Paper 3: Selecting rapid review methods for complex questions related to health policy and system issues

Approaches for rapid reviews that focus on streamlining systematic review methods are not always suitable for exploring complex policy questions, as developing and testing theories to explain these complexities requires configuring diverse qualitative, quantitative, and mixed methods studies. Our objective was therefore to provide a guide to selecting approaches for rapidly (i.e., within days to months) addressing complex questions related to health policy and system issues. We provide a two-stage, transdisciplinary collaborative process to select a rapid review approach to address complex policy questions, which consists of scoping the breadth and depth of the literature and then selecting an optimal approach to synthesis. The first stage (scoping the literature) begins with a discussion with the stakeholders requesting evidence to identify and refine the question for the review, which is then used to conduct preliminary searches and conceptually map the documents identified. In the second stage (selection of an optimal approach), further stakeholder consultation is required to refine and tailor the question and approach to identifying relevant documents to include. The approach to synthesizing the included documents is then guided by the final question, the breadth and depth of the literature, and the time available and can include a static or evolving conceptual framework to code and analyze a range of evidence. For areas already covered extensively by existing systematic reviews, the focus can be on summarizing and integrating the review findings, resynthesizing the primary studies, or updating the search and reanalyzing one or more of the systematic reviews. The choice of approaches for conducting rapid reviews is intertwined with decisions about how to manage projects, the amount of work to be done, and the knowledge already available, and our guide offers support to help make these strategic decisions

Morphology and Nanomechanics of Sensory Neurons Growth Cones following Peripheral Nerve Injury

A prior peripheral nerve injury in vivo, promotes a rapid elongated mode of sensory neurons neurite regrowth in vitro. This in vitro model of conditioned axotomy allows analysis of the cellular and molecular mechanisms leading to an improved neurite re-growth. Our differential interference contrast microscopy and immunocytochemistry results show that conditioned axotomy, induced by sciatic nerve injury, did not increase somatic size of adult lumbar sensory neurons from mice dorsal root ganglia sensory neurons but promoted the appearance of larger neurites and growth cones. Using atomic force microscopy on live neurons, we investigated whether membrane mechanical properties of growth cones of axotomized neurons were modified following sciatic nerve injury. Our data revealed that neurons having a regenerative growth were characterized by softer growth cones, compared to control neurons. The increase of the growth cone membrane elasticity suggests a modification in the ratio and the inner framework of the main structural proteins

Water induced sediment levitation enhances downslope transport on Mars

On Mars, locally warm surface temperatures (~293 K) occur, leading to the possibility of (transient) liquid water on the surface. However, water exposed to the martian atmosphere will boil, and the sediment transport capacity of such unstable water is not well understood. Here, we present laboratory studies of a newly recognized transport mechanism: “levitation” of saturated sediment bodies on a cushion of vapor released by boiling. Sediment transport where this mechanism is active is about nine times greater than without this effect, reducing the amount of water required to transport comparable sediment volumes by nearly an order of magnitude. Our calculations show that the effect of levitation could persist up to ~48 times longer under reduced martian gravity. Sediment levitation must therefore be considered when evaluating the formation of recent and present-day martian mass wasting features, as much less water may be required to form such features than previously thought

Alternative patterns of sex chromosome differentiation in Aedes aegypti (L).

BACKGROUND: Some populations of West African Aedes aegypti, the dengue and zika vector, are reproductively incompatible; our earlier study showed that divergence and rearrangements of genes on chromosome 1, which bears the sex locus (M), may be involved. We also previously described a proposed cryptic subspecies SenAae (PK10, Senegal) that had many more high inter-sex FST genes on chromosome 1 than did Ae.aegypti aegypti (Aaa, Pai Lom, Thailand). The current work more thoroughly explores the significance of those findings. RESULTS: Intersex standardized variance (FST) of single nucleotide polymorphisms (SNPs) was characterized from genomic exome capture libraries of both sexes in representative natural populations of Aaa and SenAae. Our goal was to identify SNPs that varied in frequency between males and females, and most were expected to occur on chromosome 1. Use of the assembled AaegL4 reference alleviated the previous problem of unmapped genes. Because the M locus gene nix was not captured and not present in AaegL4, the male-determining locus, per se, was not explored. Sex-associated genes were those with FST values ≥ 0.100 and/or with increased expected heterozygosity (H exp , one-sided T-test, p < 0.05) in males. There were 85 genes common to both collections with high inter-sex FST values; all genes but one were located on chromosome 1. Aaa showed the expected cluster of high inter-sex FST genes proximal to the M locus, whereas SenAae had inter-sex FST genes along the length of chromosome 1. In addition, the Aaa M-locus proximal region showed increased H exp levels in males, whereas SenAae did not. In SenAae, chromosomal rearrangements and subsequent suppressed recombination may have accelerated X-Y differentiation. CONCLUSIONS: The evidence presented here is consistent with differential evolution of proto-Y chromosomes in Aaa and SenAae

Towards nationally curated data archives for clinical radiology image analysis at scale: Learnings from national data collection in response to a pandemic

The prevalence of the coronavirus SARS-CoV-2 disease has resulted in the unprecedented collection of health data to support research. Historically, coordinating the collation of such datasets on a national scale has been challenging to execute for several reasons, including issues with data privacy, the lack of data reporting standards, interoperable technologies, and distribution methods. The coronavirus SARS-CoV-2 disease pandemic has highlighted the importance of collaboration between government bodies, healthcare institutions, academic researchers and commercial companies in overcoming these issues during times of urgency. The National COVID-19 Chest Imaging Database, led by NHSX, British Society of Thoracic Imaging, Royal Surrey NHS Foundation Trust and Faculty, is an example of such a national initiative. Here, we summarise the experiences and challenges of setting up the National COVID-19 Chest Imaging Database, and the implications for future ambitions of national data curation in medical imaging to advance the safe adoption of artificial intelligence in healthcare

Immunolocalization of Influenza A Virus and Markers of Inflammation in the Human Parkinson's Disease Brain

Although much is known regarding the molecular mechanisms leading to neuronal cell loss in Parkinson's disease (PD), the initiating event has not been identified. Prevailing theories including a chemical insult or infectious agent have been postulated as possible triggers, leading to neuroinflammation. We present immunohistochemical data indicating the presence of influenza A virus within the substantia nigra pars compacta (SNpc) from postmortem PD brain sections. Influenza A virus labeling was identified within neuromelanin granules as well as on tissue macrophages in the SNpc. Further supporting a role for neuroinflammation in PD was the identification of T-lymphocytes that colocalized with an antibody to caspase-cleaved Beclin-1 within the SNpc. The presence of influenza A virus together with macrophages and T-lymphocytes may contribute to the neuroinflammation associated with this disease