Detector requirements for single mask edge illumination x-ray phase contrast imaging applications

Edge illumination (EI) is a non-interferometric X-ray phase contrast imaging (XPCI) method that has been successfully implemented with conventional polychromatic sources, thanks to its relaxed coherence requirements. Like other XPCI methods, EI enables the retrieval of absorption, refraction and ultra-small angle X-ray scattering (USAXS) signals. However, current retrieval algorithms require three input frames, which have so far been acquired under as many different illumination conditions, in separate exposures. These illumination conditions can be achieved by deliberately misaligning the set-up in different ways. Each one of these misaligned configurations can then be used to record frames containing a mixture of the absorption, refraction and scattering signals. However, this acquisition scheme involves lengthy exposure times, which can also introduce errors to the retrieved signals. Such errors have, so far, been mitigated by careful image acquisition and analysis. However, further reduction to image acquisition time and errors due to sample mask/sample movement can increase the advantages offered by the EI technique, and enable targeting more challenging applications. In this paper, we describe two simplified set-ups that exploit state-of-the-art detector technologies to achieve single-shot multi-modal imaging.Comment: 10 pages, 5 figures, Position Sensitive Detectors 11 conferenc

Simple and robust synchrotron and laboratory solutions for high-resolution multimodal X-ray phase-based imaging

Edge illumination X-ray phase contrast imaging techniques are capable of quantitative retrieval of differential phase, absorption and X-ray scattering. We have recently developed a series of approaches enabling high-resolution implementations, both using synchrotron radiation and laboratory-based set-ups. Three-dimensional reconstruction of absorption, phase and dark-field can be achieved with a simple rotation of the sample. All these approaches share a common trait which consists in the use of an absorber that shapes the radiation field, in order to make the phase modulations introduced by the sample detectable. This enables a well-defined and high-contrast structuring of the radiation field as well as an accurate modelling of the effects that are related to the simultaneous use of a wide range of energies. Moreover, it can also be adapted for use with detectors featuring large pixel sizes, which could be desirable when a high detection efficiency is important

Monochromatic Propagation-Based Phase-Contrast Microscale Computed-Tomography System with a Rotating-Anode Source

We present an experimental setup for monochromatic propagation-based x-ray phase-contrast imaging based on a conventional rotating-copper-anode source, capable of an integrated flux up to 108 photons/s at 8 keV. In our study, the system is characterized in terms of spatial coherence, resolution, contrast sensitivity, and stability. Its quantitativeness is demonstrated by comparing theoretical predictions with experimental data on simple wire phantoms both in planar and computerized-tomography-scan geometries. Application to two biological samples of medical interest shows the potential for bioimaging on the millimeter scale with spatial resolution of the order of 10 \u3bcm and contrast resolution below 1%. All the scans are performed within laboratory-compatible exposure times, from 10 min to a few hours, and trade-offs between scan time and image quality are discussed

Signal of harm in morphine use in adults with acute pulmonary oedema: A rapid systematic review

Background. Heart failure affects nearly 65 million people globally, resulting in recurrent hospital admissions and substantial healthcare expenditure. The use of morphine in the management of acute pulmonary oedema remains controversial, with conflicting guidance and significant variation in practice. Synthesised evidence is needed to inform standard treatment guidelines and clinical practice. Objective. To determine whether morphine should be used in the treatment of acute pulmonary oedema (APE) in adults. Methods. A rapid review of systematic reviews of randomised controlled trials or observational studies, and then randomised controlled trials, was conducted searching three electronic databases (PubMed, Embase, Cochrane Library) and one clinical trial registry on 12 February 2022. We used a prespecified protocol following Cochrane rapid review methods and aligned to the National Standard Treatment Guidelines and Essential Medicines List methodology. We first considered relevant high-quality systematic reviews of randomised controlled trials or observational studies, then (if required) randomised controlled trials to inform time-sensitive or urgent evidence requests, clinical practice, policy, or standard treatment guidelines. Results. We identified four systematic reviews of observational studies. The two most relevant, up-to-date, and highest-quality reviews were used to inform evidence for critical outcomes. Morphine may increase in-hospital mortality (odds ratio (OR) 1.78; 95% confidence interval (CI) 1.01 - 3.13; low certainty of evidence; six observational studies, n=151 735 participants), resulting in 15 more per 1 000 hospital deaths, ranging from 0 to 40 more hospital deaths. Morphine may result in a large increase in invasive mechanical ventilation (OR 2.72; 95% CI 1.09 - 6.80; low certainty of evidence; four observational studies, n=167 847 participants), resulting in 45 more per 1 000 ventilations, ranging from 2 more to 136 more. Adverse events and hospital length of stay were not measured across reviews or trials. Conclusion. Based on the most recent, relevant and best-available quality evidence, morphine use in adults with APE may increase in-hospital and all-cause mortality and may result in a large increase in the need for invasive mechanical ventilation compared to not using morphine. Recommending against the use of morphine in pulmonary oedema may improve patient outcomes. Disinvesting in morphine for this indication may result in cost savings, noting the possible accrued benefits of fewer patients requiring invasive ventilation and management of morphine-related side-effects

Incidence and risk factors of surgical site infections and related antibiotic resistance in Freetown, Sierra Leone: a prospective cohort study

BACKGROUND: There is limited information on surgical site infections (SSI) and the related antibiotic resistance needed to guide their management and prevention in Sierra Leone. In this study, we aimed to establish the incidence and risk factors of SSI and the related antibiotic resistance among adults attending a tertiary hospital, and a secondary health facility in Freetown, Sierra Leone. METHODS: This is a prospective cohort study designed to collect data from adult (18 years or older) patients who attended elective and emergency surgeries at two hospitals in Freetown between February and July, 2021. Data analysis was done using STATA version 16. RESULTS: Of 338 patients, 245 (72.5%) and 93 (27.5%) had their surgeries at the tertiary and secondary hospitals, respectively. Many were males 192 (56.8%), less than 35 years 164 (48.5%), and 39 (11.5%) developed an SSI. Of the 39 patients who acquired an SSI, 7 (17.9%) and 32 (82.1%) had their surgeries at the secondary and tertiary hospitals, respectively. The incidence of SSI is higher in contaminated 17 (43.6%) than in clean-contaminated 12 (30.8%) and clean 10 (25.6%) wounds. Wound swabs were collected in 29 (74.4%) patients, of which 18 (62.1%) had bacterial growth. In total, 49 isolates of 14 different bacteria including gram-negative 41 (83.7%) and gram-positive 8 (16.3%) isolates were identified. Of these, 32 (65.3%) were Enterobacteriaceae, 9 (18.4%) were Non-fermenting gram-negative bacilli and 10 (12.2%) were Enterococci. The most common isolates were Escherichia coli (12, 24.5%), Klebsiella pneumoniae (10, 20.4%), Acinetobacter baumannii (5, 10.2%), Klebsiella oxytoca (4, 8.2%) and Enterococcus faecalis (4, 8.2%). The Enterobacteriaceae were either resistance to carbapenems (4, 8.2%) or were extended-spectrum beta-lactamase (ESBL) producing organisms (29, 59.2%). Male sex [p = 0.031], an ASA score >/= 2 [p = 0.020), administration of general anaesthesia [p = 0.018] and elevated fasting glucose [p = 0.033] were predictive of SSI. CONCLUSION: The incidence of SSI in this study is comparable to other low- and middle-income countries, but a substantial proportion of these postoperative wounds have an ESBL-producing Enterobacteriaceae. Therefore, routine surveillance of SSI and related antibiotic resistance is required in resource-limited settings

An intra-COVID-19 assessment of hand hygiene facility, policy and staff compliance in two hospitals in Sierra Leone: is there a difference between regional and capital city hospitals?

Although hand hygiene (HH) is the most effective intervention to reduce the spread of infections, there are limited data on HH facilities, policy, and compliance in sub-Saharan Africa. This cross-sectional study is aimed at assessing HH using the WHO HH self-assessment framework, HH technical reference manual, and a modified infection control self-assessment tool in two hospitals in Sierra Leone. Only 10% and 9% of regional and capital city hospitals had running tap water, respectively. Veronica buckets were the resources for HH in 89% of units in the regional hospital and 92% of units in capital city hospital. Constant supply of soap and alcohol-based hand rub was available in 82% and 68%; and 74% and 79% of units in the capital city and regional hospitals, respectively. Only 10% of the units in both hospitals had hand-drying facilities and functional sinks. Overall HH compliance for the two hospitals was 18.6% and was higher in the regional (20.8%) than the capital city (17.0%) hospitals. The HH levels for the capital city and regional hospitals were 277.5 and 262.5 respectively. Despite the COVID-19 pandemic, there are still challenges with HH compliance in Sierra Leone. It is, therefore, necessary to strengthen the HH multi-modal strategy

High levels of surgical antibiotic prophylaxis: implications for hospital-based antibiotic stewardship in Sierra Leone

OBJECTIVE: Despite the impact of inappropriate prescribing on antibiotic resistance, data on surgical antibiotic prophylaxis in sub-Saharan Africa are limited. In this study, we evaluated antibiotic use and consumption in surgical prophylaxis in 4 hospitals located in 2 geographic regions of Sierra Leone. METHODS: We used a prospective cohort design to collect data from surgical patients aged 18 years or older between February and October 2021. Data were analyzed using Stata version 16 software. RESULTS: Of the 753 surgical patients, 439 (58.3%) were females, and 723 (96%) had received at least 1 dose of antibiotics. Only 410 (54.4%) patients had indications for surgical antibiotic prophylaxis consistent with local guidelines. Factors associated with preoperative antibiotic prophylaxis were the type of surgery, wound class, and consistency of surgical antibiotic prophylaxis with local guidelines. Postoperatively, type of surgery, wound class, and consistency of antibiotic use with local guidelines were important factors associated with antibiotic use. Of the 2,482 doses administered, 1,410 (56.8%) were given postoperatively. Preoperative and intraoperative antibiotic use was reported in 645 (26%) and 427 (17.2%) cases, respectively. The most commonly used antibiotic was ceftriaxone 949 (38.2%) with a consumption of 41.6 defined daily doses (DDD) per 100 bed days. Overall, antibiotic consumption was 117.9 DDD per 100 bed days. The Access antibiotics had 72.7 DDD per 100 bed days (61.7%). CONCLUSIONS: We report a high rate of antibiotic consumption for surgical prophylaxis, most of which was not based on local guidelines. To address this growing threat, urgent action is needed to reduce irrational antibiotic prescribing for surgical prophylaxis

Reliable Estimation of CD8 T Cell Inhibition of In Vitro HIV-1 Replication

The HIV-1 viral inhibition assay (VIA) measures CD8 T cell-mediated inhibition of HIV replication in CD4 T cells and is increasingly used for clinical testing of HIV vaccines and immunotherapies. The VIA has multiple sources of variability arising from in vitro HIV infection and co-culture of two T cell populations. Here, we describe multiple modifications to a 7-day VIA protocol, the most impactful being the introduction of independent replicate cultures for both HIV infected-CD4 (HIV-CD4) and HIV-CD4:CD8 T cell cultures. Virus inhibition was quantified using a ratio of weighted averages of p24+ cells in replicate cultures and the corresponding 95% confidence interval. An Excel template is provided to facilitate calculations. Virus inhibition was higher in people living with HIV suppressed on antiretroviral therapy (n=14, mean: 40.0%, median: 43.8%, range: 8.2 to 73.3%; p < 0.0001, two-tailed, exact Mann-Whitney test) compared to HIV-seronegative donors (n = 21, mean: -13.7%, median: -14.4%, range: -49.9 to 20.9%) and was stable over time (n = 6, mean %COV 9.4%, range 0.9 to 17.3%). Cross-sectional data were used to define 8% inhibition as the threshold to confidently detect specific CD8 T cell activity and determine the minimum number of culture replicates and p24+ cells needed to have 90% statistical power to detect this threshold. Last, we note that, in HIV seronegative donors, the addition of CD8 T cells to HIV infected CD4 T cells consistently increased HIV replication, though the level of increase varied markedly between donors. This co-culture effect may contribute to the weak correlations observed between CD8 T cell VIA and other measures of HIV-specific CD8 T cell function

CD8 T Cell Virus Inhibition Assay Protocol

The human immunodeficiency virus (HIV)-1 viral inhibition assay (VIA) measures CD8+ T cell-mediated inhibition of HIV replication in CD4+ T cells and is increasingly used for clinical testing of HIV vaccines and immunotherapies. Different VIAs that differ in length of CD8:CD4 T cell culture periods (6-13 days), purity of CD4 cultures [isolated CD4+ T cells or CD8+ depleted peripheral blood mononuclear cells (PBMCs)], HIV strains (laboratory strains, isolates, reporter viruses) and read-outs of virus inhibition (p24 ELISA, intracellular measurement of p24, luciferase reporter expression, and viral gag RNA) have been reported. Here, we describe multiple modifications to a 7-day VIA protocol, the most impactful being the introduction of independent replicate cultures for both HIV infected-CD4 (HIV-CD4) and HIV-CD4:CD8 T cell cultures. Virus inhibition was quantified using a ratio of weighted averages of p24+ cells in replicate cultures and the corresponding 95% confidence intervals. We identify methodological and analysis changes that could be incorporated into other protocols to improve assay reproducibility. We found that in people living with HIV (PLWH) on antiretroviral therapy (ART), CD8 T cell virus inhibition was largely stable over time, supporting the use of this assay and/or analysis methods to examine therapeutic interventions