Ozone Exposure Limits Cardiorespiratory Function During Maximal Cycling Exercise in Endurance Athletes.

Ground-level ozone (O3) is a potent air pollutant well recognized to acutely induce adverse respiratory symptoms and impairments in pulmonary function. However, it is unclear how the hyperpnea of exercise may modulate these effects, and the subsequent consequences on exercise performance. We tested the hypothesis that pulmonary function and exercise capability would be diminished, and symptom development would be increased during peak real-world levels of O3 exposure compared to room air. Twenty aerobically trained participants [13M, 7F; maximal O2 uptake (O2max), 64.1 ± 7.0 mL·kg-1·min-1)] completed a three-visit double-blinded, randomized crossover trial. Following a screening visit, participants were exposed to 170 ppb O3 or room air (<10 ppb O3) on separate visits during exercise trials, consisting of a 25-minute moderate intensity warmup, 30-minute heavy intensity bout, and a subsequent time-to-exhaustion (TTE) performance test. No differences in O2 uptake or ventilation were observed during submaximal exercise between conditions. During the TTE test, we observed significantly lower end-exercise O2 uptake (-3.2 ± 4.3%, p=0.004), minute ventilation (-3.2 ± 6.5%, p=0.043), tidal volume (-3.6 ± 5.1%, p=0.008), and a trend towards lower exercise duration in O3 compared to room air(-10.8 ± 26.5%, p=0.092). As decreases in O2 uptake and alterations in respiratory pattern were also present at matched time segments between conditions, a limitation of oxygen transport seems likely during maximal exercise. A more comprehensive understanding of the direct mechanisms that limit oxygen transport during exercise in high-pollutant concentrations is key for mitigating performance changes.

A serological assay using Tropheryma whipplei antigens for the presumptive exclusion of Whipple disease.

Whipple disease (WD) is a rare infection in genetically susceptible people caused by the bacterium Tropheryma whipplei. An indirect immunofluorescence serological assay (IFA), detecting patient antibodies to the bacterium, was developed using T. whipplei as antigen. We hypothesised that this assay could be used to rule out WD in patients in whom the diagnosis was being considered, based on high immunoglobulin (Ig) G titres to T. whipplei. In this study, 16 confirmed WD patients and 156 age-matched controls from across Australia were compared serologically. WD patients mostly underproduced IgG antibody to T. whipplei, with titres of ≤1:32 being common. While at an antibody titre of <1:64 the assay sensitivity for WD was only 69% [95% confidence interval (CI) 41-89%], its specificity for excluding WD was 91% (95% CI 85-95%). This specificity increased to 95% (95% CI 90-98%) at an antibody titre of <1:16. Patients with antibody titres of >1:64 were unlikely to have WD. At this titre, the seroprevalence of T. whipplei IgG antibody was 92% (223/242) in Australian blood donors. Unlike other serological assays, which are used to confirm a specific infection, this novel assay is designed to rule out WD infection with a specificity in Australia of 91%. Further validation of this assay, by trialling in other countries, should now be undertaken, as its usefulness is dependent on there being a high background seropositivity to T. whipplei in the general population at the location in which the assay is being used.

Intermuscular coherence of plantar and dorsiflexor muscles in older adults with Parkinson's disease and age-matched controls during bipedal and unipedal stance.

Introduction: Postural instability increases with age and is exacerbated in neurological disorders such as Parkinson's disease (PD). Reducing the base of support from bipedal to unipedal stance increases center of pressure (CoP) parameters and intermuscular coherence in lower-leg muscles of healthy older adults. To further develop an understanding of postural control in an altered state of neurological impairment, we explored intermuscular coherence in lower-leg muscles and CoP displacement in older adults with PD. Methods: This study measured surface EMG from the medial (MG) and lateral (LG) gastrocnemii, soleus (SOL), and tibialis anterior (TA), and examined EMG amplitude and intermuscular coherence during bipedal and unipedal stance on a force plate with firm (no foam) and compliant (standing on foam) surface conditions in nine older adults with PD (70±5 years, 6 females) and 8 age-matched non-Parkinsonian older adults (5 females). Intermuscular coherence was analyzed between agonist-agonist and agonist-antagonist muscle pairs in the alpha (8-13 Hz) and beta (15-35 Hz) frequency bands. Results: CoP parameters increased from bipedal to unipedal stance in both groups (p < 0.01), but did not increase from the firm to compliant surface condition (p > 0.05). During unipedal stance, CoP path length was shorter in older adults with PD (2027.9 ± 1074.1 mm) compared to controls (3128.5 ± 1198.7 mm) (p < 0.01). Alpha and beta agonist-agonist and agonist-antagonist coherence increased by 28% from bipedal to unipedal stance (p > 0.05), but did not differ between older adults with PD (0.09 ± 0.07) and controls (0.08 ± 0.05) (p > 0.05). The older adults with PD also had greater normalized EMG amplitude of the LG (63.5 ± 31.7%) and TA (60.6 ± 38.4%) during the balance tasks (p > 0.05) than the non-Parkinsonian counterparts. Discussion: Older adults with PD had shorter path lengths during unipedal stance and required greater muscle activation than older adults without PD to perform the tasks, but intermuscular coherence did not differ between the groups. This may be attributable to their early disease stage and high motor function.

Insights into the Evolution of P. aeruginosa Antimicrobial Resistance in a Patient Undergoing Intensive Therapy.

Whole genome sequencing (WGS) provides insights into the evolution of antimicrobial resistance, an urgent global health threat. Using WGS, we observe evolutionary adaptation of a Pseudomonas aeruginosa strain within an immunocompromised patient undergoing antibiotic therapy. Two blood isolates (EA-86 and EA-87) from the patient evolved separate adaptations for antibiotic resistance, while sharing common adaptive mutations for host immune evasion. In EA-86, a silencing mutation in the antibiotic efflux pump repressor, NfxB, increased antibiotic resistance, while in EA-87, a similar mutation was seen in the antibiotic efflux pump repressor mexR. The number of genomic variants between the two isolates give a divergence time estimate of the order of 1000 generations. This time is sufficient for a bacterial lineage to have evolved an SNP in every position in the genome and been fixed if advantageous. This demonstrates the evolutionary adaptive power accessible to bacteria and the timescale for a brute-force functional survey of the SNP fitness landscape.

Imaging and Molecular Annotation of Xenographs and Tumours (IMAXT): High throughput data and analysis infrastructure.

With the aim of producing a 3D representation of tumors, imaging and molecular annotation of xenografts and tumors (IMAXT) uses a large variety of modalities in order to acquire tumor samples and produce a map of every cell in the tumor and its host environment. With the large volume and variety of data produced in the project, we developed automatic data workflows and analysis pipelines. We introduce a research methodology where scientists connect to a cloud environment to perform analysis close to where data are located, instead of bringing data to their local computers. Here, we present the data and analysis infrastructure, discuss the unique computational challenges and describe the analysis chains developed and deployed to generate molecularly annotated tumor models. Registration is achieved by use of a novel technique involving spherical fiducial marks that are visible in all imaging modalities used within IMAXT. The automatic pipelines are highly optimized and allow to obtain processed datasets several times quicker than current solutions narrowing the gap between data acquisition and scientific exploitation.

The impact of infectious diseases consultation on the management and outcomes of Pseudomonas aeruginosa bacteraemia in adults: a retrospective cohort study.

BACKGROUND: Pseudomonas aeruginosa bacteraemia (PAB) is associated with high mortality. The benefits of infectious diseases consultation (IDC) has been demonstrated in Staphylococcal aureus bacteraemia and other complex infections. Impact of IDC in PAB is unclear. This study aimed to evaluate the impact of IDC on the management and outcomes in patients with PAB. METHODS: This is a retrospective cohort single-centre study from 1 November 2006 to 29 May 2019, in all adult patients admitted with first episode of PAB. Data collected included demographics, clinical management and outcomes for PAB and whether IDC occurred. In addition, 29 Pseudomonas aeruginosa (PA) stored isolates were available for Illumina whole genome sequencing to investigate if pathogen factors contributed to the mortality. RESULTS: A total of 128 cases of PAB were identified, 71% received IDC. Patients who received IDC were less likely to receive inappropriate duration of antibiotic therapy (4.4%; vs 67.6%; p < 0.01), more likely to be de-escalated to oral antibiotic in a timely manner (87.9% vs 40.5%; p < 0.01), undergo removal of infected catheter (27.5% vs 13.5%; p = 0.049) and undergo surgical intervention (20.9% vs 5.4%, p = 0.023) for source control. The overall 30-day all-cause mortality rate was 24.2% and was significantly higher in the no IDC group in both unadjusted (56.8% vs 11.0%, odds ratio [OR] = 10.63, p < 0.001) and adjusted analysis (adjusted OR = 7.84; 95% confidence interval, 2.95-20.86). The genotypic analysis did not reveal any PA genetic features associated with increased mortality between IDC versus no IDC groups. CONCLUSION: Patients who received IDC for PAB had lower 30-day mortality, better source control and management was more compliant with guidelines. Further prospective studies are necessary to determine if these results can be validated in other settings.

Development and validation of a novel prediction score for cardiac tamponade in emergency department patients with pericardial effusion.

AIMS: Determining which patients with pericardial effusion require urgent intervention can be challenging. We sought to develop a novel, simple risk prediction score for patients with pericardial effusion. METHODS AND RESULTS: Adult patients admitted through the emergency department (ED) with pericardial effusion were retrospectively evaluated. The overall cohort was divided into a derivation and validation cohort for the generation and validation of a novel risk score using logistic regression. The primary outcome was a pericardial drainage procedure or death attributed to cardiac tamponade within 24 h of ED arrival. Among 195 eligible patients, 102 (52%) experienced the primary outcome. Four variables were selected for the novel score: systolic blood pressure < 100 mmHg (1.5 points), effusion diameter [1-2 cm (0 points), 2-3 cm (1.5 points), >3 cm (2 points)], right ventricular diastolic collapse (2 points), and mitral inflow velocity variation > 25% (1 point). The need for pericardial drainage within 24 h was stratified as low (<2 points), intermediate (2-4 points), or high (≥4 points), which corresponded to risks of 8.1% [95% confidence interval (CI) 3.0-16.8%], 63.8% [95% CI 50.1-76.0%], and 93.7% [95% CI 84.5-98.2%]. The area under the curve of the simplified score was 0.94 for the derivation and 0.91 for the validation cohort. CONCLUSION: Among ED patients with pericardial effusion, a four-variable prediction score consisting of systolic blood pressure, effusion diameter, right ventricular collapse, and mitral inflow velocity variation can accurately predict the need for urgent pericardial drainage. Prospective validation of this novel score is warranted.

Use of a Refresher Course Increases Confidence in Point-of-Care Ultrasound Skills in Emergency Medicine Faculty.

Introduction All practicing emergency medicine (EM) physicians need to maintain a skillset in emergency ultrasound (US) after their initial training. EM physicians in academic practice may be supervising trainees performing ultrasound applications that they aren't comfortable with. This study investigates the effectiveness of a US refresher course. The hypothesis was that a series of short courses would increase confidence in performing and supervising US applications. Methods Nine basic emergency ultrasound applications were taught over the course of one year by ultrasound fellowship-trained EM faculty in a simulation center at a single academic institution. Each session included 30-minutes of didactics/image review and 30-minutes of hands-on practice on normal volunteers and was followed by an anonymous questionnaire evaluating comfort level performing and supervising the ultrasound application before and after the course using a Likert scale from 1 "not at all confident" to 5 "very confident". Results Thirty-six of 60 EM physicians participated in at least 1 of the 9 sessions (median 3, interquartile range 2-4). Faculty who attended had a median of 10 (interquartile range 7-15) years in practice and 61% work at both academic and community sites. For all sessions combined, confidence in performing US increased from a mean score on the Likert scale of 3.3 to 4.4 (difference 1.1, confidence interval (CI) (0.94, 1.29), p < 0.001) and confidence in supervising trainees increased from a mean of 3.4 to 4.5 (difference 1.1, CI (0.88, 1.23), p < 0.001). The largest increases were seen in musculoskeletal (MSK), nerve, and pelvic applications and the least increase was seen with the session focused on intravenous access, but confidence was increased in all sessions. Physicians in practice ≥10 years increased in confidence in performing and supervising the applications by 1.4 (CI (1.11, 1.60), p < 0.001) and 1.3, (CI (1.01, 1.49), p < 0.001), respectively. Physicians in practice <10 years increased 0.8 (CI (0.57, 1.03), p < 0.001) and 0.8 (CI (0.55, 1.05), p < 0.001), respectively. Conclusion An emergency ultrasound refresher course for EM physicians at a single institution improved self-reported confidence in both performing and supervising trainees in all applications reviewed. Those in practice ≥10 years showed the largest increases.

Forgotten but not gone - Scrofuloderma in a migrant student from India.

A 34-year-old Indian student who immigrated to Australia five years ago presented with a four-week history of neck pain. Physical examination revealed two firm fixed cervical lymph nodes in the anterior triangle and midline region which were tender on palpation and erythematous on inspection. Cording phenomenon was found on ZN staining of FNA sample and mycobacterium tuberculosis (M.tb ) PCR confirmed the diagnosis with incomplete resistance to isoniazid. Patient was treated with other three first line antituberculosis medications for nine months with an excellent outcome. Prednisolone was also used as adjunctive therapy and tapered during the course of treatment.

The effectiveness of a single-stage versus traditional three-staged protocol of hospital disinfection at eradicating vancomycin-resistant Enterococci from frequently touched surfaces.

BACKGROUND: Environmental contamination is a reservoir for vancomycin-resistant enterococcus (VRE) in hospitals. METHODS: Environmental sampling of surfaces was undertaken anytime before disinfection and 1 hour after disinfection utilizing a sodium dichloroisocyanurate-based, 3-staged protocol (phase 1) or benzalkonium chloride-based, single-stage clean (phase 2). VRE colonization and infection rates are presented from 2010 to 2011, and audits of cleaning completeness were also analyzed. RESULTS: Environmental samples collected before disinfection were significantly more likely to be contaminated with VRE during phase 1 than phase 2: 25.2% versus 4.6%, respectively; odds ratio (OR), 7.01 (P < .01). Environmental samples collected after disinfection were also significantly more likely to yield VRE during phase 1 compared with phase 2: 11.2% versus 1.1%, respectively; OR, 11.73 (P < .01). Rates of VRE colonization were higher during 2010 than 2011. Cleaning audits showed similar results over both time periods. CONCLUSION: During use of a chlorine-based, 3-staged protocol, significantly higher residual levels of VRE contamination were identified, compared with levels detected during use of a benzalkonium chloride-based product for disinfection. This reduction in VRE may be due to a new disinfection product, more attention to the thoroughness of cleaning, or other supplementary efforts in our institution.

Evaluation of a generalizable approach to clinical information retrieval using the automated retrieval console (ARC).

Reducing custom software development effort is an important goal in information retrieval (IR). This study evaluated a generalizable approach involving with no custom software or rules development. The study used documents "consistent with cancer" to evaluate system performance in the domains of colorectal (CRC), prostate (PC), and lung (LC) cancer. Using an end-user-supplied reference set, the automated retrieval console (ARC) iteratively calculated performance of combinations of natural language processing-derived features and supervised classification algorithms. Training and testing involved 10-fold cross-validation for three sets of 500 documents each. Performance metrics included recall, precision, and F-measure. Annotation time for five physicians was also measured. Top performing algorithms had recall, precision, and F-measure values as follows: for CRC, 0.90, 0.92, and 0.89, respectively; for PC, 0.97, 0.95, and 0.94; and for LC, 0.76, 0.80, and 0.75. In all but one case, conditional random fields outperformed maximum entropy-based classifiers. Algorithms had good performance without custom code or rules development, but performance varied by specific application.

Q fever outbreak at a cosmetics supply factory.

Q fever is a zoonotic disease that is most commonly associated with outbreaks in slaughterhouses. We describe an outbreak of 4 cases occurring in a factory that processes ovine fetal products for the cosmetics industry. It is important that industries typically not associated with risk of Q fever are made aware of potential health risks that workers might be exposed to so further outbreaks might be prevented.

Peritonitis due to Curvularia inaequalis in an elderly patient undergoing peritoneal dialysis and a review of six cases of peritonitis associated with other Curvularia spp.

Fungal peritonitis due to Curvularia species in patients undergoing peritoneal dialysis is a very rare problem. We report a case of peritonitis caused by Curvularia inaequalis. This is the first report in the English literature of this species causing human infection. We also review the six previously reported cases of continuous ambulatory peritoneal dialysis peritonitis caused by other Curvularia species.