bluuebunny/crossref_metadata_2025 huggingface dataset:
Lifestyle of the biotroph Agrobacterium tumefaciens in the ecological niche constructed on its host plant
Authors: González‐Mula Almudena , Lang Julien , Grandclément Catherine , Naquin Delphine , Ahmar Mohammed , Soulère Laurent , Queneau Yves , Dessaux Yves , Faure Denis
Published: April 2018

Agrobacterium tumefaciens constructs an ecological niche in its host plant by transferring the T‐DNA from its Ti plasmid into the host genome and by diverting the host metabolism.

We combined transcriptomics and genetics for understanding the A. tumefaciens lifestyle when it colonizes Arabidopsis thaliana tumors.

Transcriptomics highlighted: a transition from a motile to sessile behavior that mobilizes some master regulators (Hfq, CtrA, DivK and PleD); a remodeling of some cell surface components (O‐antigen, succinoglucan, curdlan, att genes, putative fasciclin) and functions associated with plant defense (Ef‐Tu and flagellin pathogen‐associated molecular pattern‐response and glycerol‐3‐phosphate and nitric oxide signaling); and an exploitation of a wide variety of host resources, including opines, amino acids, sugars, organic acids, phosphate, phosphorylated compounds, and iron. In addition, construction of transgenic A. thaliana lines expressing a lactonase enzyme showed that Ti plasmid transfer could escape host‐mediated quorum‐quenching. Finally, construction of knock‐out mutants in A. tumefaciens showed that expression of some At plasmid genes seemed more costly than the selective advantage they would have conferred in tumor colonization.

We provide the first overview of A. tumefaciens lifestyle in a plant tumor and reveal novel signaling and trophic interplays for investigating host–pathogen interactions.
Effects of multidisciplinary interventions on weight loss and health outcomes in children and adolescents with morbid obesity
Authors: Zolotarjova J. , ten Velde G. , Vreugdenhil A. C. E.
Published: April 2018

Objective

Morbid obesity is the fastest growing subcategory of childhood obesity, associated with an increased health risk that persists into adulthood. There is an urgent need to develop multifaceted interventions that target initial and long‐term lifestyle changes. This review investigates the effects of multidisciplinary interventions on weight loss and health outcomes in children and adolescents with morbid obesity. The influence of age, gender and family participation on health outcomes and intensive treatment alternatives are explored.

Methods

The review includes 16 studies conducted between 1995 and 2017. Studies examined youth with morbid obesity, 4–18 years old, undergoing multidisciplinary treatment.

Results

All studies found a reduction in body mass index (BMI or z‐score) and if measured, cardiovascular risk factors. Physical activity, nutrition education, behavioural modification and family involvement are commonly included treatment components and have improved weight loss and health‐related outcomes. However, initial weight loss was often not sustainable, despite the favourable interventional effect on cardiometabolic risk markers. Weight loss was prolonged in younger children and among the male sex.

Conclusions

There is not a ‘one‐size‐fits‐all’ treatment approach, and matched care to personal needs is preferable. The integration of a chronic care approach is critical for the successful adaption of sustainable health behaviours.
A cumulative meta‐analysis of the effects of individual physical activity interventions targeting healthy adults
Authors: Love R. , Adams J. , van Sluijs E. M. F. , Foster C. , Humphreys D.
Published: April 2018

Despite a large and increasing evidence base on physical activity interventions, the high rates of physical inactivity and associated chronic diseases are continuing to increase globally. The purpose of this cumulative meta‐analysis was to investigate the evolution of randomized controlled trial evidence of individual‐level physical activity interventions to asses if new trials are contributing novel evidence to the field. Through a two‐staged search process, primary studies examining the effects of interventions targeted at increasing physical activity within healthy adult populations were pooled and selected from eligible systematic reviews. Cumulative meta‐analyses were performed on effect sizes immediately post‐intervention (n = 62), and for long‐term behaviour change (≥12‐month post‐baseline; n = 27). Sufficiency and stability of the evidence was assessed through application of pre‐published indicators. Meta‐analyses suggest overall positive intervention effects on physical activity. The evidence base for effectiveness immediately post‐intervention reached levels of sufficiency and stability in 2007; and for long‐term follow‐up in 2011. In the time since, intervention effectiveness has not substantially changed, and further trials are unlikely to change the direction and magnitude of effect. Substantial evidence exists demonstrating that physical activity interventions can modify individual behaviour in controlled settings. Researchers are urged to shift focus towards investigating the optimization, implementation, sustainability and cost‐effectiveness of interventions.
Being respected by nurses: Measuring older patients’ perceptions
Authors: Koskenniemi Jaana , Leino‐Kilpi Helena , Puukka Pauli , Stolt Minna , Suhonen Riitta
Published: April 2018

Aim and objective

To investigate older patients’ perceptions of respect in hospital nursing care and to test a newly developed instrument measuring the phenomenon.

Background

Respect manifests itself in the older patient–nurse relationship in terms of nurses being with and doing for the patient. Empirical studies investigating respect from the older patients’ perspective are rare. There is a need to maintain respectful behaviours and attitudes within hospital‐based nursing practice. Furthermore, there is a lack of instruments measuring respect in the care provided by nurses.

Design and methods

A descriptive, cross‐sectional explorative survey design was used. Data were collected between February and May 2016 by interviewing face‐to‐face 196 older patients in two hospitals in Finland. Respect was measured using the ReSpect scale (Parts A and B) developed for this study. Respect is based on the two dimensions of respect, nurses’ Being with and Doing for patients. Data were analysed using descriptive and inferential statistical methods including the psychometric testing of the new instrument.

Results

Older patients perceived respect in their care frequently and to a great extent, although there were also shortcomings. The findings highlight the need to improve respect to patients in care delivery by showing an interest in their views, acknowledging them positively and supporting their individual capacities. A two‐factor structure of the ReSpect scale Part A and a four‐factor structure of the Part B were confirmed.

Conclusions

Findings from this study suggest that older hospital patients perceived respect by nurses overall, but the area where there is the most room for improvement is that of listening and encouraging. The psychometric analysis demonstrated that the ReSpect scale shows promise in measuring respect.

Implications for practice

The ReSpect scale could be a useful tool to measure respect, an important element of value‐based health care.
Co‐production as a route to employability: Lessons from services with lone parents
Authors: Lindsay Colin , Pearson Sarah , Batty Elaine , Cullen Anne Marie , Eadson Will
Published: April 2018

Policy‐makers claim to support personalized approaches to improving the employability of disadvantaged groups. Yet, in liberal welfare states, mainstream activation programmes targeting these groups often deliver standardized, low‐quality services. Such failures may be related to a governance and management regime that uses tightly defined contracting and performance targets to incentivize (mainly for‐profit) service providers to move people into any job as quickly as possible. This article draws on evidence from third sector/public sector‐led services in Scotland to discuss an alternative approach. These services co‐produced personalized support in partnership with disadvantaged service users (in this case vulnerable lone parents). We suggest that, in this case, street‐level co‐production and personalization were facilitated by co‐governance and co‐management in the design and organization of provision. We conclude by identifying lessons for future employability services.
Calcification Moderates the Increased Susceptibility to UV Radiation of the Coccolithophorid Gephryocapsa oceanica Grown under Elevated CO2 Concentration: Evidence Based on Calcified and Non‐calcified Cells
Authors: Miao Hangbin , Beardall John , Gao Kunshan
Published: April 2018

The physiological performance of calcified and non‐calcified cells of Gephyrocapsa oceanica (NIES‐1318) and their short‐term responses to UV radiation were compared for cultures grown under present‐day (LC, 400 μatm) and high pCO2 (HC, 1000 μatm) conditions. Similar growth rates and Fv/Fm values were observed in both types of cell under LC conditions, indicating that the loss of calcification in the non‐calcified cells did not lead to a competitive disadvantage under such conditions. Detrimental effects of elevated pCO2 were observed in both cell types, with the growth rate of non‐calcified cells decreasing more markedly, which might reflect a negative impact of higher cytoplasmic H+. When exposed to short‐term UV radiation, similar trends in effective quantum yield were observed in both cell types acclimated to LC conditions. Elevated pCO2 and associated seawater chemical changes strongly reduced effective quantum yield in non‐calcified cells but no significant influence was observed in calcified cells. Based on these findings and comparisons with previous studies, we suggest that the negative impact of elevated cytoplasmic H+ would exacerbate the detrimental effects of UV radiation while the possession of calcification attenuated this influence.
Impact of Behavioral Factors on Performance of Multi‐Server Queueing Systems
Authors: Do Hung T. , Shunko Masha , Lucas Marilyn T. , Novak David C.
Published: April 2018

Recent studies have shown that the processing speed of employees in service‐based queueing systems is impacted by various behavioral factors. However, there is limited analytical work to investigate how these behavioral factors affect the overall performance of different queueing system designs. In this study, we focus on the response of human servers to the design and congestion level of the queueing system in which they operate. Specifically, we incorporate two behavioral factors into multi‐server analytical queueing models: (1) server speedup due to increase of workload, and (2) server slowdown due to social loafing when multiple workers share the workload. We evaluate how these factors affect the performance of both the multi‐server single‐queue ( SQ) and multi‐server parallel‐queue ( PQ) system and the relative superiority of each system with respect to the number of customers in queue and the expected wait time in queue. We show that the impact of workload‐dependent speedup can be decomposed into a direct effect and indirect effect on system performance. The direct effect leads to a reduced queue size due to increased expected service rate, while the indirect effect decreases queue size due to the “smoothing” effect. We quantify the performance impacts associated with both behavioral factors, illustrate the conditions where each effect dominates, and derive threshold values for these behavioral effects beyond which PQ systems outperform SQ systems. We also consider strategic routing and its impact on the performance of PQ systems. Our analytical contributions and numerical analyses offer important managerial guidance regarding the choice of the queueing system design and provide a theoretical foundation for future research in behavioral queueing.
The reward‐like nature of social cues that indicate successful altruistic punishment
Authors: Mussel Patrick , Hewig Johannes , Weiß Martin
Published: April 2018

Altruistic punishment is the attempt to penalize deviant behavior of another person even though it is accompanied by personal costs. Here, we investigated the influence of the reaction on the socioemotional level of the other person following altruistic punishment behavior on future decision making and neural responses. We used a modified ultimatum game, which included an emotional facial feedback of the proposer following the decision of the participant. We found higher acceptance rates for proposers showing a smile upon acceptance or a sad face upon rejection of an offer, compared to proposers showing a neutral facial expression. On the neural level, we found a reversed N2 effect for negative emotional faces in the context of altruistic punishment, compared to a control condition. Specifically, when following the rejection of an unfair offer, negative emotional faces showed a reward‐like positivity that might signal successful altruistic punishment. In addition, differential effects for P3 amplitudes might signal the subjective importance of a desired outcome. Our results are in line with the interpretation that rejection of unfair offers in the ultimatum game is due to intended altruistic punishment. Social cues may exhibit reward‐like properties when indicating successful altruistic punishment and can influence subsequent decision making.
Is prescribed fire a suitable management tool to reduce shrub encroachment in palm savannas?
Authors: Policelli Nahuel , Picca Pablo , Gómez Villafañe Isabel E.
Published: April 2018

Shrub encroachment in grasslands is a worldwide problem that has many ecological consequences, transforming previously open environments into dense forests. Disruption of natural fire regimes is one of the main causes of shrub encroachment, and the use of prescribed fire is a common strategy used to restore these ecosystems. In this study, we provide information about how a palm tree savanna under a process of shrub encroachment responds to the reintroduction of fire. We describe the effects of a first fire event on vegetation composition and structure using an experimental approach. We examine a species‐specific response to the fire. After one prescribed fire event applied to four study areas of 16 ha each, we analyzed the change in vegetation physiognomy and composition in burned and control plots for 1 year. Low‐intensity prescribed fire decreased height and cover of most shrub species and increased herbaceous vegetation cover over time. We classified shrub and herbaceous species response to fire according to the time they became present and their phenological characteristics. Our results can help stakeholders to determine if prescribed fire is helpful at reducing shrub encroachment in short term in similar ecosystems, considering how plant community responds to the reintroduction of fire after decades of fire suppression.
The peculiar insertion of Brazil into global value chains
Authors: Callegari Julia , Melo Tatiana Massaroli , Carvalho Carlos Eduardo
Published: April 2018

Brazil plays a very peculiar role in global value chains (GVC): the country imports high technological goods in general while going through early deindustrialization and relying mainly on basic goods for its exports. Even after developing a broad, diversified industrial framework and becoming one of the countries that has received more foreign direct investments since the 1990s, Brazil has been struggling to occupy a more technologically oriented place inGVCs. This paper examines the conditionings of this pattern of insertion by characterizing the country's quantitative and qualitative model of integration intoGVCs and by analyzing the elements that can explain this performance.
Mutual and Self Perceptions of Opposing Advocacy Coalitions: Devil Shift and Angel Shift in a German Policy Subsystem
Authors: Vogeler Colette S. , Bandelow Nils C.
Published: April 2018

In political conflicts, actors tend to assume that opponents behave maliciously. This phenomena is part of the “devil shift,” which was introduced in advocacy coalition framework research. We present a multivariate analysis of the perceptions of motives and actions of opposing coalitions in a political conflict and thereby analyze a major dimension of the “devil shift” and of its antonym “angel shift.” The conflict concerning the German infrastructure project Stuttgart 21 serves as a case study. We show that the radicalness of policy‐specific beliefs is the most important predictor for the intensity of mutual misperception in the researched conflict. The results further point to a more systematic inclusion of an actor's deep normative core beliefs in future analyses of distorted perception. Another central finding relates to the importance of the personal environment: actors in the subsystem share the same policy core beliefs with the majority of people in their personal environment.
Dynamics of Child Malnutrition in Rural and Small‐Town Ethiopia
Authors: Seff Ilana , Baird Sarah , Jolliffe Dean
Published: April 2018

Improving the status of malnourished children, and preventing children from becoming malnourished, lies at the heart of several of the Sustainable Development Goals. While many cross‐sectional studies examine correlates of stunting, they largely cannot identify drivers of change in stunting. We use two waves of panel data from Ethiopia and incrementally larger sets of fixed effects to control for time‐variant observable characteristics and time‐invariant unobservable characteristics. After controlling for these potential confounders, our analysis reveals that many factors that are associated with stunting in the cross‐section do not impact stunting dynamics. We also estimate individual fixed‐effects regressions, separately, according to baseline stunting status. We find evidence suggesting that while improved societal conditions drive many children out of a stunted state, certain exogenous factors may lead previously healthy children to become stunted. Overall, policymakers and practitioners would be wise to consult research utilising both cross‐sectional and panel data analyses in order to more effectively target already stunted children as well as vulnerable children who may be at risk of becoming stunted.
SIRT1 attenuates murine allergic rhinitis by downregulated HMGB 1/TLR4 pathway
Authors: Yuan Y. , Liu Q. , Zhao J. , Tang H. , Sun J.
Published: April 2018

Conventional allergic rhinitis (AR) treatments have limitations due to the lack of safety and complete cure strategy. We evaluated the effects of silent information regulator 1 (SIRT1), a multifunctional molecule involved in a variety of inflammatory pathways, on murine AR model. Ovalbumin (OVA)‐induced murine model was constructed, and recombinant SIRT1 was administered into the nostril continuously. The expression of SIRT1 was measured at mRNA and protein levels, and the allergic symptoms were evaluated. Protein levels of OVA‐specific IgE, leukotriene C4 (LTC4), eosinophil cation protein (ECP), prostaglandin D2 (PGD2), as well as different inflammatory cytokine mediators in the serum and nasal lavage fluid (NLF), were assessed by ELISA. The effects of SIRT1 on human primary nasal epithelial cells challenged with tumour necrosis factor (TNF)‐α were also evaluated by investigating the HMGB1/TLR4 signalling pathway. Administration of SIRT1 significantly alleviated OVA‐induced AR symptoms with lower numbers of sneezing and nasal rubbing events, decreased levels of OVA‐specific IgE, LTC4, ECP, PGD2, less inflammatory cells and downregulated levels of Th2 type cytokines. SIRT1 also reduced the genes of HMGB1/TLR4 signalling pathway in the murine model and cultured human nasal epithelial cells. Expression of SIRT1 is impaired in OVA‐induced AR model. The administration of SIRT1 alleviates the allergic symptoms of mice, regulates the production of pro‐inflammatory mediators predominantly produced by Th2 cells in AR and attenuates expressions of proteins relevant to HMGB1/TLR4 signalling pathway. All the results showed that SIRT1 is promising as a therapeutic agent of AR.
Semiparametric maximum likelihood inference for nonignorable nonresponse with callbacks
Authors: Guan Zhong , Leung Denis H. Y. , Qin Jing
Published: April 2018

We model the nonresponse probabilities as logistic functions of the outcome variable and other covariates in the survey study with callback. The identification aspect of this callback model is investigated. Semiparametric maximum likelihood estimators of the parameters in the response probabilities are proposed and studied. As a result, an efficient estimator of the mean of the outcome variable is constructed using the estimated response probabilities. Moreover, if a regression model for the conditional mean of the outcome variable given some covariate is available, then we can obtain an even more efficient estimate of the mean of the outcome variable by fitting the regression model using an adjusted least‐squares method based on the estimated underlying distributions of the observed values. Simulation results show that the proposed method is more efficient compared with some existing competitors. The method is applied to data from the Singapore Life Panel, a survey of health spending using a population‐based sample of individuals aged 50–70 years, where nonresponse may be related to health.
Retinal vascular diameters in relation to physical activity in Danish children — The CHAMPS Eye Study
Authors: Lundberg K. , Tarp J. , Vestergaard A. H. , Jacobsen N. , Thykjær A. S. , Rønne M. S. , Bugge A. , Goldschmidt E. , Peto T. , Wedderkopp N. , Grauslund J.
Published: April 2018

Our objective was to determine associations between retinal vascular caliber and physical activity (PA) in a school‐based child cohort. In a prospective study, we created a childhood cumulative average PA‐index using objectively measured PA (accelerometry) assessed at four periods between 2009 and 2015. Cumulative exposure to PA intensities was estimated. Cross‐sectional examinations on biomarkers, anthropometry, and ophthalmological data including retinal fundus photographs were performed in 2015. Semi‐automated measurements of retinal vascular diameters were performed and summarized into central retinal arteriolar and venular equivalents (CRAE, CRVE). We included 307 participants. Mean age in 2015 was 15.4 years (0.7). The mean CRAE and CRVE were 156.5 μm (2.8) and 217.6 μm (7.7), respectively. After adjusting for age, gender, and axial length, more time in PA was independently related to thinner retinal venules (β‐coefficient = −1.25 μm/%, 95% confidence interval = −2.20, −0.30, P < .01). Sedentary time was associated with wider venules (P < .01). Furthermore, birthweight (β‐coefficient = 0.56 μm/%, 95% confidence interval = 0.18, 0.95, P < .01) was associated with CRVE. Blood pressure was associated with thinner retinal arterioles (β‐coefficient = −0.19 μm/mmHg, 95% confidence interval = −0.36, −0.01, P = .04). We concluded that children with higher PA in childhood had thinner retinal venular caliber. Our results suggest that PA during childhood positively impacts the retinal microcirculation and that retinal vascular analysis may be a possible assessment to detect microvascular impairments in children with an increased risk of future cardiovascular disease.
Therapeutic potential to reduce brain injury in growth restricted newborns
Authors: Wixey Julie A. , Chand Kirat K. , Pham Lily , Colditz Paul B. , Bjorkman S. Tracey
Published: April 2018

Brain injury in intrauterine growth restricted (IUGR) infants is a major contributing factor to morbidity and mortality worldwide. Adverse outcomes range from mild learning difficulties, to attention difficulties, neurobehavioral issues, cerebral palsy, epilepsy, and other cognitive and psychiatric disorders. While the use of medication to ameliorate neurological deficits in IUGR neonates has been identified as warranting urgent research for several years, few trials have been reported. This review summarises clinical trials focusing on brain protection in the IUGR newborn as well as therapeutic interventions trialled in animal models of IUGR. Therapeutically targeting mechanisms of brain injury in the IUGR neonate is fundamental to improving long‐term neurodevelopmental outcomes. Inflammation is a key mechanism in neonatal brain injury; and therefore an appealing target. Ibuprofen, an anti‐inflammatory drug currently used in the preterm neonate, may be a potential therapeutic candidate to treat brain injury in the IUGR neonate. To better understand the potential of ibuprofen and other therapeutic agents to be neuroprotective in the IUGR neonate, long‐term follow‐up information of neurodevelopmental outcomes must be studied. Where agents such as ibuprofen are shown to be effective, have a good safety profile and are relatively inexpensive, they can be widely adopted and lead to improved outcomes.
A wavenumber approach to quantifying the isotropy of the sound field in reverberant spaces
Authors: Nolan Mélanie , Fernandez-Grande Efren , Brunskog Jonas , Jeong Cheol-Ho
Published: April 2018

This study proposes an experimental method for evaluating isotropy in enclosures, based on an analysis of the wavenumber spectrum in the spherical harmonics domain. The wavenumber spectrum, which results from expanding an arbitrary sound field into a plane-wave basis, is used to characterize the spatial properties of the observed sound field. Subsequently, the obtained wavenumber spectrum is expanded into a series of spherical harmonics, and the moments from this spherical expansion are used to characterize the isotropy of the wave field. The analytical framework is presented. The method is examined numerically and experimentally, based on array measurements in four chambers: two anechoic chambers (one with a single source and another with an array of 52 sources), a reverberation chamber, and the same reverberation chamber with a sample of absorbing material on the floor. The results indicate that the proposed methodology is suitable for assessing the isotropy of a sound field.
Distribution and Diversity of Rhodopsin-Producing Microbes in the Chesapeake Bay
Authors: Maresca Julia A. , Miller Kelsey J. , Keffer Jessica L. , Sabanayagam Chandran R. , Campbell Barbara J.
Published: April 2018

Although sunlight is an abundant source of energy in surface environments, less than 0.5% of the available photons are captured by (bacterio)chlorophyll-dependent photosynthesis in plants and bacteria. Metagenomic data indicate that 30 to 60% of the bacterial genomes in some environments encode rhodopsins, retinal-based photosystems found in heterotrophs, suggesting that sunlight may provide energy for more life than previously suspected. However, quantitative data on the number of cells that produce rhodopsins in environmental systems are limited. Here, we use total internal reflection fluorescence microscopy to show that the number of free-living microbes that produce rhodopsins increases along the salinity gradient in the Chesapeake Bay. We correlate this functional data with environmental data to show that rhodopsin abundance is positively correlated with salinity and with indicators of active heterotrophy during the day. Metagenomic and metatranscriptomic data suggest that the microbial rhodopsins in the low-salinity samples are primarily found in
Actinobacteria
and
Bacteroidetes
, while those in the high-salinity samples are associated with SAR-11 type
Alphaproteobacteria
.

IMPORTANCE
Microbial rhodopsins are common light-activated ion pumps in heterotrophs, and previous work has proposed that heterotrophic microbes use them to conserve energy when organic carbon is limiting. If this hypothesis is correct, rhodopsin-producing cells should be most abundant where nutrients are most limited. Our results indicate that in the Chesapeake Bay, rhodopsin gene abundance is correlated with salinity, and functional rhodopsin production is correlated with nitrate, bacterial production, and chlorophyll
a
. We propose that in this environment, where carbon and nitrogen are likely not limiting, heterotrophs do not need to use rhodopsins to supplement ATP synthesis. Rather, the light-generated proton motive force in nutrient-rich environments could be used to power energy-dependent membrane-associated processes, such as active transport of organic carbon and cofactors, enabling these organisms to more efficiently utilize exudates from primary producers.
Conservation of Intracellular Pathogenic Strategy among Distantly Related Cryptococcal Species
Authors: Freij Joudeh B. , Fu Man Shun , De Leon Rodriguez Carlos M. , Dziedzic Amanda , Jedlicka Anne E. , Dragotakes Quigly , Rossi Diego C. P. , Jung Eric H. , Coelho Carolina , Casadevall Arturo
Published: April 2018

The genus
Cryptococcus
includes several species pathogenic for humans. Until recently, the two major pathogenic species were recognized to be
Cryptococcus neoformans
and
Cryptococcus gattii
. We compared the interaction of murine macrophages with three
C. gattii
species complex strains (WM179, R265, and WM161, representing molecular types VGI, VGIIa, and VGIII, respectively) and one
C. neoformans
species complex strain (H99, molecular type VNI) to ascertain similarities and differences in the yeast intracellular pathogenic strategy. The parameters analyzed included nonlytic exocytosis frequency, phagolysosomal pH, intracellular capsular growth, phagolysosomal membrane permeabilization, and macrophage transcriptional response, assessed using time-lapse microscopy, fluorescence microscopy, flow cytometry, and gene expression microarray analysis. The most striking result was that the intracellular pathogenic strategies of
C. neoformans
and
C. gattii
species complex strains were qualitatively similar, despite the species having separated an estimated 100 million years ago. Macrophages exhibited a leaky phagolysosomal membrane phenotype and nonlytic exocytosis when infected with either
C. gattii
or
C. neoformans
. Conservation of the intracellular strategy among species that separated long ago suggests that it is ancient and possibly maintained by similar selection pressures through eons.
Comparing standard office-based follow-up with text-based remote monitoring in the management of postpartum hypertension: a randomised clinical trial
Authors: Hirshberg Adi , Downes Katheryne , Srinivas Sindhu
Published: April 2018

Background

Monitoring blood pressure at 72 hours and 7–10 days post partum in women with hypertensive disorders is recommended to decrease morbidity. However, there are no recommendations as to how to achieve this.

Objective

To compare the effectiveness of text-based blood pressure monitoring to in-person visits for women with hypertensive disorders of pregnancy in the immediate postpartum period.

Methods

Randomised clinical trial among 206 postpartum women with pregnancy-related hypertension diagnosed during the delivery admission between August 2016 and January 2017. Women were randomised to 2 weeks of text-based surveillance using a home blood pressure cuff and previously tested automated platform or usual care blood pressure check at their prenatal clinic 4–6 days following discharge. The primary study outcome was a single recorded blood pressure in the first 10 days post partum. The ability to meet American Congress of Obstetricians and Gynecologists (ACOG) guidelines, defined as having a blood pressure recorded on postpartum days 3–4 and 7–10 was evaluated in the text message group. The study was powered to detect a 1.4-fold increase in a single recorded blood pressure using text messaging. All outcomes were analysed as intention to treat.

Results

206 women were randomised (103 in each arm). Baseline characteristics were similar. There was a statistically significant increase in a single blood pressure obtained in the texting group in the first 10 days post partum as compared with the office group (92.2% vs 43.7%; adjusted OR 58.2 (16.2–208.1), p<0.001). Eighty-four per cent of patients undergoing text-based surveillance met ACOG criteria for blood pressures at both recommended points.

Conclusions

Text-based monitoring is more effective in obtaining blood pressures and meeting current clinical guidelines in the immediate postdischarge period in women with pregnancy-related hypertension compared with traditional office-based follow-up.

Trial registration number

NCT03185455, Remote Surveillance of Postpartum Hypertension (TextBP), https://clinicaltrials.gov.
Fifty years of preventing and treating childhood behaviour disorders: a systematic review to inform policy and practice
Authors: Waddell Charlotte , Schwartz Christine , Andres Caitlyn , Barican Jenny Lou , Yung Donna
Published: April 2018

Question

Oppositional defiant and conduct disorders (ODD and CD) start early and persist, incurring high individual and collective costs. To inform policy and practice, we therefore asked: What is the best available research evidence on preventing and treating these disorders?

Study selection and analysis

We sought randomised controlled trials (RCTs) evaluating interventions addressing the prevention or treatment of behaviour problems in individuals aged 18 years or younger. Our criteria were tailored to identify higher-quality RCTs that were also relevant to policy and practice. We searched the CINAHL, ERIC, MEDLINE, PsycINFO and Web of Science databases, updating our initial searches in May 2017. Thirty-seven RCTs met inclusion criteria—evaluating 15 prevention programmes, 8 psychosocial treatments and 5 medications. We then conducted narrative synthesis.

Findings

For prevention, 3 notable programmes reduced behavioural diagnoses: Classroom-Centered Intervention; Good Behavior Game; and Fast Track. Five other programmes reduced serious behaviour symptoms such as criminal activity. Prevention benefits were long term, up to 35 years. For psychosocial treatment, Incredible Years reduced behavioural diagnoses. Three other interventions reduced criminal activity. Psychosocial treatment benefits lasted from 1 to 8 years. While 4 medications reduced post-test symptoms, all caused important adverse events.

Conclusions

Considerable RCT evidence favours prevention.

Clinical implications

Effective prevention programmes should therefore be made widely available. Effective psychosocial treatments should also be provided for all children with ODD/CD. But medications should be a last resort given associated adverse events and given only short-term evidence of benefits. Policymakers and practitioners can help children and populations by acting on these findings.
Prehospital neurological deterioration in stroke
Authors: Slavin Sabreena J , Sucharew Heidi , Alwell Kathleen , Moomaw Charles J , Woo Daniel , Adeoye Opeolu , Flaherty Matthew L , Ferioli Simona , McMullan Jason , Mackey Jason , De Los Rios La Rosa Felipe , Martini Sharyl , Kissela Brett M , Kleindorfer Dawn O
Published: April 2018

Background and purpose

Patients with stroke can experience neurological deterioration in the prehospital setting. We evaluated patients with stroke to determine factors associated with prehospital neurological deterioration (PND).

Methods

Among the Greater Cincinnati/Northern Kentucky region (population ~1.3 million), we screened all 15 local hospitals’ admissions from 2010 for acute stroke and included patients aged ≥20. The GCS was compared between emergency medical services (EMS) arrival and hospital arrival, with decrease ≥2 points considered PND. Data obtained retrospectively included demographics, medical history and medication use, stroke subtype (eg, ischaemic stroke (IS), intracerebral haemorrhage (ICH), subarachnoid haemorrhage (SAH)) and IS subtype (eg, small vessel, large vessel, cardioembolic), seizure at onset, time intervals between symptom onset, EMS arrival and hospital arrival, EMS level of training, and blood pressure and serum glucose on EMS arrival.

Results

Of 2708 total patients who had a stroke, 1092 patients (median (IQR) age 74 (61–83) years; 56% women; 21% black) were analysed. PND occurred in 129 cases (12%), including 9% of IS, 24% of ICH and 16% of SAH. In multivariable analysis, black race, atrial fibrillation, haemorrhagic subtype and ALS level of transport were associated with PND.

Conclusion

Haemorrhage and atrial fibrillation is associated with PND in stroke, and further investigation is needed to establish whether PND can be predicted. Further studies are also needed to assess whether preferential transport of patients with deterioration to hospitals equipped with higher levels of care is beneficial, identify why race is associated with deterioration and to test therapies targeting PND.
Impact of sustained virological response on the extrahepatic manifestations of chronic hepatitis C: a meta-analysis
Authors: Cacoub Patrice , Desbois Anne Claire , Comarmond Cloe , Saadoun David
Published: April 2018

Background and aims

Extrahepatic manifestations of HCV are responsible for morbidity and mortality in many chronically infected patients. New, interferon-free antiviral treatment regimens, which present the opportunity to treat all HCV-infected patients, call for a better understanding of the benefits of treating non-cirrhotic chronically infected individuals.

Methods

A systematic review was conducted. Identified studies from targeted database searches on Embase and Medline were screened. The methodological quality of the included publications was evaluated. Random-effect model meta-analyses were performed. Strength of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation system.

Results

Data were extracted from a total of 48 identified studies. Achieving sustained virological response (SVR) was associated with reduced extrahepatic mortality (vs no SVR, OR 0.44 (95% CI 0.28 to 0.67)). SVR was associated with higher complete remissions in patients with cryoglobulinemia vasculitis (OR 20.76 (6.73 to 64.05)) and a higher objective response in those with malignant B-cell lymphoproliferative diseases (OR 6.49 (2.02 to 20.85)). Achieving SVR was also associated with reduced insulin resistance at follow-up (OR 0.42 (0.33 to 0.53)) and a significant protective effect on the incidence of diabetes (OR 0.34 (0.21 to 0.56)). Lack of randomised data comparing SVR versus non-SVR patients for the relevant extrahepatic indications attenuated these analyses.

Conclusion

Antiviral therapy can reduce extrahepatic manifestations related to HCV when SVR is achieved. Higher quality data, and reporting over longer follow-up periods, will be required to thoroughly explore comprehensive HCV treatment strategies.
Hyperpolarised magnetic resonance for in vivo real-time metabolic imaging
Authors: Apps Andrew , Lau Justin , Peterzan Mark , Neubauer Stefan , Tyler Damian , Rider Oliver
Published: April 2018

Although non-invasive perfusion and viability imaging often provide the gateway to coronary revascularisation, current non-invasive imaging methods only report the surrogate markers of inducible hypoperfusion and presence or absence of myocardial scar, rather than actually visualising areas of ischaemia and/or viable myocardium. This may lead to suboptimal revascularisation decisions. Normally respiring (viable) cardiomyocytes convert pyruvate to acetyl-CoA and CO2/bicarbonate (via pyruvate dehydrogenase), but under ischaemic conditions characteristically shift this conversion to lactate (by lactate dehydrogenase). Imaging pyruvate metabolism thus has the potential to improve upon current imaging techniques. Using the novel hyperpolarisation technique of dynamic nuclear polarisation (DNP), the magnetic resonance signal of injected [1-13C]pyruvate can be transiently magnified >10 000 times over that seen in conventional MR spectroscopy, allowing the characteristic metabolic signatures of ischaemia (lactate production) and viability (CO2/bicarbonate production) to be directly imaged. As such DNP imaging of the downstream metabolism of [1-13C]pyruvate could surpass the diagnostic capabilities of contemporary ischaemia and viability testing. Here we review the technique, and with brief reference to the salient biochemistry, discuss its potential applications within cardiology. These include ischaemia and viability testing, and further characterisation of the altered metabolism seen at different stages during the natural history of heart failure.
Evaluation of the correlation betweenKRASmutated allele frequency and pathologist tumorous nuclei percentage assessment in colorectal cancer suggests a role for zygosity status
Authors: Libbrecht Louis , Baldin Pamela , Dekairelle Anne-France , Jouret-Mourin Anne
Published: April 2018

Evaluation of molecular tumour heterogeneity relies on the tumorous nuclei percentage (TNP) assessment by a pathologist, which has been criticised for being inaccurate and suffering from interobserver variability. Based on the ‘Big Bang theory’ which states thatKRASmutation in colorectal cancer is mostly homogeneous, we investigated this issue by performing a critical analysis of the correlation of theKRASmutant allele fraction with the TNP in 99 colorectal tumour samples with a positiveKRASmutation status as determined by next-generation sequencing. Our results yield indirect evidence that the KRAS zygosity status influences the correlation between these parameters and we show that a well-trained pathologist is indeed capable of accurately assessing TNP. Our findings indicate that tumour zygosity, a feature which has largely been neglected until now, should be taken into account in future studies on (colorectal) molecular tumour heterogeneity.
Telomerase promoter mutations and copy number alterations in solitary fibrous tumours
Authors: Lin Yingbo , Seger Nelly , Tsagkozis Panagiotis , Hesla Asle C , Ghaderi Mehran , Chen Yi , Ehnman Monika , Warsito Dudi , Wejde Johan , Larsson Olle , Haglund Felix
Published: April 2018

Aims

Solitary fibrous tumour (SFT) is an infrequently metastasising mesenchymal tumour defined by theNAB2–STAT6fusion gene. Activating mutations in thetelomerase reverse transcriptase(hTERT) gene promoter has been reported to associate with adverse patient outcome in SFTs.

Methods

We analysed thehTERTgene for promoter mutations and copy number alterations in 43 primary extrameningeal SFTs (9 malignant and 34 benign tumours according to WHO 2013 criteria), six local recurrences and three metastatic lesions.

Results

Activating −124 C>T (n=12) or −148 C>T (n=2) mutations were found in 33% of the tumours and associated with older age (P=0.006), necrosis (P=0.009), higher mitotic rate (P=0.003), nuclear atypia (P=0.002), malignant histological diagnosis (P=0.04) and worse progression-free survival (P=0.023). We also observed frequent (24%)hTERTpromoter mutations in histologically benign tumours without metastasis (mean follow-up >9 years), and in 14%–18% of low-risk SFTs as determined by three risk-stratification models. Mutations were seen in 2/6 metastatic tumours and metastatic lesions.hTERTcopy number gain was seen in 11/28hTERTpromoter wild-type cases.

Conclusions

ActivatinghTERTpromoter mutations associate with aggressive histopathological features, indicating a role in tumour progression. Given the comparatively high prevalence ofhTERTpromoter mutations in low-risk and non-metastasising lesions, further studies are required to clarify the prognostic value ofhTERTpromoter analysis before implementing the analysis in clinical diagnostics.
Immune checkpoint inhibitor-induced gastrointestinal and hepatic injury: pathologists’ perspective
Authors: Karamchandani Dipti M , Chetty Runjan
Published: April 2018

Immune checkpoint inhibitors (CPIs) are a relatively new class of ‘miracle’ dugs that have revolutionised the treatment and prognosis of some advanced-stage malignancies, and have increased the survival rates significantly. This class of drugs includes cytotoxic T lymphocyte antigen-4 inhibitors such as ipilimumab; programmed cell death protein-1 inhibitors such as nivolumab, pembrolizumab and avelumab; and programmed cell death protein ligand-1 inhibitors such as atezolizumab. These drugs stimulate the immune system by blocking the coinhibitory receptors on the T cells and lead to antitumoural response. However, a flip side of these novel drugs is immune-related adverse events (irAEs), secondary to immune-mediated process due to disrupted self-tolerance. The irAEs in the gastrointestinal (GI) tract/liver may result in diarrhoea, colitis or hepatitis. An accurate diagnosis of CPI-induced colitis and/or hepatitis is essential for optimal patient management. As we anticipate greater use of these drugs in the future given the significant clinical response, pathologists need to be aware of the spectrum of histological findings that may be encountered in GI and/or liver biopsies received from these patients, as well as differentiate them from its histopathological mimics. This present review discusses the clinical features, detailed histopathological features, management and the differential diagnosis of the luminal GI and hepatic irAEs that may be encountered secondary to CPI therapy.
Old gene, new phenotype: splice-altering variants in CEACAM16 cause recessive non-syndromic hearing impairment
Authors: Booth Kevin T , Kahrizi Kimia , Najmabadi Hossein , Azaiez Hela , Smith Richard JH
Published: April 2018

Background

Hearing loss is a genetically and phenotypically heterogeneous disorder.

Objectives

The purpose of this study was to determine the genetic cause underlying the postlingual progressive hearing loss in two Iranian families.

Methods

We used OtoSCOPE, a next-generation sequencing platform targeting >150 genes causally linked to deafness, to screen two deaf probands. Data analysis was completed using a custom bioinformatics pipeline, and variants were functionally assessed using minigene splicing assays.

Results

We identified two homozygous splice-altering variants (c.37G>T and c.662–1G>C) in the CEACAM16 gene, segregating with the deafness in each family. The minigene splicing results revealed the c.37G>T results in complete skipping of exon 2 and loss of the AUG start site. The c.662–1G>C activates a cryptic splice site inside exon 5 resulting in a shift in the mRNA reading frame.

Conclusions

These results suggest that loss-of-function mutations in CEACAM16 result in postlingual progressive hearing impairment and further support the role of CEACAM16 in auditory function.
Home treatment of COPD exacerbation selected by DECAF score: a non-inferiority, randomised controlled trial and economic evaluation
Authors: Echevarria Carlos , Gray Joanne , Hartley Tom , Steer John , Miller Jonathan , Simpson A John , Gibson G John , Bourke Stephen C
Published: April 2018

Background

Previous models of Hospital at Home (HAH) for COPD exacerbation (ECOPD) were limited by the lack of a reliable prognostic score to guide patient selection. Approximately 50% of hospitalised patients have a low mortality risk by DECAF, thus are potentially suitable.

Methods

In a non-inferiority randomised controlled trial, 118 patients admitted with a low-risk ECOPD (DECAF 0 or 1) were recruited to HAH or usual care (UC). The primary outcome was health and social costs at 90 days.

Results

Mean 90-day costs were £1016 lower in HAH, but the one-sided 95% CI crossed the non-inferiority limit of £150 (CI −2343 to 312). Savings were primarily due to reduced hospital bed days: HAH=1 (IQR 1–7), UC=5 (IQR 2–12) (P=0.001). Length of stay during the index admission in UC was only 3 days, which was 2 days shorter than expected. Based on quality-adjusted life years, the probability of HAH being cost-effective was 90%. There was one death within 90 days in each arm, readmission rates were similar and 90% of patients preferred HAH for subsequent ECOPD.

Conclusion

HAH selected by low-risk DECAF score was safe, clinically effective, cost-effective, and preferred by most patients. Compared with earlier models, selection is simpler and approximately twice as many patients are eligible. The introduction of DECAF was associated with a fall in UC length of stay without adverse outcome, supporting use of DECAF to direct early discharge.

Trial registration number

Registered prospectively ISRCTN29082260.