Classroom assessment is purposeful when the information is utilised by teachers to support learning. Such formative assessment practices can be difficult to enact in a primary science classroom, with ...the whole class often involved in practical activities and with limited lesson time. This preliminary study seeks to explore formative decision-making and the subsequent actions taken by teachers in the classroom. Primary teachers who used a Teacher Assessment in Primary Science (TAPS) Focused Assessment activity were asked to describe what action they took as a result of the classroom interactions stimulated by the activity. 142 teachers in 9 regions of England completed a paper questionnaire at a training day. The qualitative data pertinent to the study was extracted and thematic content analysis carried out to determine the kinds of actions and changes to practice that were described. It was found that the “next step” described by teachers varied in timing; some made changes within the lesson, others provided follow up activities or made longer-term adaptation to teaching practices. Being responsive to the assessment information provided by the children took many forms, for example, supporting pupils to reflect on investigations during the lesson, discussing vocabulary or concepts, providing time for further exploration, or explicit modeling of science skills. Formative decisions were taken at a whole class level, rather than making individual adaptations. It is argued that enabling teachers to be more explicit about their tacit decision-making could support them to make more formative use of assessment information to support pupil learning.
Multilocus sequence typing (MLST) was proposed in 1998 as a portable sequence-based method for identifying clonal relationships among bacteria. Today, in the whole-genome era of microbiology, the ...need for systematic, standardized descriptions of bacterial genotypic variation remains a priority. Here, to meet this need, we draw on the successes of MLST and 16S rRNA gene sequencing to propose a hierarchical gene-by-gene approach that reflects functional and evolutionary relationships and catalogues bacteria 'from domain to strain'. Our gene-based typing approach using online platforms such as the Bacterial Isolate Genome Sequence Database (BIGSdb) allows the scalable organization and analysis of whole-genome sequence data.
The rise of antibiotic-resistant bacteria has led to an urgent need for rapid detection of drug resistance in clinical samples, and improvements in global surveillance. Here we show how de Bruijn ...graph representation of bacterial diversity can be used to identify species and resistance profiles of clinical isolates. We implement this method for Staphylococcus aureus and Mycobacterium tuberculosis in a software package ('Mykrobe predictor') that takes raw sequence data as input, and generates a clinician-friendly report within 3 minutes on a laptop. For S. aureus, the error rates of our method are comparable to gold-standard phenotypic methods, with sensitivity/specificity of 99.1%/99.6% across 12 antibiotics (using an independent validation set, n=470). For M. tuberculosis, our method predicts resistance with sensitivity/specificity of 82.6%/98.5% (independent validation set, n=1,609); sensitivity is lower here, probably because of limited understanding of the underlying genetic mechanisms. We give evidence that minor alleles improve detection of extremely drug-resistant strains, and demonstrate feasibility of the use of emerging single-molecule nanopore sequencing techniques for these purposes.
In common with other bacterial taxa, members of the genus Neisseria are classified using a range of phenotypic and biochemical approaches, which are not entirely satisfactory in assigning isolates to ...species groups. Recently, there has been increasing interest in using nucleotide sequences for bacterial typing and taxonomy, but to date, no broadly accepted alternative to conventional methods is available. Here, the taxonomic relationships of 55 representative members of the genus Neisseria have been analysed using whole-genome sequence data. As genetic material belonging to the accessory genome is widely shared among different taxa but not present in all isolates, this analysis indexed nucleotide sequence variation within sets of genes, specifically protein-coding genes that were present and directly comparable in all isolates. Variation in these genes identified seven species groups, which were robust to the choice of genes and phylogenetic clustering methods used. The groupings were largely, but not completely, congruent with current species designations, with some minor changes in nomenclature and the reassignment of a few isolates necessary. In particular, these data showed that isolates classified as Neisseria polysaccharea are polyphyletic and probably include more than one taxonomically distinct organism. The seven groups could be reliably and rapidly generated with sequence variation within the 53 ribosomal protein subunit (rps) genes, further demonstrating that ribosomal multilocus sequence typing (rMLST) is a practicable and powerful means of characterizing bacteria at all levels, from domain to strain.
Many invasive bacterial diseases are caused by organisms that are ordinarily harmless components of the human microbiome. Effective interventions against these microbes require an understanding of ...the processes whereby symbiotic or commensal relationships transition into pathology. Here, we describe bacterial genome-wide association studies (GWAS) of
Neisseria meningitidis
, a common commensal of the human respiratory tract that is nevertheless a leading cause of meningitis and sepsis. An initial GWAS discovered bacterial genetic variants, including single nucleotide polymorphisms (SNPs), associated with invasive meningococcal disease (IMD)
versus
carriage in several loci across the meningococcal genome, encoding antigens and other extracellular components, confirming the polygenic nature of the invasive phenotype. In particular, there was a significant peak of association around the
fHbp
locus, encoding factor H binding protein (fHbp), which promotes bacterial immune evasion of human complement by recruiting complement factor H (CFH) to the meningococcal surface. The association around
fHbp
with IMD was confirmed by a validation GWAS, and we found that the SNPs identified in the validation affected the 5’ region of
fHbp
mRNA, altering secondary RNA structures, thereby increasing fHbp expression and enhancing bacterial escape from complement-mediated killing. This finding is consistent with the known link between complement deficiencies and CFH variation with human susceptibility to IMD. These observations demonstrate the importance of human and bacterial genetic variation across the fHbp:CFH interface in determining IMD susceptibility, the transition from carriage to disease.
Pyomyositis is a severe bacterial infection of skeletal muscle, commonly affecting children in tropical regions, predominantly caused by
. To understand the contribution of bacterial genomic factors ...to pyomyositis, we conducted a genome-wide association study of
cultured from 101 children with pyomyositis and 417 children with asymptomatic nasal carriage attending the Angkor Hospital for Children, Cambodia. We found a strong relationship between bacterial genetic variation and pyomyositis, with estimated heritability 63.8% (95% CI 49.2-78.4%). The presence of the Panton-Valentine leucocidin (PVL) locus increased the odds of pyomyositis 130-fold (p=10
). The signal of association mapped both to the PVL-coding sequence and to the sequence immediately upstream. Together these regions explained over 99.9% of heritability (95% CI 93.5-100%). Our results establish staphylococcal pyomyositis, like tetanus and diphtheria, as critically dependent on a single toxin and demonstrate the potential for association studies to identify specific bacterial genes promoting severe human disease.
Bacteria pose unique challenges for genome-wide association studies because of strong structuring into distinct strains and substantial linkage disequilibrium across the genome(1,2). Although methods ...developed for human studies can correct for strain structure(3,4), this risks considerable loss-of-power because genetic differences between strains often contribute substantial phenotypic variability(5). Here, we propose a new method that captures lineage-level associations even when locus-specific associations cannot be fine-mapped. We demonstrate its ability to detect genes and genetic variants underlying resistance to 17 antimicrobials in 3,144 isolates from four taxonomically diverse clonal and recombining bacteria: Mycobacterium tuberculosis, Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae. Strong selection, recombination and penetrance confer high power to recover known antimicrobial resistance mechanisms and reveal a candidate association between the outer membrane porin nmpC and cefazolin resistance in E. coli. Hence, our method pinpoints locus-specific effects where possible and boosts power by detecting lineage-level differences when fine-mapping is intractable.
Diabetes mellitus is a global health problem and one of the most common medical conditions in pregnancy. A wide range of modifiable risk factors are associated with diabetes mellitus in pregnancy, ...and it is widely acknowledged that preconception care (PCC) is beneficial for women with pre-existing diabetes mellitus. However, uptake of PCC services is low.
To systematically review qualitative research on PCC for women with pre-existing diabetes mellitus of childbearing age, identify facilitators of and barriers to uptake of PCC and establish themes and gaps in knowledge. Through qualitative interviews explore views on the provision of, and facilitators of and barriers to the uptake of, PCC.
Mixed methods encompassing a systematic review and qualitative interviews.
Two secondary care sites and 11 primary care sites.
Women of childbearing age with pre-existing type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) of white British or Pakistani origin.
None.
A narrative synthesis of the literature using thematic analysis and a thematic analysis of the qualitative interview data using the method of constant comparison.
Eighteen qualitative studies were included in the systematic review and a quality appraisal was carried out using relevant criteria for qualitative research appraisal, including a narrative summary of study quality. Twelve interviews with women with pre-existing T1DM or T2DM were carried out. This fell short of the original aim of interviewing 48 women owing to challenges in recruitment, especially in primary care. A synthesis of these data shows that uptake of PCC is influenced by a range of factors, including the complexity of pregnancy planning, the skill and expertise of health professionals who provide care to women with diabetes mellitus, the role of health professionals in the delivery of PCC, and the quality of relationships between women and health professionals.
Owing to significant challenges with recruitment of participants, particularly in primary care, 12 interviews with women with pre-existing T1DM or T2DM were carried out, which fell short of the a priori sample size.
Reconceptualising PCC to place greater emphasis on pregnancy planning, fertility and contraception would lower some of the existing barriers to uptake of care. It is important to clarify who is responsible for the delivery of PCC to women with pre-existing diabetes mellitus and to ensure that the correct expertise is available so that opportunities for advice giving are maximised. Relationships between women and health professionals should be based on a partnership approach that encourages mutual trust and respect, focusing on positive change rather than negative outcomes.
Further research is needed to investigate the views and experiences of stakeholders that commission, design and deliver PCC services for women with pre-existing diabetes mellitus; to explore experiences of women from minority or ethnically diverse backgrounds; to investigate the role of family support in contraception, pregnancy planning and PCC; and to investigate the management of diabetes mellitus in neonatal care and its role in breastfeeding.
This study is registered as PROSPERO CRD42014015592 and ISRCTN12983949.
The National Institute for Health Research Health Technology Assessment programme.
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