Effects of two alveolar recruitment manoeuvres (sustained inflation and stepwise) followed by positive end-expiratory pressure on cardiac output (measured with lithium dilution), invasive blood pressure and arterial oxygen tension in isoflurane-anaesthetised goats.

Alveolar recruitment manoeuvres (ARM) performed during general anaesthesia improve oxygenation; however cardiovascular depression may be observed. The aim of the study was to compare the effects of sustained inflation (SI) and stepwise ARMs on cardiac output (CO), mean arterial blood pressure and arterial oxygen tension (PaO2) in ten mechanically ventilated goats anaesthetised with isoflurane. In the SI ARM, peak inspiratory presure (PIP) was increased to 30 cmH2O and sustained for 20 s. In the stepwise ARM, the PIP was increased by 5 cmH2O each minute for three minutes from 10 to 25 cmH2O. Both ARMs were followed by positive end-expiratory pressure of 5 cmH2O. Paired lithium dilution CO measurements and arterial blood samples were obtained before and after each ARM. The order of the ARM was randomised and each goat was subjected to both techniques. Data was reported as median and interquartile range (IQR). Significance was set at 0.05. The median change in CO (measured by subtracting values after and before ARM) was -0.15 L min-1 (IQR -0.51; 0.03) and - 0.90 L min-1 (IQR -1.69; -0.58) for SI and stepwise ARM respectively (p = 0.04). The median change in PaO2 was 3 kPa (IQR -2.7; 7.6) and 0.4 kPa (IQR -3.4; 5.5) for SI and stepwise ARM respectively (p = 0.03). In conclusion, SI ARM causes less impact on CO and provides a better improvement in PaO2 compared to stepwise ARM in goats.

Correlates of psychological intimate partner violence with HIV care outcomes on patients in HIV care.

BACKGROUND: Among people living with HIV (PLWH), physical intimate partner violence (IPV) is associated with poor virologic, psychiatric, and behavioral outcomes. We examined non-physical, psychological intimate partner violence (psy-IPV) and HIV care outcomes using data from two U.S. consortia. METHODS: We conducted multivariable analyses with robust standard errors to compare patients indicating/not indicating psy-IPV. RESULTS: Among PLWH (n = 5950), 9.5% indicated psy-IPV; these individuals were younger (- 3; 95% CI [- 2,-4], p-value < 0.001), less likely to be on antiretroviral treatment (ART) (0.73 [0.55,0.97], p = 0.03), less adherent to ART (- 4.2 [- 5.9,-2.4], p < 0.001), had higher odds of detectable viral load (1.43 [1.15,1.78], p = 0.001) and depression (2.63 [2.18,3.18], p < 0.001), and greater use of methamphetamines/crystal [2.98 (2.30,3.87),p < 0.001], cocaine/crack [1.57 (1.24,1.99),p < 0.001], illicit opioids [1.56 (1.13,2.16),p = 0.007], and marijuana [1.40 (1.15,1.70), p < 0.001]. CONCLUSION: Psychological IPV, even in the absence of physical or sexual IPV, appears to be associated with HIV care outcomes and should be included in IPV measures integrated into routine HIV care.

The Dorsal Periosteal Curtain for Distal Radius Osteotomy Via the Volar Approach.

Volar wedge osteotomy and angle stable volar plating is now considered a standard approach for correction of distal radius malunion. In previous descriptions of the technique, soft tissue release has been performed with periosteal incision in line with the bony osteotomy. We present a technique whereby the dorsal periosteum is incised more proximally creating a dorsal vascularized periosteal "curtain." Our technique has several advantages including systematic release of restraining soft tissues to allow better distraction and reduction of the malunion; a dorsal periosteal curtain of vascular tissue with which to contain bone graft, protect extensor tendons and expedite healing; and better access to locally available bone graft. The previously described rotation-advancement of pronator quadratus is also used for plate coverage. We have found this technique straightforward to execute and teach, and useful in mitigating against some of the potential risks of the standard technique.

Radiological characterisation of graphite components in Advanced Gas-cooled Reactor cores.

As the Advanced Gas-cooled Reactors approach the end of generation, research and characterisation are required to support the decommissioning strategy. Radiological data for AGR graphite are negligible and the radiological inventory of the AGR core and other graphite components rely on activation modelling. This is the first study of C-14 activity and its release behaviour in AGR core graphite and its associated carbonaceous deposits and provides valuable information that can support decommissioning activities. In combination with corresponding studies on Magnox core graphite, significant understanding is attained on the main C-14 precursors in the graphite and the deposits. In addition, this study reports C-14, H-3 and gamma spectrometry data on AGR graphite fuel sleeves. This is a waste stream that is currently stored in heavily engineered stores at a significant cost. The data indicate that alternative storage and disposal options with a lower environmental and financial impact are worth considering.

The NHS visitor and migrant cost recovery programme - a threat to health?

BACKGROUND: In April 2014 the UK government launched the 'NHS Visitor and Migrant Cost Recovery Programme Implementation Plan' which set out a series of policy changes to recoup costs from 'chargeable' (largely non-UK born) patients. In England, approximately 75% of tuberculosis (TB) cases occur in people born abroad. Delays in TB treatment increase risk of morbidity, mortality and transmission in the community. We investigated whether diagnostic delay has increased since the Cost Recovery Programme (CRP) was introduced. METHODS: There were 3342 adult TB cases notified on the London TB Register across Barts Health NHS Trust between 1st January 2011 and 31st December 2016. Cases with missing relevant information were excluded. The median time between symptom onset and treatment initiation before and after the CRP was calculated according to birthplace and compared using the Mann Whitney test. Delayed diagnosis was considered greater or equal to median time to treatment for all patients (79 days). Univariable logistic regression was used to manually select exposure variables for inclusion in a multivariable model to test the association between diagnostic delay and the implementation of the CRP. RESULTS: We included 2237 TB cases. Among non-UK born patients, median time-to-treatment increased from 69 days to 89 days following introduction of CRP (p < 0.001). Median time-to-treatment also increased for the UK-born population from 75.5 days to 89.5 days (p = 0.307). The multivariable logistic regression model showed non-UK born patients were more likely to have a delay in diagnosis after the CRP (adjOR 1.37, 95% CI 1.13-1.66, p value 0.001). CONCLUSION: Since the introduction of the CRP there has been a significant delay for TB treatment among non-UK born patients. Further research exploring the effect of policies restricting access to healthcare for migrants is urgently needed if we wish to eliminate TB nationally.

Umbilical Cord-derived Mesenchymal Stem Cells for COVID-19 Patients with Acute Respiratory Distress Syndrome (ARDS).

The coronavirus SARS-CoV-2 is cause of a global pandemic of a pneumonia-like disease termed Coronavirus Disease 2019 (COVID-19). COVID-19 presents a high mortality rate, estimated at 3.4%. More than 1 out of 4 hospitalized COVID-19 patients require admission to an Intensive Care Unit (ICU) for respiratory support, and a large proportion of these ICU-COVID-19 patients, between 17% and 46%, have died. In these patients COVID-19 infection causes an inflammatory response in the lungs that can progress to inflammation with cytokine storm, Acute Lung Injury (ALI), Acute Respiratory Distress Syndrome (ARDS), thromboembolic events, disseminated intravascular coagulation, organ failure, and death. Mesenchymal Stem Cells (MSCs) are potent immunomodulatory cells that recognize sites of injury, limit effector T cell reactions, and positively modulate regulatory cell populations. MSCs also stimulate local tissue regeneration via paracrine effects inducing angiogenic, anti-fibrotic and remodeling responses. MSCs can be derived in large number from the Umbilical Cord (UC). UC-MSCs, utilized in the allogeneic setting, have demonstrated safety and efficacy in clinical trials for a number of disease conditions including inflammatory and immune-based diseases. UC-MSCs have been shown to inhibit inflammation and fibrosis in the lungs and have been utilized to treat patients with severe COVID-19 in pilot, uncontrolled clinical trials, that reported promising results. UC-MSCs processed at our facility have been authorized by the FDA for clinical trials in patients with an Alzheimer's Disease, and in patients with Type 1 Diabetes (T1D). We hypothesize that UC-MSC will also exert beneficial therapeutic effects in COVID-19 patients with cytokine storm and ARDS. We propose an early phase controlled, randomized clinical trial in COVID-19 patients with ALI/ARDS. Subjects in the treatment group will be treated with two doses of UC-MSC (l00 × 106 cells). The first dose will be infused within 24 hours following study enrollment. A second dose will be administered 72 ± 6 hours after the first infusion. Subject in the control group will receive infusion of vehicle (DPBS supplemented with 1% HSA and 70 U/kg unfractionated Heparin, delivered IV) following the same timeline. Subjects will be evaluated daily during the first 6 days, then at 14, 28, 60, and 90 days following enrollment (see Schedule of Assessment for time window details). Safety will be determined by adverse events (AEs) and serious adverse events (SAEs) during the follow-up period. Efficacy will be defined by clinical outcomes, as well as a variety of pulmonary, biochemical and immunological tests. Success of the current study will provide a framework for larger controlled, randomized clinical trials and a means of accelerating a possible solution for this urgent but unmet medical need. The proposed early phase clinical trial will be performed at the University of Miami (UM), in the facilities of the Diabetes Research Institute (DRI), UHealth Intensive Care Unit (ICU) and the Clinical Translational Research Site (CTRS) at the University of Miami Miller School of Medicine and at the Jackson Memorial Hospital (JMH).

Correction to: Effects of New Zealand blackcurrant extract on sport climbing performance.

The authors would like to correct the following errors in the online publication of the article. Incorrect values for % changes for climb duration were provided in the abstract, results and discussion session. The  % changes in climb duration was 15% with intake of New Zealand blackcurrant extract and -15% for the placebo condition. This correction does not change the conclusions derived from the study.

Effects of New Zealand blackcurrant extract on sport climbing performance.

PURPOSE: Blood flow to skeletal muscles and removal of metabolic by-products during a sport climb are essential to optimise performance and recovery. New Zealand blackcurrant (NZBC) extract has enhanced blood flow and performance in other exercise modalities. We examined the effect of NZBC extract on sport climbing performance and recovery. METHODS: The study employed a double-blind, randomised, crossover design. Male sport climbers (n = 18, age 24 ± 6 years, height 179 ± 6 cm, mass 71.4 ± 7.8 kg, French grade 6a-8b) undertook 7 days supplementation of NZBC extract (600 mg day-1 CurraNZ™ containing 210 mg anthocyanins) or a placebo (PL). Climbing ability was assessed through hang time (HT), pull-ups and total climbing time (TCT) in 3 intermittent climbing bouts on a Treadwall M6 rotating climbing wall to exhaustion with 20 min recovery between climbs. Heart rate (HR), blood lactate (BL), forearm girth (FG) and hand grip strength (HGS) were recorded. RESULTS: NZBC extract had no effect on pull-ups but provided a trend for higher HT and significantly improved TCT (+23%) compared to PL (-11%) over three climbs. HR, BL, FG and HGS all indicated that 20 min was insufficient for physiological recovery between the three climbing bouts indicating accumulative fatigue regardless of supplement condition. CONCLUSION: Despite indices of progressive fatigue across three bouts of climbing, NZBC extract facilitated not only a maintenance of TCT but an improved climbing endurance as compared with the PL condition. Blackcurrant anthocyanin-derived metabolites seem to affect physiological responses that facilitate sport climbing performance.

Breast cancer and cytomegalovirus.

PURPOSE: To determine whether cytomegalovirus is causally associated with breast cancer and whether cytomegalovirus should be categorised as an oncogenic virus. METHODS: We undertook a review of published epidemiological and laboratory studies, using established causal criteria: Bradford Hill criteria to determine whether cytomegalovirus is associated with breast cancer; and Evans/Mueller criteria to determine whether cytomegalovirus should be categorised as an oncogenic virus. RESULTS: Although there are inconsistencies in the findings of published epidemiological and laboratory studies, these may be explained by factors such as: differences in timing of blood samples, differences in selection of cases and controls, or high cytomegalovirus seroprevalence among participants in the epidemiological studies; and, in the laboratory studies, differences in sample preparations, age of sample, whether or not paired breast cancer and normal breast tissue samples were used, differences in the tests, primers and/or antibodies used, differences in histological types of breast cancer studied, and/or features of the virus. CONCLUSIONS: Overall, the results of published studies of cytomegalovirus and breast cancer suggest cytomegalovirus is a causal factor for at least some types of breast cancer. If the evidence for a link between cytomegalovirus and breast cancer continues to strengthen, further research could lead to: targeted screening; therapy using antiviral drugs; and, perhaps, primary prevention of a significant proportion of breast cancer. Vaccination against viruses has already been shown to be effective in preventing cervix and liver cancer; cytomegalovirus vaccines are already under development.

A population-based study of soft tissue sarcoma incidence and survival in Australia: An analysis of 26,970 cases.

BACKGROUND: Soft tissue sarcomas (STS) are rare, often fatal tumors, but little is known of the epidemiology and survival in the Australian population. This study aims to provide the first epidemiological analysis of incidence and survival rates of STS in the Australian population. METHODS: A retrospective population-based observational study was conducted between 1982 and 2009 of all patients with a diagnosis of STS using the Australian Institute of Health and Welfare (AIHW) Australian Cancer Database. Incidence rates per 100,000; incidence rate ratios, age-standardized incidence rates, prevalence and incidence rates of subtypes of STS, median, one-year and 5-year survival rates were examined. RESULTS: A total of 26,970 patients were identified. Between 1982 and 2009 STS incidence rates significantly increased from 3.99 [95% CI 3.68-4.32] to 6.12 [95% CI 5.80-6.46] per 100,000 Australian population, with a peak incident rate ratio (IRR) of 1.59 [95% CI 1.51-1.69] (p < 0.0001) in 2001. Median age at diagnosis increased from 58 to 63 years. Incidence rates were stable across all 10-year age cohorts, except for people aged over 70 where it increased. Overall, age-standardized incidence rates increased from 4.70 [95% CI 4.42-5.00] in 1982 to 5.87 [95% CI 5.63-6.11] per 100 000 Australians in 2009. Leiomyosarcoma (20.43%), malignant fibrous histiocytoma (16.14%), and soft tissue tumors/sarcomas, not otherwise specified (10.18%) were the most common STS subtypes. Median survival from diagnosis increased from 5.80 years [95% CI 5.06-6.54] in 1985-1989 cohort to 8.18 years [95% CI 7.54-8.81] in the 2000-2004 cohort (log-rank test p < 0.0001). CONCLUSION: The incidence of STS is increasing in Australia, most noticeably in those aged over 70 years, with a small but statistically significant increase in overall survival rates.

Estimated glomerular filtration rate and risk of poor outcomes after stroke.

BACKGROUND AND PURPOSE: The relationship of the estimated glomerular filtration rate (eGFR) with complications after stroke has not been fully characterized for the entire clinical spectrum of eGFR and for the fluctuation in eGFR during hospital stay. METHODS: Data from the Norfolk and Norwich Stroke Registry recorded between January 2003 and April 2015 were analysed. eGFR was categorized into six clinically relevant categories as per the Kidney Disease Improving Global Outcomes guidelines. The change in eGFR during acute admission was categorized into the following: within 5% change (reference), 5%-20% decline, >20% decline, 5%-20% increase and >20% increase. All-cause mortality, recurrent stroke, incident myocardial infarction, prolonged hospital stay and stroke disability at discharge were outcomes of interest. RESULTS: In all, 10 329 stroke patients (mean age 77.8 years) were followed for a mean of 2.9 years (30 126 person-years). Multivariable adjusted hazard ratios (95% confidence interval) for all-cause mortality were 0.91 (0.80-1.04), 0.96 (0.83-1.11), 1.23 (1.06-1.43), 1.54 (1.31-1.82) and 2.38 (1.91-2.97) for eGFR levels 60-89, 45-59, 30-44, 15-29 and <15 respectively, compared to eGFR ≥ 90 ml/min/1.73 m2 . The hazard ratios (95% confidence interval) for eGFR change were 1.56 (1.36-1.79), 1.17 (1.05-1.30), 1.47 (1.32-1.62) and 1.71 (1.55-1.88) for >20% decline, 5%-20% decline, 5%-20% increase and >20% increase, respectively, compared to change within 5%. Results were similar for other outcomes except recurrent stroke. CONCLUSIONS: Stroke patients with eGFR < 45 ml/min/1.73 m2 at hospital admission and >5% decline or increase in eGFR during hospital stay were at substantially higher risk of poor outcomes, particularly all-cause mortality, myocardial infarction, prolonged hospital stay and disability at discharge.

Impact of stroke-associated pneumonia on mortality, length of hospitalization, and functional outcome.

OBJECTIVES: Stroke-associated pneumonia (SAP) is common and associated with adverse outcomes. Data on its impact beyond 1 year are scarce. MATERIALS AND METHODS: This observational study was conducted in a cohort of stroke patients admitted consecutively to a tertiary referral center in the east of England, UK (January 2003-April 2015). Logistic regression models examined inpatient mortality and length of stay (LOS). Cox regression models examined longer-term mortality at predefined time periods (0-90 days, 90 days-1 year, 1-3 years, and 3-10 years) for SAP. Effect of SAP on functional outcome at discharge was assessed using logistic regression. RESULTS: A total of 9238 patients (mean age [±SD] 77.61 ± 11.88 years) were included. SAP was diagnosed in 1083 (11.7%) patients. The majority of these cases (n = 658; 60.8%) were aspiration pneumonia. After controlling for age, sex, stroke type, Oxfordshire Community Stroke Project (OCSP) classification, prestroke modified Rankin scale, comorbidities, and acute illness markers, mortality estimates remained significant at 3 time periods: inpatient (OR 5.87, 95%CI [4.97-6.93]), 0-90 days (2.17 [1.97-2.40]), and 91-365 days (HR 1.31 [1.03-1.67]). SAP was also associated with higher odds of long LOS (OR 1.93 [1.67-2.22]) and worse functional outcome (OR 7.17 [5.44-9.45]). In this cohort, SAP did not increase mortality risk beyond 1 year post-stroke, but it was associated with reduced mortality beyond 3 years. CONCLUSIONS: Stroke-associated pneumonia is not associated with increased long-term mortality, but it is linked with increased mortality up to 1 year, prolonged LOS, and poor functional outcome on discharge. Targeted intervention strategies are required to improve outcomes of SAP patients who survive to hospital discharge.

Diffuse field full matrix capture for near surface ultrasonic imaging.

This article reports a technique for near-surface ultrasonic array imaging. Information equivalent to an undelayed full matrix of inter-element responses is produced through cross-correlation of a later time diffuse full matrix. This reconstructed full matrix lacks the nonlinear effects of early time saturation present in a directly acquired response. Consequently the near-surface material information usually obscured by this effect is retrieved. Furthermore it is shown that a hybrid full matrix formed through a temporally weighted sum of coherent and reconstructed matrices allows for effective near-surface and bulk material imaging from a single direct-contact experimental realisation.

Patterns of head and neck sarcoma in Australia.

BACKGROUND: Sarcomas affecting the head and neck often require complex management due to the combination of anatomic, aesthetic and oncological considerations. The incidence and patterns of presentation are poorly understood and have not been reviewed in the Australian population. METHOD: This study sourced incidence and demographic data from the National Cancer Registry at the Australian Institute of Health and Welfare for the years 1982-2009 (corresponding to 97.3% of the Australian population). All cases of sarcoma, according to ICD-O-3 classification ((International Classification of Diseases for Oncology, 3rd edition), were assessed. RESULTS: A total of 3911 new cases of sarcoma affecting the head and neck were recorded during the period 1982-2009, including 1383, 2106 and 442 cases arising from skin, soft tissue and bone, respectively. The annual incidence rate of sarcomas affecting the head and neck was 1.59 per 100 000 population. The incidence of head and neck sarcoma rose substantially in older age groups (age 65 years and above) and was most common in male patients (69%). Malignant fibrous histiocytoma (MFH) was the most common pathology. There was an increase in incidence in skin-origin sarcoma in the head and neck, particularly affecting elderly males. CONCLUSION: The incidence of head and neck sarcoma in Australia is higher than that reported for an equivalent European population. The increase in MFH arising from the skin in elderly male patients mirrors the patterns of common cutaneous malignancy, particularly melanoma, suggesting that ultraviolet radiation is an epidemiological factor. Management of head and neck sarcoma is complex and best managed in a specialist multidisciplinary environment.

Effectiveness and cost-effectiveness of screening migrants for active tuberculosis and latent tuberculous infection.

With the advent of the World Health Organization End TB strategy, there has been renewed interest in screening for active tuberculosis (TB), and particularly latent tuberculous infection (LTBI). In low-incidence countries, a high proportion of TB cases are notified among migrants, which often occurs due to LTBI reactivation. We aimed to review the effectiveness and cost-effectiveness of screening migrants for active TB LTBI to inform and support the TB elimination strategy in low-incidence countries. We carried out a narrative review of English language articles published between 1 January 2000 and 31 June 2016 using the PubMed database. All studies that described the effectiveness or cost-effectiveness of active TB or LTBI screening among migrants were included. We identified 55 studies, and included 40 for the effectiveness of screening, 11 for cost-effectiveness and 4 that reported both. Screening for active TB can be effective and cost-effective depending on the setting, target group and screening approach. Pre-entry screening programmes have some impact on the epidemiology of the receiving countries. The effectiveness and cost-effectiveness of LTBI screening as predicted in mathematical models is also highly setting-specific, with best potential results achieved if screening is restricted to high-risk groups and/or to migrants from high-burden countries.

'Aussie Normals': an a priori study to develop reference intervals in a healthy Australian population using the Beckman Coulter LH 750 Haematology Analyser as candidates for harmonised values.

Reference limits or intervals are important benchmarks or tools that help the clinician to distinguish between a result that is most likely to lie within a 'healthy' or diseased category. It has been suggested that a review of haematology reference intervals is long overdue. In this study we report on our findings for analytes routinely measured in a complete blood count (CBC) performed on the Beckman Coulter LH 750 analyser and an additional comparative study using the Beckman Coulter LH 750, the Sysmex XN and Abbott Sapphire. The results from the comparative study indicate that bias would not prevent harmonisation of reference intervals for these common haematology parameters. The results offered by the Aussie Normals study represent good candidates as the basis for harmonisation reference intervals.

Intestinal tuberculosis: a diagnostic challenge.

OBJECTIVE: To describe characteristics, presentation, time to diagnosis and diagnostic findings of patients with intestinal tuberculosis (ITB) in a low-burden country. METHOD: Retrospective study of 61 consecutive ITB patients diagnosed between 2008 and 2014 at a large East London hospital. RESULTS: Forty of sixty-one patients were male. Mean age was 34.6 years. 93% of patients were born abroad, mostly from TB-endemic areas (Indian subcontinent: 88%, Africa: 9%). 25% had concomitant pulmonary TB. Median time from symptom onset to ITB diagnosis was 13 weeks (IQR 3-26 weeks). Ten patients were initially treated for IBD, although patients had ITB. The main sites of ITB involvement were the ileocaecum (44%) or small bowel (34%). Five patients had isolated perianal disease. Colonoscopy confirmed a diagnosis of ITB in 77% of those performed. 42 of 61 patients had a diagnosis of ITB confirmed on positive histology and/or microbiology. CONCLUSION: Diagnosis of ITB is often delayed, which may result in significant morbidity. ITB should be excluded in patients with abdominal complaints who come from TB-endemic areas to establish prompt diagnosis and treatment. Diagnosis is challenging but aided by axial imaging, colonoscopy and tissue biopsy for TB culture and histology.