The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Sulphur Abatement Globally in Maritime Shipping

In 2016, the International Maritime Organization (IMO) decided on global regulations to reduce sulphur emissions to air from maritime shipping starting 2020. The regulation implies that ships can continue to use residual fuels with a high sulphur content, such as heavy fuel oil (HFO), if they employ scrubbers to desulphurise the exhaust gases. Alternatively, they can use fuels with less than 0.5% sulphur, such as desulphurised HFO, distillates (diesel) or liquefied natural gas (LNG). The options of lighter fuels and desulphurisation entail costs, including higher energy consumption at refineries, and the present study identifies and compares compliance options as a function of ship type and operational patterns. The results indicate distillates as an attractive option for smaller vessels, while scrubbers will be an attractive option for larger vessels. For all vessels, apart from the largest fuel consumers, residual fuels desulphurised to less than 0.5 % sulphur are also a competing abatement option. Moreover, we analyse the interaction between global SOX reductions and CO2 (and fuel consumption), and the results indicate that the higher fuel cost for distillates will motivate shippers to lower speeds, which will offset the increased CO2 emissions at the refineries. Scrubbers, in contrast, will raise speeds and CO2 emissions.acceptedVersio

Sulphur Abatement Globally in Maritime Shipping

In 2016, the International Maritime Organization (IMO) decided on global regulations to reduce sulphur emissions to air from maritime shipping starting 2020. The regulation implies that ships can continue to use residual fuels with a high sulphur content, such as heavy fuel oil (HFO), if they employ scrubbers to desulphurise the exhaust gases. Alternatively, they can use fuels with less than 0.5% sulphur, such as desulphurised HFO, distillates (diesel) or liquefied natural gas (LNG). The options of lighter fuels and desulphurisation entail costs, including higher energy consumption at refineries, and the present study identifies and compares compliance options as a function of ship type and operational patterns. The results indicate distillates as an attractive option for smaller vessels, while scrubbers will be an attractive option for larger vessels. For all vessels, apart from the largest fuel consumers, residual fuels desulphurised to less than 0.5% sulphur are also a competing abatement option. Moreover, we analyse the interaction between global SOX reductions and CO2 (and fuel consumption), and the results indicate that the higher fuel cost for distillates will motivate shippers to lower speeds, which will offset the increased CO2 emissions at the refineries. Scrubbers, in contrast, will raise speeds and CO2 emissions

Using judgement bias to measure positive emotional states in dogs

Interest in the induction and measurement of positive affective states in non-human animals is increasing. Here, we used a test of cognitive (judgement) bias, based on the finding that individuals experiencing different affective states judge ambiguous stimuli differently, to measure whether a positive low arousal affective state (e.g. ‘satisfaction’/’contentment’) could be induced in domestic dogs as a result of their experiencing a food-based rewarding event. In this rewarding event, subjects (1yr old female Beagles) had to search for small amounts of food randomly placed within a maze arena. Using a balanced within-subjects design, the dogs (N=12) received a cognitive bias test either without experiencing the rewarding event (the ‘Neutral’ treatment), or directly after experiencing the rewarding event (the ‘Post-consumption’ treatment). In the test, dogs were trained that one visual cue (e.g. dark grey card) predicted a positive event (food in a bowl) while a different cue (e.g. light grey card) predicted a relatively ‘negative’ event (empty bowl). We hypothesised that dogs tested after experiencing the rewarding event, and in a presumed post-consummatory positive affective state, would be more likely to judge visually ambiguous stimuli (intermediate grey cards) positively, compared to dogs in the ‘Neutral’ treatment. In contrast, we found that they took significantly longer to approach an intermediate ambiguous stimulus, suggesting that they were less likely to anticipate food (a negative judgement) compared to dogs in the ‘Neutral’ treatment group. Various explanations for the observed results are discussed, in particular how reward acquisition and consumption may influence positive affective state induction in animals

Performance benefits and costs for children using cochlear implants and hearing aids [Abstract]

The value of cochlear implants as an established clinical option for profoundly hearing impaired adults and children has been supported by significant research results over a number of years which has clearly established the benefits available (U.S. National Institutes of Health Consensus Statement 1995). Benefit has traditionally been considered as the direct impact of the cochlear implant procedure on speech perception, or in the case of children, on the use of that auditory information to develop understandable speech and to acquire a knowledge of language. As a consequence of continuing research to improve hardware and speech processing strategies, mean scores on open-set tests of monosyllables or sentence materials for implanted adults using the cochlear implant alone without lipreading have continued to show an upwards trend. In response to the increased mean scores in quiet, perception tests in background noise are now being used as a more accurate direct measure of the potential benefits of cochlear implants to severely-to-profoundly hearing-impaired candidates. Consideration should also be given to indirect benefits, such as reduction in the stress of listening and lipreading, improved performance at work, enhanced opportunity to maintain speech, or in children to develop speech which is understandable to the general community, and the social effects of reducing the isolating effects of profound deafness. Measurement of indirect benefit can be combined with an analysis of the costs of the procedure, enabling evaluation of the implant procedure from a cost-utility standpoint, and a comparison of outcomes using other technologies such as hearing aids. This study will present data on direct and indirect benefits for hearing-impaired children using Nucleus cochlear implant systems, and compare this data with benefits shown for similarly hearing impaired children using hearing aids. The significance of these results to cost-effective delivery of services will be discussed.14-17 Jun

The ADAMTS1 protease gene is required for mammary tumor growth and metastasis

A disintegrin and metalloprotease with thrombospondin motifs protein 1 (ADAMTS1) is a protease commonly up-regulated in metastatic carcinoma. Its overexpression in cancer cells promotes experimental metastasis, but whether ADAMTS1 is essential for metastatic progression is unknown. To address this question, we investigated mammary cancer progression and spontaneous metastasis in the MMTV-PyMT mouse mammary tumor model in Adamts1 knockout mice. Adamts1(-/-)/PyMT mice displayed significantly reduced mammary tumor and lung metastatic tumor burden and increased survival, compared with their wild-type and heterozygous littermates. Histological examination revealed an increased proportion of tumors with ductal carcinoma in situ and a lower proportion of high-grade invasive tumors in Adamts1(-/-)/PyMT mice, compared with Adamts1(+/+)/PyMT mice. Increased apoptosis with unaltered proliferation and vascular density in the Adamts1(-/-)/PyMT tumors suggested that reduced cell survival accounts for the lower tumor burden in ADAMTS1-deficient mice. Furthermore, Adamts1(-/-) tumor stroma had significantly lesser amounts of proteolytically cleaved versican and increased numbers of CD45(+) leukocytes. Characterization of immune cell gene expression indicated that cytotoxic cell activation was increased in Adamts1(-/-) tumors, compared with Adamts1(+/+) tumors. This finding is supported by significantly elevated IL-12(+) cell numbers in Adamts1(-/-) tumors. Thus, in vivo ADAMTS1 may promote mammary tumor growth and progression to metastasis in the PyMT model and is a potential therapeutic target to prevent metastatic breast cancer.Carmela Ricciardelli, Kate M. Frewin, Izza de Arao Tan, Elizabeth D. Williams, Kenneth Opeskin, Melanie A. Pritchard, Wendy V. Ingman, and Darryl L. Russellhttp://www.elsevier.com/wps/find/journaldescription.cws_home/724906/description#descriptio