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Table 1 Characteristics of patients undergoing two treatment strategies for coronary heart disease Treatment strategy p Value CABG Angioplasty Number 270 487 Mean age (years) 65 62 Men 217 (80%) 352 (72%) Medication Antiplatelet (aspirin) 236 (87%) 482 (99%) <0.05 Lipid lowering (statin) 235 (87%) 447 (92%) NS BP lowering (ACE inhibitor) 64 (24%) 286 (59%) <0.001 Angiotensin II receptor blocker 5 (2%) 34 (7%) NS β Blocker 99 (37%) 379 (78%) <0.001 Calcium channel blocker 30 (11%) 49 (34%) NS Thiazide diuretic 1 (<1%) 33 (7%) NS Combinations Antiplatelet, statin at least 219 (81%) 447 (92%) <0.05 Antiplatelet, statin, [= or >, slanted]1 BP lowering 131 (49%) 433 (90%) <0.001 Antiplatelet, statin, [= or >, slanted]2 BP lowering 26 (10%) 321 (66%) <0.001 Antiplatelet, statin, [= or >, slanted]3 BP lowering 1 (<1) 65 (13) <0.001 ACE, angiotensin converting enzyme; BP, blood pressure; CABG, coronary artery bypass surgery; NS, not significant.

BackgroundThe optimal duration of clopidogrel treatment, particularly following drug-eluting stent (DES) implantation, remains contentious. Previous studies have observed a clustering of adverse events following clopidogrel cessation 1 year after DES, the aetiology of which is poorly understood.ObjectiveTo investigate, in the prospective CESSATION study, the effect of clopidogrel withdrawal at 1 year after DES implantation on (i) arachidonic acid (AA)- and adenosine diphosphate (ADP)-induced platelet aggregation, and (ii) biomarkers of vascular inflammation, including soluble CD40 ligand (sCD40L), high-sensitivity C-reactive protein (hsCRP) and interleukin 6 (IL-6).Methods and resultsThe prospective CESSATION study was undertaken in 33 patients receiving aspirin and due to discontinue clopidogrel 1 year after DES. Platetet reactivity was measured using short thromboelastography, and compliance with aspirin determined from serum thromboxane B2 (TXB2) levels. Venesection was performed at 4 weeks and 24 h before, and at 24 h, 48 h, 1, 2 and 4 weeks after, clopidogrel cessation. Following clopidogrel withdrawal, there was (i) a predictable increase in ADP-induced platelet aggregation (ii) an unexpected significant increase in AA-induced platelet aggregation (iii) a decline in IL-6 and hsCRP at 1 week and 4 weeks respectively; and (iv) a non-significant increase in sCD40L at 4 weeks TXB2 levels were consistently suppressed, indicating complete inhibition of cyclo-oxygenase-1 by aspirin.ConclusionAn aspirin-independent, time-dependent increase in AA-induced platelet activation following clopidogrel withdrawal in patients with a DES has been described. New insights into a potential mechanism for the observed clustering of adverse events that occur early after clopidogrel cessation have been provided. These findings raise the question as to whether AA-induced clotting is an appropriate test of aspirin sensitivity.

IntroductionA clustering of adverse events, in particular stent thrombosis (ST) has been observed following clopidogrel cessation 1-year after drug-eluting stenting (DES), the aetiology of which is poorly understood. We investigated the effect of withdrawing clopidogrel in DES patients using a simple, rapid, reproducible near-patient platelet function test known as short Thrombelastography (s-TEG) that has been developed and validated by this group.Methods33 patients on aspirin and due to stop clopidogrel at 1 year following DES were investigated. Venesection was performed at (i) 4 weeks and 24 h pre clopidogrel cessation (ii) 24 h, 48 h, 1, 2 and 4 weeks post clopidogrel cessation. At all time-points, platelet reactivity was determined using s-TEG and thromboxane (TX) B2, IL-6, CD40 ligand and high sensitivity CRP were measured.ResultsClopidogrel cessation produced (i) a predictable increase in ADP-induced platelet aggregation, and (ii) an unexpected and significant rise in AA-induced platelet aggregation. TXB2 was consistently suppressed confirming inhibition of COX by aspirin.Abstract 20 Figure 1ConclusionWe have described for the first time an aspirin-independent increase in AA-induced clotting following clopidogrel withdrawal in DES patients. As well as potentially helping to explain the observed clustering of ST events early after clopidogrel withdrawal, these findings raise the question as to whether AA-induced clotting is an appropriate test of aspirin sensitivity. Our results also confirm s-TEG as a plausible candidate for near-patient platelet function testing in this field.

The inner \\(\\sim\\)200 pc region of the Galaxy contains a 4 million M\\(_{\\odot}\\) supermassive black hole (SMBH), significant quantities of molecular gas, and star formation and cosmic ray energy densities that are roughly two orders of magnitude higher than the corresponding levels in the Galactic disk. At a distance of only 8.2 kpc, the region presents astronomers with a unique opportunity to study a diverse range of energetic astrophysical phenomena, from stellar objects in extreme environments, to the SMBH and star-formation driven feedback processes that are known to influence the evolution of galaxies as a whole. We present a new survey of the Galactic center conducted with the South African MeerKAT radio telescope. Radio imaging offers a view that is unaffected by the large quantities of dust that obscure the region at other wavelengths, and a scene of striking complexity is revealed. We produce total intensity and spectral index mosaics of the region from 20 pointings (144 hours on-target in total), covering 6.5 square degrees with an angular resolution of 4\\(\"\\),at a central frequency of 1.28 GHz. Many new features are revealed for the first time due to a combination of MeerKAT's high sensitivity, exceptional \\(u,v\\)-plane coverage, and geographical vantage point. We highlight some initial survey results, including new supernova remnant candidates, many new non-thermal filament complexes, and enhanced views of the Radio Arc Bubble, Sgr A and Sgr B regions. This project is a SARAO public legacy survey, and the image products are made available with this article.

We present the SARAO MeerKAT Galactic Plane Survey (SMGPS), a 1.3 GHz continuum survey of almost half of the Galactic Plane (251\\deg \\(\\le l \\le\\) 358\\deg and 2\\deg \\(\\le l \\le\\) 61\\deg at \\(|b| \\le 1.5\\deg \\)). SMGPS is the largest, most sensitive and highest angular resolution 1 GHz survey of the Plane yet carried out, with an angular resolution of 8\" and a broadband RMS sensitivity of \\(\\sim\\)10--20 \\(\\mu\\) Jy/beam. Here we describe the first publicly available data release from SMGPS which comprises data cubes of frequency-resolved images over 908--1656 MHz, power law fits to the images, and broadband zeroth moment integrated intensity images. A thorough assessment of the data quality and guidance for future usage of the data products are given. Finally, we discuss the tremendous potential of SMGPS by showcasing highlights of the Galactic and extragalactic science that it permits. These highlights include the discovery of a new population of non-thermal radio filaments; identification of new candidate supernova remnants, pulsar wind nebulae and planetary nebulae; improved radio/mid-IR classification of rare Luminous Blue Variables and discovery of associated extended radio nebulae; new radio stars identified by Bayesian cross-matching techniques; the realisation that many of the largest radio-quiet WISE HII region candidates are not true HII regions; and a large sample of previously undiscovered background HI galaxies in the Zone of Avoidance.

Background Insecticide resistance is a serious threat to the continued effectiveness of insecticide-based malaria vector control measures, such as long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS). This paper describes trends and dynamics of insecticide resistance and its underlying mechanisms from annual resistance monitoring surveys on Anopheles gambiae sensu lato (s.l.) populations conducted across mainland Tanzania from 2004 to 2020. Methods The World Health Organization (WHO) standard protocols were used to assess susceptibility of the wild female An. gambiae s.l. mosquitoes to insecticides, with mosquitoes exposed to diagnostic concentrations of permethrin, deltamethrin, lambdacyhalothrin, bendiocarb, and pirimiphos-methyl. WHO test papers at 5× and 10× the diagnostic concentrations were used to assess the intensity of resistance to pyrethroids; synergist tests using piperonyl butoxide (PBO) were carried out in sites where mosquitoes were found to be resistant to pyrethroids. To estimate insecticide resistance trends from 2004 to 2020, percentage mortalities from each site and time point were aggregated and regression analysis of mortality versus the Julian dates of bioassays was performed. Results Percentage of sites with pyrethroid resistance increased from 0% in 2004 to more than 80% in the 2020, suggesting resistance has been spreading geographically. Results indicate a strong negative association (p = 0.0001) between pyrethroids susceptibility status and survey year. The regression model shows that by 2020 over 40% of An. gambiae mosquitoes survived exposure to pyrethroids at their respective diagnostic doses. A decreasing trend of An. gambiae susceptibility to bendiocarb was observed over time, but this was not statistically significant (p = 0.8413). Anopheles gambiae exhibited high level of susceptibility to the pirimiphos-methyl in sampled sites. Conclusions Anopheles gambiae Tanzania’s major malaria vector, is now resistant to pyrethroids across the country with resistance increasing in prevalence and intensity and has been spreading geographically. This calls for urgent action for efficient malaria vector control tools to sustain the gains obtained in malaria control. Strengthening insecticide resistance monitoring is important for its management through evidence generation for effective malaria vector control decision.

Background In 2015, Tanzania National Malaria Control Programme (NMCP) established a longitudinal malaria vector entomological surveillance (MVES). The MVES is aimed at a periodical assessment of malaria vector composition and abundance, feeding and resting behaviours, and Plasmodium falciparum infection in different malaria epidemiological strata to guide the NMCP on the deployment of appropriate malaria vector interventions. This work details the dynamics of malaria vector composition and transmission in different malaria epidemiological strata. Methods The MVES was conducted from 32 sentinel district councils across the country. Mosquitoes were collected by the trained community members and supervised by the NMCP and research institutions. Three consecutive night catches (indoor collection with CDC light trap and indoor/outdoor collection using bucket traps) were conducted monthly in three different households selected randomly from two to three wards within each district council. Collected mosquitoes were sorted and morphologically identified in the field. Thereafter, the samples were sent to the laboratory for molecular characterization using qPCR for species identification and detection of P. falciparum infections (sporozoites). ELISA technique was deployed for blood meal analysis from samples of blood-fed mosquitoes to determine the blood meal indices (BMI). Results A total of 63,226 mosquitoes were collected in 32 district councils from January 2017 to December 2021. Out of which, 39,279 (62%), 20,983 (33%) and 2964 (5%) were morphologically identified as Anopheles gambiae sensu lato (s.l.), Anopheles funestus s.l., and as other Anopheles species, respectively. Out of 28,795 laboratory amplified mosquitoes, 13,645 (47%) were confirmed to be Anopheles arabiensis, 9904 (34%) as An. funestus sensu stricto (s.s.), and 5193 (19%) as An. gambiae s.s. The combined average entomological inoculation rates (EIR) were 0.46 (95% CI 0.028–0.928) for An. gambiae s.s., 0.836 (95% CI 0.138–1.559) for An. arabiensis , and 0.58 (95% CI 0.165–0.971) for An. funestus s.s. with variations across different malaria transmission strata. Anopheles funestus s.s. and An. arabiensis were predominant in the Lake and South-Eastern zones, respectively, mostly in high malaria transmission areas. Monthly mosquito densities displayed seasonal patterns, with two peaks following the rainy seasons, varying slightly across species and district councils. Conclusion Anopheles arabiensis remains the predominant vector species followed by An. funestus s.s. in the country. Therefore, strengthening integrated vector management including larval source management is recommended to address outdoor transmission by An. arabiensis to interrupt transmission particularly where EIR is greater than the required elimination threshold of less than one (< 1) to substantially reduce the prevalence of malaria infection.

Background Improving child survival for HIV-infected children remains an important health agenda. We present progress regarding care and treatment services to HIV infected children in Tanzania. Methods The National AIDS Control Programme Care and Treatment (CTC 2) database was used to obtain information of all children aged 0-14yearsenrolled in the HIV Care and Treatment Program between January 2011 and December 2014. We assessed eligibility for ART, time from enrolment to ART initiation, nutritional status, and mortality using Kaplan-Meier methods. Results A total of 29,531 (14,304 boys and 15,227 girls) ART-naive children aged 0–14 years were enrolled during the period, approximately 6700 to 8000 children per year. The male to female ratio was 48:50. At enrolment 72% were eligible for ART, 2–3% of children were positive for TB, and 2–4% were severely malnourished. Between 2011 and 2014, 2368 (8%) died, 9243 (31%) were Lost to Follow-up and 17,920 (61%) were on care or ART. The probability of death was 31% (95% CI 26–35), 43% (40–47), 52% (49–55) and 61% (58–64) by 1,2, 5 and 10 years of age, respectively. The hazard of death was greatest at very young ages (<2 years old), and decreased sharply by 4 years old. Children who were on ART had around 10–15% higher survival over time. Conclusions Significant progress has been made regarding provision of paediatric HIV care and treatment in Tanzania. On average 7000 children are enrolled annually, and that approximately two thirds of children diagnosed under the age of 2 years were initiated on ART within a month. Provision of ART as soon as the child is diagnosed is the biggest factor in improving survival. However we noted that i) most children had advanced disease at the time of enrolment ii) approximately two-thirds of children were missing a baseline CD4 measurement and only 35% of children had either a CD4 count or percentage recorded, indicating limited access to CD4 testing services, and iii) 31% were lost to follow-up (LTFU). These challenges need to be addressed to improve early detection, enrolment and retention of HIV-infected children into care and improve documentation of services offered.