The burden of imported malaria in Gauteng Province

OBJECTIVES: To describe the burden of malaria in Gauteng Province, and to identify potential risk factors for severe disease. DESIGN: We conducted a prospective survey of malaria cases diagnosed in hospitals throughout Gauteng from December 2005 to end November 2006. OUTCOME MEASURES: Malaria frequency, severity, and treatment. Results. We identified 1 701 malaria cases; 1 548 (91%) were seen at public sector hospitals and 153 (9%) at private hospitals; 1 149 (68%) patients were male. Median age was 27 years (range 1 month - 89 years). Most (84%) infections were acquired in Mozambique. Disease severity did not differ by age or sex. Patients who were South African-born were more likely to have severe disease (OR=1.43 (1.08 - 1.91)), as were patients who experienced a delay >48 hours between onset of symptoms and diagnosis or treatment (OR=1.98 (1.48 - 2.65)). While most patients appropriately received quinine, only 9% of severe malaria cases received the recommended loading dose. CONCLUSIONS: The incidence of malaria in Gauteng was higher than previously reported, emphasising the need to prevent malaria in travellers by correct use of non-drug measures and, when indicated, malaria chemoprophylaxis. Disease severity was increased by delays between onset and treatment and lack of partial immunity. Providers should consult the latest guidelines for treatment of malaria in South Africa, particularly about treatment of severe malaria. A change in drug policy to artemisinin combination therapy for imported uncomplicated malaria in non-malaria risk provinces should be strongly considered

Safety and immunogenicity of two Haemophilus influenzae type b conjugate vaccines

Objectives. Haemophilus influenzae type b (Hib) infection remains a major public health problem inthe developing world. We evaluated the safety and immunogenicity of a new PRP-CRM197 conjugate Hib vaccine (Vaxem Hib, Chiron Vacdnes), compared with theHibTITER vaccine (WyethLederle Vaccines), following the World Health Organisation (WHO)'s accelerated schedule which allows 4-week intervals between doses.Study design. A phase II, observer-blind, multicentre, randomised, controlled, non-inferiority study.Methods. In total, 331 babies were immunised with either Vaxem Hib (N = 167) or HibTITER (N = 164) vaccine at 6, 10 and 14 weeks of age, in parallel with oral polio, diphtheriatetanus- pertussis and hepatitis B vaccines. Postimmunisation reactions were recorded after each immunisation and arfollow-up visits. Anti-polyribosylribitol phosphate (PRP) antibodies were measured using enzyme-linked immunosorbent assays (ELISAs) before and 1 month after the third immunisation. Results. Overall, there was no significant difference in the anti-PRP levels between the two groups .. One month after the third immunisation, 76% of vacdnees in the Vaxem Hib group and 70% in the HibTITER group hadanti-PRP antibody mres i:: 1.0 vg/ tnl, while 96% of the Vaxem l-Iib group and.90% of the HibTITER gn;mp d.e!l}onstrated a),lt1- PRP antibody titres;:: 0.15 vg/ml. The geometric me<t:ntitre at day 90 was 3.77 pg/ml for the VaxemHib and 3.0 Jlg/Inl for the HibTITER groups. Although the Vaxem Hib vaccine produced more redness (6% versus 1 %; p = 0.006) and swelling (5% versus 1%, p = 0.037), overall it was well tolerated compared with the B:ibTITER vaccine. There wa~ no significant difference in vaccine-relateq elevated temperature (;:: 38°(:) between the two groups (p = 0. 11), Conclusion. Both vaccines showed comparable safety llJ:\d immunogenicity profiles when administered to SouthAfrican babies at 6, 10 and 14weeks of age

In situ investigation of the mechanochemically promoted Pd–Ce interaction under stoichiometric methane oxidation conditions

The optimization of the supported Pd phase for CH4 activation on Pd/CeO2 catalysts has been a matter of great interest in the recent literature, aiming at the design of efficient methane abatement catalysts for Natural Gas fueled Vehicles (NGVs). Under lean conditions, a mixed Pd0 /PdO combination has been indicated as exhibiting the best performance, while controversial results have been reported under stoichiometric conditions depending on the support oxide, where either Al2O3 or zeolite-based supports are usually considered. Here, by means of synchrotron-based in situ NAP-XPS and XRD measurements, we follow the evolution of Pd species on Pd/CeO2 samples prepared by dry mechanochemical synthesis (M) under stoichiometric CH4 oxidation feed, unravelling a stable Pd0 /Pd2+ arrangement in a close to 1 : 1 ratio as the most active palladium state for CH4 activation when excess oxygen is not available, in contrast to what was reported for Pd/alumina materials, where metallic Pd0 nanoparticles showed the highest activity. The combination of NAP-XPS analysis and activity test results highlights the promotional effect of the Pd–Ce interaction, resulting in enhanced oxygen transfer and improved activity and stability of the Pd/CeO2 catalyst prepared by a novel mechanochemical approach even under low O2 content, large excess of water vapor (10 vol%) and high temperature exposure (4700 1C)

Impact of AKT1 on cell invasion and radiosensitivity in a triple negative breast cancer cell line developing brain metastasis

Introduction: The PI3K/AKT pathway is activated in 43-70% of breast cancer (BC)-patients and promotes the metastatic potential of BC cells by increasing cell proliferation, invasion and radioresistance. Therefore, AKT1-inhibition in combination with radiotherapy might be an effective treatment option for triple-negative breast cancer (TNBC)-patients with brain metastases. Methods: The impact of AKT1-knockout (AKT1_KO) and AKT-inhibition using Ipatasertib on MDA-MB-231 BR cells was assessed using in vitro cell proliferation and migration assays. AKT1-knockout in MDA-MB-231BR cells was performed using CRISPR/Cas9. The effect of AKT1-knockout on radiosensitivity of MDA-MB-231BR cell lines was determined via colony formation assays after cell irradiation. To detect genomic variants in AKT1_KO MDA-MB-231BR cells, whole-genome sequencing (WGS) was performed. Results: Pharmacological inhibition of AKT with the pan-AKT inhibitor Ipatasertib led to a significant reduction of cell viability but did not impact cell migration. Moreover, only MDA-MB-231BR cells were sensitized following Ipatasertib-treatment. Furthermore, specific AKT1-knockout in MDA-MB-231BR showed reduced cell viability in comparison to control cells, with significant effect in one of two analyzed clones. Unexpectedly, AKT1 knockout led to increased cell migration and clonogenic potential in both AKT1_KO clones. RNAseq-analysis revealed the deregulation of CTSO, CYBB, GPR68, CEBPA, ID1, ID4, METTL15, PBX1 and PTGFRN leading to the increased cell migration, higher clonogenic survival and decreased radiosensitivity as a consequence of the AKT1 knockout in MDA-MB-231BR. Discussion; Collectively, our results demonstrate that Ipatasertib leads to radiosensitization and reduced cell proliferation of MDA-MB-231BR. AKT1-inhibition showed altered gene expression profile leading to modified cell migration, clonogenic survival and radioresistance in MDA-MB-231BR. We conclude, that AKT1-inhibition in combination with radiotherapy contribute to novel treatment strategies for breast cancer brain metastases

Investigation of the evolution of Pd-Pt supported on ceria for dry and wet methane oxidation

Efficiently treating methane emissions in transportation remains a challenge. Here, we investigate palladium and platinum mono- and bimetallic ceria-supported catalysts synthesized by mechanical milling and by traditional impregnation for methane total oxidation under dry and wet conditions, reproducing those present in the exhaust of natural gas vehicles. By applying a toolkit of in situ synchrotron techniques (X-ray diffraction, X-ray absorption and ambient pressure photoelectron spectroscopies), together with transmission electron microscopy, we show that the synthesis method greatly influences the interaction and structure at the nanoscale. Our results reveal that the components of milled catalysts have a higher ability to transform metallic Pd into Pd oxide species strongly interacting with the support, and achieve a modulated PdO/Pd ratio than traditionally-synthesized catalysts. We demonstrate that the unique structures attained by milling are key for the catalytic activity and correlate with higher methane conversion and longer stability in the wet feed.Peer ReviewedPostprint (published version

Monitoring of microbial hydrocarbon remediation in the soil

Bioremediation of hydrocarbon pollutants is advantageous owing to the cost-effectiveness of the technology and the ubiquity of hydrocarbon-degrading microorganisms in the soil. Soil microbial diversity is affected by hydrocarbon perturbation, thus selective enrichment of hydrocarbon utilizers occurs. Hydrocarbons interact with the soil matrix and soil microorganisms determining the fate of the contaminants relative to their chemical nature and microbial degradative capabilities, respectively. Provided the polluted soil has requisite values for environmental factors that influence microbial activities and there are no inhibitors of microbial metabolism, there is a good chance that there will be a viable and active population of hydrocarbon-utilizing microorganisms in the soil. Microbial methods for monitoring bioremediation of hydrocarbons include chemical, biochemical and microbiological molecular indices that measure rates of microbial activities to show that in the end the target goal of pollutant reduction to a safe and permissible level has been achieved. Enumeration and characterization of hydrocarbon degraders, use of micro titer plate-based most probable number technique, community level physiological profiling, phospholipid fatty acid analysis, 16S rRNA- and other nucleic acid-based molecular fingerprinting techniques, metagenomics, microarray analysis, respirometry and gas chromatography are some of the methods employed in bio-monitoring of hydrocarbon remediation as presented in this review

REVIEW OF THE CENTRAL AND SOUTH ATLANTIC SHELF AND DEEP-SEA BENTHOS: SCIENCE, POLICY, AND MANAGEMENT

The Central and South Atlantic represents a vast ocean area and is home to a diverse range of ecosystems and species. Nevertheless, and similar to the rest of the global south, the area is comparatively understudied yet exposed to increasing levels of multisectoral pressures. To counteract this, the level of scientific exploration in the Central and South Atlantic has increased in recent years and will likely continue to do so within the context of the United Nations (UN) Decade of Ocean Science for Sustainable Development. Here, we compile the literature to investigate the distribution of previous scientific exploration of offshore (30 m+) ecosystems in the Central and South Atlantic, both within and beyond national jurisdiction, allowing us to synthesise overall patterns of biodiversity. Furthermore, through the lens of sustainable management, we have reviewed the existing anthropogenic activities and associated management measures relevant to the region. Through this exercise, we have identified key knowledge gaps and undersampled regions that represent priority areas for future research and commented on how these may be best incorporated into, or enhanced through, future management measures such as those in discussion at the UN Biodiversity Beyond National Jurisdiction negotiations. This review represents a comprehensive summary for scientists and managers alike looking to understand the key topographical, biological, and legislative features of the Central and South Atlantic.This paper is an output of the UN Ocean Decade endorsed Challenger 150 Programme (#57). Challenger 150 is supported by the Deep Ocean Stewardship Initiative (DOSI) and the Scientific Committee on Oceanic Research’s (SCOR) working group 159 (NSF Grant OCE-1840868) for which KLH is co-chair. AEHB, KLH, KAM, SBu, and KS are supported by the UKRI funded One Ocean Hub NE/S008950/1. TA is supported by the BiodivRestore ERA-NET Cofund (GA N°101003777) with the EU and the following funding organisations: FCT, RFCT, AEI, DFG, and ANR. TA also acknowledges financial support to CESAM by FCT/MCTES (UIDP/50017/2 020+UIDB/50017/2020+ LA/P/0094/2020) through national funds. NB is supported by the John Ellerman Foundation. AB is supported by the German Research Foundation. DH, CO, AFB, LA, SBr, and KS received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 818123 (iAtlantic); this output reflects only the author’s view and the European Union cannot be held responsible for any use that may be made of the information contained therein. DH, AF, JT, and CW were additionally supported through the Cluster of Excellence “The Ocean Floor – Earth’s Uncharted Interface” (EXC-2077 – 390741603 by Deutsche Forschungsgemeinschaft). CO also extends thanks to the HWK – Institute for Advanced Study, and PM to Dr. Alberto Martín, retired professor of Universidad Simón Bolívar in Caracas, Venezuela for facilitating references used in the Venezuela section.Peer reviewe