Haemoglobin Video Imaging provides novel in vivo high-resolution imaging and quantification of human aqueous outflow in glaucoma patients

Purpose Non-invasive, detailed measurement of the dynamics of human aqueous outflow is difficult to achieve with currently available clinical tools. Here we used haemoglobin video imaging (HVI) to develop a technique to image and quantify human aqueous outflow non-invasively and in real time. Design A prospective observational study to describe characteristics of aqueous veins and a pilot prospective interventional feasibility study to develop quantification parameters. Subjects Participants and/or Controls: Patients were recruited from the Addenbrookes Hospital Glaucoma clinic. The observational study included 30 eyes and the pilot interventional feasibility study was performed on 8 eyes undergoing selective laser trabeculoplasty (SLT). Our SLT protocol also included the installation of pilocarpine and apraclonidine eye drops. Methods, Intervention, or Testing Participants underwent HVI alongside their usual clinic visit. Main Outcome Measures The change in cross sectional area (CSA) of the aqueous column (AQC) within episcleral veins was correlated with IOP reduction and change in visual field mean deviation before and after intervention. Fluctuations in contrast and pixel intensity of red blood cells in an aqueous vein were calculated to compare the flow rate before and after intervention using autocorrelation analysis. Results HVI enables the direct observation of aqueous flow into the vascular system. Aqueous is seen to centralise within a laminar venous column. Flow is pulsatile, and fluctuations of flow through globe pressure or compression of the aqueous vein are observed. There was a significant increase in the AQC following the administration of our SLT protocol (n=13; p<0.05). This correlated with the degree of IOP reduction (n=13; Pearson’s correlation coefficient 0.7; p=0.007) and the improvement in mean deviation (MD) observed post intervention (n=8; Pearson’s correlation coefficient 0.75; p=0.03). Autocorrelation analysis demonstrated a faster rate of decay in an aqueous vein following intervention indicating an increase in flow rate. Conclusions HVI can be incorporated into a routine clinic slit lamp examination to allow a detailed assessment and quantification of aqueous outflow in real time. It has the potential to be used to help target therapeutic interventions to improve aqueous outflow and further advance our understanding of aqueous outflow dysregulation in the pathogenesis of glaucoma.This work was supported by grants from Addenbrooke’s Charitable Trust, the HB Allen Charitable Trust, the Cambridge Eye Trust, the Jukes Glaucoma Research Fund and a core support grant from the Wellcome Trust and MRC to the Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute

Evaluating multidisciplinary glaucoma care: visual field progression and loss of sight year analysis in the community versus hospital setting

Background: A variety of shared care models have been developed, which aim to stratify glaucoma patients according to risk of disease progression. However, there is limited published data on the rate of glaucoma progression in the hospital vs community setting. Here we aimed to compare rates of glaucomatous visual field progression in the Cambridge Community Optometrist Glaucoma Scheme (COGS) and Addenbrooke’s Hospital Glaucoma Clinic (AGC). Methods: A retrospective comparative cohort review was performed. Patients with five or more visual field tests were included. Zeiss Forum software was used to calculate the MD progression rate (dB/year). Loss of sight years (LSY) were also calculated for both COGS and AGC. Results: Overall, 8465 visual field tests from 854 patients were reviewed. In all, 362 eyes from the AGC group and 210 eyes from COGS were included. The MD deterioration rate was significantly lower in the COGS patients compared with the AGC group (−0.1 vs −0.3 dB/year; p < 0.0001). No patients in the COGS group were predicted to become blind within their lifetime by LSY analysis. Fifteen patients were at risk in the AGC group. Conclusion: This service evaluation shows that COGS is an effective scheme to stratify lower risk glaucoma patients, increasing the capacity within hospital eye services. COGS patients have a lower rate of visual field deterioration compared to AGC patients. Effective communication between community and tertiary schemes is essential to facilitate transfer of patients requiring further hospital management reliably and efficiently, with the potential for low-risk patients to be followed safely in the community

Hemoglobin Video Imaging Provides Novel In Vivo High-Resolution Imaging and Quantification of Human Aqueous Outflow in Patients with Glaucoma.

Purpose:Noninvasive, detailed measurement of the dynamics of human aqueous outflow is difficult to achieve with currently available clinical tools. We used hemoglobin video imaging (HVI) to develop a technique to image and quantify human aqueous outflow noninvasively and in real time. Design:A prospective observational study to describe characteristics of aqueous veins and a pilot prospective interventional feasibility study to develop quantification parameters. Participants:Patients were recruited from the Cambridge University Hospitals NHS Foundation Trust Glaucoma clinic. The observational study included 30 eyes, and the pilot interventional feasibility study was performed on 8 eyes undergoing selective laser trabeculoplasty (SLT). Our SLT protocol also included the installation of pilocarpine and apraclonidine eye drops. Methods:Participants underwent HVI alongside their usual clinic visit. Main Outcome Measures:The change in cross-sectional area (CSA) of the aqueous column within episcleral veins was correlated with intraocular pressure (IOP) reduction and change in visual field mean deviation (MD) before and after intervention. Fluctuations in contrast and pixel intensity of red blood cells in an aqueous vein were calculated to compare the flow rate before and after intervention using autocorrelation analysis. Results:Hemoglobin video imaging enables the direct observation of aqueous flow into the vascular system. Aqueous is seen to centralize within a laminar venous column. Flow is pulsatile, and fluctuations of flow through globe pressure or compression of the aqueous vein are observed. There was a significant increase in the aqueous column after the administration of our SLT protocol (n = 13; P < 0.05). This correlated with the degree of IOP reduction (n = 13; Pearson's correlation coefficient 0.7; P = 0.007) and the improvement in MD observed postintervention (n = 8; Pearson's correlation coefficient 0.75; P = 0.03). Autocorrelation analysis demonstrated a faster rate of decay in an aqueous vein after intervention, indicating an increase in flow rate. Conclusions:Hemoglobin video imaging can be incorporated into a routine clinic slit-lamp examination to allow a detailed assessment and quantification of aqueous outflow in real time. It has the potential to be used to help target therapeutic interventions to improve aqueous outflow and further advance our understanding of aqueous outflow dysregulation in the pathogenesis of glaucoma

Coronary atherosclerotic burden in veteran male recreational athletes with low to intermediate cardiovascular risk.

INTRODUCTION: Although there is evidence that a significant proportion of veteran athletes have coronary atherosclerotic disease (CAD), its prevalence in recreational athletes with low to intermediate cardiovascular (CV) risk is not established. This study aimed to characterize the coronary atherosclerotic burden in veteran male recreational athletes with low to intermediate CV risk. METHODS: Asymptomatic male athletes aged ≥40 years with low to intermediate risk, who exercised >4 hours/week for >5 years, underwent cardiac computed tomography (CT) for coronary artery calcium (CAC) scoring and CT angiography. High coronary atherosclerotic burden was defined as at least one of the following: CAC score >100; CAC score ≥75th percentile; obstructive CAD; disease involving the left main, three vessels or two vessels including the proximal left anterior descending artery; segment involvement score >5; or CT Leaman score ≥5. Athletes were categorized by tertiles of exercise volume, calculated by metabolic equivalent of task (MET) scores. RESULTS: A total of 105 athletes were included, all with SCORE 100, 13 (12.4%) had CAC score ≥75th percentile and six (5.7%) had obstructive lesions. The extent and severity of coronary plaques did not differ according to exercise volume. CONCLUSIONS: The prevalence of subclinical CAD detected by cardiac CT in veteran male recreational athletes with low to intermediate CV risk was high. Up to a quarter of our cohort had a high coronary atherosclerotic burden

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Understanding the plant-microbe interaction molecular mechanisms for better exploitation of bio-control agents to enhance sustainable agricultural practices

Trichoderma spp. are well-known bio-control agents which promote the plant growth and suppress the pathogen infection. The beneficial effects are attributed to the production of phytohormones, antibiotics, siderophores and secondary metabolites (SM). Trichodermin and Harzianum A, SMs have documented anti-fungal activities as well. Tri5 gene encodes for trichodiene synthase (TS) contains a terpene fold and involved at the initial step of the biosynthetic pathway of these molecules. Furthermore, domain analysis of proteins from diverse organisms showed that the terpene fold has functional diversity with diverse applications in agriculture, medicine and applied biotechnology. These proteins can be classified into single and multi-domains based on their structures. It was observed that multi-domain proteins carry additional helices which may regulate the catalytic efficiency. Further, activity enhancing mutations with potentially higher catalytic activities were screened. In an offshoot to the above work, we have analyzed binding of Trichodermin with the 25S rRNA that constitutes the petidyltransferase centre (PTC). The trichodermin resistance protein (60S ribosomal protein L3) was reported to overcome the inhibitory effects of trichothecene compounds. Normal mode analysis and MD of trichodermin resistance protein and 25S consisting of PTC showed that the W-finger region of the protein may move towards 25S rRNA and may block the binding pocket of the trichodermin. These results may lead to develop strategies for higher TS activity and the mechanism of action of these molecules involved in plant-microbe interactions. These may be further exploited for enhancing the efficiency of these biotechnological agents used in sustainable agriculture

Haemoglobin Video Imaging provides novel in vivo high-resolution imaging and quantification of human aqueous outflow in glaucoma patients

Purpose Non-invasive, detailed measurement of the dynamics of human aqueous outflow is difficult to achieve with currently available clinical tools. Here we used haemoglobin video imaging (HVI) to develop a technique to image and quantify human aqueous outflow non-invasively and in real time. Design A prospective observational study to describe characteristics of aqueous veins and a pilot prospective interventional feasibility study to develop quantification parameters. Subjects Participants and/or Controls: Patients were recruited from the Addenbrookes Hospital Glaucoma clinic. The observational study included 30 eyes and the pilot interventional feasibility study was performed on 8 eyes undergoing selective laser trabeculoplasty (SLT). Our SLT protocol also included the installation of pilocarpine and apraclonidine eye drops. Methods, Intervention, or Testing Participants underwent HVI alongside their usual clinic visit. Main Outcome Measures The change in cross sectional area (CSA) of the aqueous column (AQC) within episcleral veins was correlated with IOP reduction and change in visual field mean deviation before and after intervention. Fluctuations in contrast and pixel intensity of red blood cells in an aqueous vein were calculated to compare the flow rate before and after intervention using autocorrelation analysis. Results HVI enables the direct observation of aqueous flow into the vascular system. Aqueous is seen to centralise within a laminar venous column. Flow is pulsatile, and fluctuations of flow through globe pressure or compression of the aqueous vein are observed. There was a significant increase in the AQC following the administration of our SLT protocol (n=13; p<0.05). This correlated with the degree of IOP reduction (n=13; Pearson’s correlation coefficient 0.7; p=0.007) and the improvement in mean deviation (MD) observed post intervention (n=8; Pearson’s correlation coefficient 0.75; p=0.03). Autocorrelation analysis demonstrated a faster rate of decay in an aqueous vein following intervention indicating an increase in flow rate. Conclusions HVI can be incorporated into a routine clinic slit lamp examination to allow a detailed assessment and quantification of aqueous outflow in real time. It has the potential to be used to help target therapeutic interventions to improve aqueous outflow and further advance our understanding of aqueous outflow dysregulation in the pathogenesis of glaucoma.This work was supported by grants from Addenbrooke’s Charitable Trust, the HB Allen Charitable Trust, the Cambridge Eye Trust, the Jukes Glaucoma Research Fund and a core support grant from the Wellcome Trust and MRC to the Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute

Synthesis and Characterization of Waste Eggshell-Based Montmorillonite Clay Catalyst for Biodiesel Production from Waste Cooking Oil

The depletion of resources and increase in demand for fossil fuel raise concerns as it is natural and non-renewable. Therefore, it will cause limitation on its availability and continuous reduction. This issue has led to the search for more economic, sustainable, and environmentally friendly alternatives which is biodiesel. The major drawback that reduces the possibility of biodiesel commercialization is the high cost of oil feedstock as it covers 75% of its total production cost. The waste cooking oil is used as feedstock in continuous transesterification as it is the primary option to lower the cost of biodiesel production. Biodiesel can be prepared using waste cooking oil and catalyst through transesterification reaction. In this research, the focus is on the utilization of chicken and quail waste eggshell to synthesize highly active Calcium Oxide (CaO)-based heterogenous catalyst with montmorillonite clay to catalyze efficient conversion of waste cooking oil to biodiesel. The formation of CaO/montmorillonite catalyst was confirmed based on the outputs from X-ray diffraction (XRD) and Scanning Electron Microscopy (SEM). The physio-chemically characteristics of catalysts exhibited a BET surface area from the ranging from 9.2-9.5 m2/g and presence of around 87% of elemental calcium as constituent through XRF characterization. In addition to this, high-performance liquid chromatography (HPLC) analysis is used to determine the conversion of biodiesel using conventional and microwave heating method which revealed a maximum biodiesel production yield of 98%. This optimum biodiesel yield was obtained at reaction temperature, molar ratio of waste cooking oil to methanol, and catalyst amount of 60 ºC, 2 h, 1:12, 2.5 wt.% and 5 wt.% for both eggshells, respectively