86 research outputs found
Complete Genome Sequences of Virus Strains Isolated from Bottle A of the South African Live Attenuated Bluetongue Virus Vaccine
This is a report of the complete genome sequences of plaque-selected isolates of five virus strains included in bottle A of the South African Onderstepoort Biological Products commercial live attenuated bluetongue virus vaccine
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Mortality during tuberculosis treatment in South Africa using an 8-year analysis of the national tuberculosis treatment register
n 2011, the South African HIV treatment eligibility criteria were expanded to allow all tuberculosis (TB) patients lifelong ART. The impact of this change on TB mortality in South Africa is not known. We evaluated mortality in all adults (≥ 15 years old) treated for drug-susceptible TB in South Africa between 2009 and 2016. Using a Cox regression model, we quantified risk factors for mortality during TB treatment and present standardised mortality ratios (SMR) stratified by year, age, sex, and HIV status. During the study period, 8.6% (219,618/2,551,058) of adults on TB treatment died. Older age, male sex, previous TB treatment and HIV infection (with or without the use of ART) were associated with increased hazard of mortality. There was a 19% reduction in hazard of mortality amongst all TB patients between 2009 and 2016 (adjusted hazard ratio: 0.81 95%CI 0.80–0.83). The highest SMR was in 15–24-year-old women, more than double that of men (42.3 in 2016). Between 2009 and 2016, the SMR for HIV-positive TB patients increased, from 9.0 to 19.6 in women, and 7.0 to 10.6 in men. In South Africa, case fatality during TB treatment is decreasing and further interventions to address specific risk factors for TB mortality are required. Young women (15–24-year olds) with TB experience a disproportionate burden of mortality and interventions targeting this age-group are needed
Clinical Validation of a Commercial LAMP Test for Ruling out Malaria in Returning Travelers: A Prospective Diagnostic Trial.
The mainstay of malaria diagnosis relies on rapid diagnostic tests (RDTs) and microscopy, both of which lack analytical sensitivity. This leads to repeat testing to rule out malaria. A prospective diagnostic trial of the Meridian illumigene Malaria assay (loop-mediated isothermal amplification [LAMP]) was conducted comparing it with reference microscopy and RDTs (BinaxNOW Malaria) in returning travelers between June 2017 and January 2018. Returning travelers with signs and symptoms of malaria were enrolled in the study. RDTs, microscopy, and LAMP assays were performed simultaneously. A total of 298 patients (50.7% male; mean age, 32.5 years) were enrolled, most visiting friends and relatives (43.3%), presenting with fever (88.9%), not taking prophylaxis (82.9%), and treated as outpatients (84.1%). In the prospective arm (n = 348), LAMP had a sensitivity of 98.1% (95% confidence interval [CI], 90.0%-100%) and a specificity of 97.6% (95% CI, 95.2%-99.1%) vs microscopy. After discrepant resolution with real-time polymerase chain reaction, LAMP had a sensitivity of 100% (95% CI, 93.7%-100%) and a specificity of 100% (95% CI, 98.7%-100%) vs microscopy. After discrepant resolution, RDTs had a sensitivity of 83.3% (95% CI, 58.6%-96.4%) and a specificity of 96.2% (95% CI, 93.2%-98.1%) vs microscopy. When including retrospective specimens (n = 377), LAMP had a sensitivity of 98.8% (95% CI, 93.2%-100%) and a specificity of 97.6% (95% CI, 95.2%-99.1%) vs microscopy, and after discrepant resolution of this set, LAMP had a sensitivity of 100% (95% CI, 95.8%-100%) and a specificity of 100% (95% CI, 98.7%-100%). A cost-benefit analysis of reagents and labor suggests savings of up to USD$13 per specimen using a novel algorithm with LAMP screening
Understanding and acting on the developmental origins of health and disease in Africa would improve health across generations.
Data from many high- and low- or middle-income countries have linked exposures during key developmental periods (in particular pregnancy and infancy) to later health and disease. Africa faces substantial challenges with persisting infectious disease and now burgeoning non-communicable disease.This paper opens the debate to the value of strengthening the developmental origins of health and disease (DOHaD) research focus in Africa to tackle critical public health challenges across the life-course. We argue that the application of DOHaD science in Africa to advance life-course prevention programmes can aid the achievement of the Sustainable Development Goals, and assist in improving health across generations. To increase DOHaD research and its application in Africa, we need to mobilise multisectoral partners, utilise existing data and expertise on the continent, and foster a new generation of young African scientists engrossed in DOHaD
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The antimalarial efficacy and mechanism of resistance of the novel chemotype DDD01034957.
New antimalarial therapeutics are needed to ensure that malaria cases continue to be driven down, as both emerging parasite resistance to frontline chemotherapies and mosquito resistance to current insecticides threaten control programmes. Plasmodium, the apicomplexan parasite responsible for malaria, causes disease pathology through repeated cycles of invasion and replication within host erythrocytes (the asexual cycle). Antimalarial drugs primarily target this cycle, seeking to reduce parasite burden within the host as fast as possible and to supress recrudescence for as long as possible. Intense phenotypic drug screening efforts have identified a number of promising new antimalarial molecules. Particularly important is the identification of compounds with new modes of action within the parasite to combat existing drug resistance and suitable for formulation of efficacious combination therapies. Here we detail the antimalarial properties of DDD01034957-a novel antimalarial molecule which is fast-acting and potent against drug resistant strains in vitro, shows activity in vivo, and possesses a resistance mechanism linked to the membrane transporter PfABCI3. These data support further medicinal chemistry lead-optimization of DDD01034957 as a novel antimalarial chemical class and provide new insights to further reduce in vivo metabolic clearance
The antimalarial efficacy and mechanism of resistance of the novel chemotype DDD01034957.
New antimalarial therapeutics are needed to ensure that malaria cases continue to be driven down, as both emerging parasite resistance to frontline chemotherapies and mosquito resistance to current insecticides threaten control programmes. Plasmodium, the apicomplexan parasite responsible for malaria, causes disease pathology through repeated cycles of invasion and replication within host erythrocytes (the asexual cycle). Antimalarial drugs primarily target this cycle, seeking to reduce parasite burden within the host as fast as possible and to supress recrudescence for as long as possible. Intense phenotypic drug screening efforts have identified a number of promising new antimalarial molecules. Particularly important is the identification of compounds with new modes of action within the parasite to combat existing drug resistance and suitable for formulation of efficacious combination therapies. Here we detail the antimalarial properties of DDD01034957-a novel antimalarial molecule which is fast-acting and potent against drug resistant strains in vitro, shows activity in vivo, and possesses a resistance mechanism linked to the membrane transporter PfABCI3. These data support further medicinal chemistry lead-optimization of DDD01034957 as a novel antimalarial chemical class and provide new insights to further reduce in vivo metabolic clearance
Google USM: Scaling Automatic Speech Recognition Beyond 100 Languages
We introduce the Universal Speech Model (USM), a single large model that
performs automatic speech recognition (ASR) across 100+ languages. This is
achieved by pre-training the encoder of the model on a large unlabeled
multilingual dataset of 12 million (M) hours spanning over 300 languages, and
fine-tuning on a smaller labeled dataset. We use multilingual pre-training with
random-projection quantization and speech-text modality matching to achieve
state-of-the-art performance on downstream multilingual ASR and speech-to-text
translation tasks. We also demonstrate that despite using a labeled training
set 1/7-th the size of that used for the Whisper model, our model exhibits
comparable or better performance on both in-domain and out-of-domain speech
recognition tasks across many languages.Comment: 20 pages, 7 figures, 8 table
Development of three triplex real-time reverse transcription PCR assays for the qualitative molecular typing of the nine serotypes of African horse sickness virus
Blood samples collected as part of routine diagnostic investigations from South African horses with clinical signs suggestive of African horse sickness (AHS) were subjected to analysis with an AHS virus (AHSV) group specific reverse transcription quantitative polymerase chain reaction (AHSV RT-qPCR) assay and virus isolation (VI) with subsequent serotyping by plaque inhibition (PI) assays using AHSV serotype-specific antisera. Blood samples that tested positive by AHSV RT-qPCR were then selected for analysis using AHSV type specific RT-qPCR (AHSV TS RT-qPCR) assays. The TS RT-qPCR assays were evaluated using both historic stocks of the South African reference strains of each of the 9 AHSV serotypes, as well as recently derived stocks of these same viruses. Of the 503 horse blood samples tested, 156 were positive by both AHSV RT-qPCR and VI assays, whereas 135 samples that were VI negative were positive by AHSV RT-qPCR assay. The virus isolates made from the various blood samples included all 9 AHSV serotypes, and there was 100% agreement between the results of conventional serotyping of individual virus isolates by PI assay and AHSV TS RT-qPCR typing results. Results of the current study confirm that the AHSV TS RT-qPCR assays for the identification of individual AHSV serotypes are applicable and practicable and therefore are potentially highly useful and appropriate for virus typing in AHS outbreak situations in endemic or sporadic incursion areas, which can be crucial in determining appropriate and timely vaccination and control strategies.Racing South Africa (Pty) Ltd, the Mary Slack and Daughters Foundation and Thoroughbred Racing Trust of South Africa.http://www.elsevier.com/locate/jviromet2016-10-31hb2016Equine Research CentreVeterinary Tropical Disease
Science opportunities with solar sailing smallsats
Recently, we witnessed how the synergy of small satellite technology and
solar sailing propulsion enables new missions. Together, small satellites with
lightweight instruments and solar sails offer affordable access to deep regions
of the solar system, also making it possible to realize hard-to-reach
trajectories that are not constrained to the ecliptic plane. Combining these
two technologies can drastically reduce travel times within the solar system,
while delivering robust science. With solar sailing propulsion capable of
reaching the velocities of ~5-10 AU/yr, missions using a rideshare launch may
reach the Jovian system in two years, Saturn in three. The same technologies
could allow reaching solar polar orbits in less than two years. Fast,
cost-effective, and maneuverable sailcraft that may travel outside the ecliptic
plane open new opportunities for affordable solar system exploration, with
great promise for heliophysics, planetary science, and astrophysics. Such
missions could be modularized to reach different destinations with different
sets of instruments. Benefiting from this progress, we present the "Sundiver"
concept, offering novel possibilities for the science community. We discuss
some of the key technologies, the current design of the Sundiver sailcraft
vehicle and innovative instruments, along with unique science opportunities
that these technologies enable, especially as this exploration paradigm
evolves. We formulate policy recommendations to allow national space agencies,
industry, and other stakeholders to establish a strong scientific,
programmatic, and commercial focus, enrich and deepen the space enterprise and
broaden its advocacy base by including the Sundiver paradigm as a part of
broader space exploration efforts.Comment: 34 pages, 12 figures, 2 table
AudioPaLM: A Large Language Model That Can Speak and Listen
We introduce AudioPaLM, a large language model for speech understanding and
generation. AudioPaLM fuses text-based and speech-based language models, PaLM-2
[Anil et al., 2023] and AudioLM [Borsos et al., 2022], into a unified
multimodal architecture that can process and generate text and speech with
applications including speech recognition and speech-to-speech translation.
AudioPaLM inherits the capability to preserve paralinguistic information such
as speaker identity and intonation from AudioLM and the linguistic knowledge
present only in text large language models such as PaLM-2. We demonstrate that
initializing AudioPaLM with the weights of a text-only large language model
improves speech processing, successfully leveraging the larger quantity of text
training data used in pretraining to assist with the speech tasks. The
resulting model significantly outperforms existing systems for speech
translation tasks and has the ability to perform zero-shot speech-to-text
translation for many languages for which input/target language combinations
were not seen in training. AudioPaLM also demonstrates features of audio
language models, such as transferring a voice across languages based on a short
spoken prompt. We release examples of our method at
https://google-research.github.io/seanet/audiopalm/examplesComment: Technical repor
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