Phylogenetic relationships within the primitive acanthomorph fish genus Polymixia, with changes to species composition and geographic distributions

The genus Polymixia is the only survivor of a Late Cretaceous marine fish radiation and is often said to be the most primitive living acanthomorph (i.e., Polymixia possesses the greatest number of primitive character states for Acanthomorpha). Recent studies, including this one, place Polymixia as the sister to all other Paracanthopterygii. Despite its importance, most species of Polymixia are extremely difficult to discriminate on the basis of morphology. As a result, the number of valid species is uncertain. Moreover, there has never been a phylogenetic analysis of the genus. Thus, a molecular phylogenetic study was needed to clarify species boundaries and to resolve relationships within the genus. Tissue or DNA samples backed by museum vouchers were obtained for most species, with additional samples from new geographic areas representing specimens with distinctively different meristics and uncertain identifications. Seven loci (five nuclear and two mitochondrial) were sequenced, from which Bayesian and maximum-likelihood trees were generated. Results reveal nine species-level clades, of which five represent previously known species (Polymixia berndti, P. japonica, P. longispina, P. lowei, and P. nobilis). Surprisingly, results also reveal four previously unknown species-level clades, one close to P. lowei, one close to P. nobilis, and two new species clades related to P. japonica. The species clades are distinguished by their phylogenetic histories, sequence differences, geographic distributions, and morphologies. The clade containing P. berndti is recovered as the sister to all other species of Polymixia. Its genetic variability suggests that it might contain two or more species and it is referred to here as a “species complex”. Polymixia nobilis, the type species, was previously thought to be restricted to the Atlantic, but is now shown to be widespread in the Pacific and possibly in the Indian Ocean. Specimens from waters off Australia identified as P. busakhini actually belong to P. nobilis. In contrast, P. japonica is confirmed only in the area near Japan and the East China Sea; other more distant records are misidentifications. Wide (antipodal) geographic distributions are seen in several clades, including P. nobilis, the P. berndti species complex, and the P. japonica species group. The new phylogeny helps explain the evolution of some morphological characters previously used to distinguish groups of species, particularly dorsal-fin soft-ray count, shape of rows of scale ctenii, and number of pyloric caec

Quantification of structural changes in the corpus callosumin children with profound hypoxic-ischaemic brain injury

Background Birth-related acute profound hypoxic–ischaemic brain injury has specific patterns of damage including the paracentral lobules. Objective To test the hypothesis that there is anatomically coherent regional volume loss of the corpus callosum as a result of this hemispheric abnormality. Materials and methods Study subjects included 13 children with proven acute profound hypoxic–ischaemic brain injury and 13 children with developmental delay but no brain abnormalities. A computerised system divided the corpus callosum into 100 segments, measuring each width. Principal component analysis grouped the widths into contiguous anatomical regions. We conducted analysis of variance of corpus callosum widths as well as support vector machine stratification into patient groups. Results There was statistically significant narrowing of the mid–posterior body and genu of the corpus callosum in children with hypoxic–ischaemic brain injury. Support vector machine analysis yielded over 95% accuracy in patient group stratification using the corpus callosum centile widths. Conclusion Focal volume loss is seen in the corpus callosum of children with hypoxic–ischaemic brain injury secondary to loss of commissural fibres arising in the paracentral lobules. Support vector machine stratification into the hypoxic–ischaemic brain injury group or the control group on the basis of corpus callosum width is highly accurate and points towards rapid clinical translation of this technique as a potential biomarker of hypoxic–ischaemic brain injur

A risk prediction model for the assessment and triage of women with hypertensive disorders of pregnancy in low-resourced settings: the miniPIERS (Pre-eclampsia Integrated Estimate of RiSk) multi-country prospective cohort study.

BACKGROUND: Pre-eclampsia/eclampsia are leading causes of maternal mortality and morbidity, particularly in low- and middle- income countries (LMICs). We developed the miniPIERS risk prediction model to provide a simple, evidence-based tool to identify pregnant women in LMICs at increased risk of death or major hypertensive-related complications. METHODS AND FINDINGS: From 1 July 2008 to 31 March 2012, in five LMICs, data were collected prospectively on 2,081 women with any hypertensive disorder of pregnancy admitted to a participating centre. Candidate predictors collected within 24 hours of admission were entered into a step-wise backward elimination logistic regression model to predict a composite adverse maternal outcome within 48 hours of admission. Model internal validation was accomplished by bootstrapping and external validation was completed using data from 1,300 women in the Pre-eclampsia Integrated Estimate of RiSk (fullPIERS) dataset. Predictive performance was assessed for calibration, discrimination, and stratification capacity. The final miniPIERS model included: parity (nulliparous versus multiparous); gestational age on admission; headache/visual disturbances; chest pain/dyspnoea; vaginal bleeding with abdominal pain; systolic blood pressure; and dipstick proteinuria. The miniPIERS model was well-calibrated and had an area under the receiver operating characteristic curve (AUC ROC) of 0.768 (95% CI 0.735-0.801) with an average optimism of 0.037. External validation AUC ROC was 0.713 (95% CI 0.658-0.768). A predicted probability ≥25% to define a positive test classified women with 85.5% accuracy. Limitations of this study include the composite outcome and the broad inclusion criteria of any hypertensive disorder of pregnancy. This broad approach was used to optimize model generalizability. CONCLUSIONS: The miniPIERS model shows reasonable ability to identify women at increased risk of adverse maternal outcomes associated with the hypertensive disorders of pregnancy. It could be used in LMICs to identify women who would benefit most from interventions such as magnesium sulphate, antihypertensives, or transportation to a higher level of care

Locomotor Adaptation versus Perceptual Adaptation when Stepping Over an Obstacle with a Height Illusion

Background During locomotion, vision is used to perceive environmental obstacles that could potentially threaten stability; locomotor action is then modified to avoid these obstacles. Various factors such as lighting and texture can make these environmental obstacles appear larger or smaller than their actual size. It is unclear if gait is adapted based on the actual or perceived height of these environmental obstacles. The purposes of this study were to determine if visually guided action is scaled to visual perception, and to determine if task experience influenced how action is scaled to perception. Methodology/Principal Findings Participants judged the height of two obstacles before and after stepping over each of them 50 times. An illusion made obstacle one appear larger than obstacle two, even though they were identical in size. The influence of task experience was examined by comparing the perception-action relationship during the first five obstacle crossings (1–5) with the last five obstacle crossings (46–50). In the first set of trials, obstacle one was perceived to be 2.0 cm larger than obstacle two and subjects stepped 2.7 cm higher over obstacle one. After walking over the obstacle 50 times, the toe elevation was not different between obstacles, but obstacle one was still perceived as 2.4 cm larger. Conclusions/Significance There was evidence of locomotor adaptation, but no evidence of perceptual adaptation with experience. These findings add to research that demonstrates that while the motor system can be influenced by perception, it can also operate independent of perception

Evidence of an Antimicrobial-Immunomodulatory Role of Atlantic Salmon Cathelicidins during Infection with Yersinia ruckeri

Cathelicidins are a family of antimicrobial peptides that act as effector molecules of the innate immune system with broad-spectrum antimicrobial properties. These evolutionary conserved cationic host-defence peptides are integral components of the immune response of fish, which are generally believed to rely heavily on innate immune defences to invading pathogens. In this study we showed that Atlantic salmon cathelicidin 1 and 2 (asCATH1 and asCATH2) stimulated peripheral blood leukocytes increasing the transcription of the chemokine interleukin-8. Further, functional differences were identified between the two cathelicidins. In the presence of serum, asCATH1 displayed greatly diminished host haemolytic activity, while the constitutively expressed asCATH2 had no haemolytic activity with or without serum. These findings support our hypothesis that fish cathelicidins exert their primary antimicrobial action at the site of pathogen invasion such as epithelial surfaces. Further, we hypothesise that like their mammalian counterparts in the presence of serum they act as mediators of the innate and adaptive immune response via the release of cytokines thus indirectly protecting against a variety of pathogens. We highlight the importance of this immunomodulatory role from the involvement of asCATHs during an infection with the fish pathogen Yersinia ruckeri. While we were able to demonstrate in vitro that asCATH1 and 2, possessed direct microbicidal activity against the fish pathogen, Vibrio anguillarum, and a common gram negative bacterium, Escherichia coli, little or no bactericidal activity was found against Y. ruckeri. The contribution of either asCATH in the immune response or as a potential virulence factor during yersiniosis is highlighted from the increased expression of asCATH1 and 2 mRNA during an in vivo challenge with Y. ruckeri . We propose that Atlantic salmon cathelicidins participate in the interplay between the innate and adaptive immune systems via the release of cytokines enabling a more effective response to invading pathogens

Rapid Evaluation in Whole Blood Culture of Regimens for XDR-TB Containing PNU-100480 (Sutezolid), TMC207, PA-824, SQ109, and Pyrazinamide

There presently is no rapid method to assess the bactericidal activity of new regimens for tuberculosis. This study examined PNU-100480, TMC207, PA-824, SQ109, and pyrazinamide, singly and in various combinations, against intracellular M. tuberculosis, using whole blood culture (WBA). The addition of 1,25-dihydroxy vitamin D facilitated detection of the activity of TMC207 in the 3-day cultures. Pyrazinamide failed to show significant activity against a PZA-resistant strain (M. bovis BCG), and was not further considered. Low, mid, and high therapeutic concentrations of each remaining drug were tested individually and in a paired checkerboard fashion. Observed bactericidal activity was compared to that predicted by the sum of the effects of individual drugs. Combinations of PNU-100480, TMC207, and SQ109 were fully additive, whereas those including PA-824 were less than additive or antagonistic. The cumulative activities of 2, 3, and 4 drug combinations were predicted based on the observed concentration-activity relationship, published pharmacokinetic data, and, for PNU-100480, published WBA data after oral dosing. The most active regimens, including PNU-100480, TMC207, and SQ109, were predicted to have cumulative activity comparable to standard TB therapy. Further testing of regimens including these compounds is warranted. Measurement of whole blood bactericidal activity can accelerate the development of novel TB regimens

Assessing the organizational context for EBP implementation: the development and validity testing of the Implementation Climate Scale (ICS)

BACKGROUND: Although the importance of the organizational environment for implementing evidence-based practices (EBP) has been widely recognized, there are limited options for measuring implementation climate in public sector health settings. The goal of this research was to develop and test a measure of EBP implementation climate that would both capture a broad range of issues important for effective EBP implementation and be of practical use to researchers and managers seeking to understand and improve the implementation of EBPs. METHODS: Participants were 630 clinicians working in 128 work groups in 32 US-based mental health agencies. Items to measure climate for EBP implementation were developed based on past literature on implementation climate and other strategic climates and in consultation with experts on the implementation of EBPs in mental health settings. The sample was randomly split at the work group level of analysis; half of the sample was used for exploratory factor analysis (EFA), and the other half was used for confirmatory factor analysis (CFA). The entire sample was utilized for additional analyses assessing the reliability, support for level of aggregation, and construct-based evidence of validity. RESULTS: The EFA resulted in a final factor structure of six dimensions for the Implementation Climate Scale (ICS): 1) focus on EBP, 2) educational support for EBP, 3) recognition for EBP, 4) rewards for EBP, 5) selection for EBP, and 6) selection for openness. This structure was supported in the other half of the sample using CFA. Additional analyses supported the reliability and construct-based evidence of validity for the ICS, as well as the aggregation of the measure to the work group level. CONCLUSIONS: The ICS is a very brief (18 item) and pragmatic measure of a strategic climate for EBP implementation. It captures six dimensions of the organizational context that indicate to employees the extent to which their organization prioritizes and values the successful implementation of EBPs. The ICS can be used by researchers to better understand the role of the organizational context on implementation outcomes and by organizations to evaluate their current climate as they consider how to improve the likelihood of implementation success. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13012-014-0157-1) contains supplementary material, which is available to authorized users

Hospital outpatient perceptions of the physical environment of waiting areas: the role of patient characteristics on atmospherics in one academic medical center

<p>Abstract</p> <p>Background</p> <p>This study examines hospital outpatient perceptions of the physical environment of the outpatient waiting areas in one medical center. The relationship of patient characteristics and their perceptions and needs for the outpatient waiting areas are also examined.</p> <p>Method</p> <p>The examined medical center consists of five main buildings which house seventeen primary waiting areas for the outpatient clinics of nine medical specialties: 1) Internal Medicine; 2) Surgery; 3) Ophthalmology; 4) Obstetrics-Gynecology and Pediatrics; 5) Chinese Medicine; 6) Otolaryngology; 7) Orthopedics; 8) Family Medicine; and 9) Dermatology. A 15-item structured questionnaire was developed to rate patient satisfaction covering the four dimensions of the physical environments of the outpatient waiting areas: 1) visual environment; 2) hearing environment; 3) body contact environment; and 4) cleanliness. The survey was conducted between November 28, 2005 and December 8, 2005. A total of 680 outpatients responded. Descriptive, univariate, and multiple regression analyses were applied in this study.</p> <p>Results</p> <p>All of the 15 items were ranked as relatively high with a range from 3.362 to 4.010, with a neutral score of 3. Using a principal component analysis' summated scores of four constructed dimensions of patient satisfaction with the physical environments (i.e. visual environment, hearing environment, body contact environment, and cleanliness), multiple regression analyses revealed that patient satisfaction with the physical environment of outpatient waiting areas was associated with gender, age, visiting frequency, and visiting time.</p> <p>Conclusion</p> <p>Patients' socio-demographics and context backgrounds demonstrated to have effects on their satisfaction with the physical environment of outpatient waiting areas. In addition to noticing the overall rankings for less satisfactory items, what should receive further attention is the consideration of the patients' personal characteristics when redesigning more comfortable and customized physical environments of waiting areas.</p

Lymphomas driven by Epstein-Barr virus nuclear antigen-1 (EBNA1) are dependant upon Mdm2

Epstein-Barr virus (EBV)-associated Burkitt's lymphoma is characterised by the deregulation of c-Myc expression and a restricted viral gene expression pattern in which the EBV nuclear antigen-1 (EBNA1) is the only viral protein to be consistently expressed. EBNA1 is required for viral genome propagation and segregation during latency. However, it has been much debated whether the protein plays a role in viral-associated tumourigenesis. We show that the lymphomas which arise in EµEBNA1 transgenic mice are unequivocally linked to EBNA1 expression and that both C-Myc and Mdm2 deregulation are central to this process. Tumour cell survival is supported by IL-2 and there is a skew towards CD8-positive T cells in the tumour environment, while the immune check-point protein PD-L1 is upregulated in the tumours. Additionally, several isoforms of Mdm2 are upregulated in the EµEBNA1 tumours, with increased phosphorylation at ser166, an expression pattern not seen in Eµc-Myc transgenic tumours. Concomitantly, E2F1, Xiap, Mta1, C-Fos and Stat1 are upregulated in the tumours. Using four independent inhibitors of Mdm2 we demonstrate that the EµEBNA1 tumour cells are dependant upon Mdm2 for survival (as they are upon c-Myc) and that Mdm2 inhibition is not accompanied by upregulation of p53, instead cell death is linked to loss of E2F1 expression, providing new insight into the underlying tumourigenic mechanism. This opens a new path to combat EBV-associated disease