Interview study exploring how global health partnership principles are enacted and recommendations for practice.

BACKGROUND: Effective global health partnerships can strengthen and improve health and healthcare systems across the world; however, establishing and maintaining effective partnerships can be challenging. Principles of Partnerships have been developed to improve the quality and effectiveness of health partnerships. It is unclear how principles are enacted in practice, and current research has not always included the voices of low-income and middle-income country partners. This study aimed to explore how The Tropical Health and Education Trust's nine Principles of Partnership are enacted in practice, from the points of view of partners from low-income, middle-income and high-income countries, to help improve partnerships' quality and sustainability. METHODS: People who had been a part of previous and/or ongoing health partnerships were interviewed virtually. Participants were purposefully sampled and interviews were conducted using an appreciative inquiry approach. Audio recordings were transcribed and deductive framework analysis was conducted. RESULTS: 13 participants from 8 partnerships were interviewed. Six participants were based in the low-income or middle-income countries and seven in the UK. Key findings identified strategies that enacted 'successful' and 'effective' partnerships within the Principles of Partnerships. These included practical techniques such as hiring a project manager, managing expectations and openly sharing information about the team's expertise and aspirations. Other strategies included the importance of consulting behavioural science to ensure the partnerships consider longevity and sustainability of the partnership. DISCUSSION: Core principles to effective partnerships do not work in isolation of each other; they are intertwined and are complimentary to support equitable partnerships. Good communication and relationships built on trust which allow all partners to contribute equally throughout the project are core foundations for sustainable partnerships. Recommendations for established and future partnerships include embedding behavioural scientists/psychologists to support change to improve the quality and sustainability of health partnerships.

Effects of methamphetamine on probability discounting in rats using concurrent chains.

How stimulant drugs affect risky choice and the role of reinforcement magnitude has been an important question for research on impulsivity. This study investigated rats' responding on a rapid acquisition, concurrent chains, probability discounting task under methamphetamine administration. In each block of four sessions, probability of reinforcement delivery was unequal (0.5/1.0, 1.0/0.5) or equal, (1.0/1.0, 0.5/0.5) while amount of reinforcement was constant and unequal. This allowed for an estimate of probability discounting and the magnitude effect (where larger reinforcers are discounted at a greater rate) in each block. Baseline, acute and chronic methamphetamine administration, and re-establish baseline phases were completed. Rats showed sensitivity to probability and magnitude in baseline, as well as a magnitude effect whereby preference for the larger reinforcement was greater with 100% than 50% reinforcement probability. Acute methamphetamine dose-dependently reduced the probability effect. There were no effects of chronic administration and only probability discounting was maintained in the re-establish baseline phase. This was the first procedure to find a magnitude effect with rats in a probability discounting procedure and demonstrates that acute methamphetamine reduces both the probability and magnitude effects which increases propensity for risky choice.

Outbreak of P.3 (Theta) SARS-CoV-2 emerging variant of concern among food service workers in Louisiana

In May, 2021, during routine oil and gas industrial quarantine/premobilization procedures, four individuals who recently arrived to Louisiana from the Philippines tested positive for SARS-CoV-2. Subsequent genomic analysis showed that all were infected with a Variant of Interest (P.3-Theta). This increases the number of known P.3 infections in the United States to eleven and highlights the importance of genomic surveillance within industries that are prone to rapidly spread the infection.

Emergence of an early SARS-CoV-2 epidemic in the United States

The emergence of the early COVID-19 epidemic in the United States (U.S.) went largely undetected, due to a lack of adequate testing and mitigation efforts. The city of New Orleans, Louisiana experienced one of the earliest and fastest accelerating outbreaks, coinciding with the annual Mardi Gras festival, which went ahead without precautions. To gain insight into the emergence of SARS-CoV-2 in the U.S. and how large, crowded events may have accelerated early transmission, we sequenced SARS-CoV-2 genomes during the first wave of the COVID-19 epidemic in Louisiana. We show that SARS-CoV-2 in Louisiana initially had limited sequence diversity compared to other U.S. states, and that one successful introduction of SARS-CoV-2 led to almost all of the early SARS-CoV-2 transmission in Louisiana. By analyzing mobility and genomic data, we show that SARS-CoV-2 was already present in New Orleans before Mardi Gras and that the festival dramatically accelerated transmission, eventually leading to secondary localized COVID-19 epidemics throughout the Southern U.S.. Our study provides an understanding of how superspreading during large-scale events played a key role during the early outbreak in the U.S. and can greatly accelerate COVID-19 epidemics on a local and regional scale.

Intra-host site-specific polymorphisms of SARS-CoV-2 is consistent across multiple samples and methodologies

Despite the potential relevance to clinical outcome, intra-host dynamics of SARS-CoV-2 are unclear. Here, we quantify and characterize intra-host variation in SARS-CoV-2 raw sequence data uploaded to SRA as of 14 April 2020, and compare results between two sequencing methods (amplicon and RNA-Seq). Raw fastq files were quality filtered and trimmed using Trimmomatic, mapped to the WuhanHu1 reference genome using Bowtie2, and variants called with bcftools mpileup. To ensure sufficient coverage, we only included samples with 10X coverage for >90% of the genome (n=406 samples), and only variants with a depth >=10. Derived (i.e. non-reference) alleles were found at 408 sites. The number of polymorphic sites (i.e. sites with multiple alleles) within samples ranged from 0-13, with 72% of samples (295/406) having at least one polymorphic site. Correlation between number of polymorphic sites and coverage was very low for both sequencing methods (R2 < 0.1, p < 0.05). Polymorphisms were observed >1 sample at 66 sites (range: 2-38 samples). The minor allele frequency (MAF) at each shared polymorphic site was 0.03% - 48.5%. 33/66 sites occurred in ORF1a1b, and 37/66 changes were non-synonymous. At 10/66 sites, derived alleles were found in samples sequenced using both methods. Polymorphic amplicon samples were found at 10/10 positions, while polymorphic RNA-Seq samples were found at 7/10 positions. In conclusion, our results suggest that intra-host variation is prevalent among clinical samples. While mutations resulting from amplification and/or sequencing errors cannot be excluded, the observation of shared polymorphic sites with high MAF across multiple samples and sequencing methods is consistent with true underlying variation. Further investigation into intra-host evolutionary dynamics, particularly with longitudinal sampling, is critical for broader understanding of disease progression.

Further delineation of the clinical spectrum of de novo TRIM8 truncating mutations.

De novo mutations of the TRIM8 gene, which codes for a tripartite motif protein, have been identified using whole exome sequencing (WES) in two patients with epileptic encephalopathy (EE), but these reports were not sufficient to conclude that TRIM8 was a novel gene responsible for EE. Here we report four additional patients presenting with EE and de novo truncating mutations of TRIM8 detected by WES, and give further details of the patient previously reported by the Epi4K consortium. Epilepsy of variable severity was diagnosed in children aged 2 months to 3.5 years of age. All patients had developmental delay of variable severity with no or very limited language, often associated with behavioral anomalies and unspecific facial features or MRI brain abnormalities. The phenotypic variability observed in these patients appeared related to the severity of the epilepsy. One patient presented pharmacoresistant EE with regression, recurrent infections and nephrotic syndrome, compatible with the brain and kidney expression of TRIM8. Interestingly, all mutations were located at the highly conserved C-terminus section of TRIM8. This collaborative study confirms that TRIM8 is a novel gene responsible for EE, possibly associated with nephrotic syndrome. This report brings new evidence on the pathogenicity of TRIM8 mutations and highlights the value of data-sharing to delineate the phenotypic characteristics and biological basis of extremely rare disorders.