The latitudinal temperature gradient and its climate dependence as inferred from foraminiferal δ18O over the past 95 million years.

SignificanceThe temperature difference between low and high latitudes is one measure of the efficiency of the global climate system in redistributing heat and is used to test the ability of models to represent the climate system through time. Here, we show that the latitudinal temperature gradient has exhibited a consistent inverse relationship with global mean sea-surface temperature for at least the past 95 million years. Our results help reduce conflicts between climate models and empirical estimates of temperature and argue for a fundamental consistency in the dynamics of heat transport and radiative transfer across vastly different background states.

Investigation of a Human Case of Francisella tularensis Infection, United Kingdom, 2023.

Tularemia, caused by Francisella tularensis, is not known to occur in the United Kingdom. We report a case of tularemia diagnosed in July 2023 in a UK patient with no travel in the 6 weeks before symptom onset. We describe the subsequent multiagency investigation into possible routes of acquisition.

Histopathological findings from the investigation of paediatric acute hepatitis of unknown aetiology, United Kingdom 2022.

In 2022, there were global reports of increased numbers of acute hepatitis not explained by hepatitis A-E virus infection in children. This manuscript summarises histopathology results from 20 patients in the United Kingdom who underwent liver transplant or had a liver biopsy as part of aetiological investigations. All available histopathological samples were reviewed centrally as part of the outbreak investigation. A working group comprised of infection specialists, hepatologists and histopathologists met virtually to review the cases, presentation, investigations and histopathology. All 20 liver samples had evidence of inflammation without significant interface activity, and submassive confluent pan-lobular or multilobular hepatocellular necrosis. Overall, the predominant histopathological findings were of acute nonspecific hepatitis with submassive hepatic necrosis and central vein perivenulitis and endothelitis. Histopathological findings were a poor indicator of aetiology.

The Reality of Antimicrobial Resistance and Antibiotic Usage Data in Asia: The CAPTURA Experience.

Antimicrobial resistance (AMR), particularly in low- and middle-income countries, is threatening to undermine advances in health and development. Scarce technical and human resources in these countries limit the collection of quality AMR data for evidence-based decision-making. The CAPTURA consortium, funded by the Fleming Fund, was implemented across 7 countries in the South and Southeast Asian region. The program focused on collating historical bacteriological data for qualitative and quantitative analyses. The team gathered standard data on the quality of laboratories and clinics and the quality and quantity of retrospective historical AMR data. In addition, retrospective data on antimicrobial use and consumption were analyzed. While standard protocols guided the project, a tailored approach for stakeholder engagement was implemented to work with countries and secure data-sharing agreements. The program also had to navigate the challenges of the COVID-19 pandemic, making some innovative adaptations to overcome logistical barriers. From 2018 through 2022, a large body of data was collected that was used to base a series of recommended key measures for strengthening the development of standardized national surveillance programs and to support alignment with international efforts.

From vision to cognition: potential contributions of cerebral visual impairment to neurodevelopmental disorders.

Vision has a crucial role to play in human development and functioning. It is, therefore, not surprising that vision plays a fundamental role in the development of the child. As a consequence, an alteration in visual function is, therefore, likely to hinder the child's development. Although ocular disorders are well known, diagnosed and taken into account, cerebral visual impairments (CVI) resulting from post-chiasmatic damage are largely underdiagnosed. However, among the disorders resulting from an episode of perinatal asphyxia and/or associated with prematurity, or neonatal hypoglycaemia, CVIs are prominent. In this article, we focus on the role of the possible effects of CVI on a child's learning abilities, leading to major difficulty in disentangling the consequences of CVI from other neurodevelopmental disorders (NDD) such as dyslexia, dyscalculia, dysgraphia, attention-deficit/hyperactivity disorder (ADHD), developmental coordination disorder (DCD) and autism spectrum disorders (ASD). Although we focus here on the possible overlap between children with CVI and children with other NDD, De Witt et al. (Wit et al. Ear Hear 39:1-19, 2018) have raised exactly the same question regarding children with auditory processing disorders (the equivalent of CVI in the auditory modality). We underline how motor, social and cognitive development as well as academic success can be impaired by CVI and raise the question of the need for systematic evaluation for disorders of vision, visual perception and cognition in all children presenting with a NDD and/or previously born under adverse neurological conditions.

Changing atmospheric CO2 concentration was the primary driver of early Cenozoic climate.

The Early Eocene Climate Optimum (EECO, which occurred about 51 to 53 million years ago), was the warmest interval of the past 65 million years, with mean annual surface air temperature over ten degrees Celsius warmer than during the pre-industrial period. Subsequent global cooling in the middle and late Eocene epoch, especially at high latitudes, eventually led to continental ice sheet development in Antarctica in the early Oligocene epoch (about 33.6 million years ago). However, existing estimates place atmospheric carbon dioxide (CO2) levels during the Eocene at 500-3,000 parts per million, and in the absence of tighter constraints carbon-climate interactions over this interval remain uncertain. Here we use recent analytical and methodological developments to generate a new high-fidelity record of CO2 concentrations using the boron isotope (δ(11)B) composition of well preserved planktonic foraminifera from the Tanzania Drilling Project, revising previous estimates. Although species-level uncertainties make absolute values difficult to constrain, CO2 concentrations during the EECO were around 1,400 parts per million. The relative decline in CO2 concentration through the Eocene is more robustly constrained at about fifty per cent, with a further decline into the Oligocene. Provided the latitudinal dependency of sea surface temperature change for a given climate forcing in the Eocene was similar to that of the late Quaternary period, this CO2 decline was sufficient to drive the well documented high- and low-latitude cooling that occurred through the Eocene. Once the change in global temperature between the pre-industrial period and the Eocene caused by the action of all known slow feedbacks (apart from those associated with the carbon cycle) is removed, both the EECO and the late Eocene exhibit an equilibrium climate sensitivity relative to the pre-industrial period of 2.1 to 4.6 degrees Celsius per CO2 doubling (66 per cent confidence), which is similar to the canonical range (1.5 to 4.5 degrees Celsius), indicating that a large fraction of the warmth of the early Eocene greenhouse was driven by increased CO2 concentrations, and that climate sensitivity was relatively constant throughout this period.

Development of a competency-based clinical assessment instrument for exit level Oral Hygiene students at the University of Western Cape.

Seminal to the process of a health sciences curriculum evaluation is the periodic review of clinical assessment instruments that measure competency. An assessment of quality is facilitated by using a well-structured, authentic and reliable instrument. This process rests on designing and measuring the instrument against a sound framework and validating it for scientific merit. This paper documents the pedagogy and the process taken in developing an improved formative competency-based assessment instrument for the final year students of the Bachelor of Oral Health program (BOH) at the University of the Western Cape (UWC). METHODS: A qualitative research study design employing the Nominal Group Technique (NGT) was used as a method for gaining small group consensus on the clinical assessment instrument for exit level Oral Hygiene (BOH3) students within the parameters of assessment principles. The key contributors to the instrument development process were the academic staff of the Department of Oral Hygiene, involved in clinical teaching and assessment of student competency. RESULTS: The domains of ethics and professionalism, patient assessment, diagnosis, treatment planning and implementation was identified as the core elements in the assessment. The principles of assessment, which include, alignment with outcomes, feedback, transparency and validity, were used to guide the instrument development. The assessment criteria were cross examined for alignment to the learning outcomes of the module and the program whilst formative feedback was foregrounded as a central feature to support student learning and progress monitoring. Transparency was obtained by providing students access to the instrument before and after the assessment including the written feedback on their performance. The instrument embodied a range of criteria to be assessed rather than on the awarding of a cumulative score. This allowed for the identification of the criteria or domain within which a student is struggling or excelling. Consensus on the instrument design was achieved using the NGT phases throughout the instrument development process including the weighting of the domains and grading. This level of engagement together with the application of scientifically sound assessment principles contributed to the validation of the instrument. CONCLUSION: The development of a competency-based assessment instrument was the result of a structured, collaborative and scientifically engaged process framed around specific assessment principles. The process culminated in the development of a formative competency-based clinical assessment instrument that was fit for purpose in the Bachelor of Oral Health program.The Nominal Group Technique served to be a valuable approach for small group consensus in developing the instrument. It served to promote individual perspectives and to generate debate and group discussion between academics that were proficient in clinical teaching and, finally to facilitate group consensus on the instrument structure and system for administration.

Vancouver General Hospital Pulmonary Embolism Response Team (VGH PERT): initial three-year experience.

PURPOSE: Clinical equipoise exists with the use of novel reperfusion therapies such as catheter-directed thrombolysis in the management of patients presenting to hospital with high risk pulmonary embolism (PE). Therapeutic options rely on clinical presentation, patient factors, physician preference, and institutional availability. We established a Pulmonary Embolism Response Team (PERT) to provide urgent assessment and multidisciplinary care for patients presenting to our institution with high-risk PE. METHODS: Data were retrospectively collected from PERT activations between January 2016 and December 2018. Chi square tests were used to determine differences in mortality across the three years of study. Logistic regression was used to evaluate 30- and 90-day mortality and occurrence of major bleeds between those receiving anticoagulation alone (AC) and those receiving advanced reperfusion therapy (ART). RESULTS: There were 128 PERT activations over three years, the majority originating from the emergency department. Eighty-five percent of activations were for submassive PE, with 56% of all activations assessed as submassive-high risk. Fifteen patients (12%) presented with massive PE. Advanced reperfusion therapy was used in 29 (23%) patients, of whom 25 (20%) received catheter-directed thrombolysis. There was an increased risk of major bleeding in the ART group compared with in the AC group (odds ratio [OR], 17.9; 95% confidence interval [CI], 4.1 to 125.0; P < 0.001), but no increased risk of mortality at 30 days (OR, 2.1; 95% CI, 0.4 to 9.1; P = 0.3). The 30-day mortality rate was 7.8%. CONCLUSION: We describe the first Canadian PERT, a multidisciplinary team aimed at providing urgent individualized care for patients with high-risk PE. Further research is necessary to determine whether a PERT improves clinical outcomes.

RéSUMé: OBJECTIF: Le concept d'équilibre clinique existe lors de l'utilisation de traitements innovants de reperfusion tels que la thrombolyse in situ (ou thrombolyse par cathéter) pour la prise en charge des patients se présentant à l'hôpital avec une embolie pulmonaire (EP) à haut risque. Les options thérapeutiques s'appuient sur la présentation clinique, les caractéristiques du patient, la préférence du médecin et la disponibilité institutionnelle. Nous avons mis sur pied une Équipe d'intervention en cas d'embolie pulmonaire (PERT - Pulmonary Embolism Response Team) afin de fournir une évaluation urgente et des soins multidisciplinaires aux patients se présentant dans notre institution avec une EP à haut risque. MéTHODE: Nous avons récolté rétrospectivement les données concernant les activations/alertes reçues par notre PERT entre janvier 2016 et décembre 2018. Des tests de chi carré ont été utilisés afin de déterminer les différences en matière de mortalité au cours des trois années de durée de l'étude. La régression logistique a été utilisée pour évaluer la mortalité à 30 et à 90 jours ainsi que la survenue de saignements majeurs entre les patients recevant uniquement un traitement anticoagulant (AC) et ceux recevant un traitement de reperfusion avancé (TRA). RéSULTATS: Il y a eu 128 alertes requérant l'activation de notre PERT en trois ans, la majorité provenant de l'urgence. Quatre-vingt-cinq pour cent des activations concernaient des EP submassives, et 56 % de toutes les activations ont été évaluées comme étant submassives à haut risque. Quinze patients (12 %) se sont présentés avec une EP massive. Un traitement de reperfusion avancé a été administré à 29 (23 %) patients, parmi lesquels 25 (20 %) ont reçu une thrombolyse in situ. Un risque accru de saignement majeur a été observé dans le groupe TRA par rapport au groupe AC (rapport de cotes [RC], 17,9; intervalle de confiance [IC] 95 %, 4,1 à 125,0; P < 0,001), mais il n'y avait pas de risque accru de mortalité à 30 jours (RC, 2,1; IC 95 %, 0,4 à 9,1; P = 0,3). Le taux de mortalité à 30 jours était de 7,8 %. CONCLUSION: Nous décrivons la première PERT canadienne, une équipe multidisciplinaire ayant pour but de prodiguer des soins personnalisés urgents aux patients avec embolie pulmonaire à haut risque. Des recherches supplémentaires sont nécessaires pour déterminer si une PERT améliore les pronostics cliniques.

Comparison of Fetal Fibronectin and Phosphorylated Insulin-Like Growth Factor Binding Protein-1 Testing to Predict Preterm Delivery in Symptomatic Women: A 10-Year Retrospective Study.

OBJECTIVE: To assess the diagnostic accuracy and cost-effectiveness of fetal fibronectin (fFN) and cervical phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) tests, individually and in combination, to predict preterm delivery within 48 hours, 7 days and 14 days in symptomatic women. METHOD: We selected women in Victoria, British Columbia, who presented between January 2008 and December 2017 at <34 weeks gestation at intermediate risk for labour (intact membrane, cervical dilatation <3 cm, and >6 contractions per hour). We calculated sensitivity, specificity, and positive and negative predictive values (PPV, NPV) for independent and concurrent testing and conducted a cost-effectiveness analysis to ensure appropriate test utilization. RESULTS: We identified 2911 cases. Both fFN and phIGFBP-1 tests showed high and comparable NPV in predicting risk of delivery within 48 hours, 7 days and 14 days (fFN: 99.3%, 98.5% and 97.3%; phIGFBP-1: 98.8%, 97.9% and 96.1%). In 1976 cases, samples for fFN and phIGFBP-1 tests were collected and analyzed concurrently. Concurrent analysis increased specificity (90.8%, 91.4%, and 91.8%) and PPV (11.8%, 19.8% and 24.2%). Independently, both tests had comparable sensitivity, while the fFN test had higher specificity. Concurrent testing offered the highest PPV. The net gain in PPV comes with a clinically insignificant net loss (<1%) in NPV when compared with either of the tests individually. CONCLUSION: Clinical usefulness of PPV for either test is limited. Routine concurrent testing comes with additional costs, and fFN has additional collection requirements. Point-of-care phIGFBP-1 testing has proven to be cheaper, simpler, and equally effective. Ordering physicians should be provided with education on how to interpret test results and should have protocols to guide clinical decision making.

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment.

Three-dimensional US Fractional Moving Blood Volume: Validation of Renal Perfusion Quantification.

Background Three-dimensional (3D) fractional moving blood volume (FMBV) derived from 3D power Doppler US has been proposed for noninvasive approximation of perfusion. However, 3D FMBV has never been applied in animals against a ground truth. Purpose To determine the correlation between 3D FMBV and the reference standard of fluorescent microspheres (FMS) for measurement of renal perfusion in a porcine model. Materials and Methods From February 2017 to September 2017, adult pigs were administered FMS before and after measurement of renal 3D FMBV at baseline (100%) and approximately 75%, 50%, and 25% flow levels by using US machines from two different vendors. The 3D power Doppler US volumes were converted and segmented, and correlations between FMS and 3D FMBV were made with simple linear regression (r2). Similarity and reproducibility of manual segmentation were determined with the Dice similarity coefficient and 3D FMBV reproducibility (intraclass correlation coefficient [ICC]). Results Thirteen pigs were studied with 33 flow measurements. Kidney volume (mean Dice similarity coefficient ± standard deviation, 0.89 ± 0.01) and renal segmentation (coefficient of variation = 12.6%; ICC = 0.86) were consistent. The 3D FMBV calculations had high reproducibility (ICC = 0.97; 95% confidence interval: 0.96, 0.98). The 3D FMBV per-pig correlation showed excellent correlation for US machines from both vendors (mean r2 = 0.96 [range, 0.92-1.0] and 0.93 [range, 0.78-1.0], respectively). The correlation between 3D FMBV and perfusion measured with microspheres was high for both US machines (r2 = 0.80 [P < .001] and 0.70 [P < .001], respectively). Conclusion The strong correlation between three-dimensional (3D) fractional moving blood volume (FMBV) and fluorescent microspheres indicates that 3D FMBV shows excellent correlation to perfusion and good reproducibility. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Morrell et al in this issue.

Accuracy of Different Bioinformatics Methods in Detecting Antibiotic Resistance and Virulence Factors from Staphylococcus aureus Whole-Genome Sequences.

In principle, whole-genome sequencing (WGS) can predict phenotypic resistance directly from a genotype, replacing laboratory-based tests. However, the contribution of different bioinformatics methods to genotype-phenotype discrepancies has not been systematically explored to date. We compared three WGS-based bioinformatics methods (Genefinder [read based], Mykrobe [de Bruijn graph based], and Typewriter [BLAST based]) for predicting the presence/absence of 83 different resistance determinants and virulence genes and overall antimicrobial susceptibility in 1,379 Staphylococcus aureus isolates previously characterized by standard laboratory methods (disc diffusion, broth and/or agar dilution, and PCR). In total, 99.5% (113,830/114,457) of individual resistance-determinant/virulence gene predictions were identical between all three methods, with only 627 (0.5%) discordant predictions, demonstrating high overall agreement (Fleiss' kappa = 0.98, P < 0.0001). Discrepancies when identified were in only one of the three methods for all genes except the cassette recombinase, ccrC(b). The genotypic antimicrobial susceptibility prediction matched the laboratory phenotype in 98.3% (14,224/14,464) of cases (2,720 [18.8%] resistant, 11,504 [79.5%] susceptible). There was greater disagreement between the laboratory phenotypes and the combined genotypic predictions (97 [0.7%] phenotypically susceptible, but all bioinformatic methods reported resistance; 89 [0.6%] phenotypically resistant, but all bioinformatics methods reported susceptible) than within the three bioinformatics methods (54 [0.4%] cases, 16 phenotypically resistant, 38 phenotypically susceptible). However, in 36/54 (67%) cases, the consensus genotype matched the laboratory phenotype. In this study, the choice between these three specific bioinformatic methods to identify resistance determinants or other genes in S. aureus did not prove critical, with all demonstrating high concordance with each other and phenotypic/molecular methods. However, each has some limitations; therefore, consensus methods provide some assurance.

Whole-Genome Sequencing Reveals the Contribution of Long-Term Carriers in Staphylococcus aureus Outbreak Investigation.

Whole-genome sequencing (WGS) makes it possible to determine the relatedness of bacterial isolates at a high resolution, thereby helping to characterize outbreaks. However, for Staphylococcus aureus, the accumulation of within-host diversity during carriage might limit the interpretation of sequencing data. In this study, we hypothesized the converse, namely, that within-host diversity can in fact be exploited to reveal the involvement of long-term carriers (LTCs) in outbreaks. We analyzed WGS data from 20 historical outbreaks and applied phylogenetic methods to assess genetic relatedness and to estimate the time to most recent common ancestor (TMRCA). The findings were compared with the routine investigation results and epidemiological evidence. Outbreaks with epidemiological evidence for an LTC source had a mean estimated TMRCA (adjusted for outbreak duration) of 243 days (95% highest posterior density interval [HPD], 143 to 343 days) compared with 55 days (95% HPD, 28 to 81 days) for outbreaks lacking epidemiological evidence for an LTC (P = 0.004). A threshold of 156 days predicted LTC involvement with a sensitivity of 0.875 and a specificity of 1. We also found 6/20 outbreaks included isolates with differing antimicrobial susceptibility profiles; however, these had only modestly increased pairwise diversity (mean 17.5 single nucleotide variants [SNVs] [95% confidence interval {CI}, 17.3 to 17.8]) compared with isolates with identical antibiograms (12.7 SNVs [95% CI, 12.5 to 12.8]) (P < 0.0001). Additionally, for 2 outbreaks, WGS identified 1 or more isolates that were genetically distinct despite having the outbreak pulsed-field gel electrophoresis (PFGE) pulsotype. The duration-adjusted TMRCA allowed the involvement of LTCs in outbreaks to be identified and could be used to decide whether screening for long-term carriage (e.g., in health care workers) is warranted. Requiring identical antibiograms to trigger investigation could miss important contributors to outbreaks.

Hemostatic effects of two desogestrel-containing combined oral contraceptive regimens: a multinational, multicenter, randomized, open-label study.

PURPOSE OF INVESTIGATION: To compare the effects of desogestrel (DSG) 150 mcg/ethinyl estradiol (EE) 20 mcg for 21 days followed by either seven days of EE ten mcg (21/7-active) or no treatment (DSG/EE+no Tx) on hemostatic markers. MATERIALS AND METHODS: This was a randomized, multicenter, open-label study that enrolled healthy premenopausal women. Non-inferiority of 21/7-active to DSG/EE+no Tx was determined if the upper limit of the two-sided 95% CI of the mean treatment difference in prothrombin fragment 1+2 (F1+2) over 24 weeks between groups was < 130 pmol/L. RESULTS: 246 subjects (n = 125, 21/7-active; n = 121, DSG/EE+no Tx) comprised the primary analysis. Mean F1+2 levels increased in both 21/7-active and DSG/EE+no Tx regimens (least square [LS] mean changes +45 pmol/L and +56.8 pmol/L, respectively). LS mean treatment difference was -11.8 pmol/L (95% CI: -54.8, 31.2). CONCLUSION: The effect of adding EE ten mcg to the seven-day hormone-free interval of DSG/EE on F1+2 levels was non-inferior to traditional DSG/EE.

A technique for the estimation of fractional moving blood volume by using three-dimensional power Doppler US.

PURPOSE: To (a) demonstrate an image-processing method that can automatically measure the power Doppler signal in a three-dimensional ( 3D three-dimensional ) ultrasonographic (US) volume by using the location of organs within the image and (b) compare 3D three-dimensional fractional moving blood volume ( FMBV fractional moving blood volume ) results with commonly used, unstandardized measures of 3D three-dimensional power Doppler by using the human placenta as the organ of interest. MATERIALS AND METHODS: This is a retrospective study of scans obtained as part of a prospective study of imaging placental biomarkers with US, performed with ethical approval and written informed consent. One hundred forty-three consecutive female patients were examined by using an image-processing technique. Three-dimensional FMBV fractional moving blood volume was measured on the vasculature from the uteroplacental interface to a depth 5 mm into the placenta by using a normalization volume 10 mm outside the uteroplacental interface and compared against the Virtual Organ Computer-aided AnaLysis ( VOCAL Virtual Organ Computer-aided AnaLysis ; GE Healthcare, Milwaukee, Wis) vascularization flow index ( VFI vascularization flow index ). Intra- and interobserver variability was assessed in a subset of 18 volumes. Wilcoxon signed rank test and intraclass correlation coefficients were used to assess measurement repeatability. RESULTS: The mean 3D three-dimensional FMBV fractional moving blood volume value ± standard deviation was 11.78% ± 9.30 (range, 0.012%-44.16%). Mean VFI vascularization flow index was 2.26 ± 0.96 (range, 0.15-6.06). Linear regression of VFI vascularization flow index versus FMBV fractional moving blood volume produced an R(2) value of 0.211 and was significantly different in distribution (P < .001). Intraclass correlation coefficient analysis showed higher FMBV fractional moving blood volume values than VFI vascularization flow index for intra- and interobserver variability; intraobserver values were 0.95 for FMBV fractional moving blood volume (95% confidence interval [ CI confidence interval ]: 0.90, 0.98) versus 0.899 for VFI vascularization flow index (95% CI confidence interval : 0.78, 0.96), and interobserver values were 0.93 for FMBV fractional moving blood volume (95% CI confidence interval : 0.82, 0.97) versus 0.67 for VFI vascularization flow index (95% CI confidence interval : 0.32, 0.86). CONCLUSION: The extension of an existing two-dimensional standardized power Doppler measurement into 3D three-dimensional by using an image-processing technique was shown in an in utero placental study. Three-dimensional FMBV fractional moving blood volume and VFI vascularization flow index produced significantly different results. FMBV fractional moving blood volume performed better than VFI vascularization flow index in repeatability studies. Further studies are needed to assess accuracy against a reference standard.

Monitoring of Cerebrovascular Reactivity for Determination of Optimal Blood Pressure in Preterm Infants.

OBJECTIVE: To define levels of mean arterial blood pressure (MABP) where cerebrovascular reactivity is strongest in preterm infants (ie, optimal MABP, or MABPOPT) and correlate deviations from MABPOPT with mortality and intraventricular hemorrhage (IVH). STUDY DESIGN: A total of 60 preterm infants born at median gestational age 26 ± 2 weeks (23 ± 2 to 32 ± 1) with indwelling arterial catheter were studied at a median 34 hours (range 5-228) of age. Tissue oxygenation heart rate (HR) reactivity index, which estimates cerebrovascular reactivity, was calculated as the moving correlation coefficient between slow waves of tissue oxygenation index, measured with near-infrared spectroscopy, and HR. MABPOPT was defined by dividing MABP into 2-mm Hg bins and averaging the tissue oxygenation HR reactivity index within those bins. A measurement of divergence from MABPOPT was calculated as the absolute difference between mean MABP and mean MABPOPT. RESULTS: Individual MABPOPT was defined in 81% of the patients. A measurement of divergence from MABPOPT was greater in those patients who died (mean 4.2 mm Hg; 95% CI 3.33-4.96) compared with those who survived (mean 2.1 mm Hg; 95% CI 1.64-2.56), P = .013. Patients who had MABP lower than MABPOPT by 4 mm Hg or more had a greater rate of mortality (40%) than those with MABP close to or above MABPOPT (13%), P = .049. Patients with MABP greater than MABPOPT by 4 mm Hg had greater IVH scores, P = .042. CONCLUSIONS: Continuous monitoring of cerebrovascular reactivity allows the determination of MABPOPT in preterm neonates. Significant deviation below MABPOPT was observed in infants who died. Deviation of MABP above optimal level was observed in infants who developed more severe IVH.

Pacing, the missing piece of the puzzle to high-intensity interval training.

This study examined physiological and perceptual responses to matched work high-intensity interval training using all-out and 2 even-paced methodologies. 15 trained male cyclists performed 3 interval sessions of three 3-min efforts with 3 min of active recovery between efforts. The initial interval session was completed using all-out pacing, with the following 2 sessions being completed with computer- and athlete-controlled pacing in a randomised and semi-counterbalanced manner. Computer- and athlete-controlled intervals were completed at the mean power from the corresponding interval during the all-out trial. Oxygen consumption and ratings of perceived exertion were recorded during each effort. 20 min following each session, participants completed a 4-km time trial and provided sessional rating of perceived exertion. Oxygen consumption was greater during all-out (54.1±6.6 ml.kg(-1).min(-1); p<0.01) and athlete-controlled (53.0±5.8 ml.kg(-1).min(-1); p<0.01) compared with computer-controlled (51.5±5.7 ml.kg(-1).min(-1)). Total time ≥85% maximal oxygen consumption was greater during all-out compared to both even-paced efforts. Sessional ratings of perceived exertion were greater after all-out compared to both even-paced sessions. Mean 4-km power output was lower after all-out compared with both even paced intervals. Distribution of pace throughout high-intensity interval training can influence perceptual and metabolic stress along with subsequent performance and should be considered during the prescription of such training.

Prediction of Staphylococcus aureus antimicrobial resistance by whole-genome sequencing.

Whole-genome sequencing (WGS) could potentially provide a single platform for extracting all the information required to predict an organism's phenotype. However, its ability to provide accurate predictions has not yet been demonstrated in large independent studies of specific organisms. In this study, we aimed to develop a genotypic prediction method for antimicrobial susceptibilities. The whole genomes of 501 unrelated Staphylococcus aureus isolates were sequenced, and the assembled genomes were interrogated using BLASTn for a panel of known resistance determinants (chromosomal mutations and genes carried on plasmids). Results were compared with phenotypic susceptibility testing for 12 commonly used antimicrobial agents (penicillin, methicillin, erythromycin, clindamycin, tetracycline, ciprofloxacin, vancomycin, trimethoprim, gentamicin, fusidic acid, rifampin, and mupirocin) performed by the routine clinical laboratory. We investigated discrepancies by repeat susceptibility testing and manual inspection of the sequences and used this information to optimize the resistance determinant panel and BLASTn algorithm. We then tested performance of the optimized tool in an independent validation set of 491 unrelated isolates, with phenotypic results obtained in duplicate by automated broth dilution (BD Phoenix) and disc diffusion. In the validation set, the overall sensitivity and specificity of the genomic prediction method were 0.97 (95% confidence interval [95% CI], 0.95 to 0.98) and 0.99 (95% CI, 0.99 to 1), respectively, compared to standard susceptibility testing methods. The very major error rate was 0.5%, and the major error rate was 0.7%. WGS was as sensitive and specific as routine antimicrobial susceptibility testing methods. WGS is a promising alternative to culture methods for resistance prediction in S. aureus and ultimately other major bacterial pathogens.