bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can traits predict individual growth performance? A test in a hyperdiverse tropical forest
Authors: Poorter Lourens , Castilho Carolina V. , Schietti Juliana , Oliveira Rafael S. , Costa Flávia R. C. 
Published: May 2018

Summary

The functional trait approach has, as a central tenet, that plant traits are functional and shape individual performance, but this has rarely been tested in the field. Here, we tested the individual‐based trait approach in a hyperdiverse Amazonian tropical rainforest and evaluated intraspecific variation in trait values, plant strategies at the individual level, and whether traits are functional and predict individual performance.

We evaluated > 1300 tree saplings belonging to > 383 species, measured 25 traits related to growth and defense, and evaluated the effects of environmental conditions, plant size, and traits on stem growth.

A total of 44% of the trait variation was observed within species, indicating a strong potential for acclimation. Individuals showed two strategy spectra, related to tissue toughness and organ size vs leaf display. In this nutrient‐ and light‐limited forest, traits measured at the individual level were surprisingly poor predictors of individual growth performance because of convergence of traits and growth rates.

Functional trait approaches based on individuals or species are conceptually fundamentally different: the species‐based approach focuses on the potential and the individual‐based approach on the realized traits and growth rates. Counterintuitively, the individual approach leads to a poor prediction of individual performance, although it provides a more realistic view on community dynamics.
The fetus at the tipping point: modifying the outcome of fetal asphyxia
Authors: Dhillon Simerdeep K. , Lear Christopher A. , Galinsky Robert , Wassink Guido , Davidson Joanne O. , Juul Sandra , Robertson Nicola J. , Gunn Alistair J. , Bennet Laura 
Published: May 2018

AbstractBrain injury around birth is associated with nearly half of all cases of cerebral palsy. Although brain injury is multifactorial, particularly after preterm birth, acute hypoxia–ischaemia is a major contributor to injury. It is now well established that the severity of injury after hypoxia–ischaemia is determined by a dynamic balance between injurious and protective processes. In addition, mothers who are at risk of premature delivery have high rates of diabetes and antepartum infection/inflammation and are almost universally given treatments such as antenatal glucocorticoids and magnesium sulphate to reduce the risk of death and complications after preterm birth. We review evidence that these common factors affect responses to fetal asphyxia, often in unexpected ways. For example, glucocorticoid exposure dramatically increases delayed cell loss after acute hypoxia–ischaemia, largely through secondary hyperglycaemia. This critical new information is important to understand the effects of clinical treatments of women whose fetuses are at risk of perinatal asphyxia.
Physiology and molecular biology of barrier mechanisms in the fetal and neonatal brain
Authors: Saunders Norman R. , Dziegielewska Katarzyna M. , Møllgård Kjeld , Habgood Mark D. 
Published: May 2018

AbstractProperties of the local internal environment of the adult brain are tightly controlled providing a stable milieu essential for its normal function. The mechanisms involved in this complex control are structural, molecular and physiological (influx and efflux transporters) frequently referred to as the ‘blood–brain barrier’. These mechanisms include regulation of ion levels in brain interstitial fluid essential for normal neuronal function, supply of nutrients, removal of metabolic products, and prevention of entry or elimination of toxic agents. A key feature is cerebrospinal fluid secretion and turnover. This is much less during development, allowing greater accumulation of permeating molecules. The overall effect of these mechanisms is to tightly control the exchange of molecules into and out of the brain. This review presents experimental evidence currently available on the status of these mechanisms in developing brain. It has been frequently stated for over nearly a century that the blood–brain barrier is not present or at least is functionally deficient in the embryo, fetus and newborn. We suggest the alternative hypothesis that the barrier mechanisms in developing brain are likely to be appropriately matched to each stage of its development. The contributions of different barrier mechanisms, such as changes in constituents of cerebrospinal fluid in relation to specific features of brain development, for example neurogenesis, are only beginning to be studied. The evidence on this previously neglected aspect of brain barrier function is outlined. We also suggest future directions this field could follow with special emphasis on potential applications in a clinical setting.
Unilateral movement preparation causes task‐specific modulation of TMS responses in the passive, opposite limb
Authors: Chye Lilian , Riek Stephan , de Rugy Aymar , Carson Richard G. , Carroll Timothy J. 
Published: May 2018

Key points
Activity in the primary motor cortices of both hemispheres increases during unilateral movement preparation, but the functional role of ipsilateral motor cortex activity is unknown.
Ipsilateral motor cortical activity could represent subliminal ‘motor planning’ for the passive limb. Alternatively, it could represent the state of the active limb, to support coordination between the limbs should a bimanual movement be required.
Here we assessed how preparation of forces toward different directions, with the left wrist, alters evoked responses to transcranial magnetic stimulation of left motor cortex.
Preparation of a unilateral movement caused excitability increases in ipsilateral motor cortex that reflected forces produced with the active limb in an intrinsic (body‐centred), rather than an extrinsic (world‐centred), coordinate system.
These results suggest that ipsilateral motor cortical activity prior to unilateral action reflects the state of the active limb, rather than subliminal motor planning for the passive limb.
AbstractCorticospinal excitability is modulated for muscles on both sides of the body during unilateral movement preparation. For the effector, there is a progressive increase in excitability, and a shift in direction of muscle twitches evoked by transcranial magnetic stimulation (TMS) toward the impending movement. By contrast, the directional characteristics of excitability changes in the opposite (passive) limb have not been fully characterized. Here we assessed how preparation of voluntary forces towards four spatially distinct visual targets with the left wrist alters muscle twitches and motor‐evoked potentials (MEPs) elicited by TMS of left motor cortex. MEPs were facilitated significantly more in muscles homologous to agonist rather than antagonist muscles in the active limb, from 120 ms prior to voluntary EMG onset. Thus, unilateral motor preparation has a directionally specific influence on pathways projecting to the opposite limb that corresponds to the active muscles rather than the direction of movement in space. The directions of TMS‐evoked twitches also deviated toward the impending force direction of the active limb, according to muscle‐based coordinates, following the onset of voluntary EMG. The data indicate that preparation of a unilateral movement increases task‐dependent excitability in ipsilateral motor cortex, or its downstream projections, that reflects the forces applied by the active limb in an intrinsic (body‐centred), rather than an extrinsic (world‐centred), coordinate system. The results suggest that ipsilateral motor cortical activity prior to unilateral action reflects the state of the active limb, rather than subliminal motor planning for the passive limb.
A Kinetic Study of the Replacement by Site Saturation Mutagenesis of Residue 119 in NDM-1 Metallo-β-Lactamase
Authors: Marcoccia Francesca , Mercuri Paola Sandra , Galleni Moreno , Celenza Giuseppe , Amicosante Gianfranco , Perilli Mariagrazia 
Published: May 2018

ABSTRACT

New Delhi metallo-β-lactamase 1 (NDM-1) is a subclass B1 metallo-β-lactamase that exhibits a broad spectrum of activity against β-lactam antibiotics. Here we report the kinetic study of 6 Q119X variants obtained by site-directed mutagenesis of NDM-1. All Q119X variants were able to hydrolyze carbapenems, penicillins and first-, second-, third-, and fourth-generation cephalosporins very efficiently. In particular, Q119E, Q119Y, Q119V, and Q119K mutants showed improvements in
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values for penicillins, compared with NDM-1. The catalytic efficiencies of the Q119K variant for benzylpenicillin and carbenicillin were about 65- and 70-fold higher, respectively, than those of NDM-1. The Q119K and Q119Y enzymes had
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values for ceftazidime about 25- and 89-fold higher, respectively, than that of NDM-1.
Ten-year incidence of primary angle closure in elderly Chinese: the Liwan Eye Study
Authors: Wang Lanhua , Huang Wenyong , Huang Shengsong , Zhang Jian , Guo Xinxing , Friedman David S , Foster Paul J , He Mingguang 
Published: May 2018

Purpose
To determine the 10-year incidence of all forms of primary angle closure (PAC) in phakic eyes and its risk factors in an urban Chinese population aged 50 years and older.

Methods
Survivors of 1405 baseline participants were invited to attend the 10-year follow-up visit in the Liwan Eye Study. Participants with established baseline angle closure, including primary angle closure suspects (PACS), PAC and primary angle closure glaucoma (PACG), or those who underwent bilateral cataract surgery during the 10-year period, as well as those who did not tolerate gonioscopic examinations, were excluded from this analysis. Incident PAC was present when those with open angles at baseline developed angle closure in any form in either eye during the 10-year period.

Results
Among 791 participants who returned during the 10-year follow-up visit, 620 (78.4%) provided data on PAC incidence. The 10-year cumulative incidence of any forms of PAC was 20.5% (127/620, 95% CI 17.4% to 24.9%), including 16.9%, 2.4% and 1.1% with incident PACS, PAC and PACG in either eye, respectively. In multiple logistic regression, significant risk factors for incident angle closure were greater baseline lens thickness (OR=1.82 per mm, p=0.003), shallower anterior chamber depth (OR=3.18 per mm decreased, p=0.010) and narrower angle width (OR=1.63 per decreased angle width, p<0.0001).

Conclusions
Approximately one in five people aged 50 years and older developed some form of angle closure over a 10-year period. Small ocular dimensions and hyperopia at baseline were associated with the development of angle closure.
New advances in amblyopia therapy I: binocular therapies and pharmacologic augmentation
Authors: Kraus Courtney L , Culican Susan M 
Published: May 2018

Amblyopia therapy options have traditionally been limited to penalisation of the non-amblyopic eye with either patching or pharmaceutical penalisation. Solid evidence, mostly from the Pediatric Eye Disease Investigator Group, has validated both number of hours a day of patching and days per week of atropine use. The use of glasses alone has also been established as a good first-line therapy for both anisometropic and strabismic amblyopia. Unfortunately, visual acuity equalisation or even improvement is not always attainable with these methods. Additionally, non-compliance with prescribed therapies contributes to treatment failures, with data supporting difficulty adhering to full treatment sessions. Interest in alternative therapies for amblyopia treatment has long been a topic of interest among researchers and clinicians alike. Incorporating new technology with an understanding of the biological basis of amblyopia has led to enthusiasm for binocular treatment of amblyopia. Early work on perceptual learning as well as more recent enthusiasm for iPad-based dichoptic training have each generated interesting and promising data for vision improvement in amblyopes. Use of pharmaceutical augmentation of traditional therapies has also been investigated. Several different drugs with unique mechanisms of action are thought to be able to neurosensitise the brain and enhance responsiveness to amblyopia therapy. No new treatment has emerged from currently available evidence as superior to the traditional therapies in common practice today. But ongoing investigation into the use of both new technology and the understanding of the neural basis of amblyopia promises alternate or perhaps better cures in the future.
Determining the pneumococcal conjugate vaccine coverage required for indirect protection against vaccine-type pneumococcal carriage in low and middle-income countries: a protocol for a prospective observational study
Authors: Chan Jocelyn , Nguyen Cattram D , Lai Jana Y R , Dunne Eileen M , Andrews Ross , Blyth Christopher C , Datta Siddhartha , Fox Kim , Ford Rebecca , Hinds Jason , La Vincente Sophie , Lehmann Deborah , Lim Ruth , Mungun Tuya , Newton Paul N , Phetsouvanh Rattanaphone , Pomat Willam S , Xeuatvongsa Anonh , von Mollendorf Claire , Dance David A B , Satzke Catherine , Muholland Kim , Russell Fiona M 
Published: May 2018

IntroductionPneumococcal conjugate vaccines (PCVs) prevent disease through both direct protection of vaccinated individuals and indirect protection of unvaccinated individuals by reducing nasopharyngeal (NP) carriage and transmission of vaccine-type (VT) pneumococci. While the indirect effects of PCV vaccination are well described, the PCV coverage required to achieve the indirect effects is unknown. We will investigate the relationship between PCV coverage and VT carriage among undervaccinated children using hospital-based NP pneumococcal carriage surveillance at three sites in Asia and the Pacific.Methods and analysisWe are recruiting cases, defined as children aged 2–59 months admitted to participating hospitals with acute respiratory infection in Lao People’s Democratic Republic, Mongolia and Papua New Guinea. Thirteen-valent PCV status is obtained from written records. NP swabs are collected according to standard methods, screened usinglytAqPCR and serotyped by microarray. Village-level vaccination coverage, for the resident communities of the recruited cases, is determined using administrative data or community survey. Our analysis will investigate the relationship between VT carriage among undervaccinated cases (indirect effects) and vaccine coverage using generalised estimating equations.Ethics and disseminationEthical approval has been obtained from the relevant ethics committees at participating sites. The results are intended for publication in open-access peer-reviewed journals and will demonstrate methods suitable for low- and middle-income countries to monitor vaccine impact and inform vaccine policy makers about the PCV coverage required to achieve indirect protection.
Arrhythmias in adult patients with congenital heart disease and pulmonary arterial hypertension
Authors: Drakopoulou Maria , Nashat Heba , Kempny Aleksander , Alonso-Gonzalez Rafael , Swan Lorna , Wort Stephen J , Price Laura C , McCabe Colm , Wong Tom , Gatzoulis Michael A , Ernst Sabine , Dimopoulos Konstantinos 
Published: May 2018

ObjectivesApproximately 5%–10% of adults with congenital heart disease (CHD) develop pulmonary arterial hypertension (PAH), which affects life expectancy and quality of life. Arrhythmias are common among these patients, but their incidence and impact on outcome remains uncertain.MethodsAll adult patients with PAH associated with CHD (PAH-CHD) seen in a tertiary centre between 2007 and 2015 were followed for new-onset atrial or ventricular arrhythmia. Clinical variables associated with arrhythmia and their relation to mortality were assessed using Cox analysis.ResultsA total of 310 patients (mean age 34.9±12.3 years, 36.8% male) were enrolled. The majority had Eisenmenger syndrome (58.4%), 15.2% had a prior defect repair and a third had Down syndrome. At baseline, 14.2% had a prior history of arrhythmia, mostly supraventricular arrhythmia (86.4%). During a median follow-up of 6.1 years, 64 patients developed at least one new arrhythmic episode (incidence 3.47% per year), mostly supraventricular tachycardia or atrial fibrillation (78.1% of patients). Arrhythmia was associated with symptoms in 75.0% of cases. The type of PAH-CHD, markers of disease severity and prior arrhythmia were associated with arrhythmia during follow-up. Arrhythmia was a strong predictor of death, even after adjusting for demographic and clinical variables (HR 3.41, 95% CI 2.10 to 5.53, p<0.0001).ConclusionsArrhythmia is common in PAH-CHD and is associated with an adverse long-term outcome, even when managed in a specialist centre.
Inhibitor of lysyl oxidase improves cardiac function and the collagen/MMP profile in response to volume overload
Authors: El Hajj Elia C. , El Hajj Milad C. , Ninh Van K. , Gardner Jason D. 
Published: May 2018

The cardiac extracellular matrix is a complex architectural network that serves many functions, including providing structural and biochemical support to surrounding cells and regulating intercellular signaling pathways. Cardiac function is directly affected by extracellular matrix (ECM) composition, and alterations of the ECM contribute to the progression of heart failure. Initially, collagen deposition is an adaptive response that aims to preserve tissue integrity and maintain normal ventricular function. However, the synergistic effects of proinflammatory and profibrotic responses induce a vicious cycle, which causes excess activation of myofibroblasts, significantly increasing collagen deposition and accumulation in the matrix. Furthermore, excess synthesis and activation of the enzyme lysyl oxidase (LOX) during disease increases collagen cross-linking, which significantly increases collagen resistance to degradation by matrix metalloproteinases (MMPs). In the present study, the aortocaval fistula model of volume overload (VO) was used to determine whether LOX inhibition could prevent adverse changes in the ECM and subsequent cardiac dysfunction. The major findings from this study were that LOX inhibition 1) prevented VO-induced increases in left ventricular wall stress; 2) partially attenuated VO-induced ventricular hypertrophy; 3) completely blocked the increases in fibrotic proteins, including collagens, MMPs, and their tissue inhibitors; and 4) prevented the VO-induced decline in cardiac function. It remains unclear whether a direct interaction between LOX and MMPs exists; however, our experiments suggest a potential link between the two because LOX inhibition completely attenuated VO-induced increases in MMPs. Overall, our study demonstrated key cardioprotective effects of LOX inhibition against adverse cardiac remodeling due to chronic VO. NEW & NOTEWORTHY Although the primary role of lysyl oxidase (LOX) is to cross-link collagens, we found that elevated LOX during cardiac disease plays a key role in the progression of heart failure. Here, we show that inhibition of LOX in volume-overloaded rats prevented the development of cardiac dysfunction and improved ventricular collagen and matrix metalloproteinase/tissue inhibitor of metalloproteinase profiles.
Effect of healthy aging and sex on middle cerebral artery blood velocity dynamics during moderate-intensity exercise
Authors: Ward Jaimie L. , Craig Jesse C. , Liu Yumei , Vidoni Eric D. , Maletsky Rebecca , Poole David C. , Billinger Sandra A. 
Published: May 2018

Blood velocity measured in the middle cerebral artery (MCAV) increases with finite kinetics during moderate-intensity exercise, and the amplitude and dynamics of the response provide invaluable insights into the controlling mechanisms. The MCAVresponse after exercise onset is well fit to an exponential model in young individuals but remains to be characterized in their older counterparts. The responsiveness of vasomotor control degrades with advancing age, especially in skeletal muscle. We tested the hypothesis that older subjects would evince a slower and reduced MCAVresponse to exercise. Twenty-nine healthy young (25 ± 1 yr old) and older (69 ± 1 yr old) adults each performed a rapid transition from rest to moderate-intensity exercise on a recumbent stepper. Resting MCAVwas lower in older than young subjects (47 ± 2 vs. 64 ± 3 cm/s, P < 0.001), and amplitude from rest to steady-state exercise was lower in older than young subjects (12 ± 2 vs. 18 ± 3 cm/s, P = 0.04), even after subjects were matched for work rate. As hypothesized, the time constant was significantly longer (slower) in the older than young subjects (51 ± 10 vs. 31 ± 4 s, P = 0.03), driven primarily by older women. Neither age-related differences in fitness, end-tidal CO2, nor blood pressure could account for this effect. Thus, MCAVkinetic analyses revealed a marked impairment in the cerebrovascular response to exercise in older individuals. Kinetic analysis offers a novel approach to evaluate the efficacy of therapeutic interventions for improving cerebrovascular function in elderly and patient populations.NEW & NOTEWORTHY Understanding the dynamic cerebrovascular response to exercise has provided insights into sex-related cerebrovascular control mechanisms throughout the aging process. We report novel differences in the kinetics response of cerebrovascular blood velocity after the onset of moderate-intensity exercise. The exponential increase in brain blood flow from rest to exercise revealed that 1) the kinetics profile of the older group was blunted compared with their young counterparts and 2) the older women demonstrated a slowed response.