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Multiple poly- and perfluoroalkyl substances (PFASs) are present in aqueous film-forming foams (AFFF) used for firefighting activities. Currently, no single analytical technique provides a complete accounting of total PFASs or total organofluorine content in AFFF-contaminated samples. To provide insight into the performance of existing methods, we compared ten previously described PFAS measurement techniques. In AFFF-amended tap water, US EPA Methods 533 and 1633, adsorbable organic fluorine with particle induced gamma emission spectroscopy (AOF-PIGE) and fluorine-19 nuclear magnetic resonance (19F NMR) provided similar estimates of total fluorine. The total oxidizable precursor (TOP) assay, suspect screening, and adsorbable organic fluorine with combustion ion chromatography (AOF-CIC) yielded estimates of total organic fluorine that were about two to three times higher than the other techniques. Proximate to AFFF sources, suspect screening and modified EPA Method 1633 yielded higher results, while the TOP assay results were between the other two sets of analyses. Further from sources, suspect screening, modified EPA Method 1633, and the TOP assay yielded similar results that were 4-fold higher than results from targeted quantification methods, such as EPA Method 1633. These results are consistent with expectations about PFAS behavior and inform the selection of analytical techniques used for PFAS contamination characterization efforts.

IntroductionThe study has investigated the lived experience of flautists, focusing on their experiences and perceptions of performance-related physical discomfort, injury and related mental health challenges that they might have encountered in practice and performance. The aims of the research have been to provide flautists with an opportunity to reflect on any physical or psychological performance issues in their own words, and to understand the subjective meaning of these experiences.MethodsA basic qualitative approach was used for gathering data. All the fieldwork was undertaken during or immediately after the Covid-19 pandemic. Consequently, the participating flautists were deliberately selected using professional networks on the basis of their answers to a pre-interview initial questionnaire related to the characteristics of their personal backgrounds and their experiences, as well as being able to participate remotely. There have been two data collection phases. Phase 1 was a specially designed pre-interview questionnaire drawing on themes from appropriate literature. Phase 2 built on the pre-interview questionnaire responses and was designed as semi-structured interviews, undertaken on Zoom, and included a ‘River of Flute-playing Experience’ activity during the interview. The ‘River of Experience’ method is an autobiographical research tool in which participants were asked to annotate key biographical experiences and challenges at various points along their drawing of a meandering river. The combined data analyses drew on thematic analysis.ResultsThe eight participants reported a personal history of performance-related health and wellbeing challenges that they had faced at some point in their lives. The findings reveal that flautists encounter health-related challenges associated with their practice and performances, and the data suggest that they each require an understanding of likely performance-related health challenges and supportive resources to assist them in managing these challenges.DiscussionThe participants’ diverse experiences highlight the importance of managing health and the value of supportive social connections. They cope with health challenges by integrating passion, resilience, and adaptability into their lives, finding ways to grow and continue to thrive in their flute-playing journey. The study underscores the need for comprehensive health education and support resources for flautists, emphasising the significance of resilience and adaptability in fostering health, wellbeing, and success.

Over the last two decades, there have been numerous initiatives to improve undergraduate student outcomes in STEM. One model for scalable reform is the inclusive Research Education Community (iREC). In an iREC, STEM faculty from colleges and universities across the nation are supported to adopt and sustainably implement course-based research – a form of science pedagogy that enhances student learning and persistence in science. In this study, we used pathway modeling to develop a qualitative description that explicates the HHMI Science Education Alliance (SEA) iREC as a model for facilitating the successful adoption and continued advancement of new curricular content and pedagogy. In particular, outcomes that faculty realize through their participation in the SEA iREC were identified, organized by time, and functionally linked. The resulting pathway model was then revised and refined based on several rounds of feedback from over 100 faculty members in the SEA iREC who participated in the study. Our results show that in an iREC, STEM faculty organized as a long-standing community of practice leverage one another, outside expertise, and data to adopt, implement, and iteratively advance their pedagogy. The opportunity to collaborate in this manner and, additionally, to be recognized for pedagogical contributions sustainably engages STEM faculty in the advancement of their pedagogy. Here, we present a detailed pathway model of SEA that, together with underpinning features of an iREC identified in this study, offers a framework to facilitate transformations in undergraduate science education.

The Statistics Expert Group was convened at the request of the Infected Blood Inquiry to provide estimates of the number of infections and deaths from blood-borne infections including hepatitis B virus, human immunodeficiency virus, hepatitis C virus (HCV) and variant Creutzfeldt Jakob disease, as a direct result of contaminated blood and blood products administered in the United Kingdom of Great Britain and Northern Ireland (UK). In the absence of databases of HCV infections and related deaths for all nations of the UK, a statistical model was required to estimate the number of infections and subsequent deaths from HCV acquired from blood transfusions from January 1970 to August 1991. We present this statistical model in detail alongside the results of its application to each of the four nations in the UK. We estimated that 26 800 people (95% uncertainty interval 21 300–38 800) throughout the UK were chronically infected with HCV because of contaminated blood transfusions between January 1970 and August 1991. The number of deaths up to the end of 2019 that occurred as a result of this chronic infection is estimated to be 1820 (95% uncertainty interval 650–3320).

In the past two decades, students have been more willing to disclose their disability status when entering higher education (HE) in the United Kingdom (UK). Concurrently, higher education institutions (HEIs) have adopted disability policies and service teams for enhancing equality, diversity, and inclusion in the UK. The purpose of this integrative review is to understand the basis of these trends. The article suggests that there have been three major key paradigm shifts that underpin this cultural change. (1) There was a paradigm shift in terms of changing the dominant models for conceptualising disability from a medical model of disability to a social model of disability and to an affirmative model of disability, together with a debate and policy development demonstrating a concern for greater social inclusion and exclusion; (2) with a massive increase in students entering HE and the rising importance of league tables and ranking systems, universities experienced a paradigm shift from teacher-centred learning (TCL) to inclusive student-centred learning and teaching (SCLT); and (3) the increase in autism disclosure in HE signifies a shift in a conceptualisation of autism from a disorder to a disability and an example of neurodiversity.

Abstract Variability in case severity and in the range of symptoms experienced has been apparent from the earliest months of the COVID-19 pandemic. From a clinical perspective, symptom variability might indicate various routes/mechanisms by which infection leads to disease, with different routes requiring potentially different treatment approaches. For public health and control of transmission, symptoms in community cases were the prompt upon which action such as PCR testing and isolation was taken. However, interpreting symptoms presents challenges, for instance, in balancing the sensitivity and specificity of individual symptoms with the need to maximise case finding, whilst managing demand for limited resources such as testing. For both clinical and transmission control reasons, we require an approach that allows for the possibility of distinct symptom phenotypes, rather than assuming variability along a single dimension. Here we address this problem by bringing together four large and diverse datasets deriving from routine testing, a population-representative household survey and participatory smartphone surveillance in the United Kingdom. Through the use of cutting-edge unsupervised classification techniques from statistics and machine learning, we characterise symptom phenotypes among symptomatic SARS-CoV-2 PCR-positive community cases. We first analyse each dataset in isolation and across age bands, before using methods that allow us to compare multiple datasets. While we observe separation due to the total number of symptoms experienced by cases, we also see a separation of symptoms into gastrointestinal, respiratory and other types, and different symptom co-occurrence patterns at the extremes of age. In this way, we are able to demonstrate the deep structure of symptoms of COVID-19 without usual biases due to study design. This is expected to have implications for the identification and management of community SARS-CoV-2 cases and could be further applied to symptom-based management of other diseases and syndromes.

The last thirty years have seen a meteoric rise in the number of sequenced bacteriophage genomes, spurred on by both the rise and success of groups working to isolate and characterize phages, and the rapid and significant technological improvements and reduced costs associated with sequencing their genomes. Over the course of these decades, the tools used to glean evolutionary insights from these sequences have grown more complex and sophisticated, and we describe here the suite of computational and bioinformatic tools used extensively by the integrated research–education communities such as SEA-PHAGES and PHIRE, which are jointly responsible for 25% of all complete phage genomes in the RefSeq database. These tools are used to integrate and analyze phage genome data from different sources, for identification and precise extraction of prophages from bacterial genomes, computing “phamilies” of related genes, and displaying the complex nucleotide and amino acid level mosaicism of these genomes. While over 50,000 SEA-PHAGES students have primarily benefitted from these tools, they are freely available for the phage community at large.

BackgroundAs of 2021, the National Kala-azar Elimination Programme (NKAEP) in India has achieved visceral leishmaniasis (VL) elimination (Methodology/principal findingsWe employed spatiotemporal models incorporating environment, climatic and demographic factors as covariates to describe monthly VL cases for 8-years (2013-2020) in 491 and 27 endemic and non-endemic blocks of Bihar and Jharkhand states. We fitted 37 models of spatial, temporal, and spatiotemporal interaction random effects with covariates to monthly VL cases for 6-years (2013-2018, training data) using Bayesian inference via Integrated Nested Laplace Approximation (INLA) approach. The best-fitting model was selected based on deviance information criterion (DIC) and Watanabe-Akaike Information Criterion (WAIC) and was validated with monthly cases for 2019-2020 (test data). The model could describe observed spatial and temporal patterns of VL incidence in the two states having widely differing incidence trajectories, with >93% and 99% coverage probability (proportion of observations falling inside 95% Bayesian credible interval for the predicted number of VL cases per month) during the training and testing periods. PIT (probability integral transform) histograms confirmed consistency between prediction and observation for the test period. Forecasting for 2021-2023 showed that the annual VL incidence is likely to exceed elimination threshold in 16-18 blocks in 4 districts of Jharkhand and 33-38 blocks in 10 districts of Bihar. The risk of VL in non-endemic neighbouring blocks of both Bihar and Jharkhand are less than 0.5 during the training and test periods, and for 2021-2023, the probability that the risk greater than 1 is negligible (PConclusions/significanceThe spatiotemporal model incorporating environmental, bioclimatic, and demographic factors demonstrated that the KAMIS database of the national programmme can be used for block level predictions of long-term spatial and temporal trends in VL incidence and risk of outbreak / resurgence in endemic and non-endemic settings. The database integrated with the modelling framework and a dashboard facility can facilitate such analysis and predictions. This could aid the programme to monitor progress of VL elimination at least one-year ahead, assess risk of resurgence or outbreak in post-elimination settings, and implement timely and targeted interventions or preventive measures so that the NKAEP meet the target of achieving elimination by 2030.

ABSTRACT Bacteriophages are large and diverse components of the biosphere, and many phages are temperate. Upon infection, temperate phages can establish lysogeny in which a prophage is typically integrated into the bacterial chromosome. Here, we describe the phenomenon of tRNA-dependent lysogeny, a previously unrecognized behavior of some temperate phages. tRNA-dependent lysogeny is characterized by two unusual features. First, a phage-encoded tyrosine family integrase mediates site-specific recombination between a phage attP site and a bacterial attB site overlapping a host tRNA gene. However, attP and attB share only a short (~10 bp) common core such that a functional tRNA is not reconstructed upon integration. Second, the phage encodes a tRNA of the same isotype as the disrupted but essential host tRNA, complementing its loss, and consequently is required for the survival of lysogenic progeny. As expected, an integrase-defective phage mutant forms turbid plaques, and bacterial progeny are immune to superinfection, but they lack stability, and the prophage is rapidly lost. In contrast, a tRNA-defective phage mutant forms clear plaques and more closely resembles a repressor mutant, and lysogens are recovered only at very low frequency through the use of secondary attachment sites elsewhere in the host genome. Integration-proficient plasmids derived from these phages must also carry a cognate phage tRNA gene for efficient integration, and these may be useful tools for mycobacterial genetics. We show that tRNA-dependent lysogeny is used by phages within multiple different groups of related viruses and may be prevalent elsewhere in the broader phage community.IMPORTANCEBacteriophages are the most numerous biological entities in the biosphere, and a substantial proportion of phages are temperate, forming stable lysogens in which a prophage copy of the genome integrates into the bacterial chromosome. Many phages encode a variety of tRNA genes whose roles are poorly understood, although it has been proposed that they enhance translational efficiencies in lytic growth or that they counteract host defenses that degrade host tRNAs. Here, we show that phage-encoded tRNAs play key roles in the establishment of lysogeny of some temperate phages. They do so by compensating for the loss of tRNA function when phages integrate at an attB site overlapping a tRNA gene but fail to reconstruct the tRNA at the attachment junction. In this system of tRNA-dependent lysogeny, the phage-encoded tRNA is required for lysogeny, and deletion of the phage tRNA gives rise to a clear plaque phenotype and obligate lytic growth.

ABSTRACTMycobacterium abscessus is a nontuberculous mycobacteria that contributes to the decline and death of patients with lung diseases such as cystic fibrosis and other muco-obstructive airway diseases. M. abscessus is challenging to treat due to its extensive antibiotic resistance and ability to survive inside mammalian cells. An alternative to antibiotics is the therapeutic use of bacteriophages (phages). There are recent cases of phage therapy being used to treat M. abscessus infections in people under compassionate-use conditions. However, little is known about the ability of phages to kill bacteria, such as M. abscessus, which reside in an intracellular environment. Here, we used M. abscessus strains and phages from recent phage therapy cases to determine if phages can enter mammalian cells and if they can infect and kill intracellular M. abscessus. Using fluorescence microscopy, we demonstrate phage uptake by macrophages and lung epithelial cells, and we further demonstrate phage infection of intracellular M. abscessus with fluorescent reporter phages. Transmission electron microscopy was additionally used to image phage infection of intracellular M. abscessus. Together, these findings provide the first visualizations of phage-M. abscessus interactions in an intracellular environment. Finally, we show that phage treatment can significantly reduce the intracellular burden of M. abscessus in a manner that depends on both the specific phage and mammalian cell type involved. These results demonstrate the potential to use phage therapy to treat intracellular bacteria, specifically M. abscessus, while also highlighting the importance of prescreening phage therapy candidates for activity in an intracellular environment.IMPORTANCEAs we rapidly approach a post-antibiotic era, bacteriophage (phage) therapy may offer a solution for treating drug-resistant bacteria. Mycobacterium abscessus is an emerging, multidrug-resistant pathogen that causes disease in people with cystic fibrosis, chronic obstructive pulmonary disease, and other underlying lung diseases. M. abscessus can survive inside host cells, a niche that can limit access to antibiotics. As current treatment options for M. abscessus infections often fail, there is an urgent need for alternative therapies. Phage therapy is being used to treat M. abscessus infections as an option of last resort. However, little is known about the ability of phages to kill bacteria in the host environment and specifically in an intracellular environment. Here, we demonstrate the ability of phages to enter mammalian cells and to infect and kill intracellular M. abscessus. These findings support the use of phages to treat intracellular bacterial pathogens.

Objective To explore factors associated with early age at entry into sex work, among a cohort of female sex workers (FSWs) in Nairobi, Kenya.Background Younger age at sex work initiation increases the risk of HIV acquisition, condom non-use, violence victimisation and alcohol and/or substance use problems. This study aimed to understand factors in childhood and adolescence that shape the vulnerability to underage sex work initiation.Design Building on previous qualitative research with this cohort, analysis of behavioural–biological cross-sectional data using hierarchical logistic regression.Participants and measures FSWs aged 18–45 years were randomly selected from seven Sex Workers Outreach Programme clinics in Nairobi, and between June and December 2019, completed a baseline behavioural–biological survey. Measurement tools included WHO Adverse Childhood Experiences, Alcohol, Smoking and Substance Involvement Screening Test and questionnaires on sociodemographic information, sexual risk behaviours and gender-based violence. Descriptive statistics and logistic regression were conducted using hierarchical modelling.Results Of the 1003 FSWs who participated in the baseline survey (response rate 96%), 176 (17.5%) initiated sex work while underage (

Course-based research pedagogy involves positioning students as contributors to authentic research projects as part of an engaging educational experience that promotes their learning and persistence in science. To develop a model for assessing and grading students engaged in this type of learning experience, the assessment aims and practices of a community of experienced course-based research instructors were collected and analyzed. This approach defines four aims of course-based research assessment—(1) Assessing Laboratory Work and Scientific Thinking; (2) Evaluating Mastery of Concepts, Quantitative Thinking and Skills; (3) Appraising Forms of Scientific Communication; and (4) Metacognition of Learning—along with a set of practices for each aim. These aims and practices of assessment were then integrated with previously developed models of course-based research instruction to reveal an assessment program in which instructors provide extensive feedback to support productive student engagement in research while grading those aspects of research that are necessary for the student to succeed. Assessment conducted in this way delicately balances the need to facilitate students’ ongoing research with the requirement of a final grade without undercutting the important aims of a CRE education.

Background: Kenya is endemic for soil-transmitted helminths (STH) with over 6 million children in 27 counties currently at-risk. A national school-based deworming programme (NSBDP) was launched in 2012 with a goal to eliminate parasitic worms as a public health problem. This study used model-based geostatistical (MBG) approach to design and analyse the impact of the NSBDP and inform treatment strategy changes. Methods: A cross-sectional study was used to survey 200 schools across 27 counties in Kenya. The study design, school selection and analysis followed the MBG approach which incorporated historical data on treatment, morbidity and environmental covariates to efficiently predict the helminths prevalence in Kenya. Results: Overall, the NSBDP geographic area prevalence for any STH was estimated to sit between 2 % and 0.999. Species-specific thresholds were between 2 % and 0.999. Conclusions: Based on the World Health Organization guidelines, STH treatment requirements can now be confidently refined. Ten counties may consider suspending treatment and implement appropriate surveillance system, while another 10 will require treatment once every two years, and the remaining seven will require treatment once every year.

ABSTRACT Bacteriophage comparative genomics is complex due to the mosaic nature of the genomes, and an underlying continuum of diversity confounds the identification of clear taxonomic boundaries. Nucleotide sequence comparison methods have been described for phage taxonomy, but they are computationally intensive and scale poorly as the number of sequenced phage genomes increases. Here, we describe PhamClust as a new bioinformatic approach for grouping phages according to their inter-genome relatedness. PhamClust calculates a proteomic equivalence quotient (PEQ) for each pair of phages based on amino acid sequence identity for those genes that are shared among phages. PEQ values span from 0% (no shared genes) to 100% (all genes shared at 100% identity), and using a large mycobacteriophage genome data set, we show that two-step clustering down to a PEQ of 25% constructs genome groupings (clusters) closely mirroring those constructed manually over time, with the differences attributable to historically arising incongruities rather than illogicalities in PhamClust. PEQ values can also faithfully divide clusters into subclusters, although the relationships are highly heterogeneous, with different PEQ values needed for the subdivision of different clusters. PhamClust can be used to assort any group of phages, including the RefSeq phage collection. IMPORTANCE Bacteriophage genomes are pervasively mosaic, presenting challenges to describing phage relatedness. Here, we describe PhamClust, a bioinformatic approach for phage genome comparisons that uses a new metric of proteomic equivalence quotient for comparative genomics. PhamClust reliably assorts genomes into groups or clusters of related phages and can subdivide clusters into subclusters. PhamClust is computationally efficient and can readily process thousands of phage genomes. It is also a useful analytic tool for exploring the different types of inter-genome relatedness characteristic of phages in different clusters.

ABSTRACT Bacterial genomes commonly carry one or more integrated prophages, although prophage prevalence varies greatly in different bacterial genera and species. We have used the recently developed DEPhT software to discover prophages present in sequenced Mycobacterium genomes. Prophages are unevenly distributed among mycobacteria; Mycobacterium tuberculosis strains are devoid of intact prophages, whereas 75% of Mycobacterium abscessus-chelonae strains carry at least one prophage, and some have up to nine. Newly discovered prophage sequences are generally distinct from those of lytic phages isolated using Mycobacterium smegmatis as a host, although assembly of over 3,800 phage and prophage genomes into clusters based on shared sequence similarity yields seven clusters containing both phage and prophage genomes. M. abscessus prophages use a usually large repertoire of attB sites for prophage integration, and new integration-proficient vectors demonstrate the functionality of integration systems identified in silico and provide tools useful for advancing M. abscessus genetics. Genomic analysis reveals additional accessory and likely mobile parts of Mycobacterium genomes including defective prophages, prophage-like regions, and satellite elements proposed to be candidate phage-inducible chromosomal islands (PICIs). M. abscessus prophages and PICIs are unusual in that they often encode phage-encoded ESX-secreted toxin (PEST) systems that are located adjacent to the phage integration functions and are lysogenically expressed and likely provide a fitness advantage to their host. IMPORTANCE Mycobacterium species include several human pathogens and mycobacteriophages show potential for therapeutic use to control Mycobacterium infections. However, phage infection profiles vary greatly among Mycobacterium abscessus clinical isolates and phage therapies must be personalized for individual patients. Mycobacterium phage susceptibility is likely determined primarily by accessory parts of bacterial genomes, and we have identified the prophage and phage-related genomic regions across sequenced Mycobacterium strains. The prophages are numerous and diverse, especially in M. abscessus genomes, and provide a potentially rich reservoir of new viruses that can be propagated lytically and used to expand the repertoire of therapeutically useful phages.

BackgroundThe kala-azar elimination programme has resulted in a significant reduction in visceral leishmaniasis (VL) cases across the Indian Subcontinent. To detect any resurgence of transmission, a sensitive cost-effective surveillance system is required. Molecular xenomonitoring (MX), detection of pathogen DNA/RNA in vectors, provides a proxy of human infection in the lymphatic filariasis elimination programme. To determine whether MX can be used for VL surveillance in a low transmission setting, large numbers of the sand fly vector Phlebotomus argentipes are required. This study will determine the best method for capturing P. argentipes females for MX.Methodology/principal findingsThe field study was performed in two programmatic and two non-programmatic villages in Bihar, India. A total of 48 households (12/village) were recruited. Centers for Disease Control and Prevention light traps (CDC-LTs) were compared with Improved Prokopack (PKP) and mechanical vacuum aspirators (MVA) using standardised methods. Four 12x12 Latin squares, 576 collections, were attempted (12/house, 144/village,192/method). Molecular analyses of collections were conducted to confirm identification of P. argentipes and to detect human and Leishmania DNA. Operational factors, such as time burden, acceptance to householders and RNA preservation, were also considered. A total of 562 collections (97.7%) were completed with 6,809 sand flies captured. Females comprised 49.0% of captures, of which 1,934 (57.9%) were identified as P. argentipes. CDC-LTs collected 4.04 times more P. argentipes females than MVA and 3.62 times more than PKP (pConclusions/significanceCDC-LTs are the most useful collection tool of those tested for MX surveillance since they collected higher numbers of P. argentipes females without compromising mosquito captures or the preservation of RNA. However, capture rates are still low.

Abstract Non-tuberculous mycobacterium (NTM) infections are often clinically challenging, with lengthy antibiotic regimens that fail to resolve the infections with few good outcomes remaining. Mycobacteriophages—viruses that infect Mycobacterium hosts—show promise as therapeutic agents for NTM infections and have been used in 20 compassionate use cases. Favorable outcomes were observed in many but not all cases, although the phages show exceptional safety profiles and no evidence of phage resistance was observed, even when only a single phage was administered. Phage-specific antibodies are commonly present following intravenous administration and are often neutralizing for the phage in vitro. However, phage neutralization does not consistently correlate with poor treatment outcomes and may not be a therapeutic limitation in all patients, even when immunocompetent. Currently, the therapeutic potential of phages is substantially limited by the great variation in phage susceptibility and a relatively small repertoire of therapeutically useful phages. As many as 45% of clinical isolates can have a smooth colony morphotype, and phages that both efficiently infect and kill these strains have yet to be described. In contrast, ~ 75% of rough strains are susceptible to and killed by one or more phages and therapeutic options can be considered on a compassionate use basis. Although therapies must currently be personalized, elucidating the determinants of phage host specificity, expanding the useful phage repertoire, and identifying the key determinants of clinical outcomes will reveal their full therapeutic potential.

Objective To explore the structural and social co-factors that shape the early lives of women who enter sex work in Nairobi, Kenya.Design Thematic analysis of qualitative data collected as part of the Maisha Fiti study among female sex workers (FSWs) in Nairobi.Participants and measures FSWs aged 18–45 years were randomly selected from seven Sex Workers Outreach Programme clinics in Nairobi and participated in baseline behavioural–biological surveys. Participants in this qualitative study were randomly selected from the Maisha Fiti study cohort and were interviewed between October 2019 and July 2020. Women described their lives from childhood, covering topics including sex work, violence and financial management.Results 48 out of 1003 Maisha Fiti participants participated in the in-depth qualitative interviews. FSWs described how physical and sexual violence, poverty and incomplete education in their childhood and adolescence intertwined with early pregnancy, marriage, intimate partner violence and relationship breakdown in their adolescence and early adulthood. The data analysis found clear syndemic relationships between these risk factors, particularly childhood violence, poverty and incomplete education and highlighted pathways leading to financial desperation and caring for dependents, and subsequent entry into sex work. Women perceived sex work as risky and most would prefer alternative work if possible, but it provided them with some financial independence and agency.Conclusions This is the first study in Kenya to qualitatively explore the early lives of sex workers from a syndemic perspective. This method identified the pivotal points of (1) leaving school early due to poverty or pregnancy, (2) breakdown of early intimate relationships and (3) women caring for dependents on their own. Complex, multi-component structural interventions before these points could help increase school retention, reduce teenage pregnancy, tackle violence, support young mothers and reduce entry into sex work and the risk that it entails by expanding livelihood options.

Increasing rates of multidrug-resistant bacterial infections has renewed interest in the therapeutic use of phages. Here the authors report an individual with cutaneous M. chelonae infection, and the improvement of disease upon treatment with a bacteriophage in combination with antimicrobial therapy.

Graduate preparation programs serve as a primary site for training new student affairs practitioners. However, scholars perennially raise concerns about the effectiveness of such graduate training and the readiness of new student affairs practitioners for the field. Whereas existing graduate preparation scholarship relies almost exclusively on a socialization framework, alternative theoretical frameworks oriented toward student learning can offer new insight into training individuals to do student affairs work. Utilizing existing literature on student affairs graduate preparation and cultural-historical activity theory (CHAT), this article offers a conceptual model of student affairs graduate preparation as sociocultural activity systems. This model maps dimensions of the coursework and fieldwork environments that graduate student navigate during their training and highlights the sociocultural contradictions that emerge within and between each of these environments. Finally, the article provides discussion of how the conceptual model can guide future research on graduate training and strengthen student learning and development within training programs.

Kenya is among the countries endemic for soil-transmitted helminthiasis (STH) with over 66 subcounties and over 6 million individuals being at-risk of infection. Currently, the country is implementing mass drug administration (MDA) to all the at-risk groups as the mainstay control strategy. This study aimed to develop and analyze an optimal control (OC) model, from a transmission interruption model, to obtain an optimal control strategy from a mix of three strategies evaluated. The study used the Pontryaginʼs maximum principle to solve, numerically, the OC model. The analysis results clearly demonstrated that water and sanitation when implemented together with the MDA programme offer the best chances of eliminating these tenacious and damaging parasites. Thus, we advocate for optimal implementation of the combined mix of the two interventions in order to achieve STH elimination in Kenya, and globally, in a short implementation period of less than eight years.

Mycobacterium abscessus infections are relatively common in patients with cystic fibrosis and are clinically challenging, with frequent intrinsic resistance to antibiotics. Therapeutic treatment with bacteriophages offers some promise but faces many challenges including substantial variation in phage susceptibilities among clinical isolates, and the need to personalize therapies for individual patients. Many strains are not susceptible to any phages or are not efficiently killed by lytic phages, including all smooth colony morphotype strains tested to-date. Here, we analyze a set of new M. abscessus isolates for the genomic relationships, prophage content, spontaneous phage release, and phage susceptibilities. We find that prophages are common in these M. abscessus genomes, but some have unusual arrangements, including tandemly integrated prophages, internal duplications, and they participate in active exchange of polymorphic toxin-immunity cassettes secreted by ESX systems. Relatively few strains are efficiently infected by any mycobacteriophages, and the infection patterns do not reflect the overall phylogenetic relationships of the strains. Characterization of these strains and their phage susceptibility profiles will help to advance the broader application of phage therapies for NTM infections.

Evaluations of the UK’s contact tracing programme have shown that it has had limited impact on COVID-19 control. Here, the authors show that with high levels of reporting and adherence, contact tracing could reduce transmission, but it should not be used as the sole control measure.

In common with other professional musicians, self-evaluation of practise and performance is an integral part of a pianist’s professional life. They will also have opportunities to listen to and evaluate the performances of others based on their own criteria. These self-constructed perspectives towards to a piano performance will have an influence on both self-evaluation and external evaluation, but whether differently or similarly is not known. Consequently, this research study aimed to explore how judgements on the perceived quality of a performance are undertaken by professional standard pianists and what criteria are applied, both with regards their own performances as well as the performance of others. Participants were six professional pianists (3 men, 3 women) who were based in the United Kingdom (Mean age = 31.5 years old. SD = 5.1). They were asked to play individually six trials of a piece of R. Schumann’s “Träumerei” Op. 15 No. 7 in a hired hall for recordings. Then, within 2 months, each participant was asked to come to a self-evaluation session to listen to and evaluate their own six recordings, using a Triadic method as a Repertory Grid. For the external evaluation focused session, the participants were asked to return again to evaluate a further six recordings made up of ‘best’ recordings as selected by each participant from their own individual self-evaluations. Analyses of the resultant data suggest that there was no significant difference between the participants in their overall ratings in the external phase, but that self-evaluation showed significant individual differences amongst several participants. The performance criteria in both self-evaluation and external evaluation predominately overlapped with each other in terms of musical factors, such as tone quality, phrasing, and pedalling. The ranking of the performances was highly correlated with perceptions of overall flow, tone quality and pedalling. It appears that pianists apply similar criteria to decide performance quality when evaluating their own performances as well as others.

Abstract Many radioisotopes with potential medical applications are difficult to produce routinely, especially those on the proton-rich side of the valley of stability. Current production methods typically use light-ion (protons or deuteron) reactions on materials of similar mass to the target radioisotope, which limits the elemental target material available and may require the use of targets with poor thermal properties (as is the case for the production of radiobromine). These reactions may also create significant amounts of proton-rich decay products which require chemical separation from the desired product in a highly radioactive environment. A promising alternative method using heavy-ion fusion-evaporation reactions for the production of the medically relevant bromine radioisotopes 76Br (t1/2 = 16.2 h) and 77Br (t1/2 = 57.0 h) is presented. Heavy-ion beams of 28Si and 16O were used to bombard natural chromium and copper targets just above the Coulomb barrier at the University of Notre Dame's Nuclear Science Laboratory to produce these bromine and precursor radioisotopes by fusion-evaporation reactions. Production yields for these reactions were measured and compared to PACE4 calculations. In addition to using more robust targets for irradiation, a simple physical–chemical separation method is proposed that will lead to very high radiopurity yields. A summary of accelerator facility requirements needed for routine production of these radioisotopes is also presented.

Mycobacteriophages-bacteriophages infecting Mycobacterium hosts-contribute substantially to our understanding of viral diversity and evolution, provide resources for advancing Mycobacterium genetics, are the basis of high-impact science education programs, and show considerable therapeutic potential. Over 10,000 individual mycobacteriophages have been isolated by high school and undergraduate students using the model organism Mycobacterium smegmatis mc2155 and 2,100 have been completely sequenced, giving a high-resolution view of the phages that infect a single common host strain. The phage genomes are revealed to be highly diverse and architecturally mosaic and are replete with genes of unknown function. Mycobacteriophages have provided many widely used tools for Mycobacterium genetics including integration-proficient vectors and recombineering systems, as well as systems for efficient delivery of reporter genes, transposons, and allelic exchange substrates. The genomic insights and engineering tools have facilitated exploration of phages for treatment of Mycobacterium infections, although their full therapeutic potential has yet to be realized.

A range of studies suggest that singing activities with young children can have a beneficial impact on other aspects of their development. However, there is little research examining the relationship between young children's singing and their developing social identity. In the current study, data were captured of young children's singing and social identity as part of a larger-scale, longitudinal evaluation of the nationwide Sing Up programme in England. Participants were 720 children aged 5-8 years old. The assessment of young children's singing ability employed an established measure and was undertaken individually. With adult support, the children were also asked to complete a simple questionnaire that focused on selected aspects of their social identity, both in general terms and also related to singing. Key themes embraced their attitudes to singing (at home, in school and in informal settings), singer identity (emotional engagement with singing and self-concept), and perceptions of self (self-efficacy, self-esteem, social integration). Comparative data were collected from young children of a similar age outside the programme. Findings suggested that the programme had a positive impact on children's singing ability, both overall and including the youngest children. The data analyses suggest that children could be identified as either “pupils with positive singing identity” or “pupils with less positive, or still developing singing identity.” Overall, pupils with a more positive singer identity—irrespective of Sing Up-related experience—tended to report more positive attitudes toward singing at school and other settings, had higher perceived levels of self-esteem and social integration, as well as more positive evaluations of their singing ability. Furthermore, the research suggests that successful participation in high-quality singing activities is likely to have a positive impact on young children's singing ability and, by implication, such positive singing development will also be associated with aspects of self that are related to contexualised singer identity and their sense of social inclusion.

Abstract Genome engineering of bacteriophages provides opportunities for precise genetic dissection and for numerous phage applications including therapy. However, few methods are available for facile construction of unmarked precise deletions, insertions, gene replacements and point mutations in bacteriophages for most bacterial hosts. Here we describe CRISPY-BRED and CRISPY-BRIP, methods for efficient and precise engineering of phages in Mycobacterium species, with applicability to phages of a variety of other hosts. This recombineering approach uses phage-derived recombination proteins and Streptococcus thermophilus CRISPR-Cas9.

Abstract Respiratory syncytial virus (RSV) is responsible for a significant burden of severe acute lower respiratory tract illness in children under 5 years old; particularly infants. Prior to rolling out any vaccination program, identification of the source of infant infections could further guide vaccination strategies. We extended a dynamic model calibrated at the individual host level initially fit to social-temporal data on shedding patterns to include whole genome sequencing data available at a lower sampling intensity. The study population was 493 individuals (55 aged

A stochastic individual based model, SCHISTOX, has been developed for the study of schistosome transmission dynamics and the impact of control by mass drug administration. More novel aspects that can be investigated include individual level adherence and access to treatment, multiple communities, human sex population dynamics, and implementation of a potential vaccine. Many of the model parameters have been estimated within previous studies and have been shown to vary between communities, such as the age-specific contact rates governing the age profiles of infection. However, uncertainty remains as there are wide ranges for certain parameter values and a few remain relatively unknown. We analyse the model dynamics by parameterizing it with published parameter values. We also discuss the development of SCHISTOX in the form of a publicly available open-source GitHub repository. The next key development stage involves validating the model by calibrating to epidemiological data.

Groundwater remediation technologies that can destroy per- and polyfluoroalkyl substances (PFAS) in situ are in high demand. To address this need, using flow-through electrochemical reactors we compared the performance of three mesh electrode materials that may be implemented in the subsurface as permeable reactive barriers. A Magnéli-phase titanium suboxides TinO2n-1 anode achieved higher perfluorooctane sulfonate (PFOS) oxidation rates and lower energy consumption than boron-doped ultrananocrystalline diamond and IrO2-Ta2O5 mixed metal oxides, and was thus selected for more detailed testing regarding the impacts of varying current density, flow velocity, electrolyte conductivity, and PFOS concentration. Over 99% of PFOS removal was achieved under continuous flow conditions. The fluorine mass balance showed that most PFOS-bonded F was released as fluoride, while no organic intermediates were detected in the aqueous phase. Each ∼2% of fluorine was recovered as HF and organofluorine intermediates in the gas phase. A comparison of 10 PFAS revealed a hydrophobicity-driven increase in oxidation rate with increasing perfluoroalkyl chain length as well as faster oxidation kinetics for perfluoroalkyl carboxylic acids compared to perfluoroalkane sulfonic acids, likely due to contributions from electrochemically activated sulfate. The energy consumption of PFAS treatment under simulated slow-flow groundwater conditions was substantially higher than in ex situ electrochemical systems optimized for enhanced mass transfer. Consequently, future work should focus on in situ treatment design optimization with an emphasis on power requirements. Collectively, our investigations demonstrate that among the few water treatment technologies capable of breaking the carbon-fluorine bond, electrochemical treatment is a promising approach for in situ destruction of PFAS in the subsurface.

The World Health Organization recently launched its 2021-2030 roadmap, Ending the Neglect to Attain the Sustainable Development Goals, an updated call to arms to end the suffering caused by neglected tropical diseases. Modelling and quantitative analyses played a significant role in forming these latest goals. In this collection, we discuss the insights, the resulting recommendations and identified challenges of public health modelling for 13 of the target diseases: Chagas disease, dengue, gambiense human African trypanosomiasis (gHAT), lymphatic filariasis (LF), onchocerciasis, rabies, scabies, schistosomiasis, soil-transmitted helminthiases (STH), Taenia solium taeniasis/ cysticercosis, trachoma, visceral leishmaniasis (VL) and yaws. This piece reflects the three cross-cutting themes identified across the collection, regarding the contribution that modelling can make to timelines, programme design, drug development and clinical trials.

As India comes closer to the elimination of visceral leishmaniasis (VL) as a public health problem, surveillance efforts and elimination targets must be continuously revised and strengthened. Mathematical modelling is a compelling research discipline for informing policy and programme design in its capacity to project incidence across space and time, the likelihood of achieving benchmarks, and the impact of different interventions. To gauge the extent to which modelling informs policy in India, this qualitative analysis explores how and whether policy makers understand, value, and reference recently produced VL modelling research. Sixteen semi-structured interviews were carried out with both users- and producers- of VL modelling research, guided by a knowledge utilisation framework grounded in knowledge translation theory. Participants reported that barriers to knowledge utilisation include 1) scepticism that models accurately reflect transmission dynamics, 2) failure of modellers to apply their analyses to specific programme operations, and 3) lack of accountability in the process of translating knowledge to policy. Political trust and support are needed to translate knowledge into programme activities, and employment of a communication intermediary may be a necessary approach to improve this process.

COVID-19 in the UK has been characterised by periods of exponential growth and decline, as different non-pharmaceutical interventions (NPIs) are brought into play. During the early uncontrolled phase of the outbreak (March 2020) there was a period of prolonged exponential growth with epidemiological observations such as hospitalisation doubling every 3–4 days. The enforcement of strict lockdown measures led to a noticeable decline in all epidemic quantities that slowed during the summer as control measures were relaxed. From August 2020, infections, hospitalisations and deaths began rising once more and various NPIs were applied locally throughout the UK in response.Controlling any rise in infection is a compromise between public health and societal costs, with more stringent NPIs reducing cases but damaging the economy and restricting freedoms. Typically, NPI imposition is made in response to the epidemiological state, are of indefinite length and are often imposed at short notice, greatly increasing the negative impact. An alternative approach is to consider planned, limited duration periods of strict NPIs aiming to purposefully reduce prevalence before such emergency NPIs are required. These “precautionary breaks” may offer a means of keeping control of the epidemic, while their fixed duration and the forewarning may limit their societal impact. Here, using simple analysis and age-structured models matched to the UK SARS-CoV-2 epidemic, we investigate the action of precautionary breaks. In particular we consider their impact on the prevalence of SARS-CoV-2 infection, as well as the total number of predicted hospitalisations and deaths caused by COVID-19 disease. We find that precautionary breaks provide the biggest gains when the growth rate is low, but offer a much needed brake on increasing infection when the growth rate is higher, potentially allowing other measures to regain control.

Infection by multidrug-resistant Mycobacterium abscessus is increasingly prevalent in cystic fibrosis (CF) patients, leaving clinicians with few therapeutic options. A compassionate study showed the clinical improvement of a CF patient with a disseminated M. abscessus (GD01) infection, following injection of a phage cocktail, including phage Muddy. Broadening the use of phage therapy in patients as a potential antibacterial alternative necessitates the development of biological models to improve the reliability and successful prediction of phage therapy in the clinic. Herein, we demonstrate that Muddy very efficiently lyses GD01 in vitro, an effect substantially increased with standard drugs. Remarkably, this cooperative activity was retained in an M. abscessus model of infection in CFTR-depleted zebrafish, associated with a striking increase in larval survival and reduction in pathological signs. The activity of Muddy was lost in macrophage-ablated larvae, suggesting that successful phage therapy relies on functional innate immunity. CFTR-depleted zebrafish represent a practical model to rapidly assess phage treatment efficacy against M. abscessus isolates, allowing the identification of drug combinations accompanying phage therapy and treatment prediction in patients. This article has an associated First Person interview with the first author of the paper.

Peg tapping tasks are commonly used as a measure of inhibitory skill in young children. However, differences in the way the task is presented may influence children’s performance. For example, if a peg tapping task is presented at regular intervals, children can entrain to the presentation pulse, which may in turn support their performance. This study assessed how speed and regularity of presentation may support or impair children’s responses. An experimenter was filmed delivering the tapping task at two different speeds (120 bpm/3,000 ms per trial and 150 bpm/2,400 ms per trial). Additionally, they were filmed delivering the task at regular intervals (i.e., the onset of each trial was predictable), or at irregular intervals (the onset of each trial was unpredictable). N = 103 children aged between 5 and 6 years old were tested on the task. They completed one block with 20 regular interval trials and another block with 20 irregular interval trials. Block presentation order was randomized. Children who achieved over 90% accuracy on the task were then presented with two more blocks at 150 bpm. Children’s response accuracy was measured. Our results show a difference in children’s accuracy across all conditions with trials presented in an irregular manner producing poorer performance on the task. The study demonstrates how speed and regularity of presentation can affect children’s scores on a tapping task used to measure inhibition. Demands on working memory, motor ability, and speed of processing are all affected by adjustments in presentation. Entrainment to a pulse is also a potential mechanism employed by children to support their performance on this task.

A framework for understanding relationships between school connectedness and student aberrant behaviors is outlined that is synthesized from Merton’s insights into anomie and Bernstein’s theory of cultural transmission (which focuses on schools’ instructional methods and students’ internalization of schools’ values). A seven-category classification system identifies students’ risk of nonconformist behavior based upon students acceptance/rejection of dominant overarching cultural aspirations (commonly material prosperity); perception of schools’ role in aspiration realization; responses to schools’ instructional methods; and internalization of schools’ values regarding conduct/character. We propose frustration weakens connectedness and is grounded in students’ perceptions regarding their school’s educational outcomes, degree of acceptance at school, and their school’s values. We then consider student dispersal across schools, and how age may affect students’ categorization and the influence of frustration risk factors. Finally, we discuss how initiatives within school organization, curriculum, and pedagogic practice may promote connectedness among different student categories and their potential adverse consequences.

Tuberculosis kills 1.5 million people each year, and resistance to commonly used antibiotics contributes to treatment failures. The therapeutic potential of bacteriophages against Mycobacterium tuberculosis

Viral genomic DNA is often modified to evade the host bacterial restriction system. Here the authors identified 2′-deoxy-7-deazaguanine modifications on phage DNA by comparative genomics and experimental validation, showing their role in genome protection.

Abstract Background The World Health Organization (WHO) has set elimination (interruption of transmission) as an end goal for schistosomiasis. However, there is currently little guidance on the monitoring and evaluation strategy required once very low prevalence levels have been reached to determine whether elimination or resurgence of the disease will occur after stopping mass drug administration (MDA) treatment. Methods We employ a stochastic individual-based model of Schistosoma mansoni transmission and MDA impact to determine a prevalence threshold, i.e. prevalence of infection, which can be used to determine whether elimination or resurgence will occur after stopping treatment with a given probability. Simulations are run for treatment programmes with varying probabilities of achieving elimination and for settings where adults harbour low to high burdens of infection. Prevalence is measured based on using a single Kato-Katz on two samples per individual. We calculate positive predictive values (PPV) using PPV ≥ 0.9 as a reliable measure corresponding to ≥ 90% certainty of elimination. We analyse when post-treatment surveillance should be carried out to predict elimination. We also determine the number of individuals across a single community (of 500–1000 individuals) that should be sampled to predict elimination. Results We find that a prevalence threshold of 1% by single Kato-Katz on two samples per individual is optimal for predicting elimination at two years (or later) after the last round of MDA using a sample size of 200 individuals across the entire community (from all ages). This holds regardless of whether the adults have a low or high burden of infection relative to school-aged children. Conclusions Using a prevalence threshold of 0.5% is sufficient for surveillance six months after the last round of MDA. However, as such a low prevalence can be difficult to measure in the field using Kato-Katz, we recommend using 1% two years after the last round of MDA. Higher prevalence thresholds of 2% or 5% can be used but require waiting over four years for post-treatment surveillance. Although, for treatment programmes where elimination is highly likely, these higher thresholds could be used sooner. Additionally, switching to more sensitive diagnostic techniques, will allow for a higher prevalence threshold to be employed.

Health disparities exist in Northeast Florida. Some locations experience morbidities at higher rates than others. Health zone 1 is a prime example. Differences in disease rates are interlaced with the social determinants of health, (SDOH). Long-standing social and structural influences of disparities are beyond the scope of Ryan White programs. However, empowerment for health promotion is a strategy for targeting health disparities. The Theory of Health Empowerment targets sense of agency and offers some leverage for helping people living with HIV/AIDS, (PLWHA) despite environments blemished by SDOH. Eclectic leadership occurring in a climate of respectful point-counter point discussions established the context for implemented projects in Northeast Florida. Nine activities directed efforts to reduce disparities. These activities are in the infancy stage of development. Some successes have been achieved, but much more remains to be accomplished to increase overall viral suppression above the 80% threshold. Directions for the future suggest that perhaps external influences of federal Ryan White Parts may be a catalyst for incentivizing the JTGA to participate in national efforts to reduce health disparities. Opportunities to strengthen understanding of approaches to nullify SDOH using science-based approaches hold promise to pursue health equity in treatment cascade outcomes for PLWHAs.

Case management is a core HIV health service that focuses on service coordination—the seamless access to an array of integrated services. Integration aims to reduce barriers to medical care. In the busy HIV health services environment, inadequate documentation of case management activities limits the capacity of stakeholders to know what happens during care encounters. This study used theory and qualitative inquiry to uncover best practices that support optimal case management documentation. Two research questions guided the inquiry: What principles should arise in higher order cognitive functioning among case managers during client encounters? What characteristics of a system level approach to care encounter documentation reinforces case management critical thinking skills? The study settings included two, Northeast Florida, Ryan White funded organizations. Findings indicated that the confluence of intrapersonal, interpersonal, organizational, community, and policy factors support more rather than less robust case management documentation. A multi-tired approach to documentation of services rendered is no panacea. However, it offers a useful framework for defining stakeholders’ roles and expectations and monitoring the performance of activities. Disseminating these findings in the local Ryan White network and the public domain may trigger dialog and more research about the preservation and effective use of documentation skills.

Introduction: Respiratory syncytial virus (RSV) causes a significant respiratory disease burden in the under 5 population. The transmission pathway to young children is not fully quantified in low-income settings, and this information is required to design interventions. Methods: We used an individual level transmission model to infer transmission parameters using data collected from 493 individuals distributed across 47 households over a period of 6 months spanning the 2009/2010 RSV season. A total of 208 episodes of RSV were observed from 179 individuals. We model competing transmission risk from within household exposure and community exposure while making a distinction between RSV groups A and B. Results: We find that 32–53% of all RSV transmissions are between members of the same household; the rate of pair-wise transmission is 58% (95% CrI: 30–74%) lower in larger households (≥8 occupants) than smaller households; symptomatic individuals are 2–7 times more infectious than asymptomatic individuals i.e. 2.48 (95% CrI: 1.22–5.57) among symptomatic individuals with low viral load and 6.7(95% CrI: 2.56–16) among symptomatic individuals with high viral load; previous infection reduces susceptibility to re-infection within the same epidemic by 47% (95% CrI: 17%–68%) for homologous RSV group and 39% (95%CrI: -8%-69%) for heterologous group; RSV B is more frequently introduced into the household, and RSV A is more rapidly transmitted once in the household. Discussion: Our analysis presents the first transmission modelling of cohort data for RSV and we find that it is important to consider the household social structuring and household size when modelling transmission. The increased infectiousness of symptomatic individuals implies that a vaccine against RSV related disease would also have an impact on infection transmission. Together, the weak cross immunity between RSV groups and the possibility of different transmission niches could form part of the explanation for the group co-existence. Keywords: Respiratory syncytial virus, Household, Transmission

Abstract Background Human papillomavirus (HPV) is the most widespread sexually transmitted infection worldwide. It causes several health consequences, in particular accounting for the majority of cervical cancer cases in women. In the United Kingdom, a vaccination campaign targeting 12-year-old girls started in 2008; this campaign has been successful, with high uptake and reduced HPV prevalence observed in vaccinated cohorts. Recently, attention has focused on vaccinating both sexes, due to HPV-related diseases in males (particularly for high-risk men who have sex with men) and an equity argument over equalising levels of protection. Methods We constructed an epidemiological model for HPV transmission in the UK, accounting for nine of the most common HPV strains. We complemented this with an economic model to determine the likely health outcomes (healthcare costs and quality-adjusted life years) for individuals from the epidemiological model. We then tested vaccination with the three HPV vaccines currently available, vaccinating either girls alone or both sexes. For each strategy we calculated the threshold price per vaccine dose, i.e. the maximum amount paid for the added health benefits of vaccination to be worth the cost of each vaccine dose. We calculated results at 3.5% discounting, and also 1.5%, to consider the long-term health effects of HPV infection. Results At 3.5% discounting, continuing to vaccinate girls remains highly cost-effective compared to halting vaccination, with threshold dose prices of £56-£108. Vaccination of girls and boys is less cost-effective (£25-£53). Compared to vaccinating girls only, adding boys to the programme is not cost-effective, with negative threshold prices (-£6 to -£3) due to the costs of administration. All threshold prices increase when using 1.5% discounting, and adding boys becomes cost-effective (£36-£47). These results are contingent on the UK’s high vaccine uptake; for lower uptake rates, adding boys (at the same uptake rate) becomes more cost effective. Conclusions Vaccinating girls is extremely cost-effective compared with no vaccination, vaccinating both sexes is less so. Adding boys to an already successful girls-only programme has a low cost-effectiveness, as males have high protection through herd immunity. If future health effects are weighted more heavily, threshold prices increase and vaccination becomes cost-effective.

Abstract Background Bacteriophages are the most abundant and diverse entities in the biosphere, and this diversity is driven by constant predator–prey evolutionary dynamics and horizontal gene transfer. Phage genome sequences are under-sampled and therefore present an untapped and uncharacterized source of genetic diversity, typically characterized by highly mosaic genomes and no universal genes. To better understand the diversity and relationships among phages infecting human pathogens, we have analysed the complete genome sequences of 205 phages of Staphylococcus sp. Results These are predicted to encode 20,579 proteins, which can be sorted into 2139 phamilies (phams) of related sequences; 745 of these are orphams and possess only a single gene. Based on shared gene content, these phages were grouped into four clusters (A, B, C and D), 27 subclusters (A1-A2, B1-B17, C1-C6 and D1-D2) and one singleton. However, the genomes have mosaic architectures and individual genes with common ancestors are positioned in distinct genomic contexts in different clusters. The staphylococcal Cluster B siphoviridae are predicted to be temperate, and the integration cassettes are often closely-linked to genes implicated in bacterial virulence determinants. There are four unusual endolysin organization strategies found in Staphylococcus phage genomes, with endolysins predicted to be encoded as single genes, two genes spliced, two genes adjacent and as a single gene with inter-lytic-domain secondary translational start site. Comparison of the endolysins reveals multi-domain modularity, with conservation of the SH3 cell wall binding domain. Conclusions This study provides a high-resolution view of staphylococcal viral genetic diversity, and insights into their gene flux patterns within and across different phage groups (cluster and subclusters) providing insights into their evolution.

Mycobacterium abscessusM. abscessus

Mycobacterium abscessusM. abscessusin vivo

BackgroundEffective case identification strategies are fundamental to capturing the remaining visceral leishmaniasis (VL) cases in India. To inform government strategies to reach and sustain elimination benchmarks, this study presents costs of active- and passive- case detection (ACD and PCD) strategies used in India's most VL-endemic state, Bihar, with a focus on programme outcomes stratified by district-level incidence.MethodsExpenditure analysis was complemented by onsite micro-costing to compare the cost of PCD in hospitals alongside index case-based ACD and a combination of blanket (house-to-house) and camp ACD from January to December 2018. From the provider's perspective, a cost analysis evaluated the overall programme cost of each activity, the cost per case detected, and the cost of scaling up ACD.ResultsDuring 2018, index case-based ACD, blanket and camp ACD, and PCD reported 1,497, 131, and 1,983 VL-positive cases at a unit cost of $522.81, $4,186.81, and $246.79, respectively. In high endemic districts, more VL cases were identified through PCD while in meso- and low-endemic districts more cases were identified through ACD. The cost of scaling up ACD to identify 3,000 additional cases ranged from $1.6-4 million, depending on the extent to which blanket and camp ACD was relied upon.ConclusionCost per VL test conducted (rather than VL-positive case identified) may be a better metric estimating unit costs to scale up ACD in Bihar. As more VL cases were identified in meso-and low-endemic districts through ACD than PCD, health authorities in India should consider bolstering ACD in these areas. Blanket and camp ACD identified fewer cases at a higher unit cost than index case-based ACD. However, the value of detecting additional VL cases early outweighs long-term costs for reaching and sustaining VL elimination benchmarks in India.