Protocolized care pathways in emergency general surgery: a systematic review and meta-analysis.

BACKGROUND: Emergency abdominal surgery is associated with significant postoperative morbidity and mortality. The delivery of standardized pathways in this setting may have the potential to transform clinical care and improve patient outcomes. METHODS: The OVID SP versions of MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched between January 1950 and October 2022. All randomized and non-randomized cohort studies comparing protocolized care streams with standard care protocols in adult patients (>18 years old) undergoing major emergency abdominal surgery with 30-day follow-up data were included. Studies were excluded if they reported on standardized care protocols in the trauma or elective setting. Outcomes assessed included length of stay, 30-day postoperative morbidity, 30-day postoperative mortality and 30-day readmission and reoperations rates. Risk of bias was assessed using ROBINS-I for non-randomized studies and RoB-2 for randomized controlled trials. Meta-analysis was performed using random effects modelling. RESULTS: Seventeen studies including 20 927 patients were identified, with 12 359 patients undergoing protocolized care pathways and 8568 patients undergoing standard care pathways. Thirteen unique protocolized pathways were identified, with a median of eight components (range 6-15), with compliance of 24-100%. Protocolized care pathways were associated with a shorter hospital stay compared to standard care pathways (mean difference -2.47, 95% c.i. -4.01 to -0.93, P = 0.002). Protocolized care pathways had no impact on postoperative mortality (OR 0.87, 95% c.i. 0.41 to 1.87, P = 0.72). A reduction in specific postoperative complications was observed, including postoperative pneumonia (OR 0.42 95% c.i. 0.24 to 0.73, P = 0.002) and surgical site infection (OR 0.34, 95% c.i. 0.21 to 0.55, P < 0.001). DISCUSSION: Protocolized care pathways in the emergency setting currently lack standardization, with variable components and low compliance; however, despite this they are associated with short-term clinical benefits.

Thoracic spine stab injury with a retained knife.

A female was admitted to a Major Trauma Centre with an isolated thoracic spine stab injury involving a retained knife. The patient was haemodynamically stable with an unremarkable peripheral neurological examination. A CT scan with three-dimensional image reconstruction showed the knife blade lodged in the T11 vertebra with its tip close to the spinal cord, aorta and inferior vena cava. A multidisciplinary trauma team, including anaesthetists, vascular, neurosurgeons and general surgeons, agreed on the treatment strategy. The lodged knife was safely withdrawn in the operating theatre with the patient in a prone position under sedation and local anaesthesia. Following the procedure, neurological examination remained normal, and an MRI scan revealed no spinal cord injury. We discuss the management of penetrating spinal injuries, the importance of detailed preoperative imaging, timely multidisciplinary input and how to safely remove a knife when a prone position prevents standard airway management.

Cohort study to characterise surgical site infections after open surgery in the UK's National Health Service.

OBJECTIVE: To characterise surgical site infections (SSIs) after open surgery in the UK's National Health Service. DESIGN: Retrospective cohort analysis of electronic records of patients from Clinical Practice Research Datalink, linked with Hospital Episode Statistics' secondary care datasets. SETTING: Clinical practice in the community and secondary care. PARTICIPANTS: Cohort of 50 000 adult patients who underwent open surgery between 2017 and 2022. OUTCOME MEASURES: Incidence of SSI, clinical outcomes, patterns of care and costs of wound management. RESULTS: 11% (5281/50 000) of patients developed an SSI a mean of 18.4±14.7 days after their surgical procedure, of which 15% (806/5281) were inpatients and 85% (4475/5281) were in the community after hospital discharge. The incidence of SSI varied according to anatomical site of surgery. The incidence also varied according to a patient's risk and whether they underwent an emergency procedure. SSI onset reduced the 6 months healing rate by a mean of 3 percentage points and increased time to wound healing by a mean of 15 days per wound. SSIs were predominantly managed in the community by practice and district nurses and 16% (850/5281) of all patients were readmitted into hospital. The total health service cost of surgical wound management following SSI onset was a mean of £3537 per wound ranging from £2542 for a low-risk patient who underwent an elective procedure to £4855 for a high-risk patient who underwent an emergency procedure. CONCLUSIONS: This study provides important insights into several aspects of SSI management in clinical practice in the UK that have been difficult to ascertain from surveillance data. Surgeons are unlikely to be fully aware of the true incidence of SSI and how they are managed once patients are discharged from hospital. Current SSI surveillance services appear to be under-reporting the actual incidence.

Development and validation of a patient reported outcome measure for health-related quality of life for locally recurrent rectal cancer: a multicentre, three-phase, mixed-methods, cohort study.

Background: Locally recurrent rectal cancer (LRRC) occurs in 5-10% of patients following previous treatment of rectal cancer. It has a significant impact on patients' overall health-related quality of life (HrQoL). Major advances in surgical treatments have led to improved survival outcomes. However, due to the lack of disease-specific, validated patient-reported outcome measure (PROM), HrQoL, is variably assessed. The aim of this study is to develop a disease-specific, psychometrically robust, and validated PROM for use in LRRC. Methods: A multicentre, three phase, mixed-methods, observational study was performed across five centres in the UK and Australia. Adult patients (>18 years old) with an existing or previously treated LRRC within the last 2 years were eligible to participate. Patients completed the proposed LRRC-QoL, EORTC QLQ-CR29, and FACT-C questionnaires. Scale structure was analysed using multi-trait scaling analysis and exploratory factor analysis, reliability was assessed using Cronbach's and the intra-class coefficient, convergent validity was assessed using Pearson's correlation, and known-groups comparison was assessed using the student t-test or ANOVA. Findings: Between 01/03/2015 and 31/12/2019, 117 patients with a diagnosis of LRRC were recruited. The final scale structure of the LRRC-QoL consisted of nine multi-item scales (healthcare services, psychological impact, pain, urostomy-related symptoms, lower limb symptoms, stoma, sexual function, sexual interest, and urinary symptoms) and three single items. Cronbach's Alpha and Intraclass correlation values of >0.7 across the majority of scales supported overall reliability. Convergent validity was demonstrated between LRRC-QoL Pain Scale and FACT-C Physical Well Being scale (r = 0.528, p < 0.001), LRRC-QoL Psychological Impact scale with EORTC QLQ CR29 Body Image (r = 0.680, p < 0.001) and the FACT-C Emotional Well Being scale (r = 0.326, p < 0.001), and LRRC-QoL Urinary Symptoms scale with EORTC QLQ-CR29 Urinary Frequency scale (r = 0.310, p < 0.001). Known-groups validity was demonstrated for gender, disease location, treatment intent, and re-recurrent disease. Interpretation: The LRRC-QoL has demonstrated robust psychometric properties and can be used in clinical and academic practice. Funding: None.

Improving health outcomes of people with diabetes: target setting for the WHO Global Diabetes Compact.

The Global Diabetes Compact is a WHO-driven initiative uniting stakeholders around goals of reducing diabetes risk and ensuring that people with diabetes have equitable access to comprehensive, affordable care and prevention. In this report we describe the development and scientific basis for key health metrics, coverage, and treatment targets accompanying the Compact. We considered metrics across four domains: factors at a structural, system, or policy level; processes of care; behaviours and biomarkers such as glycated haemoglobin (HbA1c); and health events and outcomes; and three risk tiers (diagnosed diabetes, high risk, or whole population), and reviewed and prioritised them according to their health importance, modifiability, data availability, and global inequality. We reviewed the global distribution of each metric to set targets for future attainment. This process led to five core national metrics and target levels for UN member states: (1) of all people with diabetes, at least 80% have been clinically diagnosed; and, for people with diagnosed diabetes, (2) 80% have HbA1c concentrations below 8·0% (63·9 mmol/mol); (3) 80% have blood pressure lower than 140/90 mm Hg; (4) at least 60% of people 40 years or older are receiving therapy with statins; and (5) each person with type 1 diabetes has continuous access to insulin, blood glucose meters, and test strips. We also propose several complementary metrics that currently have limited global coverage, but warrant scale-up in population-based surveillance systems. These include estimation of cause-specific mortality, and incidence of end-stage kidney disease, lower-extremity amputations, and incidence of diabetes. Primary prevention of diabetes and integrated care to prevent long-term complications remain important areas for the development of new metrics and targets. These metrics and targets are intended to drive multisectoral action applied to individuals, health systems, policies, and national health-care access to achieve the goals of the Global Diabetes Compact. Although ambitious, their achievement can result in broad health benefits for people with diabetes.

Short-term outcomes of health-related quality of life in patients with locally recurrent rectal cancer: multicentre, international, cross-sectional cohort study.

BACKGROUND: Overall survival rates for locally recurrent rectal cancer (LRRC) continue to improve but the evidence concerning health-related quality of life (HrQoL) remains limited. The aim of this study was to describe the short-term HrQoL differences between patients undergoing surgical and palliative treatments for LRRC. METHODS: An international, cross-sectional, observational study was undertaken at five centres across the UK and Australia. HrQoL in LRRC patients was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-CR29 and functional assessment of cancer therapy - colorectal (FACT-C) questionnaires and subgroups (curative versus palliative) were compared. Secondary analyses included the comparison of HrQoL according to the margin status, location of disease and type of treatment. Scores were interpreted using minimal clinically important differences (MCID) and Cohen effect size (ES). RESULTS: Out of 350 eligible patients, a total of 95 patients participated, 74.0 (78.0 per cent) treated with curative intent and 21.0 (22.0 per cent) with palliative intent. Median time between LRRC diagnosis and HrQoL assessments was 4 months. Higher overall FACT-C scores denoting better HrQoL were observed in patients undergoing curative treatment, demonstrating a MCID with a mean difference of 18.5 (P < 0.001) and an ES of 0.6. Patients undergoing surgery had higher scores denoting a higher burden of symptoms for the EORTC CR29 domains of urinary frequency (P < 0.001, ES 0.3) and frequency of defaecation (P < 0.001, ES 0.4). Higher overall FACT-C scores were observed in patients who underwent an R0 resection versus an R1 resection (P = 0.051, ES 0.6). EORTC CR29 scores identified worse body image in patients with posterior/central disease (P = 0.021). Patients undergoing palliative chemoradiation reported worse HrQoL scores with a higher symptom burden on the frequency of defaecation scale compared with palliative chemotherapy (P = 0.041). CONCLUSION: Several differences in short-term HrQoL outcomes between patients undergoing curative and palliative treatment for LRRC were documented. Patients undergoing curative surgery reported better overall HrQoL and a higher burden of pelvic symptoms.

The current status of robotic colorectal surgery training programmes.

Robotic-assisted colorectal surgery (RACS) is steadily increasing in popularity with an annual growth in the number of colorectal procedures undertaken robotically. Further upscaling of RACS requires structured and standardised robotic training to safeguard high-quality clinical outcomes. The aims of this systematic review were to assess the structure and assessment metrics of currently established RACS training programmes. A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines was performed. Searches were performed of the Ovid Medline, Embase and Web of Science databases between 2000 and 27th November 2021 to identify studies reporting on training curricula in RACS. Core components of training programmes and their relevant outcome assessment metrics were extracted. Thirteen studies were identified, with all training programmes designed for the da Vinci platform (Intuitive Surgical, Inc., Sunnyvale, CA, USA). Common elements of multimodal programmes included theoretical knowledge (76.9%), case observation (53.8%), simulation (100%) and proctored training (76.9%). Robotic skills acquisition was assessed primarily during the simulation phase (n = 4, 30.1%) and proctoring phase (n = 10, 76.9%). Performance metrics, consisting of time or assessment scores for VR simulation were only mandated in four (30.1%) studies. Objective assessment following proctored training was variably reported and employed a range of assessment metrics, including direct feedback (n = 3, 23.1%) or video feedback (n = 8, 61.5%). Five (38.4%) training programmes used the Global Assessment Score (GAS) forms. There is a broad consensus on the core multimodal components across current RACS training programmes; however, validated objective assessment is limited and needs to be appropriately standardised to ensure reproducible progression criteria and competency-based metrics are produced to robustly assess progression and competence.

Recruiting to surgical trials in the emergency setting: using a mixed methods study to understand clinician and patient perspectives.

BACKGROUND: Undertaking randomized clinical trials (RCTs) in emergency surgical settings is associated with methodological and practical challenges. This study explored patients' and clinicians' perspectives associated with the conduct of an RCT comparing laparoscopic and open colorectal surgery in the acute setting. METHODS: All eligible patients screened and enrolled for the 'Laparoscopic versus open colorectal surgery in the acute setting (LaCeS)' multicentre, randomized clinical feasibility trial in five UK NHS Trusts were invited to respond to a survey. Patients and healthcare professionals were also invited to take part in semi-structured interviews. Survey and interviews explored the acceptability of the feasibility trial. Interviews were audio recorded, transcribed verbatim, and analysed using thematic analysis. Survey data were analysed descriptively to assess patient views of the trial and intervention. RESULTS: Out of 72 patients enrolled for the LaCeS RCT, survey data were collected from 28 patients (38.9 per cent), and interviews were conducted with 16 patients and 14 healthcare professionals. Thirteen out of 28 patients (46 per cent) had treatment preferences but these were not strong enough to deter participation. Twelve of the patients interviewed believed that their surgeon preferred laparoscopic surgery, but this did not deter them from participating in the trial. Half of the surgeons interviewed expressed the view that laparoscopic surgery was of benefit in this setting, but recognized that the need for research evidence outweighed their personal treatment preferences. Eight of the 14 recruiters reported that the emergency setting affected recruitment, especially in centres with fewer recruiting surgeons. Interviewees reported that recruitment was helped significantly by using surgical trainees to consent patients. CONCLUSION: This study identified specific challenges for the LaCeS trial design to address and adds significant insights to our understanding of recruiting to emergency surgical trials more broadly.

Utilising quality of life outcome trajectories to aid patient decision making in pelvic exenteration.

BACKGROUND: Shared decision-making in pelvic exenteration is a complex and detailed process, which must balance clinical, oncological and patient-reported outcomes (PROs), whilst addressing and valuing the patient priorities. Communicating patient-centred information on quality of life (QoL) and functional outcomes is an essential component of this. The aim of this systematic review was to understand the impact of pelvic exenteration on QoL PROs over a longitudinal period and to develop QoL trajectories to support decision-making in this context. METHODS: MEDLINE, Embase and Web of Science databases were searched between 1st January 2000 and 20th December 2021 Studies reporting on PROs, including QoL, in adults undergoing pelvic exenteration were included. Risk of bias was assessed using the ROBINS-I assessment tool. Data from studies reporting QoL using the same outcome measure at the same candidate timepoint were extracted and synthesised to develop a longitudinal QoL trajectory. RESULTS: Fourteen studies consisting of 1370 patients were included in this review. QoL trajectories were constructed in the domains of physical function, psychological function, role function, sexual function, body image and general and specific symptoms. Decision-making was only assessed by one study, with satisfaction with decision-making reported to be high. There is an initial decline in QoL scores in the domains of physical function, role function, sexual function, body image and general health and symptoms deteriorating during the first 3-6 months post-operatively. Psychological function is the only QoL domain that remains stable throughout the post-operative period. CONCLUSION: Mapping QoL trajectories provides a visual representation of post-operative progress, highlighting the enduring impact of pelvic exenteration on patients and can be used to inform pre-operative shared decision-making.

The importance of PEOPLE who use drugs within drug policy reform debates: Findings from the UK Drug Policy Voices online survey.

BACKGROUND: Drug Policy Voices is a UK-based project designed to integrate the voices and experiences of people who use drugs (PWUD) into debates about drug policy reform. An online survey was conducted in 2020 to understand opinions connected to drug use and drug policy. We used a blended values approach combining Moral Foundations Theory (Haidt and Joseph, 2004; Haidt and Graham, 2007) and MacCoun and Reuter's (2001) four philosophical positions that underpin the drug policy. This paper asks, what values do people who use drugs hold surrounding drug use and drug policy, and what factors predict these values? METHODS: We used online-purposive sampling and achieved 1217 survey responses, which captured sociodemographic characteristics, patterns of drug use, sourcing and supply of drugs used within the last 12 months, experiences of criminal justice sanctions in connection to drugs, and experiences of alcohol or other drug treatment. In addition, we devised 37 attitudinal questions about drug use and drug policy, which included both progressive and prohibitionist value positions. RESULTS: The exploratory factor analysis revealed a six-factor solution that identified important value positions for this respondent group, which are personal autonomy, paternalism 1; paternalism 2; legal injustice 1; legal injustice 2; and neoliberal governance. Age, gender, religious beliefs, political views, identifying as a recreational drug taker, using drugs recently, and having experience of working or studying in the substance use/drug policy field are predictors of these value positions. CONCLUSION: The Drug Policy Voices survey has identified collective values and ideology connected to lived experience that illustrate a clear goal conflict with prohibitionist ideology. PWUD have valuable contributions to make to the policy reform debate, but we must acknowledge that opinions are not formed through drug-related experiences alone. The findings of this research highlight the importance of emphasising the person who uses drugs within participatory approaches.

Anatomical approaches in locally advanced and recurrent pelvic malignancy.

Pelvic exenteration is a complex, technically challenging procedure requiring detailed anatomical knowledge. Understanding the complexity of the pelvis beyond TME is an essential requirement for both operative planning and execution. This paper highlights the key anatomical approaches to extended pelvic resection as relevant to the Colorectal Surgeon.

Protocol to develop a core outcome set in incisional hernia surgery: the HarMoNY Project.

INTRODUCTION: Incisional hernia has an incidence of up to 20% following laparotomy and is associated with significant morbidity and impairment of quality of life. A variety of surgical strategies including techniques and mesh types are available to manage patients with incisional hernia. Previous works have reported significant heterogeneity in outcome reporting for abdominal wall herniae, including ventral and inguinal hernia. This is coupled with under-reporting of important clinical and patient-reported outcomes. The lack of standardisation in outcome reporting contributes to reporting bias, hinders evidence synthesis and adequate data comparison between studies. This project aims to develop a core outcome set (COS) of clinically important, patient-oriented outcomes to be used to guide reporting of future research in incisional hernia. METHODS: This project has been designed as an international, multicentre, mixed-methods project. Phase I will be a systematic review of current literature to examine the current clinical and patient-reported outcomes for incisional hernia and abdominal wall reconstruction. Phase II will identify the outcomes of importance to all key stakeholders through in depth qualitative interviews. Phase III will achieve consensus on outcomes of most importance and for inclusion into a COS through a Delphi process. Phase IV will achieve consensus on the outcomes that should be included in a final COS. ETHICS AND DISSEMINATION: The adoption of this COS into clinical and academic practice will be endorsed by the American, British and European Hernia Societies. Its utilisation in future clinical research will enable appropriate data synthesis and comparison and will enable better clinical interpretation and application of the current evidence base. This study has been registered with the Core Outcome Measures in Effectiveness Trials initiative. PROSPERO REGISTRATION NUMBER: CRD42018090084.

Adaptive responses to air pollution in human dermal fibroblasts and their potential roles in aging.

The damaging effects of air pollution on the skin are becoming increasingly researched and the outcomes of this research are now a major influence in the selection and development of protective ingredients for skincare formulations. However, extensive research has not yet been conducted into the specific cellular defense systems that are being affected after exposure to such pollutants. Research investigating the affected systems is integral to the development of suitable interventions that are capable of augmenting the systems most impacted by air pollutant exposure. The following studies involved exposing primary human dermal fibroblasts to different concentrations of particulate matter and analyzing its effects on mitochondrial complex activity, nuclear factor erythroid 2-related factor 2 localization using immunocytochemistry and protein expression of electron transport chain complex proteins, sirtuin-1 (SIRT1), and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) using western blotting. Particulate matter-induced alterations in both mitochondrial complex protein and activity, indicating oxidative stress, which was also complimented by increased expression of antioxidant proteins GSTP1/2 and SOD2. Particulate matter also seemed to modify expression of the proteins SIRT1 and PGC-1α which are heavily involved in the regulation of mitochondrial biogenesis and energy metabolism. Given the reported results indicating that particulate matter induces damage through oxidative stress and has a profound effect on mitochondrial homeostasis, interventions involving targeted mitochondrial antioxidants may help to minimize the damaging downstream effects of pollutant-induced oxidative stress originating from the mitochondria.

A Biologic Surgical Implant in Complex Abdominal Wall Repair: 3-Year Follow-Up Results of a Multicentric Prospective Study.

PURPOSE: Despite the advancements in the reinforcement and closure techniques available, complex abdominal wall reconstruction (CAWR) remains a challenging surgical undertaking with considerable risk of postoperative complications. Biological meshes were developed that may help to complement standard closure techniques and offer an alternative to synthetic meshes, which carry significant risks with their use in complex cases. PATIENTS AND METHODS: A total of 114 patients underwent surgical treatment for CAWR with a Permacol™ (a biologic surgical implant). The study objective was to evaluate the short-term (6 months), mid-term (12-24 months), and long-term (36 months) clinical outcomes (through 36 months) associated with the use of a biologic surgical implant in these cases. RESULTS: The cumulative hernia recurrence rate was 18.7% (17/91) at 24 months and 22.4% (19/85) at 36 months. Twelve (14.1%) subjects required reoperation for hernia repair within 36 months for repair of recurrent hernias. Between 6- and 36-months post-surgery, patients reported improvement in their Carolina comfort scale (CSS) measures of severity of pain, sensation of mesh, and movement limitations. CONCLUSION: A biologic surgical implant can provide long-term benefit to complex abdominal wall repairs in patients staged grade III according to the Ventral Hernia Working Group (VHWG).

Two-year outcomes from the Australian and New Zealand Emergency Laparotomy Audit-Quality Improvement pilot study.

BACKGROUND: The aim of the Australian and New Zealand Emergency Laparotomy Audit-Quality Improvement (ANZELA-QI) pilot study was to determine (i) the outcomes of emergency laparotomy (EL) and (ii) the feasibility of a national, multi-disciplinary quality improvement (QI) project based on a bundle of evidence-based care standards. METHODS: An online database was created using the Research Electronic Data Capture (REDCap) programme. National ethics approval with waiver of consent was obtained. Data were entered directly onto REDCap and extracted monthly for eight care standards (preoperative consultant radiologist reporting of computed tomography scans, preoperative mortality risk score, consultant presence in theatre, timely access to theatre and critical care commensurate with risk and involvement of aged care). Monthly QI run charts using 'traffic' light graphics (green ≥80%, amber ≥50% to <80% and red <50%) reported compliance with the standards. RESULTS: Sixty hospitals indicated interest, but difficulties with site-specific ethics approval resulted in only 24 hospitals participating (2886 EL in 2755 patients). The overall in-hospital mortality was 7.1% (2.3%-13.3%) and average length of stay 15.5 (8.6-22.7) days. Both significantly declined. Preoperative risk assessment (overall 45%) improved almost three-fold during the study. Only 60% had timely access to theatre and only 70% with a predicted mortality risk of >10% were admitted to critical care. CONCLUSION: Overall mortality compared favourably with similar international studies and declined in association with participation in the audit. Compliance with some care standards shows considerable scope to improve EL care using QI methodology.

Closed incision negative pressure wound therapy is associated with reduced surgical site infection after emergency laparotomy: A propensity matched-cohort analysis.

BACKGROUND: Surgical site infection contributes to a significant proportion of postoperative morbidity in patients undergoing emergency laparotomy. Surgical site infections cause significant patient burden, increase duration of stay, and have economic implications. Closed incision negative pressure therapy has been shown to reduce surgical site infection rates in patients undergoing elective laparotomy; however, there is limited evidence for their use in the emergency setting. This study aims to compare rates of surgical site infection between patients receiving closed incision negative pressure therapy and standard surgical dressing after emergency laparotomy through a propensity matched analysis. METHODS: A registry-based, prospective cohort study was undertaken using data from the National Emergency Laparotomy Audit database at our center. The primary outcome measure was surgical site infection as defined by the Centers for Disease Control criteria. Secondary outcomes included 30-day postoperative morbidity and grade, duration of stay, 30-day mortality, and readmission rates. A propensity-score matching was performed in a 1:1 ratio to mitigate for selection bias. RESULTS: A total of 1,484 patients were identified from the National Emergency Laparotomy Audit data set, and propensity-score matching resulted in 2 equally matched cohorts with 237 patients in each arm. The rate of surgical site infection was significantly lower in the closed incision negative pressure therapy cohort (16.9% vs 33.8%, P < .001). There were no overall differences in 30-day morbidity, Clavien-Dindo grade, Comprehensive Complication Index severity, length of hospital stay, reoperation rates, and 30-day mortality between the 2 groups. CONCLUSIONS: Prophylactic closed incision negative pressure therapy in emergency laparotomy patients is associated with a reduction in surgical site infection rates.

Exploring cation disorder in mixed-metal pyrochlore ceramics using 17 O NMR spectroscopy and first-principles calculations.

Characterising the local structures (e.g., the cation distribution) of mixed-metal ceramics by NMR spectroscopy is often challenging owing to the unfavourable properties (low γ, large quadrupole moment and/or low abundance) of many metal nuclei. 17 O is an attractive option owing to the prevalence of oxygen within ceramics. The moderate γ and small quadrupole moment of 17 O mean that the greatest barrier to accessing the information available from this nucleus is isotopic enrichment. We explore the challenges of ensuring uniform isotopic enrichment with 17 O2 (g) for the pyrochlore solid solutions, Y2 Snx Ti2-x O7 , La2 Snx Zr2-x O7 and La2 Snx Hf2-x O7 , demonstrating that high enrichment temperatures (900 °C for 12 hr) are required. In addition, for sites with very high symmetry (such as the tetrahedral OY4 and OLa4 sites with CQ ≈ 0 present here), we demonstrate that quantitative 17 O NMR spectra require correction for the differing contributions from the centreband of the satellite transitions, which can be as high as a factor of ~3.89. It is common to use first-principles calculations to aid in interpreting NMR spectra of disordered solids. Here, we use an ensemble modelling approach to ensure that all possible cation arrangements are modelled in the minimum possible number of calculations. By combining uniform isotopic enrichment, quantitative NMR spectroscopy and a comprehensive computational approach, we are able to show that the cation distribution in Y2 Snx Ti2-x O7 is essentially random, whereas in La2 Snx Zr2-x O7 and La2 Snx Hf2-x O7 , OLa2SnZr and OLa2SnHf sites are slightly energetically disfavoured, leading to a weak preference for clustering of like cations.

luox: validated reference open-access and open-source web platform for calculating and sharing physiologically relevant quantities for light and lighting.

Light exposure has a profound impact on human physiology and behaviour. For example, light exposure at the wrong time can disrupt our circadian rhythms and acutely suppress the production of melatonin. In turn, appropriately timed light exposure can support circadian photoentrainment. Beginning with the discovery that melatonin production is acutely suppressed by bright light more than 40 years ago, understanding which aspects of light drive the 'non-visual' responses to light remains a highly active research area, with an important translational dimension and implications for "human-centric" or physiologically inspired architectural lighting design. In 2018, the International Commission on Illumination (CIE) standardised the spectral sensitivities for predicting the non-visual effects of a given spectrum of light with respect to the activation of the five photoreceptor classes in the human retina: the L, M and S cones, the rods, and the melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs). Here, we described a novel, lean, user-friendly, open-access and open-source platform for calculating quantities related to light. The platform, called luox, enables researchers and research users in vision science, lighting research, chronobiology, sleep research and adjacent fields to turn spectral measurements into reportable quantities. The luox code base, released under the GPL-3.0 License, is modular and therefore extendable to other spectrum-derived quantities. luox calculations of CIE quantities and indices have been endorsed by the CIE following black-box validation.

Exposing human primary dermal fibroblasts to particulate matter induces changes associated with skin aging.

With a large proportion of the world's population living in areas where air quality does not meet current WHO guidelines, combined with the knowledge that pollutants can interact with human skin, it is now of even greater importance that the effects of air pollutant exposure on human skin be investigated. To evaluate the damaging effects of a known component of air pollution (particulate matter) on human primary dermal fibroblasts. These studies were undertaken by exposing primary human dermal fibroblasts to different concentrations of particulate matter and analyzing the effects over time using resazurin reduction assays. Immunofluorescence microscopy was used to determine if particulate matter caused activation of the aryl hydrocarbon receptor, and phosphorylation of histone H2AX, a known marker of double-strand DNA breaks. Dot blotting was also used to analyze expression changes in secreted MMP-1, MMP-3, and TGFß. Particulate matter was found to dose-dependently increase cellular viability, activate the aryl hydrocarbon receptor, increase double-strand DNA breaks, and increase the expression of MMP-1, MMP-3, and TGFß. With the potential of air pollutants such as particulate matter to not only modulate the expression of proteins implicated in skin aging, but also affect cells at a genetic level, brings a pressing need for further investigation so protective strategies can be implemented.