In situ crosslinking bionanocomposite hydrogels with potential for wound healing applications

In situ forming hydrogels are a class of biomaterials that can fulfil a variety of important biomedically relevant functions and hold promise for the emerging field of patient-specific treatments (e.g., cell therapy, drug delivery). Here we report the results of our investigations on the generation of in situ forming hydrogels with potential for wound healing applications (e.g., complex blast injuries). The combination of polysaccharides that were oxidized to display aldehydes, amine displaying chitosan and nanostructured ZnO yields in situ forming bionanocomposite hydrogels. The physicochemical properties of the components, their cytotoxicity towards HaCat cells and the in vitro release of zinc ions on synthetic skin were studied. The in situ gel formation process was complete within minutes, the components were non-toxic towards HaCat cells at functional levels, Zn2+ was released from the gels, and such materials may facilitate wound healing

Accelerated discharge of patients in the event of a major incident: observational study of a teaching hospital

BACKGROUND: Since October 2002 in the UK Primary Care Trusts (PCTs) have had statutory responsibility for having and maintaining a Major Incident plan and since 2005 they have been obliged to co-operate with other responders to an incident. We aimed to establish the number of beds in our Trust which could be freed up over set periods of time in the event of a major incident and the nature and quantity of support which might be required from PCTs in order to achieve this. METHODS: Repeated survey over 12 days in 3 months of hospital bed occupancy by type of condition and discharge capacity in an 855-bed UK tertiary teaching hospital also providing secondary care services. Outcome measures were bed spaces which could be generated, timescale over which this could happen and level and type of PCT support which would be required to achieve this. RESULTS: Mean beds available were 78 immediately, a further 69 in 1–4 hours and a further 155 in 4–12 hours, generating a total of 302 beds (36% of hospital capacity) within 12 hours of an incident. This would require support from a PCT of 150,000 population of 10 nursing care beds, 20 therapy-supported intermediate care beds, and 25 care packages in patients' own homes. CONCLUSION: In order to fulfill the requirements of the Civil Contingencies Act 2004, PCTs should plan to have surge capacity in the order of 30 residential placements and 25 community support packages per 150,000 population to support Acute Trusts in the event of a major incident

Emergency management in health: key issues and challenges in the UK

Background Emergency planning in the UK has grown considerably in recent years, galvanised by the threat of terrorism. However, deficiencies in NHS emergency planning were identified and the evidence-base that underpins it is questionable. Inconsistencies in terminologies and concepts also exist. Different models of emergency management exist internationally but the optimal system is unknown. This study examines the evidence-base and evidence requirements for emergency planning in the UK health context. Methods The study involved semi-structured interviews with key stakeholders and opinion leaders. Purposive sampling was used to obtain a breadth of views from various agencies involved in emergency planning and response. Interviews were then analysed using a grounded approach using standard framework analysis techniques. Results We conducted 17 key informant interviews. Interviewees identified greater gaps in operational than technical aspects of emergency planning. Social and behavioural knowledge gaps were highlighted with regards to how individuals and organisations deal with risk and behave in emergencies. Evidence-based approaches to public engagement and for developing community resilience to disasters are lacking. Other gaps included how knowledge was developed and used. Conflicting views with regards to the optimal configuration and operation of the emergency management system were voiced. Conclusions Four thematic categories for future research emerged: (i) Knowledge-base for emergency management: Further exploration is needed of how knowledge is acquired, valued, disseminated, adopted and retained. (ii) Social and behavioural issues: Greater understanding of how individuals approach risk and behave in emergencies is required. (iii) Organisational issues in emergencies: Several conflicting organisational issues were identified; value of planning versus plans, flexible versus standardized procedures, top-down versus bottom-up engagement, generic versus specific planning, and reactive versus proactive approaches to emergencies. (iv) Emergency management system: More study is required of system-wide issues relating to system configuration and operation, public engagement, and how emergency planning is assessed

Preparedness of emergency departments in northwest England for managing chemical incidents: a structured interview survey

<p>Abstract</p> <p>Background</p> <p>A number of significant chemical incidents occur in the UK each year and may require Emergency Departments (EDs) to receive and manage contaminated casualties. Previously UK EDs have been found to be under-prepared for this, but since October 2005 acute hospital Trusts have had a statutory responsibility to maintain decontamination capacity. We aimed to evaluate the level of preparedness of Emergency Departments in North West England for managing chemical incidents.</p> <p>Methods</p> <p>A face-to-face semi-structured interview was carried out with the Nurse Manager or a nominated deputy in all 18 Emergency Departments in the Region.</p> <p>Results</p> <p>16/18 departments had a written chemical incident plan but only 7 had the plan available at interview. All had a designated decontamination area but only 11 felt that they were adequately equipped. 12/18 had a current training programme for chemical incident management and 3 had no staff trained in decontamination. 13/18 could contain contaminated water from casualty decontamination and 6 could provide shelter for casualties before decontamination.</p> <p>Conclusion</p> <p>We have identified major inconsistencies in the preparedness of North West Emergency Departments for managing chemical incidents. Nationally recognized standards on incident planning, facilities, equipment and procedures need to be agreed and implemented with adequate resources. Issues of environmental safety and patient dignity and comfort should also be addressed.</p

Combined multiplex panel test results are a poor estimate of disease prevalence without adjustment for test error

This is the uncorrected proof.Data Availability: All data and code used for running experiments, model fitting, and plotting is available on a GitHub repository at https://bristol-vaccine-centre.github.io/testerror/. This is in the form of an R package providing methods to support the estimation of epidemiological parameters based on the results of multiplex panel tests and it is deployed on the Bristol Vaccine Centre r-universe (https://bristol-vaccine-centre.r-universe.dev/testerror). We have also used Zenodo to assign a DOI to the repository: doi:10.5281/zenodo.7691196.Multiplex panel tests identify many individual pathogens at once, using a set of component tests. In some panels the number of components can be large. If the panel is detecting causative pathogens for a single syndrome or disease then we might estimate the burden of that disease by combining the results of the panel, for example determining the prevalence of pneumococcal pneumonia as caused by many individual pneumococcal serotypes. When we are dealing with multiplex test panels with many components, test error in the individual components of a panel, even when present at very low levels, can cause significant overall error. Uncertainty in the sensitivity and specificity of the individual tests, and statistical fluctuations in the numbers of false positives and false negatives, will cause large uncertainty in the combined estimates of disease prevalence. In many cases this can be a source of significant bias. In this paper we develop a mathematical framework to characterise this issue, we determine expressions for the sensitivity and specificity of panel tests. In this we identify a counter-intuitive relationship between panel test sensitivity and disease prevalence that means panel tests become more sensitive as prevalence increases. We present novel statistical methods that adjust for bias and quantify uncertainty in prevalence estimates from panel tests, and use simulations to test these methods. As multiplex testing becomes more commonly used for screening in routine clinical practice, accumulation of test error due to the combination of large numbers of test results needs to be identified and corrected for.Engineering and Physical Sciences Research Council (EPSRC)Medical Research Council (MRC)National Institute for Health and Care Research (NIHR

Where is the evidence for emergency planning: a scoping review

Background Recent terrorist attacks and natural disasters have led to an increased awareness of the importance of emergency planning. However, the extent to which emergency planners can access or use evidence remains unclear. The aim of this study was to identify, analyse and assess the location, source and quality of emergency planning publications in the academic and UK grey literature. Methods We conducted a scoping review, using as data sources for academic literature Embase, Medline, Medline in Process, Psychinfo, Biosis, Science Citation Index, Cinahl, Cochrane library and Clinicaltrials.gov. For grey literature identification we used databases at the Health Protection Agency, NHS Evidence, British Association of Immediate Care Schemes, Emergency Planning College and the Health and Safety Executive, and the websites of UK Department of Health Emergency Planning Division and UK Resilience. Aggregative synthesis was used to analyse papers and documents against a framework based on a modified FEMA Emergency Planning cycle. Results Of 2736 titles identified from the academic literature, 1603 were relevant. 45% were from North America, 27% were commentaries or editorials and 22% were event reports. Of 192 documents from the grey literature, 97 were relevant. 76% of these were event reports. The majority of documents addressed emergency planning and response. Very few documents related to hazard analysis, mitigation or capability assessment. Conclusions Although a large body of literature exists, its validity and generalisability is unclear There is little evidence that this potential evidence base has been exploited through synthesis to inform policy and practice. The type and structure of evidence that would be of most value of emergency planners and policymakers has yet to be identified

Comparison of CATs, CURB-65 and PMEWS as Triage Tools in Pandemic Influenza Admissions to UK Hospitals: Case Control Analysis Using Retrospective Data

Triage tools have an important role in pandemics to identify those most likely to benefit from higher levels of care. We compared Community Assessment Tools (CATs), the CURB-65 score, and the Pandemic Medical Early Warning Score (PMEWS); to predict higher levels of care (high dependency - Level 2 or intensive care - Level 3) and/or death in patients at or shortly after admission to hospital with A/H1N1 2009 pandemic influenza. This was a case-control analysis using retrospectively collected data from the FLU-CIN cohort (1040 adults, 480 children) with PCR-confirmed A/H1N1 2009 influenza. Area under receiver operator curves (AUROC), sensitivity, specificity, positive predictive values and negative predictive values were calculated. CATs best predicted Level 2/3 admissions in both adults [AUROC (95% CI): CATs 0.77 (0.73, 0.80); CURB-65 0.68 (0.64, 0.72); PMEWS 0.68 (0.64, 0.73), p<0.001] and children [AUROC: CATs 0.74 (0.68, 0.80); CURB-65 0.52 (0.46, 0.59); PMEWS 0.69 (0.62, 0.75), p<0.001]. CURB-65 and CATs were similar in predicting death in adults with both performing better than PMEWS; and CATs best predicted death in children. CATs were the best predictor of Level 2/3 care and/or death for both adults and children. CATs are potentially useful triage tools for predicting need for higher levels of care and/or mortality in patients of all ages

Genome sequence of the button mushroom Agaricus bisporus reveals mechanisms governing adaptation to a humic-rich ecological niche

Agaricus bisporus is the model fungus for the adaptation, persistence, and growth in the humic-rich leaf-litter environment. Aside from its ecological role, A. bisporus has been an important component of the human diet for over 200 y and worldwide cultivation of the "button mushroom" forms a multibillion dollar industry. We present two A. bisporus genomes, their gene repertoires and transcript profiles on compost andduringmushroomformation.The genomes encode a full repertoire of polysaccharide-degrading enzymes similar to that of wood-decayers. Comparative transcriptomics of mycelium grown on defined medium, casing-soil, and compost revealed genes encoding enzymes involved in xylan, cellulose, pectin, and protein degradation aremore highly expressed in compost. The striking expansion of heme-thiolate peroxidases and β-etherases is distinctive from Agaricomycotina wood-decayers and suggests a broad attack on decaying lignin and related metabolites found in humic acid-rich environment. Similarly, up-regulation of these genes together with a lignolytic manganese peroxidase, multiple copper radical oxidases, and cytochrome P450s is consistent with challenges posed by complex humic-rich substrates. The gene repertoire and expression of hydrolytic enzymes in A. bisporus is substantially different from the taxonomically related ectomycorrhizal symbiont Laccaria bicolor. A common promoter motif was also identified in genes very highly expressed in humic-rich substrates. These observations reveal genetic and enzymatic mechanisms governing adaptation to the humic-rich ecological niche formed during plant degradation, further defining the critical role such fungi contribute to soil structure and carbon sequestration in terrestrial ecosystems. Genome sequence will expedite mushroom breeding for improved agronomic characteristics

IRAK4 mediates colitis-induced tumorigenesis and chemoresistance in colorectal cancer

Aberrant activation of the NF-κB transcription factors underlies chemoresistance in various cancer types, including colorectal cancer (CRC). Targeting the activating mechanisms, particularly with inhibitors to the upstream IκB kinase (IKK) complex, is a promising strategy to augment the effect of chemotherapy. However, clinical success has been limited, largely because of low specificity and toxicities of tested compounds. In solid cancers, the IKKs are driven predominantly by the Toll-like receptor (TLR)/IL-1 receptor family members, which signal through the IL-1 receptor-associated kinases (IRAKs), with isoform 4 (IRAK4) being the most critical. The pathogenic role and therapeutic value of IRAK4 in CRC have not been investigated. We found that IRAK4 inhibition significantly abrogates colitis-induced neoplasm in APCMin/+ mice, and bone marrow transplant experiments showed an essential role of IRAK4 in immune cells during neoplastic progression. Chemotherapy significantly enhances IRAK4 and NF-κB activity in CRC cells through upregulating TLR9 expression, which can in turn be suppressed by IRAK4 and IKK inhibitors, suggesting a feed-forward pathway that protects CRC cells from chemotherapy. Lastly, increased tumor phospho-IRAK4 staining or IRAK4 mRNA expression is associated with significantly worse survival in CRC patients. Our results support targeting IRAK4 to improve the effects of chemotherapy and outcomes in CRC