Suppression of Richtmyer-Meshkov Instability via Special Pairs of Shocks and Phase Transitions.

The classical Richtmyer-Meshkov instability (RMI) is a hydrodynamic instability characterizing the evolution of an interface following shock loading. In contrast to other hydrodynamic instabilities such as Rayleigh-Taylor, it is known for being unconditionally unstable: regardless of the direction of shock passage, any deviations from a flat interface will be amplified. In this article, we show that for negative Atwood numbers, there exist special sequences of shocks which result in a nearly perfectly suppressed instability growth. We demonstrate this principle computationally and experimentally with stepped fliers and phase transition materials. A fascinating immediate corollary is that in specific instances, a phase-transitioning material may self-suppress RMI.

Measurement of the Isolated Nuclear Two-Photon Decay in

The nuclear two-photon or double-gamma (2γ) decay is a second-order electromagnetic process whereby a nucleus in an excited state emits two gamma rays simultaneously. To be able to directly measure the 2γ decay rate in the low-energy regime below the electron-positron pair-creation threshold, we combined the isochronous mode of a storage ring with Schottky resonant cavities. The newly developed technique can be applied to isomers with excitation energies down to ∼100 keV and half-lives as short as ∼10 ms. The half-life for the 2γ decay of the first-excited 0^{+} state in bare ^{72}Ge ions was determined to be 23.9(6) ms, which strongly deviates from expectations.

A multi-centre retrospective study of Nocardia speciation and antimicrobial susceptibility in Queensland, Australia.

The study aims to characterise the species identification and antimicrobial susceptibility testing (AST) results of Nocardial isolates from adult patients across major public hospitals in Queensland, Australia, over a 15-year period. A multi-centre retrospective observational study of Nocardia sp. isolates was conducted from 7 major public hospitals in Queensland, Australia, over a 15-year period. Clinical samples from patients aged ≥ 18 years that isolated Nocardia sp. were included. Demographic and clinical data were collected, along with species identification and AST results. Overall, 484 Nocardia sp. were isolated. Most patients were male (297, 61%) with a mean (IQR) age of 60 (51-75) and a median (IQR) Charlson Comorbidity Index of 4 (2-6). Of these, 239 (49%) patients were immunosuppressed. Organisms were most frequently isolated from sputum (174, 36%), and superficial swabs (102, 21%). Patients presented with pulmonary infections (165, 35%) and superficial skin and soft tissue infections (87, 18%) most commonly. One hundred (21%) isolates were deemed pulmonary colonisation and were not treated. Of the speciated organisms, N. nova complex was the most common (93, 19%), followed by N. farcinica complex (79, 16%). Organisms were reliably susceptible to linezolid (240/245, 98%), amikacin (455/470, 97%), and trimethoprim/sulfamethoxazole (459/476, 96%), but less so to imipenem (243/472, 51%) and ceftriaxone (261/448, 58%). This is the largest Australian description of Nocardia sp. to date. Given antimicrobials are often commenced prior to AST results and sometimes even speciation, characterisation of local species and antibiogram data is important to guide empiric choices and local guidelines.

Outcomes of normothermic machine perfusion of liver grafts in repeat liver transplantation (NAPLES initiative).

BACKGROUND: Retransplantation candidates are disadvantaged owing to lack of good-quality liver grafts. Strategies that can facilitate transplantation of suboptimal grafts into retransplant candidates require investigation. The aim was to determine whether late liver retransplantation can be performed safely with suboptimal grafts, following normothermic machine perfusion. METHODS: A prospectively enrolled group of patients who required liver retransplantation received a suboptimal graft preserved via normothermic machine perfusion. This group was compared with both historical and contemporaneous cohorts of patient who received grafts preserved by cold storage. The primary outcome was 6-month graft and patient survival. RESULTS: The normothermic machine perfusion group comprised 26 patients. The historical (cold storage 1) and contemporaneous (cold storage 2) groups comprised 31 and 25 patients respectively. The 6-month graft survival rate did not differ between groups (cold storage 1, 27 of 31, cold storage 2, 22 of 25; normothermic machine perfusion, 22 of 26; P = 0.934). This was despite the normothermic machine perfusion group having significantly more steatotic grafts (8 of 31, 7 of 25, and 14 of 26 respectively; P = 0.006) and grafts previously declined by at least one other transplant centre (5 of 31, 9 of 25, and 21 of 26; P < 0.001). CONCLUSION: In liver retransplantation, normothermic machine perfusion can safely expand graft options without compromising short-term outcomes.

Liver transplantation is a life-saving procedure for many different diseases. In the UK, one in 10 patients awaiting transplant have had a previous liver transplant. These retransplant operations are complex, and the general belief is that a good-quality donor liver graft is required for best outcomes. However, there is a significant shortage of good-quality organs for liver transplantation, so many patients awaiting retransplantation spend longer on the waiting list. This study investigated whether a new technology, called normothermic machine perfusion, could be used to preserve lower-quality donor livers and have successful outcomes for patients undergoing retransplantation. Traditionally, good-quality livers are preserved in an ice box and the study compared the outcomes of these two different approaches. The aim was to prove that normothermic machine perfusion improves access to transplantation for this group of patients, without compromising outcomes. A group of patients who underwent retransplantation and received a lesser-quality liver preserved with normothermic machine perfusion was compared with two groups of patients who had received a transplant with traditional ice-box preservation. The complications, graft, and patient survival of the former group was compared with those in the latter two groups who underwent liver retransplantation with better-quality liver grafts. The rate of survival and adverse surgical outcomes were comparable between the groups of patients who received a liver preserved via traditional ice-box preservation, and those who received a lesser-quality liver preserved via normothermic machine perfusion. Normothermic machine perfusion can potentially expand the number of suitable donor livers available for retransplant candidates.

Human Melioidosis.

The causative agent of melioidosis, Burkholderia pseudomallei, a tier 1 select agent, is endemic in Southeast Asia and northern Australia, with increased incidence associated with high levels of rainfall. Increasing reports of this condition have occurred worldwide, with estimates of up to 165,000 cases and 89,000 deaths per year. The ecological niche of the organism has yet to be clearly defined, although the organism is associated with soil and water. The culture of appropriate clinical material remains the mainstay of laboratory diagnosis. Identification is best done by phenotypic methods, although mass spectrometric methods have been described. Serology has a limited diagnostic role. Direct molecular and antigen detection methods have limited availability and sensitivity. Clinical presentations of melioidosis range from acute bacteremic pneumonia to disseminated visceral abscesses and localized infections. Transmission is by direct inoculation, inhalation, or ingestion. Risk factors for melioidosis include male sex, diabetes mellitus, alcohol abuse, and immunosuppression. The organism is well adapted to intracellular survival, with numerous virulence mechanisms. Immunity likely requires innate and adaptive responses. The principles of management of this condition are drainage and debridement of infected material and appropriate antimicrobial therapy. Global mortality rates vary between 9% and 70%. Research into vaccine development is ongoing.

Novel Mechanisms of Ozone-Induced Pulmonary Inflammation and Resolution, and the Potential Protective Role of Scavenger Receptor BI.

INTRODUCTION: Increases in ambient levels of ozone (O3), a criteria air pollutant, have been associated with increased susceptibility and exacerbations of chronic pulmonary diseases through lung injury and inflammation. O3 induces pulmonary inflammation, in part by generating damage-associated molecular patterns (DAMPs), which are recognized by pattern recognition receptors (PRRs), such as toll-like receptors (TLRs) and scavenger receptors (SRs). This inflammatory response is mediated in part by alveolar macrophages (AMs), which highly express PRRs, including scavenger receptor BI (SR-BI). Once pulmonary inflammation has been induced, an active process of resolution occurs in order to prevent secondary necrosis and to restore tissue homeostasis. The processes known to promote the resolution of inflammation include the clearance by macrophages of apoptotic cells, known as efferocytosis, and the production of specialized pro-resolving mediators (SPMs). Impaired efferocytosis and production of SPMs have been associated with the pathogenesis of chronic lung diseases; however, these impairments have yet to be linked with exposure to air pollutants. SPECIFIC AIMS: The primary goals of this study were: Aim 1 - to define the role of SR-BI in O3-derived pulmonary inflammation and resolution of injury; and Aim 2 - to determine if O3 exposure alters pulmonary production of SPMs and processes known to promote the resolution of pulmonary inflammation and injury. METHODS: To address Aim 1, female wild-type (WT) and SR-BI-deficient, or knock-out (SR-BI KO), mice were exposed to either O3 or filtered air. In one set of experiments mice were instilled with an oxidized phospholipid (oxPL). Bronchoalveolar lavage fluid (BALF) and lung tissue were collected for the analyses of inflammatory and injury markers and oxPL. To estimate efferocytosis, mice were administered apoptotic cells (derived from the Jurkat T cell line) after O3 or filtered air exposure.To address Aim 2, male WT mice were exposed to either O3 or filtered air, and levels of SPMs were assessed in the lung, as well as markers of inflammation and injury in BALF. In some experiments SPMs were administered before exposure to O3or filtered air, to determine whether SPMs could mitigate inflammatory or resolution responses. Efferocytosis was measured as in Aim 1. RESULTS: For Aim 1, SR-BI protein levels increased in the lung tissue of mice exposed to O3, compared with mice exposed to filtered air. Compared with WT controls, SR-BI KO mice had a significant increase in the number of neutrophils in their airspace 24 hours post O3 exposure. The oxPL levels increased in the airspace of both WT and SR-BI KO mice after O3 exposure, compared with filtered air controls. Four hours after instillation of an oxPL, SR-BI KO mice had an increase in BALF neutrophils and total protein, and a nonsignificant increase in macrophages compared with WT controls. O3 exposure decreased efferocytosis in both WT and SR-BI KO female mice.For Aim 2, mice given SPM supplementation before O3 exposure showed significantly increased AM efferocytosis when compared with the O3exposure control mice and also showed some mitigation of the effects of O3 on inflammation and injury. Several SPMs and their precursors were measured in lung tissue using reverse-phase high performance liquid chromatography (HPLC) with tandem mass spectrometry (MS/MS). At 24 hours after O3 exposure 14R-hydroxydocosahexaenoic acid (HDHA) and 10,17-dihydroxydocosahexaenoic acid (diHDoHE) were significantly decreased in lung tissue, but at 6 hours after exposure, levels of these SPMs increased. CONCLUSIONS: Our findings identify novel mechanisms by which O3 may induce pulmonary inflammation and also increase susceptibility to and exacerbations of chronic lung diseases.

Peculiarities of Cirrhosis due to Nonalcoholic Steatohepatitis (NASH).

The prevalence of cirrhosis due to nonalcoholic steatohepatitis (NASH) has increased 2.5-fold in the United States in the last decade. These patients pose new challenges to hepatologists given their older age and higher frequency of coexisting metabolic diseases such as obesity and diabetes compared with other etiologies of liver disease. Patients with NASH cirrhosis are at higher risk for renal and cardiovascular disease, and the presence of these extrahepatic comorbidities has a significant impact on outcomes and survival. This review outlines how NASH cirrhosis differs from other etiologies of cirrhosis including natural history, noninvasive assessment, and the challenges in the management of the complications of cirrhosis including hepatic encephalopathy and hepatocellular carcinoma. Nutritional assessment and the impact of sarcopenic obesity and frailty in this population, and strategies to address the latter, are discussed. This review also addresses liver transplantation in patients with NASH cirrhosis in relation to assessment and posttransplant care.

Identification of Burkholderia pseudomallei by Use of the Vitek Mass Spectrometer.

Burkholderia pseudomallei is the causative agent of melioidosis. This condition most often presents as pneumonia and bacteremia, with mortality rates of 9% to 70%. Therefore, early identification of this organism may aid in directing appropriate management. This study aimed to use the Vitek matrix-assisted laser desorption ionization-time of flight mass spectrometer to create a spectrum for the rapid identification of B. pseudomallei Spectra from 85 isolate cultures were acquired using the Vitek mass spectrometer research mode. A SuperSpectrum was created using peak matching and subsequently activated for analysis of organism identification. All 85 isolates were correctly identified as B. pseudomallei A total of 899 spectra were analyzed and demonstrated a specificity of 99.8%. Eighty-one clinical isolates were used, of which 10 were neuromelioidosis, and no discernible spectrum difference was appreciated. Spectrum acquisition from a single spot was only successful in 374/899 (41%) of isolates. This increased to 100% when 3 spots of the same extract were analyzed. The Vitek mass spectrometer can be used for the rapid identification of B. pseudomallei with a high level of specificity.

Fluorescence spectroscopy for assessing trihalomethane precursors removal by MIEX resin.

This study investigated the applicability of fluorescence excitation-emission matrix spectroscopy (EEMS) to assess total trihalomethane formation potentials (TTHMFPs) and the ability of magnetic ion exchange (MIEX®) resin to reduce TTHMFP. We treated a surface water and secondary wastewater effluent with MIEX mimicking full-scale operation by repeatedly exposing the same resin batch to additional feed water, with batches ranging from 500 to 5,000 resin bed volumes. Results showed that MIEX was more effective at removing or reducing ultraviolet absorbance (UVA254), dissolved organic carbon (DOC), and TTHMFP in surface water than in secondary effluent. The greater UVA254, DOC and TTHMFP removal for surface waters was explained by the stronger affinity of MIEX for terrestrial dissolved organic matter (DOM) compared to microbial DOM. Fluorescence EEMS results showed that the ratio between terrestrial and microbial fluorescent signals of DOM was significantly greater in surface water than in secondary effluent. Fluorescence surrogate parameters were strongly correlated with TTHMFP, namely, fluorescence intensity of humic-like peak C (R2 = 0.98, p < 0.01), protein-like peak T (R2 = 0.96, p < 0.01), and fulvic-like peak A (R2 = 0.87, p < 0.01). Correlations between fluorescence surrogate parameters and TTHMFP were substantially stronger than correlations between DOC and TTHMFP. Overall, the results indicate that fluorescent parameters extracted from EEMS data can be used as quick surrogate parameters to monitor TTHMFP for a diverse group of raw and MIEX-treated waters.

Dysregulation of metabolic pathways in a mouse model of allergic asthma.

BACKGROUND: Asthma is a complex lung disease resulting from the interplay of genetic and environmental factors. To understand the molecular changes that occur during the development of allergic asthma without genetic and environmental confounders, an experimental model of allergic asthma in mice was used. Our goals were to (1) identify changes at the small molecule level due to allergen exposure, (2) determine perturbed pathways due to disease, and (3) determine whether small molecule changes correlate with lung function. METHODS: In this experimental model of allergic asthma, matched bronchoalveolar lavage (BAL) fluid and plasma were collected from three groups of C57BL6 mice (control vs sensitized and/or challenged with ovalbumin, n=3-5/group) 6 hour, 24 hour, and 48 hour after the last challenge. Samples were analyzed using liquid chromatography-mass spectrometry-based metabolomics. Airway hyper-responsiveness (AHR) measurements and differential cell counts were performed. RESULTS: In total, 398 and 368 dysregulated metabolites in the BAL fluid and plasma of sensitized and challenged mice were identified, respectively. These belonged to four, interconnected pathways relevant to asthma pathogenesis: sphingolipid metabolism (P=6.6×10-5 ), arginine and proline metabolism (P=1.12×10-7 ), glycerophospholipid metabolism (P=1.3×10-10 ), and the neurotrophin signaling pathway (P=7.0×10-6 ). Furthermore, within the arginine and proline metabolism pathway, a positive correlation between urea-1-carboxylate and AHR was observed in plasma metabolites, while ornithine revealed a reciprocal effect. In addition, agmatine positively correlated with lung eosinophilia. CONCLUSION: These findings point to potential targets and pathways that may be central to asthma pathogenesis and can serve as novel therapeutic targets.

Relationships between different nutritional anthropometric statuses and health-related fitness of South African primary school children.

BACKGROUND: A double burden of both under- and over-nutrition exists among South African children. AIM: To describe associations between nutritional statuses and health-related fitness test performances. SUBJECTS AND METHODS: Height and weight of 10 285 children (6-13 years; n = 5604 boys and 4681 girls) were measured and used to calculate body mass index (BMI) and prevalence of overweight and obesity, stunting, wasting and underweight. Physical fitness scores for standing long jump, shuttle run, sit-and-reach, sit-up (EUROFIT) and cricket ball throw were assessed. Age- and gender-specific z-scores were calculated for these variables. Physical fitness for each nutritional status group was compared to children of normal weight. RESULTS: Compared to normal weight children, overweight and obese children scored lower on all fitness tests (p < .001), except cricket ball throw (p = .235) and sit-and-reach (p = .015). Stunted and underweight children performed poorer than normal weight children on most fitness tests (p < .001), except sit-and-reach (stunted: p = .829; underweight: p = .538) and shuttle run (underweight: p = .017). Performance of wasted children was not as highly compromised as other under-nourished groups, but they performed poorer on the cricket ball throw (p < .001). CONCLUSIONS: When compared to normal weight children, both under- and over-nourished children performed poorer on some, but not all, health-related fitness tests.

Point-of-care monitoring of haemostasis.

Recent research in the management of haemorrhage has led to several changes in clinical practice. Evidence is accumulating that point-of-care testing results in fewer transfusions, improved patient outcomes, and reduced hospital costs. However, there is still insufficient high quality evidence to support transfusion guidelines and algorithms based on point-of-care tests alone, and more robust studies are needed. The implementation of point-of-care testing requires institutional support and senior clinical leadership to realise the benefits, with educational programmes, audit, and feedback regarding transfusion practice. A change in philosophy is required, from performing testing only when there is an obvious bleeding problem, towards the concept of routinely monitoring high-risk patients throughout the surgical procedure. This informs clinical practice, establishes normal ranges for that population, identifies patients at risk and allows early identification and treatment of evolving coagulopathy.

Abdominal subcutaneous adipose tissue insulin resistance and lipolysis in patients with non-alcoholic steatohepatitis.

BACKGROUND: Systemic insulin resistance (IR) is a primary feature in non-alcoholic steatohepatitis (NASH), however, there remain limited data on tissue-specific insulin sensitivity in vivo. METHODS: We examined tissue-specific (adipose, muscle and liver) insulin sensitivity and inflammation in 16 European Caucasian patients with biopsy-confirmed NASH and in 15 healthy controls. All underwent a two-step hyperinsulinaemic euglycaemic clamp incorporating stable isotope measurements of carbohydrate and lipid metabolism with concomitant subcutaneous adipose tissue (SAT) microdialysis. RESULTS: Hepatic and muscle insulin sensitivity were decreased in patients with NASH compared with controls, as demonstrated by reduced suppression of hepatic glucose production and glucose disposal (Gd) rates following insulin infusion. In addition, rates of lipolysis were higher in NASH patients with impaired insulin-mediated suppression of free fatty acid levels. At a tissue specific level, abdominal SAT in patients with NASH was severely insulin resistant, requiring >sixfold more insulin to cause ½-maximal suppression of glycerol release when compared with healthy controls. Furthermore, patients with NASH had significantly higher circulating levels of pro-inflammatory adipocytokines than controls. CONCLUSION: NASH patients have profound IR in the liver, muscle and in particular adipose tissues. This study represents the first in vivo description of dysfunctional SAT in patients with NASH.

Patient perspectives on informed consent for anaesthesia and surgery: American attitudes.

BACKGROUND: Principles of informed consent are ethically, morally, and legally grounded in physicians' responsibility to patients. This study examined patient expectations regarding the informed consent during the perioperative process, specifically risk information exchange, preferred method and timing of delivery, and the roles that patient anxiety and understanding might play. METHODS: Five hundred patients seen in our pre-operative clinic were surveyed by written questionnaire. Patients were asked about their level of agreement with a number of statements pertaining to informed consent and their preferences for discussion of types of risks. Anxiety concerns, impact of ability to understand complexities of care, preferences for timing, and method of presentation were assessed. RESULTS: Four hundred eleven of 500 surveys (82%) were completed. A majority of respondents (92% and 80%, respectively) believed the risk of common but less consequential complications and rare yet severe complications should be discussed. Only 21% agreed that anxiety generated by discussion of risks outweighed benefit and only 6% agreed that discussion of risks should be restricted based on patient inability to appreciate complexities of care. Discussion was preferred on the day of surgery, 1 week before, and 1 month before in 46%, 35%, and 16% of respondents, respectively, and independent of level of anxiety generated by such discussion (P = 0.87). Respondents preferred discussion with their anaesthesia provider alone (44%) or in combination with written information (52%) as compared with written information only (4%) (P < 0.01). CONCLUSIONS: Greater awareness of patient preferences and expectations may result in better information exchange between anaesthesia providers and their patients.

Operator training requirements and diagnostic accuracy of Fibroscan in routine clinical practice.

BACKGROUND: Fibroscan is a quick, non-invasive technique used to measure liver stiffness (kPa), which correlates with fibrosis. To achieve a valid liver stiffness evaluation (LSE) the operator must obtain all the following three criteria: (1) ≥10 successful liver stiffness measurements; (2) IQR/median ratio <0.30 and (3) ≥60% measurement success rate. OBJECTIVES: To assess the operator training requirements and the importance of adhering to the LSE validity criteria in routine clinical practice. METHODS: We retrospectively analysed the LSE validity rates of 2311 Fibroscans performed (1 August 2008 to 31 July 2011) in our tertiary liver outpatients department at the University Hospital Birmingham, UK. The diagnostic accuracy of Fibroscan was assessed in 153 patients, by comparing LSE (valid and invalid) with the modified Ishak fibrosis stage on liver biopsy. RESULTS: Learning curve analysis highlighted that the greatest improvement in validity of LSE rates occurs in the operator's first 10 Fibroscans, reaching 64.7% validity by the 50th Fibroscan. The correlation between LSE and the fibrosis stage on liver biopsy was superior in patients with a valid LSE (n=97) compared with those with an invalid LSE (n=56) (rs 0.577 vs 0.259; p=0.022). Area under receiving operating characteristics for significant fibrosis was greater when LSE was valid (0.83 vs 0.66; p=0.048). Using an LSE cut-off of 8 kPa, the negative predictive value of valid LSE was superior to invalid LSE for the detection of significant (84% vs 71%) and advanced fibrosis (100% vs 93%). CONCLUSIONS: Fibroscan requires minimal operator training (≥10 observed on patients), and when a valid LSE is obtained, it is an accurate tool for excluding advanced liver fibrosis. To ensure the diagnostic accuracy of Fibroscan it is essential that the recommended LSE validity criteria are adhered to in routine clinical practice.

Involving stakeholders in the commissioning and implementation of fishery science projects: experiences from the U.K. Fisheries Science Partnership.

Following from similar initiatives worldwide, the U.K.'s Fisheries Science Partnership (FSP) was established in 2003 to provide the fishing industry with opportunities to propose and participate in scientific studies in collaboration with fishery scientists. Key concepts were that most of the available funding would support industry participation, that industry, not scientists, would come up with the ideas for projects, and that commercial fishing vessels and fishing methods would be used to address specific concerns of the fishing industry in a scientifically controlled manner. Nearly 100 projects had been commissioned by March 2012, covering annual time-series surveys of stocks subject to traditional assessment, and ad hoc projects on, e.g. gear selectivity, discard survival, tagging and migration and fishery development. The extent to which the results of the projects have been used by stakeholders, fishery scientists and fishery managers at a national and E.U. level is evaluated, along with the degree of industry interest and involvement, and reasons are identified for successes or failures in the uptake of the results into management and policy. Finally, the question is posed whether the programme has been successful in improving the engagement of the fishing community in the science-management process and in fostering communication and greater trust between fishers, scientists and managers.

MIF is a common genetic determinant of COVID-19 symptomatic infection and severity.

BACKGROUND: Genetic predisposition to coronavirus disease 2019 (COVID-19) may contribute to its morbidity and mortality. Because cytokines play an important role in multiple phases of infection, we examined whether commonly occurring, functional polymorphisms in macrophage migration inhibitory factor (MIF) are associated with COVID-19 infection or disease severity. AIM: To determine associations of common functional polymorphisms in MIF with symptomatic COVID-19 or its severity. METHODS: This retrospective case-control study utilized 1171 patients with COVID-19 from three tertiary medical centers in the USA, Hungary and Spain, together with a group of 637 pre-pandemic, healthy control subjects. Functional MIF promoter alleles (-794 CATT5-8,rs5844572), serum MIF and soluble MIF receptor levels, and available clinical characteristics were measured and correlated with COVID-19 diagnosis and hospitalization. Experimental mice genetically engineered to express human high- or low-expression MIF alleles were studied for response to coronavirus infection. RESULTS: In patients with COVID-19, there was a lower frequency of the high-expression MIF CATT7 allele when compared to healthy controls [11% vs. 19%, odds ratio (OR) 0.54 [0.41-0.72], P < 0.0001]. Among inpatients with COVID-19 (n = 805), there was a higher frequency of the MIF CATT7 allele compared to outpatients (n = 187) (12% vs. 5%, OR 2.87 [1.42-5.78], P = 0.002). Inpatients presented with higher serum MIF levels when compared to outpatients or uninfected healthy controls (87 ng/ml vs. 35 ng/ml vs. 29 ng/ml, P < 0.001, respectively). Among inpatients, circulating MIF concentrations correlated with admission ferritin (r = 0.19, P = 0.01) and maximum CRP (r = 0.16, P = 0.03) levels. Mice with a human high-expression MIF allele showed more severe disease than those with a low-expression MIF allele. CONCLUSIONS: In this multinational retrospective study of 1171 subjects with COVID-19, the commonly occurring -794 CATT7MIF allele is associated with reduced susceptibility to symptomatic SARS-CoV-2 infection but increased disease progression as assessed by hospitalization. These findings affirm the importance of the high-expression CATT7MIF allele, which occurs in 19% of the population, in different stages of COVID-19 infection.

Nurse-delivered universal point-of-care testing for HIV in an open-access returning traveller clinic.

BACKGROUND: Early diagnosis of HIV infection reduces morbidity and mortality associated with late presentation. Despite UK guidelines, the HIV testing rate has not increased. We have introduced universal HIV screening in an open-access returning traveller clinic. METHODS: Data were prospectively recorded for all patients attending the open-access returning traveller clinic between August 2008 and December 2010. HIV testing was offered to all patients from May 2009; initially testing with laboratory samples (phase 1) and subsequently a point-of-care test (POCT) (phase 2). RESULTS: A total of 4965 patients attended the clinic; 1342 in phase 0, 792 in phase 1 and 2831 in phase 2. Testing rates for HIV increased significantly from 2% (38 of 1342) in phase 0 to 23.1% (183 of 792) in phase 1 and further increased to 44.5% (1261 of 2831) during phase 2 (P < 0.0001). Two new diagnoses of HIV-1 were identified in phase 1 (1.1% of tested); seven patients had a reactive POCT test in phase 2, of whom five (0.4% of those tested) were confirmed in a 4th generation assay. The patients with false reactive tests had a concurrent Plasmodium falciparum infection. Patients travelling to the Middle East and Europe were less likely to accept an HIV test with POCT. CONCLUSIONS: A nurse-delivered universal point-of-care HIV testing service has been successfully introduced and sustained in an acute medical clinic in a low-prevalence country. Caution is required in communicating reactive results in low-prevalence settings where there may be alternative diagnoses or a low population prevalence of HIV infection.