Rapid Chlorophyll a Fluorescence Light Response Curves Mechanistically Inform Photosynthesis Modeling.

Crop improvement is crucial to ensuring global food security under climate change, and hence there is a pressing need for phenotypic observations that are both high throughput and improve mechanistic understanding of plant responses to environmental cues and limitations. In this study, chlorophyll a fluorescence light response curves and gas-exchange observations are combined to test the photosynthetic response to moderate drought in four genotypes of Brassica rapa The quantum yield of PSII (ϕ PSII ) is here analyzed as an exponential decline under changing light intensity and soil moisture. Both the maximum ϕ PSII and the rate of ϕ PSII decline across a large range of light intensities (0-1,000 µmol photons m-2 s-1; ß PSII ) are negatively affected by drought. We introduce an alternative photosynthesis model (ß PSII model) incorporating parameters from rapid fluorescence response curves. Specifically, the model uses ß PSII as an input for estimating the photosynthetic electron transport rate, which agrees well with two existing photosynthesis models (Farquhar-von Caemmerer-Berry and Yin). The ß PSII model represents a major improvement in photosynthesis modeling through the integration of high-throughput fluorescence phenotyping data, resulting in gained parameters of high mechanistic value.

The contribution of field efficacy studies to the evaluation of applications for veterinary vaccines evaluated through the European Union centralised authorisation procedure.

To examine the contribution that field efficacy studies made to the assessment of marketing authorisation (MA) applications, a retrospective analysis was conducted for 100 veterinary vaccines that had been evaluated by the European Medicines Agency (EMA) between 1996 and 2017. For 52 veterinary vaccines, scrutiny of the European Public Assessment Report (EPAR) and/or the summary of product characteristics (SPC) identified objective evidence that field efficacy studies made an important or substantial impact on the efficacy claims and/or benefit-risk evaluation. For 24 applications, the contribution of field efficacy studies was classified as either supportive or was not detectable from the publicly available documents on which the analysis was based. For a further 24 applications, data exemptions were applied and the MAs were granted in the absence of field studies. The difficulty in achieving challenge in the field was highlighted by the observation that natural exposure was reported in less than half of the applications where field efficacy studies were conducted (34 out of 76). This analysis may help to inform policy decisions on the role, conduct and contribution that field efficacy studies make to the assessment of efficacy for veterinary vaccines.

Report of the second international conference on next generation sequencing for adventitious virus detection in biologics for humans and animals.

The IABS-EU, in association with PROVAXS and Ghent University, hosted the "2nd Conference on Next Generation Sequencing (NGS) for Adventitious Virus Detection in Human and Veterinary Biologics" held on November 13th and 14th 2019, in Ghent, Belgium. The meeting brought together international experts from regulatory agencies, the biotherapeutics and biologics industries, contract research organizations, and academia, with the goal to develop a scientific consensus on the readiness of NGS for detecting adventitious viruses, and on the use of this technology to supplement or replace/substitute the currently used assays. Participants discussed the progress on the standardization and validation of the technical and bioinformatics steps in NGS for characterization and safety evaluation of biologics, including human and animal vaccines. It was concluded that NGS can be used for the detection of a broad range of viruses, including novel viruses, and therefore can complement, supplement or even replace some of the conventional adventitious virus detection assays. Furthermore, the development of reference viral standards, complete and correctly annotated viral databases, and protocols for the validation and follow-up investigations of NGS signals is necessary to enable broader use of NGS. An international collaborative effort, involving regulatory authorities, industry, academia, and other stakeholders is ongoing toward this goal.

Regulatory pathways to enable the licencing of alternatives to antibiotics.

Effective alternatives to antibiotics (ATA) such as vaccines, antibodies, phage therapies, prebiotics, probiotics and herbal medicines can be used in place of traditional antibiotics in a way that does not compromise animal health as means of tackling the growing threat to both animal and human health from antimicrobial resistance (AMR). This paper reflects the key points on the approaches that were discussed during the 2nd International Symposium on ATA between regulatory agencies, veterinary product companies representing largely the pharmaceutical and feed-additive sectors, academia and other stakeholders on regulatory pathways to enable the licensing of alternatives to antibiotics for food producing animals. The need to demonstrate compliance with generally accepted standards for quality, safety and efficacy is considered a pre-requisite for all veterinary medicinal products receiving an authorisation including ATA, irrespective of the region in which they are approved. ATA are often based on novel technologies, with complex mechanisms of action; therefore, early and close communication with regulators is encouraged. In addition, strategic use by ATA applicants of all regulatory tools available to support innovation is highly recommended. The veterinary product manufacturers consider that the regulation of veterinary medicines should evolve to accommodate innovative ATA technologies and incentives from regulatory agencies provided to stimulate further ATA development.

A restatement of the natural science evidence base concerning the health effects of low-level ionizing radiation.

Exposure to ionizing radiation is ubiquitous, and it is well established that moderate and high doses cause ill-health and can be lethal. The health effects of low doses or low dose-rates of ionizing radiation are not so clear. This paper describes a project which sets out to summarize, as a restatement, the natural science evidence base concerning the human health effects of exposure to low-level ionizing radiation. A novel feature, compared to other reviews, is that a series of statements are listed and categorized according to the nature and strength of the evidence that underpins them. The purpose of this restatement is to provide a concise entrée into this vibrant field, pointing the interested reader deeper into the literature when more detail is needed. It is not our purpose to reach conclusions on whether the legal limits on radiation exposures are too high, too low or just right. Our aim is to provide an introduction so that non-specialist individuals in this area (be they policy-makers, disputers of policy, health professionals or students) have a straightforward place to start. The summary restatement of the evidence and an extensively annotated bibliography are provided as appendices in the electronic supplementary material.

Variations in the sales and sales patterns of veterinary antimicrobial agents in 25 European countries.

OBJECTIVES: To describe sales and sales patterns of veterinary antimicrobial agents in 25 European Union (EU)/European Economic Area (EEA) countries for 2011. METHODS: Data on the sales of veterinary antimicrobial agents from 25 EU member states and EEA countries for 2011 were collected at package level (name, formulation, strength, pack size, number of packages sold) according to a standardized protocol and template and presented in a harmonized manner. These data were calculated to express amounts sold, in metric tonnes, of active ingredient of each package. A population correction unit (PCU) was applied as a proxy for the animal biomass potentially treated with antimicrobial agents. The indicator used to express sales was milligrams of active substance per PCU. RESULTS: Substantial variations in the sales patterns and in the magnitude of sales of veterinary antimicrobial agents, expressed as mg/PCU, between the countries were observed. The proportion of sales, in mg/PCU, of products applicable for treatment of groups or herds of animals (premixes, oral powders and oral solution) varied considerably between the countries. CONCLUSIONS: Some countries reported much lower sales of veterinary antimicrobial agents than others, when expressed as mg/PCU. Sales patterns varied between countries, particularly with respect to pharmaceutical forms. Further studies are needed to understand the factors that explain the observed differences.

Radiological outcomes following surgical fixation with wires versus moulded cast for patients with a dorsally displaced fracture of the distal radius: a radiographic analysis from the DRAFFT2 trial.

Aims: The primary aim of this study was to report the radiological outcomes of patients with a dorsally displaced distal radius fracture who were randomized to a moulded cast or surgical fixation with wires following manipulation and closed reduction of their fracture. The secondary aim was to correlate radiological outcomes with patient-reported outcome measures (PROMs) in the year following injury. Methods: Participants were recruited as part of DRAFFT2, a UK multicentre clinical trial. Participants were aged 16 years or over with a dorsally displaced distal radius fracture, and were eligible for the trial if they needed a manipulation of their fracture, as recommended by their treating surgeon. Participants were randomly allocated on a 1:1 ratio to moulded cast or Kirschner wires after manipulation of the fracture in the operating theatre. Standard posteroanterior and lateral radiographs were performed in the radiology department of participating centres at the time of the patient's initial assessment in the emergency department and six weeks postoperatively. Intraoperative fluoroscopic images taken at the time of fracture reduction were also assessed. Results: Patients treated with surgical fixation with wires had less dorsal angulation of the radius versus those treated in a moulded cast at six weeks after manipulation of the fracture; the mean difference of -4.13° was statistically significant (95% confidence interval 5.82 to -2.45). There was no evidence of a difference in radial shortening. However, there was no correlation between these radiological measurements and PROMs at any timepoint in the 12 months post-injury. Conclusion: For patients with a dorsally displaced distal radius fracture treated with a closed manipulation, surgical fixation with wires leads to less dorsal angulation on radiographs at six weeks compared with patients treated in a moulded plaster cast alone. However, the difference in dorsal angulation was small and did not correlate with patient-reported pain and function.

Application of the Nagoya Protocol to veterinary pathogens: concerns for the control of foot-and-mouth disease.

The Nagoya Protocol is an international agreement adopted in 2010 (and entered into force in 2014) which governs access to genetic resources and the fair and equitable sharing of benefits from their utilisation. The agreement aims to prevent misappropriation of genetic resources and, through benefit sharing, create incentives for the conservation and sustainable use of biological diversity. While the equitable sharing of the benefits arising from the utilisation of genetic resources is a widely accepted concept, the way in which the provisions of the Nagoya Protocol are currently being implemented through national access and benefit-sharing legislation places significant logistical challenges on the control of transboundary livestock diseases such as foot-and-mouth disease (FMD). Delays to access FMD virus isolates from the field disrupt the production of new FMD vaccines and other tailored tools for research, surveillance and outbreak control. These concerns were raised within the FMD Reference Laboratory Network and were explored at a recent multistakeholder meeting hosted by the European Commission for the Control of FMD. The aim of this paper is to promote wider awareness of the Nagoya Protocol, and to highlight its impacts on the regular exchange and utilisation of biological materials collected from clinical cases which underpin FMD research activities, and work to develop new epidemiologically relevant vaccines and other diagnostic tools to control the disease.

Sales of veterinary antibacterial agents in nine European countries during 2005-09: trends and patterns.

OBJECTIVES: To identify trends and patterns of sales of veterinary antimicrobial agents in nine European countries during 2005-09 in order to document the situation. METHODS: Existing sales data, in tonnes of active ingredients, of veterinary antimicrobial agents by class were collected from nine European countries in a standardized manner for the years 2005-09 (one country for 2006-09). A population correction unit (PCU) is introduced as a proxy for the animal population potentially treated with antimicrobial agents. The sales data are expressed as mg of active substance/PCU. RESULTS: Data coverage was reported to be 98%-100% for the nine countries. Overall, sales of veterinary antimicrobials agents, in mg/PCU, declined during the reporting period in the nine countries. Substantial differences in the sales patterns and in the magnitude of sales of veterinary antimicrobial agents, expressed as mg/PCU, between the nine countries are observed. The major classes sold were penicillins, sulphonamides and tetracyclines. The sales accounted for by the various veterinary antimicrobial agents have changed substantially for most countries. An increase in the sales of third- and fourth-generation cephalosporins and fluoroquinolones were observed for the majority of the countries. CONCLUSIONS: Through re-analysis of existing data by application of a harmonized approach, an overall picture of the trends in the sales of veterinary antimicrobial agents in the nine countries was obtained. Notable differences in trends in sales between the countries were observed. Further studies, preferably including data by animal species, are needed to understand the factors that explain these observations.

Approach of an Academic Ophthalmology Department to Recovery During the Coronavirus Pandemic.

Introduction: A methodology for safe recovery of an ophthalmology department during a pandemic does not currently exist. This study describes successful recovery strategies for an urban, multi-specialty ophthalmology department serving a high-risk patient population. Methods: The study took place at a large multi-specialty tertiary care academic ophthalmology department in a metropolitan city during a seven-month period (March-October 2020). Five recovery ad hoc committees were charged with formulating metrics and initiatives to manage clinical volumes while maintaining safe practices, providing patient access, and minimizing financial damage. A six-tier system was created to resume non-urgent appointments in May 2020. Educational and research activities were maintained through the development of virtual curricula and research platforms. Results: The number of clinical and surgical visits per month in 2020 compared to 2019 and the time to reach ≥95% of pre-COVID patient volumes were monitored. In October 2020, ≥95% of pre-COVID volumes were attained (11,975 vs 12,337 patient visits in October 2019; 266 vs 272 surgical cases in October 2019). Despite significant financial losses, the department surpassed December 2019 collections in December 2020. No faculty, staff, or trainees received furloughs or pay cuts. There was no COVID-19 transmission between faculty, staff, and patients. Discussion: With strategic implementation of recovery strategies following CDC safety measures, it was possible to safely deliver care to patients with urgent and non-urgent eye conditions. Patient volumes were fully recovered in an ambulatory urban healthcare setting within a high-risk COVID-19 population within seven months while educational and research missions were successfully sustained.

Comparison of the sales of veterinary antibacterial agents between 10 European countries.

OBJECTIVES: To compare the sales of veterinary antibacterial agents between 10 European countries. METHODS: Data were compiled from published reports from the 10 countries. We express the usage as amounts sold of veterinary antibacterial agents per country and year, in mg active substances per kg biomass of slaughtered pigs, poultry and cattle plus estimated biomass of (live) dairy cattle for the corresponding year. RESULTS: The usage, as expressed in mg antibacterial drugs sold/kg biomass of slaughtered pigs, poultry and cattle and of (live) dairy cattle, varied from 18 to 188 mg/kg. The relative proportion of the various classes of antibacterial agents sold varied considerably. CONCLUSIONS: The apparent wide variations in the usage of veterinary antimicrobial agents between countries cannot be explained by differences in the animal species demographics alone. Further in-depth analyses are required to identify the factors underlying the observed differences.

Predicting and understanding the stability of G-quadruplexes.

MOTIVATION: G-quadruplexes are stable four-stranded guanine-rich structures that can form in DNA and RNA. They are an important component of human telomeres and play a role in the regulation of transcription and translation. The biological significance of a G-quadruplex is crucially linked with its thermodynamic stability. Hence the prediction of G-quadruplex stability is of vital interest. RESULTS: In this article, we present a novel Bayesian prediction framework based on Gaussian process regression to determine the thermodynamic stability of previously unmeasured G-quadruplexes from the sequence information alone. We benchmark our approach on a large G-quadruplex dataset and compare our method to alternative approaches. Furthermore, we propose an active learning procedure which can be used to iteratively acquire data in an optimal fashion. Lastly, we demonstrate the usefulness of our procedure on a genome-wide study of quadruplexes in the human genome. AVAILABILITY: A data table with the training sequences is available as supplementary material. Source code is available online at http://www.inference.phy.cam.ac.uk/os252/projects/quadruplexes. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Current challenges in viral safety and extraneous agent testing.

There are three principal elements related to viral safety in the context of immunological veterinary medicinal products: the presence of extraneous agents in either raw material used for production or in the finished product, residual pathogenicity of live viruses used as active ingredients, and incomplete inactivation of inactivated viruses used as active ingredients. Although the approach to controlling these areas of risk has not substantially changed in the recent past, a number of events, combined with advances in science and changes in the regulatory approach, make it timely to review the requirements in this area. This article reviews the major areas of change and progress with respect to the viral safety of immunological veterinary medicinal products and identifies current challenges from the perspectives of both industry and regulators.

Online learning to improve hand hygiene knowledge and compliance among health care workers.

BACKGROUND: The Centers for Disease Control and Prevention published a hand hygiene guideline for health care workers. The emergence of online learning approaches has introduced new opportunities for providing continuing education regarding hand hygiene. METHODS: This study assessed the effectiveness of an online continuing education program in increasing health care workers' knowledge of hand hygiene practices and guidelines and promoting behavioral change as measured by self-assessment of adherence to guidelines. A total of 256 health care workers at two hospitals completed all three sessions of the online continuing education program. RESULTS: Health care workers reported a significant improvement in hand hygiene knowledge and self-assessed compliance with hand hygiene behaviors. Most (97%) of the participating health care workers reported that the program was effective in improving clinical compliance behaviors. CONCLUSION: The results of this study indicated that individual health care workers can and will use self-assessment to prompt improvement in hand hygiene.

Ticker: An Adaptive Single-Switch Text Entry Method for Visually Impaired Users.

Ticker is a probabilistic stereophonic single-switch text entry method for visually-impaired users with motor disabilities who rely on single-switch scanning systems to communicate. Such scanning systems are sensitive to a variety of noise sources, which are inevitably introduced in practical use of single-switch systems. Ticker uses a novel interaction model based on stereophonic sound coupled with statistical models for robust inference of the user's intended text in the presence of noise. As a consequence of its design, Ticker is resilient to noise and therefore a practical solution for single-switch scanning systems. Ticker's performance is validated using a combination of simulations and empirical user studies.

Guidelines for the Treatment of PTSD Using Clinical EFT (Emotional Freedom Techniques).

Clinical EFT (Emotional Freedom Techniques) is an evidence-based method that combines acupressure with elements drawn from cognitive and exposure therapies. The approach has been validated in more than 100 clinical trials. Its efficacy for post-traumatic stress disorder (PTSD) has been investigated in a variety of demographic groups including war veterans, victims of sexual violence, the spouses of PTSD sufferers, motor accident survivors, prisoners, hospital patients, adolescents, and survivors of natural and human-caused disasters. Meta-analyses of EFT for anxiety, depression, and PTSD indicate treatment effects that exceed those of both psychopharmacology and conventional psychotherapy. Studies of EFT in the treatment of PTSD show that (a) time frames for successful treatment generally range from four to 10 sessions; (b) group therapy sessions are effective; (c) comorbid conditions such as anxiety and depression improve simultaneously; (d) the risk of adverse events is low; (e) treatment produces physiological as well as psychological improvements; (f) patient gains persist over time; (g) the approach is cost-effective; (h) biomarkers such as stress hormones and genes are regulated; and (i) the method can be adapted to online and telemedicine applications. This paper recommends guidelines for the use of EFT in treating PTSD derived from the literature and a detailed practitioner survey. It has been reviewed by the major institutions providing training or supporting research in the method. The guidelines recommend a stepped-care model, with five treatment sessions for subclinical PTSD, 10 sessions for PTSD, and escalation to intensive psychotherapy or psychopharmacology or both for nonresponsive patients and those with developmental trauma. Group therapy, social support, apps, and online and telemedicine methods also contribute to a successful treatment plan.

Unsuccessful introduced biocontrol agents can act as pollinators of invasive weeds: Bitou Bush (Chrysanthemoides monilifera ssp. rotundata) as an example.

The extent of self-compatibility and reliance on pollinators for seed set are critical determinants of reproductive success in invasive plant species. Seed herbivores are commonly used as biocontrol agents but may also act as flower visitors, potentially resulting in pollination. However, such contrasting or potentially counterproductive interaction effects are rarely considered or evaluated for biological control programs. We investigated the breeding system and pollinators of Bitou Bush (Chrysanthemoides monilifera ssp. rotundata), an invasive species in Australia that has been the subject of biocontrol programs since 1987. We found the species to be obligate outcrossing in all six populations tested. From 150 video hours, we found 21 species of potential pollinators, including Mesoclanis polana, the Bitou Seedfly, native to South Africa and released in Australia as a biocontrol agent in 1996. Mesoclanis polana transferred pollen to stigmas and was the most common pollinator (52% of pollinator visits), followed by the syrphid fly Simosyrphus grandicornis (9%) and introduced honeybee, Apis mellifera (6.5%). Fruit-to-flower ratios ranged from 0.12 to 0.45 and were highest in the population with the greatest proportion of Mesoclanis polana visits. In an experimental trial, outside the naturalized range, the native bee Homalictus sphecodoides and the native syrphid Melangyna viridiceps were the primary pollinators, and fruit-to-flower ratios were 0.35, indicating that Bitou Bush would have ready pollinators if its range expanded inland. Synthesis. Invasive Bitou Bush requires pollinators, and this is effected by a range of generalist pollinators in eastern Australia including the Bitou Seedfly, introduced as a biocontrol agent, and the major pollinator detected in this study. Fruit-to-flower ratios were highest when the Bitou Seedfly was in high abundance. This study underscores the importance of evaluating the pollination biology of invasive species in their native ranges and prior to the introduction of biocontrol agents.

DASHER--an efficient writing system for brain-computer interfaces?

DASHER is a human-computer interface for entering text using continuous or discrete gestures. Through its use of an internal language model, DASHER efficiently converts bits received from the user into text, and has been shown to be a competitive alternative to existing text-entry methods in situations where an ordinary keyboard cannot be used. We propose that DASHER would be well-matched to the low bit-rate, noisy output obtained from brain-computer interfaces (BCIs), and discuss the issues surrounding the use of DASHER with BCI systems.

Development and evaluation of an indirect enzyme-linked immunosorbent assay for detection of foot-and-mouth disease virus nonstructural protein antibody using a chemically synthesized 2B peptide as antigen.

Forty peptides were synthesized corresponding to hydrophilic clusters of amino acids within the sequences of foot-and-mouth disease virus (FMDV) nonstructural proteins (NSP). Six peptides were studied in more detail and the most promising, a 2B peptide, was evaluated in enzyme-linked immunosorbent assay (ELISA) using sera from naive, vaccinated, and vaccinated-and-challenged cattle as well as bovine sera from field outbreaks. The performance of the new NSP peptide ELISA was compared to that of 4 commercial NSP ELISA kits. Antibody to 2B was detectable from the end of the first week to the second week after infection in most of the nonvaccinated animals and by the second to third week in vaccinated-and-challenged animals. The sensitivity of the 2B peptide ELISA was comparable to the 3ABC Ceditest (Ceditest FMDV-NS, Cedi Diagnostics B.V.; Chung et al., 2002). With some modification and further validation, this 2B test could be useful as a screening or conformational NSP test in postvaccination surveillance for FMD.