“The system is a bit broken…” a qualitative exploration of barriers in the pathway for diagnosing Developmental Coordination Disorder

by Lucy H. Eddy, Nat K. Merrick, Cara E. Staniforth, Jade L. Jukes, Liam J. B. Hill, Mark Mon-Williams, Farid Bardid, Rebecca Murray

Background

Approximately 5% of children are affected by a neurodevelopmental disorder of their sensorimotor skills. DSM-V and ICD-10, the two most widely used diagnostic systems, define this diagnostically as ‘Developmental Coordination Disorder’ (DCD) or ‘Specific Developmental Disorder of Motor Function’ (SDDMF), respectively. A diagnosis of DCD has been found to have a detrimental impact on a range of outcomes (e.g., health and education). It is therefore crucial that these children receive timely intervention. This is reliant, however, on effective assessment and support pathways. Research has shown there is great parental dissatisfaction, but there has been limited research exploring a clinical and education perspective. This study therefore aimed to understand barriers and facilitators for clinical and education practitioners in the pathway in a diverse district in the UK (Bradford).

Methods

Semi-structured interviews were completed with stakeholders across the pathway to identify barriers and facilitators to assessing, diagnosing, and supporting children with sensorimotor skill difficulties. Theoretical thematic analysis aligned to the Capability, Opportunity, Motivation model of Behaviour change (COM-B) was used to analyse the qualitative data.

Results

Interviews revealed many barriers in the DCD pathway related to capability (confusing terminology, inconsistent knowledge, inappropriate referrals), opportunity (resource constraints, DCD being considered low priority, and disconnected services), and motivation (overlapping job roles, a desire to consider those with difficulties not eligible for a diagnosis). No facilitators were consistently identified across interviews.

Conclusion

Families face multiple barriers to obtaining a diagnosis for their child through existing clinical pathways for assessment and support. These findings are unlikely to be unique to Bradford, due to international research highlighting these issues via parental interviews. These findings therefore may reflect challenges both nationally and internationally within DCD pathways. There is an urgent need for: (i) clear communication across different services (with consistency in terminology), and (ii) a more collaborative and integrated approach to assessment, diagnosis, and support in order to help these children thrive.

A live cell biosensor protocol for high-resolution screening of therapy-resistant cancer cells

by Viral D. Oza, Colin S. Williams, Jessica S. Blackburn

The Genetically Encoded Death Indicator (GEDI) is a ratiometric, dual-fluorescence biosensor that enables real-time detection of cell death through calcium influx. Originally developed for use in neurodegeneration models, GEDI can be applied to cancer cells to quantify therapy-induced death at single-cell resolution. This protocol details how to generate GEDI-expressing cancer cell lines, empirically determine stress-induced GEDI thresholds using radiation or chemotherapeutic agents, and perform time-resolved imaging and image analysis to track cell fate. This workflow is optimized for high-throughput drug and radiation screening in heterogeneous populations and is especially useful for identifying chemo- and radio-resistant subclones. Key limitations include the need for empirical GEDI threshold calibration for each treatment condition and careful standardization of imaging parameters. The protocol outputs include GEDI ratio values, single-cell time-of-death annotations, and whole-cell morphological data in parallel, which can be linked to downstream applications such as FACS-based isolation of live or dying subpopulations, transcriptomic profiling of resistant clones, or in vivo validation using xenografts or organotypic slice culture.

Conplastic FVB/N-mt129S6/SvEvTac mice: A new tool for cancer research

by Artiom Gruzdev, Wendy N. Jefferson, Thomas B. Hagler, Gregory J. Scott, Manas K. Ray, Ginger W. Muse, Rani S. Sellers, Carmen J. Williams

FVB/N mice, which are commonly used for cancer studies, have accelerated onset of endometrial cancer following developmental estrogenic chemical exposure. These mice also have a polymorphism in the mitochondrial gene, mt-Atp8, leading to increased production of reactive oxygen species. We hypothesized that this polymorphism contributes to the enhanced endometrial cancer phenotype in FVB/N mice. To test this idea, we generated conplastic FVB/N-mt129S6/SvEvTac mice (FVB/N nuclear genome; 129S6/SvEvTac mitochondria: FVB/N-mt129). The impact of 129S6 versus FVB/N mitochondrial genomes on endometrial cancer development following neonatal exposure to the xenoestrogen, diethylstilbestrol, was tested by comparing the cancer phenotypes of FVB/N mice to FVB/N-mt129 mice. There was no difference in cancer incidence regardless of mitochondria source, but cancer grade was higher in the conplastic strain. Additionally, while the FVB/N genetic background is considered non-permissive for generation of pluripotent mouse embryonic stem cells, blastocysts from the conplastic background readily generated mouse embryonic stem cell clones that supported gene editing in culture and subsequently generated germline competent chimeric founder mice. FVB/N-mt129 mice are a potentially powerful resource for generating germline competent embryonic stem cells with an FVB/N nuclear genome and for studying cancer phenotypes.

Protocol for a systematic review and meta-analysis of the impact of cervical cancer prevention initiatives in Ghana

by Emmanuel Timmy Donkoh, Iddrisu Wahab Abdul, Abraham Kwadzo Ahiakpa, Isaac Williams, Rita Nyaaba Akologo, Stephen Danyo, Chrysantus Kubio, Kofi Effah, Joseph Emmanuel Amuah

Background

Cervical cancer, though preventable, remains the second most diagnosed cancer and the primary cause of cancer-related deaths among females in Sub-Saharan Africa. The significance of coordinated screening programmes for reducing the burden of cervical cancer in Africa is not well documented. This systematic review will summarize published reports from key databases, grey literature and programme reports to assess the performance of cervical cancer prevention programmes in Ghana.

Methods

To be eligible for inclusion, interventions must target Ghanaian women with cervical cancer screening and prevention strategies using methods such as visual inspection with acetic acid (VIA), mobile colposcopy, HPV DNA testing, cytology (Pap smear), and treatment approaches such as cryotherapy, thermal ablation, loop electrosurgical excision procedure (LEEP). A comprehensive electronic search strategy will be used to identify studies published since database inception, and indexed in MEDLINE, EMBASE, CINAHL and Web of Science. The search strategy will include MeSH terms (and synonyms) relevant to cervical cancer, screening/treatment methods, geographic focus and implementing institution. We will include searches for grey literature, recognizing the value of programmatic and governmental reports that might not appear in traditional databases. Search results will be summarized in line with PRISMA guidelines. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach will be used to evaluate and document evidence certainty for all outcomes, internal validity of included reports, inconsistency, indirectness, imprecision, and publication bias. Where sufficient homogeneity exists among included studies in terms of interventions, study designs, populations, and outcome measures, we will perform a meta-analysis to calculate pooled effect estimates and their corresponding 95% confidence intervals.

Significance

This systematic review will assess the performance and impact of cervical cancer screening and prevention programmes conducted in Ghana to date and identify what contextual strategies have delivered the most impact as well as highlight what gaps remain in our understanding of how a nationwide screening programme can be properly construed for maximum impact.