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Homicide is considered a crime against the state rather than the covictims, which impacts on criminal justice system (CJS) processes and can lead to secondary victimization. This review explores the experience of co-victims (i.e., family members) engaging with the CJS. Thirty studies met the inclusion criteria and were identified through searching six bibliographic databases (MEDLINE, HMIC, CINAHL, ASSIA, IBSS, and SSCI) and supplementary searches. Two reviewers conducted screening, data extraction, and quality appraisal. Thematic synthesis resulted in three themes: (a) information and meaningful inclusion, (b) who is the justice system for?, and (c) relating to victims as people. These themes highlight concerns regarding the marginalization of co-victims within the CJS and suggest ways to enhance processes to avoid further marginalizing and traumatizing co-victims., (© 2024 Springer Publishing Company.)

Objectives: We aimed to map the systematic review evidence available to inform the optimal prescribing of statins and antihypertensive medication., Design: Systematic umbrella review and evidence and gap map (EGM)., Data Sources: Eight bibliographic databases (Cochrane Database of Systematic Reviews, CINAHL, EMBASE, Health Management Information Consortium, MEDLINE ALL, PsycINFO, Conference Proceedings Citation Index-Science and Science Citation Index) were searched from 2010 to 11 August 2020. Update searches conducted in MEDLINE ALL 2 August 2022. We searched relevant websites and conducted backwards citation chasing., Eligibility Criteria for Selecting Studies: We sought systematic reviews of quantitative or qualitative research where adults 16 years+ were currently receiving, or being considered for, a prescription of statin or antihypertensive medication. Eligibility criteria were applied to the title and abstract and full text of each article independently by two reviewers., Data Extraction and Synthesis: Quality appraisal was completed by one reviewer and checked by a second. Review characteristics were tabulated and incorporated into an EGM based on a patient care pathway. Patients with lived experience provided feedback on our research questions and EGM., Results: Eighty reviews were included within the EGM. The highest quantity of evidence focused on evaluating interventions to promote patient adherence to antihypertensive medication. Key gaps included a lack of reviews synthesising evidence on experiences of specific interventions to promote patient adherence or improve prescribing practice. The evidence was predominantly of low quality, limiting confidence in the findings from individual reviews., Conclusions: This EGM provides an interactive, accessible format for policy developers, service commissioners and clinicians to view the systematic review evidence available relevant to optimising the prescribing of statin and antihypertensive medication. To address the paucity of high-quality research, future reviews should be conducted and reported according to existing guidelines and address the evidence gaps identified above., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Introduction: We conducted a systematic review of qualitative evidence to improve understanding of the processes and outcomes of redress and reconciliation following a life-changing event from the perspectives of individuals experiencing the event and their families., Methods: We searched six bibliographic databases for primary qualitative evidence exploring the views of individuals who have experienced a life-changing event, and/or their family or carers, of redress or reconciliation processes. This was supplemented with targeted database searches, forward and backward citation chasing and searches of Google Scholar and relevant websites. Title and abstract and full-text screening were undertaken independently by two reviewers. Data extraction and quality appraisal were conducted by one reviewer and checked by a second. We used a best-fit framework synthesis approach, drawing upon procedural and restorative justice concepts., Findings: Fifty-three studies (61 papers) were eligible for inclusion. Forty-one studies (47 papers) were included in the synthesis, from which we identified four themes. Three themes 'Transparency', 'Person-centered' and 'Trustworthy' represent the procedural elements required to support a fair and objective process. The fourth, 'Restorative justice' encapsulates how a fair process feels to those who have experienced a life-changing event. This theme highlights the importance of an empathic relationship between the different parties involved in the redress-reconciliation process and the significance of being able to engage in meaningful action., Conclusion: Our findings highlight the procedural aspects and context of redress-reconciliation processes required to ensure that the process and outcomes are experienced as fair. These criteria may be applied to the processes used to investigate both recent and historical patient safety events., Public Contribution: One member of the public affiliated with the Exeter Policy Research Programme Evidence Review Facility helped develop the review protocol. Two people with experience of medically life-changing events provided insight which corroborated our findings and identified important limitations of the evidence included in this review., (© 2023 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Objectives: We set out to map the quantitative and qualitative systematic review evidence available to inform the optimal prescribing of drugs that can cause dependency (benzodiazepines, opioids, non-benzodiazepine hypnotics, gabapentinoids and antidepressants). We also consider how this evidence can be used to inform decision-making in the patient care pathway for each type of medication., Methods: Eight bibliographic databases were searched for the period 2010 to 2020. All included reviews were initially appraised using four items from the Collaboration for Environmental Evidence Synthesis Assessment Tool, with reviews that scored well on all items proceeding to full quality appraisal. Key characteristics of the reviews were tabulated, and each review was incorporated into an evidence and gap map based on a patient care pathway. The care pathway was based upon an amalgamation of existing NICE guidelines and feedback from clinical and patient stakeholders., Results: We identified 80 relevant reviews and displayed them in an evidence and gap map. The evidence included in these reviews was predominantly of low overall quality. Areas where systematic reviews have been conducted include barriers and facilitators to the deprescribing of drugs that may cause dependency, although we identified little evidence exploring the experiences or evaluations of specific interventions to promote deprescribing. All medications of interest, apart from gabapentinoids, were included in at least one review., Conclusions: The evidence and gap map provides an interactive resource to support (i) policy developers and service commissioners to use evidence in the development and delivery of services for people receiving a prescription of drugs that may cause dependency, where withdrawal of medication may be appropriate, (ii) the clinical decision-making of prescribers and (iii) the commissioning of further research. The map can also be used to inform the commissioning of further systematic reviews. To address the concerns regarding the quality of the existing evidence based raised in this report, future reviews should be conducted according to best-practice guidelines. Systematic reviews focusing on evaluating interventions to promote deprescribing would be particularly beneficial, as would reviews focusing on addressing the paucity of evidence regarding the deprescription of gabapentinoids.

Unicellular protozoa that encyst individually upon starvation evolved at least eight times into organisms that instead form multicellular fruiting bodies with spores. The Dictyostelia are the largest and most complex group of such organisms. They can be subdivided into 4 major groups, with many species in groups 1-3 having additionally retained encystment. To understand fitness differences between spores and cysts, we measured long-term survival of spores and cysts under climate-mimicking conditions, investigated spore and cyst ultrastructure, and related fitness characteristics to species ecology. We found that spores and cysts survived 22 °C equally well, but that spores survived wet and dry frost better than cysts, with group 4 spores being most resilient. Spore walls consist of three layers and those of cysts of maximally two, while spores were also more compacted than cysts, with group 4 spores being the most compacted. Group 4 species were frequently isolated from arctic and alpine zones, which was rarely the case for group 1-3 species. We inferred a fossil-calibrated phylogeny of Dictyostelia, which showed that its two major branches diverged 0.52 billion years ago, following several global glaciations. Our results suggest that Dictyostelium multicellular sporulation was a likely adaptation to a cold climate.

Background: Dictyostelid social amoebas self-organize into fruiting bodies, consisting of spores and up to four supporting cell types in the phenotypically most complex taxon group 4. High quality genomes and stage- and cell-type specific transcriptomes are available for representative species of each of the four taxon groups. To understand how evolution of gene regulation in Dictyostelia contributed to evolution of phenotypic complexity, we analysed conservation and change in abundance, functional domain architecture and developmental regulation of their transcription factors (TFs)., Results: We detected 440 sequence-specific TFs across 33 families, of which 68% were upregulated in multicellular development and about half conserved throughout Dictyostelia. Prespore cells expressed two times more TFs than prestalk cells, but stalk cells expressed more TFs than spores, suggesting that gene expression events that define spores occur earlier than those that define stalk cells. Changes in TF developmental expression, but not in TF abundance or functional domains occurred more frequently between group 4 and groups 1-3, than between the more distant branches formed by groups 1 + 2 and 3 + 4., Conclusions: Phenotypic innovation is correlated with changes in TF regulation, rather than functional domain- or TF acquisition. The function of only 34 TFs is known. Of 12 TFs essential for cell differentiation, 9 are expressed in the cell type for which they are required. The information acquired here on conserved cell type specifity of 120 additional TFs can effectively guide further functional analysis, while observed evolutionary change in TF developmental expression may highlight how genotypic change caused phenotypic innovation.

The Dictyostelid social amoebas are a popular model system for cell- and developmental biology and for evolution of sociality. Small subunit (SSU) ribosomal DNA-based phylogenies subdivide the known 150 species into four major and some minor groups, but lack resolution within groups, particularly group 4, and, as shown by genome-based phylogenies of 11 species, showed errors in the position of the root and nodes separating major clades. We are interested in the evolution of cell-type specialization, which particularly expanded in group 4. To construct a more robust phylogeny, we first included 7 recently sequenced genomes in the genome-based phylogeny of 47 functionally divergent proteins and next selected 6 proteins (Agl, AmdA, PurD, PurL, RpaA, SmdA) that independently or in sets of two fully reproduced the core-phylogeny. We amplified their coding regions from 34 Dictyostelium species and combined their concatenated sequences with those identified in the 18 genomes to generate a fully resolved phylogeny. The new AAPPRS based phylogeny (after the acronym of the 6 proteins) subdivides group 4 into 2 branches. These branches further resolve into 5 clades, rather than the progressively nested group 4 topology of the SSU rDNA tree, and also re-orders taxa in the other major groups. Ancestral state reconstruction of 25 phenotypic traits returned higher "goodness of fit" metrics for evolution of 19 of those traits over the AAPPRS tree, than over the SSU rDNA tree. The novel tree provides a solid framework for studying the evolution of cell-type specialization, signalling and other cellular processes in particularly group 4, which contains the model Dictyostelid D. discoideum., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Annotation of gene models and transcripts is a fundamental step in genome sequencing projects. Often this is performed with automated prediction pipelines, which can miss complex and atypical genes or transcripts. RNA sequencing (RNA-seq) data can aid the annotation with empirical data. Here we present de novo transcriptome assemblies generated from RNA-seq data in four Dictyostelid species: D. discoideum, P. pallidum, D. fasciculatum and D. lacteum. The assemblies were incorporated with existing gene models to determine corrections and improvement on a whole-genome scale. This is the first time this has been performed in these eukaryotic species., Results: An initial de novo transcriptome assembly was generated by Trinity for each species and then refined with Program to Assemble Spliced Alignments (PASA). The completeness and quality were assessed with the Benchmarking Universal Single-Copy Orthologs (BUSCO) and Transrate tools at each stage of the assemblies. The final datasets of 11,315-12,849 transcripts contained 5,610-7,712 updates and corrections to >50% of existing gene models including changes to hundreds or thousands of protein products. Putative novel genes are also identified and alternative splice isoforms were observed for the first time in P. pallidum, D. lacteum and D. fasciculatum., Conclusions: In taking a whole transcriptome approach to genome annotation with empirical data we have been able to enrich the annotations of four existing genome sequencing projects. In doing so we have identified updates to the majority of the gene annotations across all four species under study and found putative novel genes and transcripts which could be worthy for follow-up. The new transcriptome data we present here will be a valuable resource for genome curators in the Dictyostelia and we propose this effective methodology for use in other genome annotation projects.

Coordination of cell movement with cell differentiation is a major feat of embryonic development. The Dictyostelium stalk always forms at the organizing tip, by a mechanism that is not understood. We previously reported that cyclic diguanylate (c-di-GMP), synthesized by diguanylate cyclase A (DgcA), induces stalk formation. Here we used transcriptional profiling of dgca- structures to identify target genes for c-di-GMP, and used these genes to investigate the c-di-GMP signal transduction pathway. We found that knockdown of cAMP-dependent protein kinase (PKA) activity in prestalk cells reduced stalk gene induction by c-di-GMP, whereas PKA activation bypassed the c-di-GMP requirement for stalk gene expression. c-di-GMP caused a persistent increase in cAMP, which still occurred in mutants lacking the adenylate cyclases ACG or ACR, or the cAMP phosphodiesterase RegA. However, both inhibition of adenylate cyclase A (ACA) with SQ22536 and incubation of a temperature-sensitive ACA mutant at the restrictive temperature prevented c-di-GMP-induced cAMP synthesis as well as c-di-GMP-induced stalk gene transcription. ACA produces the cAMP pulses that coordinate Dictyostelium morphogenetic cell movement and is highly expressed at the organizing tip. The stalk-less dgca- mutant regained its stalk by expression of a light-activated adenylate cyclase from the ACA promoter and exposure to light, indicating that cAMP is also the intermediate for c-di-GMP in vivo. Our data show that the more widely expressed DgcA activates tip-expressed ACA, which then acts on PKA to induce stalk genes. These results explain why stalk formation in Dictyostelia always initiates at the site of the morphogenetic organizer., Competing Interests: The authors declare no conflict of interest.

Background: The developmental cycle of Dictyostelid amoebae represents an early form of multicellularity with cell type differentiation. Mutant studies in the model Dictyostelium discoideum revealed that its developmental program integrates the actions of genes involved in signal transduction, adhesion, motility, autophagy and cell wall and matrix biosynthesis. However, due to functional redundancy and fail safe options not required in the laboratory, this single organism approach cannot capture all essential genes. To understand how multicellular organisms evolved, it is essential to recognize both the conserved core features of their developmental programs and the gene modifications that instigated phenotypic innovation. For complex organisms, such as animals, this is not within easy reach, but it is feasible for less complex forms, such as the Dictyostelid social amoebas., Results: We compared global profiles of gene expression during the development of four social amoebae species that represent 600 mya of Dictyostelia evolution, and identified orthologous conserved genes with similar developmental up-regulation of expression using three different methods. For validation, we disrupted five genes of this core set and examined the phenotypic consequences., Conclusion: At least 71 of the developmentally regulated genes that were identified with all methods were likely to be already present in the last ancestor of all Dictyostelia. The lack of phenotypic changes in null mutants indicates that even highly conserved genes either participate in functionally redundant pathways or are necessary for developmental progression under adverse, non-standard laboratory conditions. Both mechanisms provide robustness to the developmental program, but impose a limit on the information that can be obtained from deleting single genes.

The evolution of multicellularity enabled specialization of cells, but required novel signalling mechanisms for regulating cell differentiation. Early multicellular organisms are mostly extinct and the origins of these mechanisms are unknown. Here using comparative genome and transcriptome analysis across eight uni- and multicellular amoebozoan genomes, we find that 80% of proteins essential for the development of multicellular Dictyostelia are already present in their unicellular relatives. This set is enriched in cytosolic and nuclear proteins, and protein kinases. The remaining 20%, unique to Dictyostelia, mostly consists of extracellularly exposed and secreted proteins, with roles in sensing and recognition, while several genes for synthesis of signals that induce cell-type specialization were acquired by lateral gene transfer. Across Dictyostelia, changes in gene expression correspond more strongly with phenotypic innovation than changes in protein functional domains. We conclude that the transition to multicellularity required novel signals and sensors rather than novel signal processing mechanisms.

Dictyostelium discoideum (DD), an extensively studied model organism for cell and developmental biology, belongs to the most derived group 4 of social amoebas, a clade of altruistic multicellular organisms. To understand genome evolution over long time periods and the genetic basis of social evolution, we sequenced the genomes of Dictyostelium fasciculatum (DF) and Polysphondylium pallidum (PP), which represent the early diverging groups 1 and 2, respectively. In contrast to DD, PP and DF have conventional telomere organization and strongly reduced numbers of transposable elements. The number of protein-coding genes is similar between species, but only half of them comprise an identifiable set of orthologous genes. In general, genes involved in primary metabolism, cytoskeletal functions and signal transduction are conserved, while genes involved in secondary metabolism, export, and signal perception underwent large differential gene family expansions. This most likely signifies involvement of the conserved set in core cell and developmental mechanisms, and of the diverged set in niche- and species-specific adaptations for defense and food, mate, and kin selection. Phylogenetic dating using a concatenated data set and extensive loss of synteny indicate that DF, PP, and DD split from their last common ancestor at least 0.6 billion years ago.