Clonal integration in Ludwigia hexapetala under different light regimes

Physiological integration among ramets of invasive plant species may support their colonization and spread in novel aquatic environments where growth-limiting resources are spatially heterogeneous. Under contrasting light conditions, we investigated how clonal integration influences growth, biomass allocation and morphology of Ludwigia hexapetala, an emergent floating-leaved macrophyte that is highly invasive in a range of wetland habitat types. In aquatic mesocosms, stolons of offspring ramets were either connected or severed from parent plants, with the pairs exposed to homogenous or heterogeneous combinations of sun or 85% shade. Morphological traits of all ramets were strongly influenced by light environment, and low light availability decreased plant growth, regardless of integration status. Allocation patterns varied with light regime; shaded plants increased allocation to leaf biomass while sun plants allocated more resources to belowground growth. Offspring ramets integrated with parents produced more biomass, suggesting a fitness advantage through integration. However, parent ramet performance declined with stoloniferous integration; integrated parents produced fewer ramets and allocated more resources to belowground biomass. For most response variables measured, there was no significant interactive effect between light treatment and integration, although parents growing in the shade attached to an offspring in the sun increased root mass ratio. The ability to establish and spread into new environments is a key trait of invasive plants, and physiological integration of resources may improve the establishment of juvenile ramets across variable light environments during early colonization. Physiological integration in patchy light environments may contribute to the invasiveness of Ludwigia hexapetala

The WHO costing and budgeting tool for national action plans on antimicrobial resistance-a practical addition to the WHOle toolkit

OBJECTIVES: The development of national action plans (NAPs) for antimicrobial resistance (AMR) has been promoted and supported by the WHO, with recent support in the form of costing and budgeting tools to aid in finance-allocation decisions within governments. METHODS: In this brief report we review this WHO costing and budgeting tool, discuss the strengths and weaknesses, and consider its place alongside other health economics and policy-support tools developed. RESULTS: We call for future analyses of the costs of AMR NAPs to consider costs beyond that of only implementation, through use of other available, open-access data and tools. These include the Global Antimicrobial Resistance and Use Surveillance System (GLASS) data and One Health tools already within the existing 'WHO toolbox'. CONCLUSIONS: We suggest that future work on evaluating AMR along the impact pipeline use this toolbox where possible, ensuring empirical work is in turn open access

Measuring the impact of Ebola control measures in Sierra Leone.

Between September 2014 and February 2015, the number of Ebola virus disease (EVD) cases reported in Sierra Leone declined in many districts. During this period, a major international response was put in place, with thousands of treatment beds introduced alongside other infection control measures. However, assessing the impact of the response is challenging, as several factors could have influenced the decline in infections, including behavior changes and other community interventions. We developed a mathematical model of EVD transmission, and measured how transmission changed over time in the 12 districts of Sierra Leone with sustained transmission between June 2014 and February 2015. We used the model to estimate how many cases were averted as a result of the introduction of additional treatment beds in each area. Examining epidemic dynamics at the district level, we estimated that 56,600 (95% credible interval: 48,300-84,500) Ebola cases (both reported and unreported) were averted in Sierra Leone up to February 2, 2015 as a direct result of additional treatment beds being introduced. We also found that if beds had been introduced 1 month earlier, a further 12,500 cases could have been averted. Our results suggest the unprecedented local and international response led to a substantial decline in EVD transmission during 2014-2015. In particular, the introduction of beds had a direct impact on reducing EVD cases in Sierra Leone, although the effect varied considerably between districts

Why is the UK subscription model for antibiotics considered successful?

Commen

Impact of consensus guidelines for breast-conserving surgery in patients with ductal carcinoma in situ

BACKGROUND: Consensus guidelines published in 2016 recommended a 2 mm free margin as the standard for negative margins in patients undergoing breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). The goal of the guideline recommendation was standardization of re-excision practices. AIMS: To evaluate the impact of this consensus guideline on our institutional practices. METHODS: We identified all patients at our institution with pure DCIS who were initially treated with BCS from September 2014 to August 2018 using a prospectively-maintained institutional database. A retrospective chart review was performed to determine margin status and re-excision rates during the 2 years before and the 2 years after the guideline was published in order to determine the effect on our re-excision rates. Close margins were defined as \u3c2 mm. RESULTS: In the 2 years before the consensus guideline was published, 184 patients with DCIS underwent BCS. Twenty-six patients had positive margins and 24 underwent re-excision, including three who had completion mastectomy. Of the remaining 159 patients, 76 had ≥2 mm (negative) margins. The remaining 82 patients had close margins and 48 of these patients (58.5%) underwent re-excision, including one who had a completion mastectomy. Excluding the patients with positive margins, our re-excision rate was 30.4% prior to the guideline. In the 2 years after the consensus guideline was published, 192 patients with DCIS underwent initial BCS. Twenty-four patients had positive margins and 22 underwent re-excision, including three who had completion mastectomy. Of the remaining 168 patients, 95 patients had ≥2 mm (negative) margins. The remaining 73 patients had close margins and 45 of those patients (61.6%) underwent re-excision, including six who had completion mastectomy. Excluding the patients with positive margins, our re-excision rate was 26.8% after the guideline. CONCLUSIONS: Our institution\u27s re-excision rate did not change significantly during the 2 years before and after the publication of the consensus guideline on adequate margins for patients undergoing BCT for DCIS. Our overall re-excision rate decreased slightly. However, of the patients who had close margins, a larger proportion underwent re-excision after the guideline was published. The guideline publication appears to have affected our institutional practices slightly, but not dramatically as many of our surgeons\u27 practices were comparable to the guideline recommendations prior to 2016. We continue to use clinical judgment based on patient and tumor characteristics in deciding which patients will benefit from margin re-excision

Associations of maternal and paternal antenatal mood with offspring anxiety disorder at age 18 years.

OBJECTIVE: Maternal antenatal depression and anxiety are associated with increased risk of childhood behavioural and emotional problems in offspring; it remains unclear to what extent this is due to a maternal biological impact on foetal development. Here, we compare associations between maternal and paternal antenatal depression and anxiety with offspring anxiety disorders, thus controlling for some genetic and shared environmental factors. METHODS: We used data from the ALSPAC population cohort including measures of antenatal parental depression and anxiety. At 18 years, offspring completed the CIS-R interview, yielding diagnoses for anxiety disorders. Results were adjusted for confounding variables including parental postnatal depression and anxiety. RESULTS: Children of women with antenatal depression (18 weeks gestation), had an increased risk of anxiety disorders at 18 years of age (11.1% vs. 6.2%; adj. OR 1.75 (1.19, 2.58); p=0.01). Children of women with antenatal anxiety had increased risk of co-morbid anxiety and depression (adj. OR 1.39 (1.06, 1.82); p=0.02). No such associations were found with paternal antenatal depression or anxiety. LIMITATIONS: There was a high attrition rate from the original cohort to the CIS-R completion at 18 years postpartum. Parental mood was only assessed together at one time point during the antenatal period. CONCLUSIONS: The differences in the association between maternal and paternal mood during pregnancy and child outcomes supports the hypothesis that foetal programming may account, at least in part, for this association. We highlight the potential opportunity for preventative intervention by optimising antenatal mental health

NIMble innovation — a networked model for public antibiotic trials

Antibiotic research and development is at an inflection point. Faced with ongoing problems with commercial innovation, we argue for a networked public approach to support and coordinate existing research and development initiatives by sustainably moving promising compounds through clinical trials. We propose a global public infrastructure of institutes tasked with (1) conducting all trial stages up to market authorisation, including small-scale compound production; (2) negotiating licensing agreements for global production and distribution by industry partners; and (3) using public purchasing agreements or subscription models to ensure commercially viable drug production at equitable prices. We invite stakeholders to consider our Networked Institute Model's benefits for unblocking the public and private antibiotic pipeline

Quality and Utility of Information Captured by Surveillance Systems Relevant to Antimicrobial Resistance (AMR): A Systematic Review.

Health surveillance systems are considered vital for combatting antimicrobial resistance (AMR); however, the evidence-base on the effectiveness of these systems in providing information that can be used by healthcare professionals, or the acceptability of these systems by users, has not been reviewed. A systematic review was conducted of a number of databases to synthesise the evidence. The review identified 43 studies that met the inclusion criteria, conducted in 18 countries and used 11 attributes in their assessment of surveillance systems. The majority of systems evaluated were for monitoring the incidence of tuberculosis. The studies found that most surveillance systems were underperforming in key attributes that relate to both effectiveness and acceptability. We identified that two features of systems (ease of use and users' awareness of systems) were associated with greater acceptability and completeness of systems. We recommend prioritising these for the improvement of existing systems, as well as ensuring consistency in the definition of attributes studied, to allow a more consistent approach in evaluations of surveillance systems, and to facilitate the identification of the attributes that have the greatest impact on the utility of data produced

Trypanosoma brucei aquaglyceroporin 2 is a high-affinity transporter for pentamidine and melaminophenyl arsenic drugs and the main genetic determinant of resistance to these drugs.

OBJECTIVES: Trypanosoma brucei drug transporters include the TbAT1/P2 aminopurine transporter and the high-affinity pentamidine transporter (HAPT1), but the genetic identity of HAPT1 is unknown. We recently reported that loss of T. brucei aquaglyceroporin 2 (TbAQP2) caused melarsoprol/pentamidine cross-resistance (MPXR) in these parasites and the current study aims to delineate the mechanism by which this occurs. METHODS: The TbAQP2 loci of isogenic pairs of drug-susceptible and MPXR strains of T. brucei subspecies were sequenced. Drug susceptibility profiles of trypanosome strains were correlated with expression of mutated TbAQP2 alleles. Pentamidine transport was studied in T. brucei subspecies expressing TbAQP2 variants. RESULTS: All MPXR strains examined contained TbAQP2 deletions or rearrangements, regardless of whether the strains were originally adapted in vitro or in vivo to arsenicals or to pentamidine. The MPXR strains and AQP2 knockout strains had lost HAPT1 activity. Reintroduction of TbAQP2 in MPXR trypanosomes restored susceptibility to the drugs and reinstated HAPT1 activity, but did not change the activity of TbAT1/P2. Expression of TbAQP2 sensitized Leishmania mexicana promastigotes 40-fold to pentamidine and >1000-fold to melaminophenyl arsenicals and induced a high-affinity pentamidine transport activity indistinguishable from HAPT1 by Km and inhibitor profile. Grafting the TbAQP2 selectivity filter amino acid residues onto a chimeric allele of AQP2 and AQP3 partly restored susceptibility to pentamidine and an arsenical. CONCLUSIONS: TbAQP2 mediates high-affinity uptake of pentamidine and melaminophenyl arsenicals in trypanosomes and TbAQP2 encodes the previously reported HAPT1 activity. This finding establishes TbAQP2 as an important drug transporter