bluuebunny/crossref_metadata_2025 huggingface dataset:
Steroids and nonsteroidal anti‐inflammatory drugs in the postoperative regime after trabeculectomy – which provides the better outcome? A systematic review and meta‐analysis
Authors: Almatlouh Amir , Bach‐Holm Daniella , Kessel Line
Published: September 2018

Surgical outcome after trabeculectomy depends on maintaining a functional bleb which requires a delicate balance between incomplete wound healing to prevent fibrosis and enough wound healing to prevent hyperfiltration. Thus, controlling the inflammatory response is essential. We conducted a systematic review and meta‐analysis to compare the effectiveness of different formulations of steroids (topical, systemic and depot) and nonsteroidal anti‐inflammatory drugs (NSAIDs) in achieving long‐term pressure control with fewer antiglaucomatous medications, preserving visual acuity and visual fields while considering surgical and postoperative complications. We used the PubMed, EMBASE and Cochrane Libraries to identify randomized controlled trials (RCTs) comparing the effect of different formulations of steroids (topical, systemic or depot) to NSAIDs. Data on prespecified outcomes from eligible references were entered into a meta‐analysis using the Review Manager 5.3 program. We identified seven RCTs with a total of 342 included patients. Topical steroids were superior to placebo in controlling intraocular pressure (IOP) and reducing the risk of complications. Supplementing topical steroids with a perioperative steroid depot (subtenon or intracamerally) or systemic steroids in the early postoperative period did not provide better outcome or a change in the risk of complications. Addition of topical NSAIDs to topical steroids in patients undergoing trabeculectomy did not change the outcome or risk profile. For patients undergoing phacotrabeculectomy and topical NSAID, there was a nonsignificant trend towards better intermediate IOP control and a reduced need for antiglaucomatous medications compared to topical steroids but there was no difference in effect for patients undergoing trabeculectomy. In conclusion, there is a low level of evidence to support the clinician in deciding which postoperative regime provides a more favourable outcome because of inconsistency in the reported outcomes between studies and a low number of patients for each comparable intervention and outcome. It does seem that topical steroids are better than no anti‐inflammatory treatment after glaucoma surgery, but further research is recommended.
High‐versus low‐dose caffeine in preterm infants: a systematic review and meta‐analysis
Authors: Brattström Petter , Russo Chiara , Ley David , Bruschettini Matteo
Published: September 2018

Aim

Though caffeine is a consolidated treatment in preterm infants, the efficacy and safety of a higher dose have not been systematically appraised.

Methods

A systematic review was conducted to compare high (loading dose >20 mg/kg and maintenance >10 mg/kg/day) versus low dose of caffeine. MEDLINE, EMBASE, Central and conference proceedings for randomised controlled trials (RCTs) and quasi‐RCTs were searched. Two authors independently screened the records, extracted the data and assessed the risk of bias.

Results

As only six RCTs enrolling a total of 816 preterm infants were included, the required information size was not reached. The loading and maintenance doses varied between 20 and 80 mg/kg/day and 3 and 20 mg/kg/day, respectively. The use of high dose had no impact on mortality (RR: 0.85; 95% CI: 0.53–1.38; RCTs = 4). However, it resulted in fewer cases of extubation failure, apnoeas and bronchopulmonary dysplasia (RR: 0.76; 95% CI: 0.60–0.96; studies = 4) and shorter duration of mechanical ventilation. The quality of the evidence was low due to imprecision of the estimates.

Conclusion

Due to imprecision, it is not possible to determine whether high‐dose caffeine is more effective and safe than a low dose. High dose might improve short‐term respiratory function and reduce bronchopulmonary dysplasia.
Effects of physical exercise during pregnancy on maternal and infant outcomes in overweight and obese pregnant women: A meta‐analysis
Authors: Du Mei‐Chen , Ouyang Yan‐Qiong , Nie Xiao‐Fei , Huang Yi , Redding Sharon R.
Published: September 2018

Background

Overweight and obesity are related to maternal and infant physical health, such as gestational diabetes, preeclampsia, and macrosomia. The purpose of this meta‐analysis was to assess the effect of physical exercise on maternal and infant outcomes in overweight and obese pregnant women.

Methods

Two researchers independently searched Cochrane Library, Embase, PubMed, Web of Science, and ClinicalTrials.gov. for English‐language articles based on randomized controlled trials examining physical exercise in overweight and obese pregnant women and its effect on maternal and infant outcomes. Primary outcomes were gestational weight gain and a relative risk of gestational diabetes. Secondary outcomes were gestational hypertension, preeclampsia, cesarean delivery, birthweight, large for gestational age, small for gestational age, macrosomia, and preterm birth. Risk bias was evaluated by Cochrane Collaboration's tool. The results of integration were reported as relative risks (RR), mean difference, or standard mean difference with 95% confidence intervals (CI). This meta‐analysis was registered on PROSPERO on November 18, 2017, with registration number CRD42017081565.

Results

Thirteen studies involving 1439 participants were included. Physical exercise reduced gestational weight gain (mean difference = −1.14 kg, 95% CI = [−1.67 to −0.62], P < 0.0001) and the risk of gestational diabetes (RR = 0.71, 95% CI = [0.57‐0.89], P = 0.004) in overweight and obese pregnant women. There were no significant differences in other outcomes such as gestational hypertension, preeclampsia, cesarean delivery, birthweight, large for gestational age, small for gestational age, macrosomia, and preterm birth.

Conclusions

Prenatal exercise interventions reduced gestational weight gain and the risk of gestational diabetes for overweight and obese pregnant women, which reinforced the benefits of exercise during pregnancy. However, no evidence was found with respect to benefits and/or harm for infants. Consideration should be taken when interpreting these findings as a result of the relative small sample size in this meta‐analysis. Further larger well‐designed randomized trials may be helpful to assess the short‐term and long‐term effects of prenatal exercise on maternal and infant outcomes.
Exploring TPACK among pre‐service teachers in Australia and Israel
Authors: Redmond Petrea , Peled Yehuda
Published: September 2018

The ubiquitous nature of technology in the world has not yet translated into the ubiquitous use of technology to transform learning and teaching. Teachers lack the confidence and competence to integrate technology across a broad range of tools within a range of contexts. Technological pedagogical content knowledge (TPACK) has become a common framework to explore technology within teaching and teacher education. However, little research exists to explore the similarities and differences of TPACK between different teacher education programmes, within different countries or even different disciplines, especially in a secondary context. Using a self‐report online survey, this study sought to compare and contrast TPACK results from pre‐service teachers studying in secondary teacher education programmes in Australia and Israel. Findings suggest that TPACK is higher in Australia, and in both countries for those students who were aged over 26. There were no significant differences between gender and disciplines reported. The paper also discusses broad‐scale implications for the future of research in TPACK.
Immediate versus delayed exercise in men initiating androgen deprivation: effects on bone density and soft tissue composition
Authors: Taaffe Dennis R. , Galvão Daniel A. , Spry Nigel , Joseph David , Chambers Suzanne K. , Gardiner Robert A. , Hayne Dickon , Cormie Prue , Shum David H.K. , Newton Robert U.
Published: September 2018

Objectives

To examine whether it is more efficacious to commence exercise medicine in men with prostate cancer at the onset of androgen‐deprivation therapy (ADT) rather than later on during treatment to preserve bone and soft‐tissue composition, as ADT results in adverse effects including: reduced bone mineral density (BMD), loss of muscle mass, and increased fat mass (FM).

Patients and methods

In all, 104 patients with prostate cancer, aged 48–84 years initiating ADT, were randomised to immediate exercise (IMEX, n = 54) or delayed exercise (DEL, n = 50) conditions. The former consisted of 6 months of supervised resistance/aerobic/impact exercise and the latter comprised 6 months of usual care followed by 6 months of the identical exercise programme. Regional and whole body BMD, lean mass (LM), whole body FM and trunk FM, and appendicular skeletal muscle (ASM) were assessed by dual X‐ray absorptiometry, and muscle density by peripheral quantitative computed tomography at baseline, and at 6 and 12 months.

Results

There was a significant time effect (P < 0.001) for whole body, spine and hip BMD with a progressive loss in the IMEX and DEL groups, although lumbar spine BMD was largely preserved in the IMEX group at 6 months compared with the DEL group (−0.4% vs −1.6%). LM, ASM, and muscle density were preserved in the IMEX group at 6 months, declined in the DEL group at 6 months (−1.4% to −2.5%) and then recovered at 12 months after training. FM and trunk FM increased (P < 0.001) over the 12‐month period in the IMEX (7.8% and 4.5%, respectively) and DEL groups (6.5% and 4.3%, respectively).

Conclusions

Commencing exercise at the onset of ADT preserves lumbar spine BMD, muscle mass, and muscle density. To avoid treatment‐related adverse musculoskeletal effects, exercise medicine should be prescribed and commenced at the onset of ADT.
Prospective comparison of a fast 1.5‐T biparametric with the 3.0‐T multiparametric ESUR magnetic resonance imaging protocol as a triage test for men at risk of prostate cancer
Authors: Van Nieuwenhove Sandy , Saussez Thibaud Pierre , Thiry Sarah , Trefois Pierre , Annet Laurence , Michoux Nicolas , Lecouvet Frédéric , Tombal Bertrand
Published: September 2018

Objective

To compare prospectively the diagnostic performance of a biparametric (T2‐weighted imaging [T2WI] and diffusion‐weighted imaging [DWI]) 1.5‐T fast magnetic resonance imaging (fMRI) protocol with the standard 3.0‐T multiparametric MRI (mpMRI) protocol of the European Society of Urological Imaging (ESUR) in men referred for a prostate biopsy.

Patients and Methods

Ninety patients with a prostate cancer (PCa) risk of ≥10% according to the SWOP calculator 4 underwent first fMRI and then the reference mpMRI. Patients with Prostate Imaging Reporting and Data System (PI‐RADS) v.2 lesions ≥3/5 on the mpMRI were scheduled for MRI/ultrasonography (US) fusion‐guided prostate biopsy. Performance of fMRI was assessed using receiver‐operating characteristic curve analysis and mpMRI as reference. Calculation of inter‐technique agreement on PI‐RADS v.2 score by Cohen's κ.

Results

The diagnostic accuracy of fMRI shown by the lesion‐based analysis was excellent: area under the curve (AUC) 0.961 (P < 0.001), sensitivity 95%, specificity 97%, positive predictive value (PPV) 99%, negative predictive value (NPV) 89%. The patient‐based analysis showed an AUC for fMRI of 0.975 (P < 0.001), a sensitivity of 98%, a specificity of 97%, a PPV of 98% and an NPV of 97%. Agreement on the PI‐RADS score between both protocols was found to be good (κ = 0.78 [0.57; 0.99]); fMRI missing PI‐RADS 4 lesions in three patients. Biopsy results showed no cancer in two patients (two cores per nodule) and Gleason 6 cancer in one patient. There was only one false‐positive fMRI, with a PI‐RADS score of 4, whose biopsy was negative.

Conclusion

In the triage of men with a high risk of PCa for prostate biopsy, an f MRI protocol (1.5‐T magnet, T2WI + DWI, <15 min) may safely replace the traditional ESUR 3.0‐T mpMRI protocol, saving time and contrast injection.
Applications of mechanistic modelling to clinical and experimental immunology: an emerging technology to accelerate immunotherapeutic discovery and development
Authors: Brown L V , Gaffney E A , Wagg J , Coles M C
Published: September 2018

The application of in silico modelling is beginning to emerge as a key methodology to advance our understanding of mechanisms of disease pathophysiology and related drug action, and in the design of experimental medicine and clinical studies. From this perspective, we will present a non-technical discussion of a small number of recent and historical applications of mathematical, statistical and computational modelling to clinical and experimental immunology. We focus specifically upon mechanistic questions relating to human viral infection, tumour growth and metastasis and T cell activation. These exemplar applications highlight the potential of this approach to impact upon human immunology informed by ever-expanding experimental, clinical and ‘omics’ data. Despite the capacity of mechanistic modelling to accelerate therapeutic discovery and development and to de-risk clinical trial design, it is not widely utilised across the field. We outline ongoing challenges facing the integration of mechanistic modelling with experimental and clinical immunology, and suggest how these may be overcome. Advances in key technologies, including multiscale modelling, machine learning and the wealth of ‘omics’ data sets, coupled with advancements in computational capacity, are providing the basis for mechanistic modelling to impact on immunotherapeutic discovery and development during the next decade.
Blood immune cell biomarkers in lung cancer
Authors: Riemann D , Cwikowski M , Turzer S , Giese T , Grallert M , Schütte W , Seliger B
Published: September 2018

Characterization of host immune cell parameters prior to treatment is expected to identify biomarkers predictive of clinical outcome as well as to elucidate why some patients fail to respond to immunotherapy. We monitored blood immune cells from 58 patients with non-small- cell lung cancer (NSCLC) undergoing surgery of the primary tumor and from 50 age-matched healthy volunteers. Complete leukocyte blood count, the number of circulating dendritic cells (DC), HLA-DRlow monocytes and several lymphocytic subpopulations were determined by eight-color flow cytometry. Furthermore, the prognostic value of the immune cell parameters investigated was evaluated by patients’ survival analysis. Compared to the control group, blood of NSCLC patients contained more neutrophils resulting in a higher neutrophil-to-lymphocyte ratio (NLR), but a lower number of blood DC, in particular of plasmacytoid DC (pDC), natural killer (NK) cells and naive CD4+ and CD8+ T cells. Furthermore, a higher frequency of CD4+ regulatory T cells (Treg) and HLA-DRlow monocytes was detected, and smoking had a significant impact on these values. HLA-DRlow monocytes were positively correlated to the number of neutrophils, monocytes and NLR, but negatively associated with the number of pDC and naive CD4+ T cells. The frequency of Treg, HLA-DRlow monocytes and naive CD4+ and CD8+ T cells as well as the ratios of CD4/HLA-DRlow monocytes and HLA-DRlow monocytes/pDC correlated with patient’s overall survival. Next to Treg, HLA-DRlow monocytes and naive T cells represent prognostic markers for NSCLC patients and might be useful for monitoring of patients’ responses to immunotherapies in future studies.
Discovery of a small molecule modulator of the Kv1.1/Kvβ1 channel complex that reduces neuronal excitability and in vitro epileptiform activity
Authors: Niespodziany Isabelle , Mullier Brice , André Véronique Marie , Ghisdal Philippe , Jnoff Eric , Moreno‐Delgado David , Swinnen Dominique , Sands Zara , Wood Martyn , Wolff Christian
Published: September 2018

Aims

Kv1.1 (KCNA1) channels contribute to the control of neuronal excitability and have been associated with epilepsy. Kv1.1 channels can associate with the cytoplasmic Kvβ1 subunit resulting in rapid inactivating A‐type currents. We hypothesized that removal of channel inactivation, by modulating Kv1.1/Kvβ1 interaction with a small molecule, would lead to decreased neuronal excitability and anticonvulsant activity.

Methods

We applied high‐throughput screening to identify ligands able to modulate the Kv1.1‐T1 domain/Kvβ1 protein complex. We then selected a compound that was characterized on recombinant Kv1.1/Kvβ1 channels by electrophysiology and further evaluated on sustained neuronal firing and on in vitro epileptiform activity using a high K+‐low Ca2+ model in hippocampal slices.

Results

We identified a novel compound able to modulate the interaction of the Kv1.1/Kvβ1 complex and that produced a functional inhibition of Kv1.1/Kvβ1 channel inactivation. We demonstrated that this compound reduced the sustained repetitive firing in hippocampal neurons and was able to abolish the development of in vitro epileptiform activity.

Conclusions

This study describes a rational drug discovery approach for the identification of novel ligands that inhibit Kv1.1 channel inactivation and provides pharmacological evidence that such a mechanism translates into physiological effects by reducing in vitro epileptiform activity.
The Effect of Social Network Size on Hashtag Adoption on Twitter
Authors: Monster Iris , Lev‐Ari Shiri
Published: September 2018

Propagation of novel linguistic terms is an important aspect of language use and language change. Here, we test how social network size influences people's likelihood of adopting novel labels by examining hashtag use on Twitter. Specifically, we test whether following fewer Twitter users leads to more varied and malleable hashtag use on Twitter, because each followed user is ascribed greater weight and thus exerts greater influence on the following user. Focusing on Dutch users tweeting about the terrorist attack in Brussels in 2016, we show that people who follow fewer other users use a larger number of unique hashtags to refer to the event, reflecting greater malleability and variability in use. These results have implications for theories of language learning, language use, and language change.
Hepatic artery stenosis after liver transplant: Donation after cardiac death donor vs donation after brain death donor grafts
Authors: Lee David D. , Paz‐Fumagalli Ricardo , Croome Kristopher P. , Paz Diego , Wright Lauren , Nguyen Justin H. , Taner C. Burcin
Published: September 2018

Background

Hepatic artery stenosis (HAS) after liver transplant (LT) is a source of significant morbidity. Some reports have suggested higher arterial complications in patients who receive donation after cardiac death (DCD) livers.

Methods

A total of 2860 consecutive LT were reviewed from a prospectively collected database. All angiograms performed in LT recipients were reviewed and primary patency rates determined by need for further intervention or graft loss due to HAT.

Results

Hepatic artery stenosis was seen in 4.6% of DCD and donation after brain death (DBD) recipients. Recipient male gender, age at transplant, complex donor hepatic artery anatomy, and prolonged operative time were all associated with HAS, but not DCD status. While HAS in recipients of DCD grafts required more stents (1.7% vs 0.6%, P = 0.04) and had worse primary patency rates (logrank, P = 0.02), outcomes as defined by HAT, patient and graft survival were not significantly different between the recipients of DCD or DBD grafts.

Conclusion

We observed no significant difference in the incidence of hepatic artery complications, patient survival, or graft survival in recipients of DCD or DBD grafts. However, HAS in DCD recipients had worse primary patency and a higher need for stent placement.
NYX‐2925, A Novel N‐methyl‐D‐aspartate Receptor Modulator: A First‐in‐Human, Randomized, Double‐blind Study of Safety and Pharmacokinetics in Adults
Authors: Houck David R. , Sindelar Laurel , Sanabria Carlos R. , Stanworth Stephanie H. , Krueger Maggie , Suh Mary , Madsen Torsten M.
Published: September 2018

NYX‐2925, a new chemical entity, acts as a co‐agonist to glutamate at the N‐methyl‐D‐aspartate receptor (NMDAR). At low concentrations of endogenous agonists (glycine/D‐serine), NYX‐2925 partially activates NMDARs, modulating neural pathways relevant for chronic pain. NYX‐2925 is being developed for the treatment of chronic pain conditions, including painful diabetic peripheral neuropathy and fibromyalgia. In this first‐in‐human, phase I, single‐ascending dose (50–1,200 mg) and multiple‐ascending dose (150–900 mg) study, the safety, tolerability, and pharmacokinetics (PKs) of NYX‐2925 were evaluated in 84 healthy adult volunteers. No safety concerns emerged, including no dissociative side effects. NYX‐2925 exhibited dose‐proportional PKs and minimal accumulation following once‐daily dosing for 7 days. Cerebrospinal fluid (CSF) measurements confirmed that NYX‐2925 crosses the blood brain barrier, with maximum CSF concentrations approximating 6–9% of maximum plasma concentrations at the same dose level. NYX‐2925 was safe and well‐tolerated in healthy volunteers, and the study results support the continued clinical development for chronic pain conditions.
Reversible cerebral vasoconstriction syndrome in paediatric patients with systemic lupus erythematosus: implications for management
Authors: Durrleman Chloé , Naggara Olivier , Grevent David , Belot Alexandre , Desgranges Marie , Boyer Olivia , Chabrier Stéphane , Bader‐Meunier Brigitte , Kossorotoff Manoelle
Published: September 2018

Microvascular brain injury is well recognized in neuropsychiatric systemic lupus erythematosus (SLE), but cerebral large artery involvement is being debated. Three females with SLE, aged 9 to 14 years, had immunosuppressive treatment intensification because of lupus nephritis. Within the following days or weeks, they presented with intense cephalalgia – isolated or associated with neurological symptoms – and no or mild hypertension. Magnetic resonance angiography showed multiple stenoses within the circle of Willis. One patient had subsequent small subcortical cerebral infarction. Two patients were treated for neuropsychiatric SLE; one patient was treated for reversible cerebral vasoconstriction syndrome (RCVS). Angiography normalized within a few weeks in all three patients. Retrospectively, clinical and radiological features suggest that RCVS was the most likely diagnosis in all patients. Multidisciplinary analysis of clinical and angiographic features is recommended, as RCVS is rare in children and its recognition may help to adjust treatment.

What this paper adds

Reversible vasoconstriction syndrome was observed in paediatric systemic lupus erythematosus.

Thorough imaging analysis was necessary to address this diagnosis in paediatric patients.
Growing the phenotype of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) in children
Authors: Tobin W Oliver
Published: September 2018

This commentary is on the case series by Sa et al. on pages 490–496 of this issue.
Contracture formation in the upper limb in cerebral palsy starts early
Authors: Pontén Eva
Published: September 2018

This commentary is on the original article by Hedberg‐Graff et al. on pages 204–211 of this issue.
Copeptin, a surrogate marker for arginine vasopressin secretion, is positively associated with glucagon
Authors: Lundegaard Asferg C. , Bjørn Andersen U. , Linneberg A. , Goetze J. P. , Holst J. J. , Jeppesen J. L.
Published: September 2018

Aim

To explore the association of plasma copeptin, the C‐terminal portion of provasopressin and a stable surrogate marker for arginine vasopressin secretion, with plasma glucagon in obese men and men of normal weight.

Methods

We measured fasting blood concentrations of copeptin and glucagon in 102 healthy obese men (mean ± sd age 49.4 ± 10.2 years) and a control group 27 healthy men of normal weight (mean ± sd age 51.5 ± 8.4 years). Differences between groups were evaluated using t‐tests, and multiple linear regression analysis, adjusting for age and weight status (normal weight vs obese), was used to calculate unstandardized regression coefficients (β) with 95% CIs between copeptin and glucagon. Copeptin was (natural) log‐transformed.

Results

The obese men had higher [median (interquartile range)] plasma copeptin concentrations [6.6 (4.6–9.5) vs 4.9 (3.5–6.8) pmol/l; P = 0.040] and higher mean ± sd plasma glucagon concentrations (8.5 ± 3.8 vs 5.3 ± 1.4 pmol/l; P < 0.001) than the normal‐weight men. Adjusted for age and weight status, copeptin was significantly associated with glucagon (β = 1.35, 95% CI 0.13–2.57; P = 0.031). No significant interaction effect between copeptin and weight status on glucagon was found (P = 0.81).

Conclusions

Obese men had higher concentrations of copeptin and glucagon than men of normal weight. Copeptin was positively associated with glucagon. Our data suggest that increased arginine vasopressin‐stimulated glucagon secretion might contribute to higher glucagon concentrations; therefore, increased arginine vasopressin secretion, in addition to other factors, could further aggravate the hyperglucagonaemic state found in obese individuals.
Effect of liraglutide on ambulatory blood pressure in patients with hypertension and type 2 diabetes: A randomized, double‐blind, placebo‐controlled trial
Authors: Liakos Aris , Lambadiari Vaia , Bargiota Alexandra , Kitsios Konstantinos , Avramidis Iakovos , Kotsa Kalliopi , Gerou Spyridon , Boura Panagiota , Tentolouris Nikolaos , Dimitriadis George , Tsapas Apostolos
Published: September 2018

Aims

To assess the effect of liraglutide on 24‐hour ambulatory blood pressure and heart rate in patients with hypertension (pre‐ and stage 1 hypertension) and inadequately controlled Type 2 diabetes (glycated haemoglobin 7%–10% [53‐86 mmol/mol]).

Materials and methods

Eligible patients for this investigator‐initiated, parallel‐group, randomized, double‐blind trial were on stable background antihyperglycaemic therapy excluding insulin, glucagon‐like peptide‐1 receptor agonists and dipeptidyl‐peptidase‐4 inhibitors. Participants were centrally randomized in a 1:1 ratio to daily liraglutide 0.6 mg, titrated to 1.2 mg after the first week, or placebo for 5 weeks. The primary outcome was change in 24‐hour ambulatory systolic blood pressure (SBP), and secondary outcomes included change in ambulatory diastolic blood pressure (DBP) and heart rate. We also assessed renal sodium handling.

Results

Of 87 patients assessed for eligibility, 62 (66.1% men) with a mean age of 60.2 years were randomized to liraglutide (n = 31) or placebo (n = 31). All participants received background therapy with metformin, whilst 35.5% were treated concomitantly with sulphonylureas and 14.5% with pioglitazone. Compared with placebo, liraglutide reduced 24‐hour SBP by −5.73 mm Hg (95% confidence interval [CI] –9.81 to −1.65) and had a neutral effect on 24‐hour DBP (mean difference − 1.42 mm Hg; 95% CI –4.25 to 1.40), whilst increasing 24‐hour heart rate by 6.16 beats/min (95% CI 3.25 to 9.07). Findings were consistent for daytime and night‐time measurements. Liraglutide did not increase urine sodium excretion.

Conclusion

Based on 24‐hour ambulatory measurements, short‐term treatment with liraglutide had a favourable effect on SBP whilst increasing heart rate.
The interplay between facilitation and habitat type drives spatial vegetation patterns in global drylands
Authors: Berdugo Miguel , Soliveres Santiago , Kéfi Sonia , Maestre Fernando T.
Published: September 2018

The spatial configuration of vascular vegetation has been linked to variations in land degradation and ecosystem functioning in drylands. However, most studies on spatial patterns conducted to date have focused on a single or a few study sites within a particular region, specific vegetation types, or in landscapes characterized by a certain type of spatial patterns. Therefore, little is known on the general typology and distribution of plant spatial patterns in drylands worldwide, and on the relative importance of biotic and abiotic factors as predictors of their variations across geographical regions and habitat types. We analyzed 115 dryland plant communities from all continents except Antarctica to: 1) investigate the general typology of spatial patterns, and 2) assess the relative importance of biotic (plant cover, frequency of facilitation, soil amelioration, height of the dominant species) and abiotic (aridity, rainfall seasonality and sand content) factors as predictors of spatial patterns (median patch size, shape of patch‐size distribution and regularity) across contrasting habitat types (shrublands and grasslands). Precipitation during the warmest period and sand content were particularly strong predictors of plant spatial patterns in grasslands and shrublands, respectively. Facilitation associated with power‐law like and irregular spatial patterns in both shrublands and grasslands, although it was mediated by different mechanisms (respectively soil ammelioration and percentage of facilitated species). The importance of biotic attributes as predictors of the shape of patch‐size distributions declined with aridity in both habitats, leading to the emergence of more regular patterns under the most arid conditions. Our results expand our knowledge about patch formation in drylands and the habitat‐dependency of their drivers. They also highlight different ways in which facilitation affects ecosystem structure through the formation of plant spatial patterns.
Towards an interactive, process‐based approach to understanding range shifts: developmental and environmental dependencies matter
Authors: Fitt Robert N. L. , Palmer Steve , Hand Casey , Travis Justin M. J. , Lancaster Lesley T.
Published: September 2018

Many species are undergoing distributional shifts in response to climate change. However, wide variability in range shifting rates has been observed across taxa, and even among closely‐related species. Attempts to link climate‐mediated range shifts to traits has often produced weak or conflicting results. Here we investigate interactive effects of developmental processes and environmental stress on the expression of traits relevant to range shifts. We use an individual‐based modelling approach to assess how different developmental strategies affect range shift rates under a range of environmental conditions. We find that under stressful conditions, such as at the margins of the species’ fundamental niche, investment in prolonged development leads to the greatest rates of range shifting, especially when longer time in development leads to improved fecundity and dispersal‐related traits. However, under benign conditions, and when traits are less developmentally plastic, shorter development times are preferred for rapid range shifts, because higher generational frequency increases the number of individual dispersal events occurring over time. Our results suggest that the ability of a species to range shift depends not only on their dispersal and colonisation characteristics but also how these characteristics interact with developmental strategies. Benefits of any trait always depended on the environmental and developmental sensitivity of life history trait combinations, and the environmental conditions under which the range shift takes place. Without considering environmental and developmental sources of variation in the expression of traits relevant to range shifts, there is little hope of developing a general understanding of intrinsic drivers of range shift potential.
Phase‐locked responses to the vowel envelope vary in scalp‐recorded amplitude due to across‐frequency response interactions
Authors: Easwar Vijayalakshmi , Banyard Ashlee , Aiken Steven J. , Purcell David W.
Published: September 2018

Neural encoding of the envelope of sounds like vowels is essential to access temporal information useful for speech recognition. Subcortical responses to envelope periodicity of vowels can be assessed using scalp‐recorded envelope following responses (EFRs); however, the amplitude of EFRs vary by vowel spectra and the causal relationship is not well understood. One cause for spectral dependency could be interactions between responses with different phases, initiated by multiple stimulus frequencies. Phase differences can arise from earlier initiation of processing high frequencies relative to low frequencies in the cochlea. This study investigated the presence of such phase interactions by measuring EFRs to two naturally spoken vowels (/ε/ and /u/), while delaying the envelope phase of the second formant band (F2+) relative to the first formant (F1) band in 45° increments. At 0° F2+ phase delay, EFRs elicited by the vowel /ε/ were lower in amplitude than the EFRs elicited by /u/. Using vector computations, we found that the lower amplitude of /ε/‐EFRs was caused by linear superposition of F1‐ and F2+‐contributions with larger F1‐F2+ phase differences (166°) compared to /u/ (19°). While the variation in amplitude across F2+ phase delays could be modeled with two dominant EFR sources for both vowels, the degree of variation was dependent on F1 and F2+ EFR characteristics. Together, we demonstrate that (a) broadband sounds like vowels elicit independent responses from different stimulus frequencies that may be out‐of‐phase and affect scalp‐based measurements, and (b) delaying higher frequency formants can maximize EFR amplitudes for some vowels.
Glial mechanisms underlying substance use disorders
Authors: Linker K. E. , Cross S. J. , Leslie F. M.
Published: September 2018

Addiction is a devastating disorder that produces persistent maladaptive changes to the central nervous system, including glial cells. Although there is an extensive body of literature examining the neuronal mechanisms of substance use disorders, effective therapies remain elusive. Glia, particularly microglia and astrocytes, have an emerging and meaningful role in a variety of processes beyond inflammation and immune surveillance, and may represent a promising therapeutic target. Indeed, glia actively modulate neurotransmission, synaptic connectivity and neural circuit function, and are critically poised to contribute to addictive‐like brain states and behaviors. In this review, we argue that glia influence the cellular, molecular, and synaptic changes that occur in neurons following drug exposure, and that this cellular relationship is critically modified following drug exposure. We discuss direct actions of abused drugs on glial function through immune receptors, such as Toll‐like receptor 4, as well as other mechanisms. We highlight how drugs of abuse affect glia‐neural communication, and the profound effects that glial‐derived factors have on neuronal excitability, structure, and function. Recent research demonstrates that glia have brain region‐specific functions, and glia in different brain regions have distinct contributions to drug‐associated behaviors. We will also evaluate the evidence demonstrating that glial activation is essential for drug reward and drug‐induced dopamine release, and highlight clinical evidence showing that glial mechanisms contribute to drug abuse liability. In this review, we synthesize the extensive evidence that glia have a unique, pivotal, and underappreciated role in the development and maintenance of addiction.
Human posterior parietal cortex responds to visual stimuli as early as peristriate occipital cortex
Authors: Regev Tamar I. , Winawer Jonathan , Gerber Edden M. , Knight Robert T. , Deouell Leon Y.
Published: September 2018

Much of what is known about the timing of visual processing in the brain is inferred from intracranial studies in monkeys, with human data limited to mainly noninvasive methods with lower spatial resolution. Here, we estimated visual onset latencies from electrocorticographic (ECoG) recordings in a patient who was implanted with 112 subdural electrodes, distributed across the posterior cortex of the right hemisphere, for presurgical evaluation of intractable epilepsy. Functional MRI prior to surgery was used to determine boundaries of visual areas. The patient was presented with images of objects from several categories. Event‐related potentials (ERPs) were calculated across all categories excluding targets, and statistically reliable onset latencies were determined, using a bootstrapping procedure over the single trial baseline activity in individual electrodes. The distribution of onset latencies broadly reflected the known hierarchy of visual areas, with the earliest cortical responses in primary visual cortex, and higher areas showing later responses. A clear exception to this pattern was a robust, statistically reliable and spatially localized, very early response, on the bank of the posterior intraparietal sulcus (IPS). The response in the IPS started nearly simultaneously with responses detected in peristriate visual areas, around 60 ms poststimulus onset. Our results support the notion of early visual processing in the posterior parietal lobe, not respecting traditional hierarchies, and give direct evidence for onset times of visual responses across the human cortex.
Demand elasticity predicts addiction endophenotypes and the therapeutic efficacy of an orexin/hypocretin‐1 receptor antagonist in rats
Authors: James Morgan H. , Bowrey Hannah E. , Stopper Colin M. , Aston‐Jones Gary
Published: September 2018

Behavioral economics is a powerful, translational approach for measuring drug demand in both humans and animals. Here, we asked if demand for cocaine in rats with limited drug experience could be used to identify individuals most at risk of expressing an addiction phenotype following either long‐ or intermittent access self‐administration schedules, both of which model the transition to uncontrolled drug‐seeking. Because the orexin‐1 receptor antagonist SB‐334867 (SB) is particularly effective at reducing drug‐seeking in highly motivated individuals, we also asked whether demand measured after prolonged drug experience could predict SB efficacy. Demand elasticity (α) measured immediately following acquisition of cocaine self‐administration (‘baseline α’) was positively correlated with α assessed after 2w of long‐ or intermittent access. Baseline α also predicted the magnitude of compulsive responding for cocaine, drug‐seeking in initial abstinence and cued reinstatement following long‐, intermittent‐ or standard short access. When demand was measured after these differential access conditions, α predicted the same addiction endophenotypes predicted by baseline α, as well as primed reinstatement and the emergence of negative emotional mood behavior following abstinence. α also predicted the efficacy of SB, such that high demand rats showed greater reductions in motivation for cocaine following SB compared to low demand rats. Together, these findings indicate that α might serve as a behavioral biomarker to predict individuals most likely to progress from controlled to uncontrolled drug use, and to identify individuals most likely to benefit from orexin‐based therapies for the treatment of addiction.
New insights on relaxant effects of (—)‐borneol monoterpene in rat aortic rings
Authors: Santos Stefânia E. , Ribeiro Fernanda P.R.A. , Menezes Pedro M.N. , Duarte‐Filho Luiz A.M. , Quintans Jullyana S.S. , Quintans‐Junior Lucindo J. , Silva Fabricio S. , Ribeiro Luciano A.A.
Published: September 2018

The monoterpene alcohol (−)‐borneol has many biological effects such as sedative, anti‐inflammatory, analgesic, anti‐nociceptive, antithrombotic and vasorelaxant effects. Our objective in this study was to investigate the mechanism of action of (−)‐borneol and determine its vasorelaxant effect. (−)‐Borneol was tested on isolated aortic rings contracted with PE (10−6 m). This study was performed in the absence or in the presence of endothelium, L‐NAME (100 μm), indomethacin (10 μm), TEA (1 and 10 mm), 4‐AP (1 mm) or glibenclamide (1 mm) to assess the participation of EDRF, nitric oxide, prostanoids and potassium channels on the relaxing effect of (−)‐borneol. In this work, (−)‐borneol induced a relaxant effect in aortic rings, with and without endothelium, in a concentration‐dependent manner. The pharmacological characterization obtained using L‐NAME, indomethacin, TEA, 4‐AP and glibenclamide demonstrates that the effect of (−)‐borneol was modified in the presence of L‐NAME, indomethacin and glibenclamide showing that these signal transduction pathways are involved in the relaxing effect of the monoterpene. (−)‐Borneol has a vasorelaxant effect that depends on the presence of vascular endothelium, with the participation of nitric oxide and prostanoids. Also, (−)‐borneol displayed a direct action on the vascular smooth muscle, greatly dependent on KATP channels.
Risk governance: Examining its impact upon bank performance and risk‐taking
Authors: Gontarek Walter , Belghitar Yacine
Published: September 2018

As policy‐makers in the United States contemplate a relaxation of financial regulation, our study contributes to this dialogue by testing the veracity of heightened standards of risk governance activities for US bank holding companies (BHCs). Our study examines evidence relating to the adoption of these standards by BHCs following regulatory intervention. We find that board‐level risk appetite practices have a profound association upon BHC performance and tail risk. Our estimates show that BHCs which adopt risk appetite practices exhibit a significant improvement in headline performance and reduced tail risk measures. Our research is relevant to academics by identifying the significance of this risk governance practice which has been introduced by global regulators. For practitioners (including board members, risk managers, policy‐makers and regulators), our study validates the efficacy of risk appetite frameworks as the future shape of financial regulation is being actively debated in the US.
Cascading effects from plants to soil microorganisms explain how plant species richness and simulated climate change affect soil multifunctionality
Authors: Valencia Enrique , Gross Nicolas , Quero José L. , Carmona Carlos P. , Ochoa Victoria , Gozalo Beatriz , Delgado‐Baquerizo Manuel , Dumack Kenneth , Hamonts Kelly , Singh Brajesh K. , Bonkowski Michael , Maestre Fernando T.
Published: September 2018

Despite their importance, how plant communities and soil microorganisms interact to determine the capacity of ecosystems to provide multiple functions simultaneously (multifunctionality) under climate change is poorly known. We conducted a common garden experiment using grassland species to evaluate how plant functional structure and soil microbial (bacteria and protists) diversity and abundance regulate soil multifunctionality responses to joint changes in plant species richness (one, three and six species) and simulated climate change (3°C warming and 35% rainfall reduction). The effects of species richness and climate on soil multifunctionality were indirectly driven via changes in plant functional structure and their relationships with the abundance and diversity of soil bacteria and protists. More specifically, warming selected for the larger and most productive plant species, increasing the average size within communities and leading to reductions in functional plant diversity. These changes increased the total abundance of bacteria that, in turn, increased that of protists, ultimately promoting soil multifunctionality. Our work suggests that cascading effects between plant functional traits and the abundance of multitrophic soil organisms largely regulate the response of soil multifunctionality to simulated climate change, and ultimately provides novel experimental insights into the mechanisms underlying the effects of biodiversity and climate change on ecosystem functioning.
Assessment of Dissolution of Silicate Rock Reference Materials with Ammonium Bifluoride and Nitric Acid in a Microwave Oven
Authors: Magaldi Thais T. , Navarro Margareth S. , Enzweiler Jacinta
Published: September 2018

The complete dissolution of representative test portions of powdered rock samples for the determination of the mass fractions of trace elements by ICP‐MS relies either on aggressive and time‐consuming acid digestions or fusion/sintering with appropriate fluxes. Here, we evaluate a microwave oven dissolution method that employs a solution of NH4HF2 and HNO3. The entire procedure occurs in a closed vessel system and takes up to 4 h. In hundreds of digestions, the precipitation of fluorides was never observed. Replicate decomposition of 100 mg of twenty‐one international reference materials (RMs) of igneous rocks, and also one of a shale presented mostly satisfactory recoveries of forty‐one trace elements. Important exceptions were Zr and Hf in G‐2 and GSP‐2 (mean recoveries of ca. 70%), although for four other felsic rock RMs, the digestion was complete. For ultramafic rock RMs, we present Cr results that indicate quantitative dissolution of Cr‐bearing phases. We discuss the findings and conclude that advances in sample preparation of geological materials for instrumental analysis would benefit from a better understanding of how specific characteristics, such as composition and crystallinity of certain minerals, may affect their reactivity.
Neurofilament is superior to cytokeratin 20 in supporting cutaneous origin for neuroendocrine carcinoma
Authors: Stanoszek Lauren M , Chan May P , Palanisamy Nallasivam , Carskadon Shannon , Siddiqui Javed , Patel Rajiv M , Harms Kelly L , Lowe Lori , Fullen Douglas R , Harms Paul W
Published: September 2018

Aim

Primary cutaneous neuroendocrine carcinoma, or Merkel cell carcinoma (MCC), cannot be distinguished morphologically from small‐cell neuroendocrine carcinomas (SmCC) from other sites. Immunohistochemistry is required to confirm cutaneous origin, and is also used for detection of sentinel lymph node (SLN) metastases of MCC. Cytokeratin 20 (CK20) expression is commonly used for these purposes, but is negative in some MCC cases, and has unclear specificity. We evaluated immunohistochemistry for neurofilament and CK20 in MCC compared with SmCC from other sites.

Methods and results

We evaluated neurofilament expression in 55 MCC specimens from 39 unique patients, including nine CK20‐negative MCC tumours. Neurofilament expression was observed in 42 of 55 (76.4%) MCC cases, including seven of nine (77.8%) CK20‐negative MCC cases. Neurofilament was expressed in nine of 12 (75%) Merkel cell polyomavirus‐positive tumours and five of 10 (50%) virus‐negative tumours. Compared to a standard immunohistochemical panel (cytokeratin cocktail and CK20), neurofilament was 87.5% sensitive for detecting SLN metastases. Neurofilament and CK20 expression was also assessed in 61 extracutaneous SmCC from 60 unique patients, with primary sites including lung (27), bladder (18), cervix (3), gastrointestinal tract (3), sinonasal tract (2) and other sites (7). The specificity of neurofilament and CK20 for MCC versus non‐cutaneous SmCC was 96.7% and 59.0%, respectively.

Conclusions

Neurofilament has superior specificity to CK20 in distinguishing MCC from non‐cutaneous SmCC. Neurofilament is frequently expressed in CK20‐ and virus‐negative MCC tumours. Limitations of neurofilament immunohistochemistry include lower sensitivity than CK20 and subtle staining in some tumours. However, our findings indicate that neurofilament is useful for excluding non‐cutaneous SmCC.