Factors affecting Plasmodium falciparum sporozoite formation in Anopheles mosquitoes

The relative contribution of different factors, including environmental and genetic variables, on the observed variation in genome numbers per oocyst was investigated. The variation in sporozoite numbers from two genetically different Plasmodium falciparum clones (3D7 and HB3) in Anopheles gambiae mosquitoes, and the pattern of inheritance of the phenotype was investigated. Membrane-feeding of cultured P. falciparum parasites to laboratory-reared Anopheles mosquitoes produced infected midguts for dissection. Microdissection of single oocysts from the infected midguts and the employment of polymerase chain reaction techniques allowed the products of self- and cross-fertilisation to be distinguished, and the number of genomes per oocyst to be counted. Utilising these methods allowed comparison of the relative productivity of oocysts from different genetic and environmental backgrounds. Environmental factors such as the size of the mosquito and the number of oocysts on the midgut appeared to have no effect on the number of genomes per oocyst. However the genomes per oocyst were signifcantly different when oocysts from the same clone were isolated from two different Anopheles mosquito species. The two parasite clones differed significantly in the number of genomes per oocyst they produced, and this trait was inherited in a dominant fashion

Investigation of perovskite oxide SrFe0.8Cu0.1Nb0.1O3-δ as cathode for a room temperature direct ammonia fuel cell

Through Pechini method, a single phase shuttle-shaped perovskite oxide was successfully synthesised at 1000 °C. It was combined with active carbon, forming a composite electrode to be used as cathode in a room temperature ammonia fuel cell based on an alkaline membrane electrolyte and Pt/C anode. Reasonable OCV and power density were observed for an ammonia fuel cell using /C composite cathode. Although the power density is not high enough for conventional portable or transport applications, it has the potential for stationary application in removal of ammonia from wastewater because the requirements on power density is relatively low. When a dilute 0.02 M ammonia solution (340 ppm) was used as the fuel, the fuel cell using this perovskite oxide can obtain an open circuit voltage of 0.35 V and a power density of 0.03 mW/cm2. In order to obtain higher OCV, NaOH is necessary to be added in the fuel, especially when the fuel contains a low concentration of ammonia. This study indicates that perovskite oxides are potential good cathode for low temperature direct ammonia or alkaline membrane fuel cells

New synchronization method for <i>Plasmodium falciparum</i>

&lt;b&gt;Background&lt;/b&gt;: Plasmodium falciparum is usually asynchronous during in vitro culture. Although various synchronization methods are available, they are not able to narrow the range of ages of parasites. A newly developed method is described that allows synchronization of parasites to produce cultures with an age range as low as 30 minutes. &lt;b&gt;Methods&lt;/b&gt;: Trophozoites and schizonts are enriched using Plasmion. The enriched late stage parasites are immobilized as a monolayer onto plastic Petri dishes using concanavalin A. Uninfected erythrocytes are placed onto the monolayer for a limited time period, during which time schizonts on the monolayer rupture and the released merozoites invade the fresh erythrocytes. The overlay is then taken off into a culture flask, resulting in a highly synchronized population of parasites. &lt;b&gt;Results&lt;/b&gt;: Plasmion treatment results in a 10- to 13-fold enrichment of late stage parasites. The monolayer method results in highly synchronized cultures of parasites where invasion has occurred within a very limited time window, which can be as low as 30 minutes. The method is simple, requiring no specialized equipment and relatively cheap reagents. &lt;b&gt;Conclusions&lt;/b&gt;: The new method for parasite synchronization results in highly synchronized populations of parasites, which will be useful for studies of the parasite asexual cell cycle

Electrooxidation of ammonia on A-site deficient perovskite oxide La0.9Ni0.6Cu0.35Fe0.05O3-δ for wastewater treatment

Wastewater can contain high amounts of ammonia which can pose as a great safety threat if released into natural waters. The electrochemical oxidation of ammonia offers a viable strategy to remove high concentrations and provides an attractive method for wastewater treatment. However, finding a highly efficient and low-cost catalyst is imperative for overcoming the sluggish nature of ammonia oxidation reaction. Herein, a modified A- and B-site perovskite is proposed as a catalyst for the oxidation of ammonia, making it suitable as an anode in an ammonia electrolyser. A series of La1-yNi0.6Cu0.4-xFexO3-δ (x = 0, 0.05 and 0.10; y = 0, 0.05 and 0.10) perovskite materials were synthesised by a conventional sol–gel method. Amongst those tested oxides, La0.9Ni0.6Cu0.35Fe0.05O3-δ was found to have superior activity towards the electrooxidation of ammonia due to an optimised amount of Fe doping and the presence of oxygen vacancies introduced by an A-site deficiency. Subsequently, La0.9Ni0.6Cu0.35Fe0.05O3-δ was employed as an anode in an ammonia electrolyser where the ammonia removal efficiency reached 95.4 % in simulated wastewater after 80 hr and a substantial reduction in real wastewater was also observed. These results demonstrate that the A-site deficient perovskite materials are a viable electrode for the removal of ammonia in a practical energy setting and paves way for future applications

Clinical trial data sharing: Here's the challenge

Objective Anonymised patient-level data from clinical research are increasingly recognised as a fundamental and valuable resource. It has value beyond the original research project and can help drive scientific research and innovations and improve patient care. To support responsible data sharing, we need to develop systems that work for all stakeholders. The members of the Independent Review Panel (IRP) for the data sharing platform Clinical Study Data Request (CSDR) describe here some summary metrics from the platform and challenge the research community on why the promised demand for data has not been observed. Summary of data From 2014 to the end of January 2019, there were a total of 473 research proposals (RPs) submitted to CSDR. Of these, 364 met initial administrative and data availability checks, and the IRP approved 291. Of the 90 research teams that had completed their analyses by January 2018, 41 reported at least one resulting publication to CSDR. Less than half of the studies ever listed on CSDR have been requested. Conclusion While acknowledging there are areas for improvement in speed of access and promotion of the platform, the total number of applications for access and the resulting publications have been low and challenge the sustainability of this model. What are the barriers for data contributors and secondary analysis researchers? If this model does not work for all, what needs to be changed? One thing is clear: that data access can realise new and unforeseen contributions to knowledge and improve patient health, but this will not be achieved unless we build sustainable models together that work for all

An efficient symmetric electrolyzer based on bifunctional perovskite catalyst for ammonia electrolysis

Ammonia is a natural pollutant in wastewater and removal technique such as ammonia electro‐oxidation is of paramount importance. The development of highly efficient and low‐costing electrocatalysts for the ammonia oxidation reaction (AOR) and hydrogen evolution reaction (HER) associated with ammonia removal is subsequently crucial. In this study, for the first time, the authors demonstrate that a perovskite oxide LaNi0.5Cu0.5O3‐δ after being annealed in Ar (LNCO55‐Ar), is an excellent non‐noble bifunctional catalyst towards both AOR and HER, making it suitable as a symmetric ammonia electrolyser (SAE) in alkaline medium. In contrast, the LNCO55 sample fired in air (LNCO55‐Air) is inactive towards AOR and shows very poor HER activity. Through combined experimental results and theoretical calculations, it is found that the superior AOR and HER activities are attributed to the increased active sites, the introduction of oxygen vacancies, the synergistic effect of B‐site cations and the different active sites in LNCO55‐Ar. At 1.23 V, the assembled SAE demonstrates ≈100% removal efficiency in 2210 ppm ammonia solution and >70% in real landfill leachate. This work opens the door for developments towards bifunctional catalysts, and also takes a profound step towards the development of low‐costing and simple device configuration for ammonia electrolysers

CompARE: study protocol for a phase III randomised controlled platform trial comparing alternative regimens for escalating treatment of intermediate and high-risk oropharyngeal cancer

BACKGROUND: Patients with intermediate and high-risk oropharyngeal cancer (OPC) have poorer response to standard treatment and poorer overall survival compared to low-risk OPC. CompARE is designed to test alternative approaches to intensified treatment for these patients to improve survival. METHODS: CompARE is a pragmatic phase III, open-label, multicenter randomised controlled trial with an adaptive multi-arm, multi-stage design and an integrated QuinteT Recruitment Intervention. Eligible OPC patients include those with human papillomavirus (HPV) negative, T1-T4, N1-N3 or T3-4, N0, or HPV positive N3, T4, or current smokers (or ≥ 10 pack years previous smoking history) with T1-T4, N2b-N3. CompARE was originally designed with four arms (one control [arm 1] and three experimental: arm 2-induction chemotherapy followed by arm 1; arm 3-dose-escalated radiotherapy plus concomitant cisplatin; and arm 4-resection of primary followed by arm 1). The three original experimental arms have been closed to recruitment and a further experimental arm opened (arm 5-induction durvalumab followed by arm 1 and then adjuvant durvalumab). Currently recruiting are arm 1 (control): standard treatment of 3-weekly cisplatin 100 mg/m2 or weekly 40 mg/m2 with intensity-modulated radiotherapy using 70 Gy in 35 fractions ± neck dissection determined by clinical and radiological assessment 3 months post-treatment, and arm 5 (intervention): one cycle of induction durvalumab 1500 mg followed by standard treatment then durvalumab 1500 mg every 4 weeks for a total of 6 months. The definitive and interim primary outcome measures are overall survival time and event-free survival (EFS) time, respectively. Secondary outcome measures include quality of life, toxicity, swallowing outcomes, feeding tube incidence, surgical complication rates, and cost-effectiveness. The design anticipates that after approximately 7 years, 84 required events will have occurred to enable analysis of the definitive primary outcome measure for this comparison. Planned interim futility analyses using EFS will also be performed. DISCUSSION: CompARE is designed to be efficient and cost-effective in response to new data, emerging new treatments or difficulties, with the aim of bringing new treatment options for these patients. TRIAL REGISTRATION: ISRCTN ISRCTN41478539 . Registered on 29 April 2015

Data challenges for international health emergencies: lessons learned from ten international COVID-19 driver projects

The COVID-19 pandemic highlighted the importance of international data sharing and access to improve health outcomes for all. The International COVID-19 Data Alliance (ICODA) programme enabled 12 exemplar or driver projects to use existing health-related data to address major research questions relating to the pandemic, and developed data science approaches that helped each research team to overcome challenges, accelerate the data research cycle, and produce rapid insights and outputs. These approaches also sought to address inequity in data access and use, test approaches to ethical health data use, and make summary datasets and outputs accessible to a wider group of researchers. This Health Policy paper focuses on the challenges and lessons learned from ten of the ICODA driver projects, involving researchers from 19 countries and a range of health-related datasets. The ICODA programme reviewed the time taken for each project to complete stages of the health data research cycle and identified common challenges in areas such as data sharing agreements and data curation. Solutions included provision of standard data sharing templates, additional data curation expertise at an early stage, and a trusted research environment that facilitated data sharing across national boundaries and reduced risk. These approaches enabled the driver projects to rapidly produce research outputs, including publications, shared code, dashboards, and innovative resources, which can all be accessed and used by other research teams to address global health challenges

Efficacy of Single-Dose Primaquine With Artemisinin Combination Therapy on Plasmodium falciparum Gametocytes and Transmission: An Individual Patient Meta-Analysis

Background Since the World Health Organization recommended single low-dose (0.25mg/kg) primaquine (PQ) in combination with artemisinin-based combination therapies (ACTs) in areas of low transmission or artemisinin-resistant P. falciparum, several single-site studies have been conducted to assess its efficacy. Methods An individual patient meta-analysis to assess the gametocytocidal and transmission-blocking efficacy of PQ used in combination with different ACTs was conducted. Random effects logistic regression was used to quantify PQ effect on (i) gametocyte carriage in the first two weeks post-treatment; (ii) the probability of infecting at least one mosquito or of a mosquito becoming infected. Results In 2,574 participants from fourteen studies, PQ reduced PCR-determined gametocyte carriage on days 7 and 14, most apparently in patients presenting with gametocytaemia on day 0 (Odds Ratio (OR)=0.22; 95%CI 0.17-0.28 and OR=0.12; 95%CI 0.08–0.16, respectively). The rate of decline in gametocyte carriage was faster when PQ was combined with artemether-lumefantrine (AL) compared to dihydroartemisinin-piperaquine (DP) (p=0.010 for day 7). Addition of 0.25mg/kg PQ was associated with near complete prevention of transmission to mosquitoes. Conclusion Primaquine’s transmission-blocking effects are achieved with 0.25 mg/kg PQ. Gametocyte persistence and infectivity are lower when PQ is combined with AL compared to DP

Efficacy of Single-Dose Primaquine With Artemisinin Combination Therapy on Plasmodium falciparum Gametocytes and Transmission: An Individual Patient Meta-Analysis.

BACKGROUND: Since the World Health Organization recommended single low-dose (0.25 mg/kg) primaquine (PQ) in combination with artemisinin-based combination therapies (ACTs) in areas of low transmission or artemisinin-resistant Plasmodium falciparum, several single-site studies have been conducted to assess efficacy. METHODS: An individual patient meta-analysis to assess gametocytocidal and transmission-blocking efficacy of PQ in combination with different ACTs was conducted. Random effects logistic regression was used to quantify PQ effect on (1) gametocyte carriage in the first 2 weeks post treatment; and (2) the probability of infecting at least 1 mosquito or of a mosquito becoming infected. RESULTS: In 2574 participants from 14 studies, PQ reduced PCR-determined gametocyte carriage on days 7 and 14, most apparently in patients presenting with gametocytemia on day 0 (odds ratio [OR],?0.22; 95% confidence interval [CI], .17-.28 and OR,?0.12; 95% CI, .08-.16, respectively). Rate of decline in gametocyte carriage was faster when PQ was combined with artemether-lumefantrine (AL) compared to dihydroartemisinin-piperaquine (DP) (P?=?.010 for day 7). Addition of 0.25 mg/kg PQ was associated with near complete prevention of transmission to mosquitoes. CONCLUSIONS: Transmission blocking is achieved with 0.25 mg/kg PQ. Gametocyte persistence and infectivity are lower when PQ is combined with AL compared to DP