Methods for the thematic synthesis of qualitative research in systematic reviews

<p>Abstract</p> <p>Background</p> <p>There is a growing recognition of the value of synthesising qualitative research in the evidence base in order to facilitate effective and appropriate health care. In response to this, methods for undertaking these syntheses are currently being developed. Thematic analysis is a method that is often used to analyse data in primary qualitative research. This paper reports on the use of this type of analysis in systematic reviews to bring together and integrate the findings of multiple qualitative studies.</p> <p>Methods</p> <p>We describe thematic synthesis, outline several steps for its conduct and illustrate the process and outcome of this approach using a completed review of health promotion research. Thematic synthesis has three stages: the coding of text 'line-by-line'; the development of 'descriptive themes'; and the generation of 'analytical themes'. While the development of descriptive themes remains 'close' to the primary studies, the analytical themes represent a stage of interpretation whereby the reviewers 'go beyond' the primary studies and generate new interpretive constructs, explanations or hypotheses. The use of computer software can facilitate this method of synthesis; detailed guidance is given on how this can be achieved.</p> <p>Results</p> <p>We used thematic synthesis to combine the studies of children's views and identified key themes to explore in the intervention studies. Most interventions were based in school and often combined learning about health benefits with 'hands-on' experience. The studies of children's views suggested that fruit and vegetables should be treated in different ways, and that messages should not focus on health warnings. Interventions that were in line with these suggestions tended to be more effective. Thematic synthesis enabled us to stay 'close' to the results of the primary studies, synthesising them in a transparent way, and facilitating the explicit production of new concepts and hypotheses.</p> <p>Conclusion</p> <p>We compare thematic synthesis to other methods for the synthesis of qualitative research, discussing issues of context and rigour. Thematic synthesis is presented as a tried and tested method that preserves an explicit and transparent link between conclusions and the text of primary studies; as such it preserves principles that have traditionally been important to systematic reviewing.</p

Process evaluation for complex interventions in primary care: understanding trials using the normalization process model

Background: the Normalization Process Model is a conceptual tool intended to assist in understanding the factors that affect implementation processes in clinical trials and other evaluations of complex interventions. It focuses on the ways that the implementation of complex interventions is shaped by problems of workability and integration.Method: in this paper the model is applied to two different complex trials: (i) the delivery of problem solving therapies for psychosocial distress, and (ii) the delivery of nurse-led clinics for heart failure treatment in primary care.Results: application of the model shows how process evaluations need to focus on more than the immediate contexts in which trial outcomes are generated. Problems relating to intervention workability and integration also need to be understood. The model may be used effectively to explain the implementation process in trials of complex interventions.Conclusion: the model invites evaluators to attend equally to considering how a complex intervention interacts with existing patterns of service organization, professional practice, and professional-patient interaction. The justification for this may be found in the abundance of reports of clinical effectiveness for interventions that have little hope of being implemented in real healthcare setting

Comparative Gene Expression Profiling of P. falciparum Malaria Parasites Exposed to Three Different Histone Deacetylase Inhibitors

Histone deacetylase (HDAC) inhibitors are being intensively pursued as potential new drugs for a range of diseases, including malaria. HDAC inhibitors are also important tools for the study of epigenetic mechanisms, transcriptional control, and other important cellular processes. In this study the effects of three structurally related antimalarial HDAC inhibitors on P. falciparum malaria parasite gene expression were compared. The three hydroxamate-based compounds, trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA; Vorinostat®) and a 2-aminosuberic acid derivative (2-ASA-9), all caused profound transcriptional effects, with ∼2–21% of genes having >2-fold altered expression following 2 h exposure to the compounds. Only two genes, alpha tubulin II and a hydrolase, were up-regulated by all three compounds after 2 h exposure in all biological replicates examined. The transcriptional changes observed after 2 h exposure to HDAC inhibitors were found to be largely transitory, with only 1–5% of genes being regulated after removing the compounds and culturing for a further 2 h. Despite some structural similarity, the three inhibitors caused quite diverse transcriptional effects, possibly reflecting subtle differences in mode of action or cellular distribution. This dataset represents an important contribution to our understanding of how HDAC inhibitors act on malaria parasites and identifies alpha tubulin II as a potential transcriptional marker of HDAC inhibition in malaria parasites that may be able to be exploited for future development of HDAC inhibitors as new antimalarial agents

Specialization Can Drive the Evolution of Modularity

Organismal development and many cell biological processes are organized in a modular fashion, where regulatory molecules form groups with many interactions within a group and few interactions between groups. Thus, the activity of elements within a module depends little on elements outside of it. Modularity facilitates the production of heritable variation and of evolutionary innovations. There is no consensus on how modularity might evolve, especially for modules in development. We show that modularity can increase in gene regulatory networks as a byproduct of specialization in gene activity. Such specialization occurs after gene regulatory networks are selected to produce new gene activity patterns that appear in a specific body structure or under a specific environmental condition. Modules that arise after specialization in gene activity comprise genes that show concerted changes in gene activities. This and other observations suggest that modularity evolves because it decreases interference between different groups of genes. Our work can explain the appearance and maintenance of modularity through a mechanism that is not contingent on environmental change. We also show how modularity can facilitate co-option, the utilization of existing gene activity to build new gene activity patterns, a frequent feature of evolutionary innovations

Introduction to “Binary Binds”: Deconstructing Sex and Gender Dichotomies in Archaeological Practice

YesGender archaeology has made significant strides toward deconstructing the hegemony of binary categorizations. Challenging dichotomies such as man/woman, sex/gender, and biology/culture, approaches informed by poststructuralist, feminist, and queer theories have moved beyond essentialist and universalist identity constructs to more nuanced configurations. Despite the theoretical emphasis on context, multiplicity, and fluidity, binary starting points continue to streamline the spectrum of variability that is recognized, often reproducing normative assumptions in the evidence. The contributors to this special issue confront how sex, gender, and sexuality categories condition analytical visibility, aiming to develop approaches that respond to the complexity of theory in archaeological practice. The papers push the ontological and epistemological boundaries of bodies, personhood, and archaeological possibility, challenging a priori assumptions that contain how sex, gender, and sexuality categories are constituted and related to each other. Foregrounding intersectional approaches that engage with ambiguity, variability, and difference, this special issue seeks to “de-contain” categories, assumptions, and practices from “binding” our analytical gaze toward only certain kinds of persons and knowledges, in interpretations of the past and practices in the present

The dental calculus metabolome in modern and historic samples.

INTRODUCTION: Dental calculus is a mineralized microbial dental plaque biofilm that forms throughout life by precipitation of salivary calcium salts. Successive cycles of dental plaque growth and calcification make it an unusually well-preserved, long-term record of host-microbial interaction in the archaeological record. Recent studies have confirmed the survival of authentic ancient DNA and proteins within historic and prehistoric dental calculus, making it a promising substrate for investigating oral microbiome evolution via direct measurement and comparison of modern and ancient specimens. OBJECTIVE: We present the first comprehensive characterization of the human dental calculus metabolome using a multi-platform approach. METHODS: Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) quantified 285 metabolites in modern and historic (200 years old) dental calculus, including metabolites of drug and dietary origin. A subset of historic samples was additionally analyzed by high-resolution gas chromatography-MS (GC-MS) and UPLC-MS/MS for further characterization of metabolites and lipids. Metabolite profiles of modern and historic calculus were compared to identify patterns of persistence and loss. RESULTS: Dipeptides, free amino acids, free nucleotides, and carbohydrates substantially decrease in abundance and ubiquity in archaeological samples, with some exceptions. Lipids generally persist, and saturated and mono-unsaturated medium and long chain fatty acids appear to be well-preserved, while metabolic derivatives related to oxidation and chemical degradation are found at higher levels in archaeological dental calculus than fresh samples. CONCLUSIONS: The results of this study indicate that certain metabolite classes have higher potential for recovery over long time scales and may serve as appropriate targets for oral microbiome evolutionary studies

Illuminating the life of GPCRs

The investigation of biological systems highly depends on the possibilities that allow scientists to visualize and quantify biomolecules and their related activities in real-time and non-invasively. G-protein coupled receptors represent a family of very dynamic and highly regulated transmembrane proteins that are involved in various important physiological processes. Since their localization is not confined to the cell surface they have been a very attractive "moving target" and the understanding of their intracellular pathways as well as the identified protein-protein-interactions has had implications for therapeutic interventions. Recent and ongoing advances in both the establishment of a variety of labeling methods and the improvement of measuring and analyzing instrumentation, have made fluorescence techniques to an indispensable tool for GPCR imaging. The illumination of their complex life cycle, which includes receptor biosynthesis, membrane targeting, ligand binding, signaling, internalization, recycling and degradation, will provide new insights into the relationship between spatial receptor distribution and function. This review covers the existing technologies to track GPCRs in living cells. Fluorescent ligands, antibodies, auto-fluorescent proteins as well as the evolving technologies for chemical labeling with peptide- and protein-tags are described and their major applications concerning the GPCR life cycle are presented

Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries

Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from −90% to +30%, were reported in many countries following early COVID-19 pandemic response measures (‘lockdowns’). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95–0.98, P value <0.0001), second (0.96, 0.92–0.99, 0.03) and third (0.97, 0.94–1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96–1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88–1.14, 0.98), third (0.99, 0.88–1.12, 0.89) and fourth (1.01, 0.87–1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02–1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03–1.15, 0.002), third (1.10, 1.03–1.17, 0.003) and fourth (1.12, 1.05–1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways