhood cancer risk in those with birth defects have been limited in previous studies by insufficient sample sizes. Objectives: To identify specific birth defect-childhood cancer (BD-CC) associations and characterize cancer risk in children by increasing number of nonchromosomal birth defects. Design, Setting, and Participants: This multistate, population-based registry linkage study pooled statewide data on births, birth defects, and cancer from Texas, Arkansas, Michigan, and North Carolina on 10181074 children born from January 1, 1992, to December 31, 2013. Children were followed up to 18 years of age for a diagnosis of cancer. Data were retrieved between September 26, 2016, and September 21, 2017, and data analysis was performed from September 2, 2017, to March 21, 2019. Exposures: Birth defects diagnoses (chromosomal anomalies and nonchromosomal birth defects) recorded by statewide, population-based birth defects registries. Main Outcomes and Measures: Cancer diagnosis before age 18 years, as recorded in state cancer registries. Cox regression models were used to generate hazard ratios (HRs) and 95% CIs to evaluate BD-CC associations and the association between number of nonchromosomal defects and cancer risk. Results: Compared with children without any birth defects, children with chromosomal anomalies were 11.6 (95% CI, 10.4-12.9) times more likely to be diagnosed with cancer, whereas children with nonchromosomal birth defects were 2.5 (95% CI, 2.4-2.6) times more likely to be diagnosed with cancer before 18 years of age. An increasing number of nonchromosomal birth defects was associated with a corresponding increase in the risk of cancer. Children with 4 or more major birth defects were 5.9 (95% CI, 5.3-6.4) times more likely to be diagnosed with cancer compared with those without a birth defect. In the analysis of 72 specific BD-CC patterns, 40 HRs were statistically significant (adjusted P <.05) after accounting for multiple comparisons. Cancers most frequently associated with nonchromosomal defects were hepatoblastoma and neuroblastoma. Conclusions and Relevance: Several significant and novel associations were observed between specific birth defects and cancers. Among children with nonchromosomal birth defects, the number of major birth defects diagnosed was significantly and directly associated with cancer risk. These findings could inform clinical treatment for children with birth defects and may elucidate mechanisms that lead to these complex outcomes