Framework synthesis to inform the ideation and design of a paper-based health information system (PHISICC)

BACKGROUND: Health information systems (HIS) are meant to support decision-making at all levels of the system, including frontline health workers. In field studies in Cote d'Ivoire, Mozambique and Nigeria, we observed health workers' interactions with the HIS and identified twelve decision-making components of HIS. The objective of this framework synthesis is to portray these components in HIS research, in order to inform the ideation of a paper-based HIS intervention (PHISICC). METHODS: We searched studies in the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Epistemonikos, Medline, in-Process on the Ovid platform, OpenGrey, PDQ Evidence ("pretty darnd quick" Evidence), the World Health Organization (WHO) Global Health Library and included studies focussing on HIS interventions, data quality, information support tools and data use for decision-making in the context of the governmental health care sector. We assessed the methodological quality of studies using the Critical Appraisal Skills Programme tool. We synthesised the findings based on the decision-making components of HIS and thematic areas. RESULTS: The search identified 6784 studies; 50 were included. Most of the 50 studies had quality concerns. All studies included at least one of the decision-making components: the most prominent were the technical aspects of 'recording' and 'reporting'. Data use for decision-making was much less represented. CONCLUSION: HIS research focuses on the more technical aspects of HIS. Further research on HIS, given the strong push towards HIS digitalisation, should consider putting at the centre the human experience of decision-making and data use, in order to make HIS relevant for quality of care

Formation of carbohydrate-functionalised polystyrene and glass slides and their analysis by MALDI-TOF MS

Glycans functionalised with hydrophobic trityl groups were synthesised and adsorbed onto polystyrene and glass slides in an array format. The adsorbed glycans could be analysed directly on these minimally conducting surfaces by MALDI-TOF mass spectrometry analysis after aluminium tape was attached to the underside of the slides. Furthermore, the trityl group appeared to act as an internal matrix and no additional matrix was necessary for the MS analysis. Thus, trityl groups can be used as simple hydrophobic, noncovalently linked anchors for ligands on surfaces and at the same time facilitate the in situ mass spectrometric analysis of such ligands

KinView: A visual comparative sequence analysis tool for integrated kinome research

Multiple sequence alignments (MSAs) are a fundamental analysis tool used throughout biology to investigate relationships between protein sequence, structure, function, evolutionary history, and patterns of disease-associated variants. However, their widespread application in systems biology research is currently hindered by the lack of user-friendly tools to simultaneously visualize, manipulate and query the information conceptualized in large sequence alignments, and the challenges in integrating MSAs with multiple orthogonal data such as cancer variants and post-translational modifications, which are often stored in heterogeneous data sources and formats. Here, we present the Multiple Sequence Alignment Ontology (MSAOnt), which represents a profile or consensus alignment in an ontological format. Subsets of the alignment are easily selected through the SPARQL Protocol and RDF Query Language for downstream statistical analysis or visualization. We have also created the Kinome Viewer (KinView), an interactive integrative visualization that places eukaryotic protein kinase cancer variants in the context of natural sequence variation and experimentally determined post-translational modifications, which play central roles in the regulation of cellular signaling pathways. Using KinView, we identified differential phosphorylation patterns between tyrosine and serine/threonine kinases in the activation segment, a major kinase regulatory region that is often mutated in proliferative diseases. We discuss cancer variants that disrupt phosphorylation sites in the activation segment, and show how KinView can be used as a comparative tool to identify differences and similarities in natural variation, cancer variants and post-translational modifications between kinase groups, families and subfamilies. Based on KinView comparisons, we identify and experimentally characterize a regulatory tyrosine (Y177PLK4) in the PLK4 C-terminal activation segment region termed the P+1 loop. To further demonstrate the application of KinView in hypothesis generation and testing, we formulate and validate a hypothesis explaining a novel predicted loss-of-function variant (D523NPKCβ) in the regulatory spine of PKCβ, a recently identified tumor suppressor kinase. KinView provides a novel, extensible interface for performing comparative analyses between subsets of kinases and for integrating multiple types of residue specific annotations in user friendly formats

Liver Graft Revascularization by Donor Portal Vein Arterialization Following “No Touch” Donor Hepatectomy

Unsatisfactory immediate function of the transplanted liver together with technical complications contribute to a persisting early mortality for hepatic transplantation in the 20% range. We report our initial clinical experience with methods, one not previously used clinically, that resulted in uniformly well-functioning liver grafts in 11 patients and contributed to a satisfactory success rate for the procedure. Donors were heart-beating. During the donor operation all manipulations of the liver were avoided until after cold preservation, achieved by external cooling at the same time as circulatory interruption, donor exsanguination and perfusion of the liver with cold oxygenated fluid of “extracellular̵ type. The organs were then gently dissected. At transplantation the livers were revascularized with arterial blood shunted from the recipient iliac artery to the graft portal vein after completion of the suprahepatic IVC anastomosis. The infrahepatic IVCs and hepatic arteries were then joined, the iliac artery shunts discontinued and the portal veins joined. Total ischaemic intervals for the allografts were 3½–8 (average 5). Anhepatic intervals were 1–2¼ (average 2). The arterio-portal shunts were operating for 18–85 (mean 46) min. Blood loss and haemodynamic, acid-base and electrolyte abnormalities at revascularization were minimal. All grafts secreted bile immediately and all parameters reflected continuing improvement of liver function thereafter. Nine patients (82%) are alive between 4 and 18 (mean 11) months after transplantation. We conclude that these methods offer effective avoidance of serious organ damage during donor hepatectomy and preservation, reduced allograft ischaemic interval and reduced recipient anhepatic time. They result in avoidance of blood loss at the time of revascularization, together with minimal haemodynamic, acid-base or biochemical changes. In addition, they allow the surgeon to perform and test all anastomoses without time constraints, provide the capability to deal with unexpected complications, and assure good early graft function

Metabolic control of BRISC–SHMT2 assembly regulates immune signalling

Serine hydroxymethyltransferase 2 (SHMT2) regulates one-carbon transfer reactions that are essential for amino acid and nucleotide metabolism, and uses pyridoxal-5′-phosphate (PLP) as a cofactor. Apo SHMT2 exists as a dimer with unknown functions, whereas PLP binding stabilizes the active tetrameric state. SHMT2 also promotes inflammatory cytokine signalling by interacting with the deubiquitylating BRCC36 isopeptidase complex (BRISC), although it is unclear whether this function relates to metabolism. Here we present the cryo-electron microscopy structure of the human BRISC–SHMT2 complex at a resolution of 3.8 Å. BRISC is a U-shaped dimer of four subunits, and SHMT2 sterically blocks the BRCC36 active site and inhibits deubiquitylase activity. Only the inactive SHMT2 dimer—and not the active PLP-bound tetramer—binds and inhibits BRISC. Mutations in BRISC that disrupt SHMT2 binding impair type I interferon signalling in response to inflammatory stimuli. Intracellular levels of PLP regulate the interaction between BRISC and SHMT2, as well as inflammatory cytokine responses. These data reveal a mechanism in which metabolites regulate deubiquitylase activity and inflammatory signalling

DOSCATs: Double standards for protein quantification

The two most common techniques for absolute protein quantification are based on either mass spectrometry (MS) or on immunochemical techniques, such as western blotting (WB). Western blotting is most often used for protein identification or relative quantification, but can also be deployed for absolute quantification if appropriate calibration standards are used. MS based techniques offer superior data quality and reproducibility, but WB offers greater sensitivity and accessibility to most researchers. It would be advantageous to apply both techniques for orthogonal quantification, but workflows rarely overlap. We describe DOSCATs (DOuble Standard conCATamers), novel calibration standards based on QconCAT technology, to unite these platforms. DOSCATs combine a series of epitope sequences concatenated with tryptic peptides in a single artificial protein to create internal tryptic peptide standards for MS as well as an intact protein bearing multiple linear epitopes. A DOSCAT protein was designed and constructed to quantify five proteins of the NF-κB pathway. For three target proteins, protein fold change and absolute copy per cell values measured by MS and WB were in excellent agreement. This demonstrates that DOSCATs can be used as multiplexed, dual purpose standards, readily deployed in a single workflow, supporting seamless quantitative transition from MS to WB

Strategic workforce planning in health and social care - an international perspective: A scoping review

YesEffective strategic workforce planning for integrated and co-ordinated health and social care is essential if future services are to be resourced such that skill mix, clinical practice and productivity meet population health and social care needs in timely, safe and accessible ways globally. This review presents international literature to illustrate how strategic workforce planning in health and social care has been undertaken around the world with examples of planning frameworks, models and modelling approaches. The databases Business Source Premier, CINAHL, Embase, Health Management Information Consortium, Medline and Scopus were searched for full texts, from 2005 to 2022, detailing empirical research, models or methodologies to explain how strategic workforce planning (with at least one-year horizon) in health and/or social care has been undertaken, yielding ultimately 101 included references. The supply/demand of differentiated medical workforce was discussed in 25 references. Nursing and midwifery were characterised as undifferentiated labour, requiring urgent growth to meet demand. Unregistered workers were poorly represented as was the social care workforce. One reference considered planning for heath and social care workers. Workforce modelling was illustrated in 66 references with predilection for quantifiable projections. Increasingly needs-based approaches were called for to better consider demography and epidemiological impacts. This review’s findings advocate for whole-system needs-based approaches that consider the ecology of co-produced health and social care workforce.Claire Sutton and Julie Prowse are seconded (from February 2022 to March 2023) to the Workforce Observatory, the University of Bradford, West Yorkshire. Their research posts at the Workforce Observatory are funded by Health Education England