bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of CYP3A5*1 expression on tacrolimus required dose after liver transplantation: A systematic review and meta‐analysis
Authors: Hendijani Fatemeh , Azarpira Negar , Kaviani Maryam
Published: June 2018

We systematically collected eligible data to measure the effect of CYP3A5*1 expression on personalized tacrolimus therapy. Six databases were searched for studies on adult liver transplant recipients and donors of liver graft which reported tacrolimus dose requirement, trough blood concentration, and/or concentration/dose (C/D) ratio in expressers and nonexpressers of CYP3A5*1. Eligible data were pooled by meta‐analysis. Sixteen observational studies (1309 recipients, 1044 donors of liver graft) were included in the analyses. Tacrolimus C/D ratio was lower, and the dose was higher in recipient expressers of CYP3A5*1 and/or carriers of expresser liver graft at 1‐4 weeks and 2‐4, 6, and 12 months post‐transplantation. Tacrolimus blood concentration was lower at the first two weeks. Pair expressers were affected by about twofold, and the effect was different between ethnic groups. CYP3A5*1 expression in recipients increased tacrolimus required dose by 0.023 at first, 0.022 at third, and 0.012 mg/kg/day at sixth month. Its expression in graft tissue increased tacrolimus required dose by 0.024 at first, 0.035 at third, and 0.032 mg/kg/day at sixth month. Considering CYP3A5*1 polymorphism can be helpful in individualization of tacrolimus efficient dose prior to administration, and it can remove initial high‐risk lag time (over/underdose period before reaching target blood level) at first few days post‐transplantation.
Climate‐driven substitution of habitat‐forming species leads to reduced biodiversity within a temperate marine community
Authors: Teagle Harry , Smale Dan A.
Published: June 2018

Aim

In marine ecosystems, habitat‐forming species (HFS) such as reef‐building corals and canopy‐forming macroalgae alter local environmental conditions and can promote biodiversity by providing biogenic living space for a vast array of associated organisms. We examined community‐level impacts of observed climate‐driven shifts in the relative abundances of two superficially similar HFS, the warm‐water kelp Laminaria ochroleuca and the cool‐water kelp Laminaria hyperborea.

Location

Western English Channel, north‐east Atlantic

Methods

We compared algal and invertebrate assemblages associated with kelp stipes and holdfasts, across multiple sites and sampling events. Significant differences were recorded in the structure of assemblages between the host kelp species at each site and event.

Results

Assemblages associated with stipes of the cool‐water HFS were, on average, >12 times more diverse and supported >3600 times more biomass compared with the warm‐water HFS. Holdfast assemblages also differed significantly between species, although to a lesser extent than those associated with stipes. Overall, assemblages associated with the warm‐water HFS were markedly impoverished and comprised far fewer rare or unique taxa.

Main conclusions

While previous research has shown how climate‐driven loss of HFS can cause biodiversity loss, our study demonstrates that climate‐driven substitutions of HFS can also lead to impoverished assemblages. The indirect effects of climate change remain poorly resolved, but shifts in the distributions and abundances of HFS may invoke widespread ecological change, especially in marine ecosystems where facilitative interactions are particularly strong.
Multifaceted biodiversity modelling at macroecological scales using Gaussian processes
Authors: Talluto Lauren , Mokany Karel , Pollock Laura J. , Thuiller Wilfried
Published: June 2018

Aim

Modelling the response of β‐diversity (i.e., the turnover in species composition among sites) to environmental variation has wide‐ranging applications, including informing conservation planning, understanding community assembly and forecasting the impacts of climate change. However, modelling β‐diversity is challenging, especially for multiple diversity facets (i.e., taxonomic, functional and phylogenetic diversity), and current methods have important limitations. Here, we present a new approach for predicting the response of multifaceted β‐diversity to the environment, called Multifaceted Biodiversity Modelling (MBM). We illustrate the approach using both a plant diversity dataset from the French Alps and a set of simulated data. We also provide an implementation via an R package.

Location

French Alps.

Methods

For both the French Alps and the simulated communities, we compute β‐diversity indices (e.g., Sørensen dissimilarity, mean functional/phylogenetic pairwise distance) among site pairs. We then apply Gaussian process regression, a flexible nonlinear modelling technique, to predict β‐diversity in response to environmental distance among site pairs. For comparison, we also perform similar analyses using Generalized Dissimilarity Modelling (GDM), a well‐established method for modelling β‐diversity in response to environmental distance.

Results

In the Alps, we observed a general increase in taxonomic (TD) and functional (FD) β‐diversity (i.e., site pairs were more different from each other) as the climatic distance between site pairs increased. GDM performed better for TD and FD when fitting to calibration data, whereas MBM performed better for both when predicting to a validation dataset. For phylogenetic β‐diversity, MBM outperformed GDM in predicting the observed decrease in phylogenetic β‐diversity with increasing climatic distance.

Main conclusions

Multifaceted Biodiversity Modelling provides a flexible new approach that expands our capacity to model multiple facets of β‐diversity. Advantages of MBM over existing methods include simpler assumptions, more flexible modelling, potential to consider multiple facets of diversity across a range of diversity indices, and robust uncertainty estimation.
Predictors of changing insulin dose requirements and glycaemic control in children, adolescents and young adults with Type 1 diabetes
Authors: Teló G. H. , Dougher C. E. , Volkening L. K. , Katz M. L. , Laffel L. M.
Published: June 2018

Aims

To investigate trajectories of daily insulin dose requirements and glycaemic control in children, adolescents and young adults with Type 1 diabetes and to identify factors associated with changing insulin needs and deterioration in HbA1c.

Methods

The sample was a dynamic cohort of 635 children, adolescents and young adults with Type 1 diabetes from one centre. Data from clinic visits occurring over 20 years (1993–2013) were extracted from medical records. From age 7–24 years, we evaluated HbA1c and insulin dose according to sex, insulin regimen and weight status.

Results

Participants provided a mean ± sd of 10.7±4.3 years of insulin dose data and 12.0±4.6 years of HbA1c data. At first observation, the mean ± sd age was 10.0±2.6 years, diabetes duration was 2.8±2.1 years, insulin dose was 0.8±0.2 units/kg and HbA1c was 74±18 mmol/mol (8.9±1.6%). Insulin dose was higher in girls at ages 8–13 years (P<0.0001 to P<0.01), but higher in boys/young men at ages 16–21 years (P<0.0001 to P=0.04). HbA1c was higher in girls/young women at ages 16–24 years (P<0.0001 to P=0.01). Compared with injection therapy, pump therapy was associated with lower insulin dose at ages 8–24 years (P<0.0001 to P=0.03) and lower HbA1c at ages 8–22 years (P<0.0001 to P=0.005). HbA1c did not differ between overweight/obese and normal weight individuals, but overweight/obese individuals had higher insulin dose at ages 8–13 years (P<0.0001 to P=0.03).

Conclusions

This longitudinal assessment identifies clinically meaningful modifiable (e.g. insulin regimen) and non‐modifiable (e.g. sex) factors predictive of insulin requirements and HbA1c levels in young people with Type 1 diabetes; anticipatory insulin adjustments may improve glycaemic control.
The effect of additional mealtime insulin bolus using an insulin‐to‐protein ratio compared to usual carbohydrate counting on postprandial glucose in those with type 1 diabetes who usually follow a carbohydrate‐restricted diet: A randomized cross‐over trial
Authors: Krebs Jeremy D. , Arahill Jacob , Cresswell Pip , Weatherall Mark , Parry‐Strong Amber
Published: June 2018

This randomized controlled cross‐over study compared postprandial glucose concentrations and incidence of hypoglycaemia for mealtime bolus insulin calculated for both meal protein and carbohydrate content, with ordinary dosing for carbohydrate content alone, in adults with type 1 diabetes who usually follow a carbohydrate‐restricted diet. All 16 participants completed three test meals under each of the two conditions. The primary outcome was the time normalized Area Under the Curve (AUC) of glucose measurements. The mean (SD) AUC glucose concentration for insulin dosing for both protein and carbohydrate was 8.3 (2.1) mmol/L compared with 10.0 (2.2) mmol/L for carbohydrate alone. The difference (95% CI) was −1.76 mmol/L (−2.87 to −0.65), P = .003. The mean (SD) glucose concentration ≥ 8.0 mmol/L was 54.8 (32.4)% for dosing for protein and carbohydrate and 73.7 (26.3)% for carbohydrate alone, rate ratio (95% CI) 0.75 (0.62 to 0.89), P = .002. For glucose concentration < 4.0 mmol/L 5.5 (15.1)% and 2.8 (11.7)%; rate ratio (95% CI): 1.97 (0.90 to 4.27), P = .087. Calculating the meal insulin requirements based on the carbohydrate and protein content may have advantages over calculations based on carbohydrate alone. Further studies are required to determine how to best optimize this.
The Determinants of Political Cleavages in Jordan, Tunisia, and Yemen: An Analysis of Political Attitudes Structure in the Arab World
Authors: Abduljaber Malek
Published: June 2018

This article investigates the determinants of political cleavages composing the structure of political attitudes in Jordan, Tunisia, and Yemen following the Arab Spring. Further, it tests whether political cleavages carry predictive weight on ordinary citizens’ electoral choices in general elections. Using the Sixth Wave of the World Values Survey, discriminant analysis was conducted to generate the dimensionality, type, and structure of political attitudes in the three nations. Findings suggest that the structure of political attitudes in Jordan, Tunisia, and Yemen is multidimensional: the Islamic‐Secular division, a conflict along economic policy visions and an emerging divisive dimension concerning political reform. Evidence indicates that political cleavages do not possess significant predictive power in determining voters’ choice at elections booths. This research also points to the significance of social transformation processes such as modernization and globalization in causing a shift in values among ordinary citizens in the Arab World. This research argues that in countries where the effects of modernization and globalization are higher, a weakening of the Islamic‐Secular division is witnessed. This research is important since it paves the way for further empirical analysis on political ideology in the Middle East. It shatters conjectures concluding that Arab polities are only divided by a single hierarchical dimension: Islamic‐Secular. It contributes to comparative research on the dimensionality of political ideology by showing that the Arab World is similar to the industrialized world in the dimensionality, nature, and structuration of political ideology.
Monoclonal antibody‐mediated killing of tumour cells by neutrophils
Authors: Heemskerk Niels , van Egmond Marjolein
Published: June 2018

Neutrophils represent the most abundant population of circulating cytotoxic effector cells. Moreover, their number can be easily increased by treatment with granulocyte‐colony stimulating factor or granulocyte macrophage‐colony stimulating factor, without the need for ex vivo expansion. Because neutrophils express Fc receptors, they have the potential to act as effector cells during monoclonal antibody therapy of cancer. Additionally, as neutrophils play a role in the regulation of adaptive immune responses, exploiting neutrophils in mAb therapy may result in long‐term antitumour immunity. There is limited evidence that neutrophils play a prominent role in current immunoglobulin G‐based immunotherapy. However, as IgA induces neutrophil recruitment, novel therapeutic strategies that aim to target the IgA Fc receptor FcαRI may fully unleash the potential of enlisting neutrophils as cytotoxic effector cells in antibody therapy of cancer.
Contribution of binaural masking release to improved speech intelligibility for different masker types
Authors: Sutojo Sarinah , van de Par Steven , Schoenmaker Esther
Published: June 2018

In situations with competing talkers or in the presence of masking noise, speech intelligibility can be improved by spatially separating the target speaker from the interferers. This advantage is generally referred to as spatial release from masking, and different mechanisms have been suggested to explain it. One proposed mechanism to benefit from spatial cues is the binaural masking release, which is purely stimulus‐driven. According to this mechanism, the spatial benefit results from differences in the binaural cues of target and masker, which need to appear simultaneously in time and frequency to improve the signal detection. In an alternative proposed mechanism, the differences in the interaural cues improve the segregation of auditory streams, a process, which involves top‐down processing rather than being purely stimulus‐driven. Other than the cues that produce binaural masking release, the interaural cue differences between target and interferer required to improve stream segregation do not have to appear simultaneously in time and frequency. This study is concerned with the contribution of binaural masking release to spatial release from masking for three masker types that differ with respect to the amount of energetic masking they exert. Speech intelligibility was measured, employing a stimulus manipulation that inhibits binaural masking release and analysed with a metric to account for the number of better‐ear glimpses. Results indicate that the contribution of the stimulus‐driven binaural masking release plays a minor role while binaural stream segregation and the availability of glimpses in the better ear had a stronger influence on improving the speech intelligibility.
Clinical activity after fingolimod cessation: disease reactivation or rebound?
Authors: Frau J. , Sormani M. P. , Signori A. , Realmuto S. , Baroncini D. , Annovazzi P. , Signoriello E. , Maniscalco G. T. , La Gioia S. , Cordioli C. , Frigeni B. , Rasia S. , Fenu G. , Grasso R. , Sartori A. , Lanzillo R. , Stromillo M. L. , Rossi S. , Forci B. , Cocco E. ,   the i‐MuST study group
Published: June 2018

Background and purpose

There is debate as to whether the apparent rebound after fingolimod discontinuation is related to the discontinuation itself or whether it is due to the natural course of highly active multiple sclerosis (MS). Our aim was to survey the prevalence of severe reactivation and rebound after discontinuation of fingolimod in a cohort of Italian patients with MS.

Methods

Patients with relapsing–remitting MS who were treated with fingolimod for at least 6 months and who stopped treatment for reasons that were unrelated to inefficacy were included in the analysis.

Results

A total of 100 patients who had discontinued fingolimod were included in the study. Fourteen patients (14%) had a relapse within 3 months after fingolimod discontinuation, and an additional 12 (12%) had a relapse within 6 months. According to this study's criteria, 10 patients (10%) had a severe reactivation. Amongst these patients, five (5%) had a reactivation that was considered to be a rebound.

Conclusions

The present study showed that more than 26% of patients are at risk of having a relapse within 6 months after fingolimod discontinuation. Nevertheless, the risk of severe reactivations and rebound is lower than has been previously described.
Mechanisms and impact of differential fouling of the zebra mussel Dreissena polymorpha on different unionid bivalves
Authors: Dzierżyńska‐Białończyk Anna , Jermacz Łukasz , Maćkiewicz Tomasz , Gajewska Joanna , Kobak Jarosław
Published: June 2018

Macrobiofouling is an important phenomenon in the aquatic environment, resulting in economic losses and environmental changes, including negative impact on hard‐shelled animals. A freshwater invasive byssate bivalve, the zebra mussel Dreissena polymorpha (Dreissenidae), strongly affects bivalves from the family Unionidae by fouling their shells. We tested potential mechanisms explaining variable fouling of different unionids (four native species: Anodonta anatina, A. cygnea, Unio pictorum, U. tumidus and the non‐native Sinanodonta woodiana) by the zebra mussel.

We conducted a field survey (unionids collected at a sandy and muddy site in a dam reservoir), field experiment (unionids exposed without sediments in suspended baskets to dreissenid settlement) and laboratory experiment (a multiple choice test with and without the possibility of unionid burrowing into sandy sediments).

In the survey, zebra mussel density was highest on A. anatina and S. woodiana, intermediate on U. pictorum and lowest on A. cygnea and U. tumidus. In the field experiment, A. anatina and S. woodiana were more fouled than Unio spp. In the laboratory, zebra mussels less often attached to U. pictorum and, when unionids could burrow themselves, also to S. woodiana. However, no unionid species was positively selected in the presence of stone substrata.

The percentage of zebra mussels attached directly to unionids (compared to those attached to conspecifics) in the field survey was negatively related to the overall zebra mussel biomass. Zebra mussel fouling negatively affected the biomass of an allopatric S. woodiana on muddy bottom.

Dreissenids overgrow different unionid species to variable extent, not only due to the differences in their exposed surface area, but, as our experimental results show, also because of their active substratum selection. Moreover, mussels seem to prefer unionid surface over conspecific shells, the latter being fouled only when overall dreissenid fouling is heavy. As unionids often constitute the main source of hard substratum for zebra mussels in waterbodies, the species composition of a unionid assemblage may affect dreissenid success by offering them variable substratum quality.
Limited prospects for future alpine treeline advance in the Canadian Rocky Mountains
Authors: Davis Emma L. , Gedalof Ze’ev
Published: June 2018

Treeline advance has occurred throughout the twentieth century in mountainous regions around the world; however, local variation and temporal lags in responses to climate warming indicate that the upper limits of some treelines are not necessarily in climatic equilibrium. These observations suggest that factors other than climate are constraining tree establishment beyond existing treelines. Using a seed addition experiment, we tested the effects of seed availability, predation and microsite limitation on the establishment of two subalpine tree species (Picea engelmannii and Abies lasiocarpa) across four treelines in the Canadian Rocky Mountains. The effect of vegetation removal on seedling growth was also determined, and microclimate conditions were monitored. Establishment limitations observed in the field were placed in context with the effects of soil properties observed in a parallel experiment. The seed addition experiment revealed reduced establishment with increasing elevation, suggesting that although establishment within the treeline ecotone is at least partially seed limited, other constraints are more important beyond the current treeline. The effects of herbivory and microsite availability significantly reduced seedling establishment but were less influential beyond the treeline. Microclimate monitoring revealed that establishment was negatively related to growing season temperatures and positively related to the duration of winter snow cover, counter to the conventional expectation that establishment is limited by low temperatures. Overall, it appears that seedling establishment beyond treeline is predominantly constrained by a combination of high soil surface temperatures during the growing season, reduced winter snowpack and unfavourable soil properties. Our study supports the assertion that seedling establishment in alpine treeline ecotones is simultaneously limited by various climatic and nonclimatic drivers. Together, these factors may limit future treeline advance in the Canadian Rocky Mountains and should be considered when assessing the potential for treeline advance in alpine systems elsewhere
Assessment of aspiration pneumonia using the Anticholinergic Risk Scale
Authors: Kose Eiji , Hirai Toshiyuki , Seki Toshiichi
Published: June 2018

Aim

The association between anticholinergic drug use and aspiration pneumonia (AP) based on the Anticholinergic Risk Scale (ARS) or clinical study reports on AP risks using the ARS are unclear in Japan. The aim of the present study was to establish whether anticholinergic load affects AP, and to clarify the risk based on the ARS score among geriatric patients in the convalescing stage.

Methods

This retrospective longitudinal cohort study included consecutive geriatric patients admitted and discharged from convalescent rehabilitation wards between 2010 and 2016. Participants were divided based on the presence or absence of an increased anticholinergic load from admission to discharge. Demographic data, laboratory data and the Functional Independence Measure were analyzed between groups. The primary outcome was the presence of AP. Multiple logistic regression analysis was carried out to analyze the relationship between anticholinergic drug use and AP.

Results

In total, 618 participants (220 men, 398 women; interquartile range 73–84 years) were included in the present study. Multiple logistic regression analysis of AP, adjusting for confounding factors, showed that anticholinergic drug use was independently and positively correlated with AP. In particular, an increase in ARS score by 2 points correlates with a 1.92‐fold greater risk for AP, and an increase of ≥3 points results in a 3.25‐fold greater risk, both being statistically significant results.

Conclusion

Increased anticholinergic load during hospitalization might be a predictor of increased AP in geriatric patients. Geriatr Gerontol Int 2018; 18: 1230–1235.
Individual thrombin generation and spontaneous bleeding rate during personalized prophylaxis with Nuwiq®(human‐cl rhFVIII) in previously treated patients with severe haemophilia A
Authors: Dargaud Y. , Negrier C. , Rusen L. , Windyga J. , Georgiev P. , Bichler J. , Solomon C. , Knaub S. , Lissitchkov T. , Klamroth R.
Published: June 2018

Introduction

For individuals with haemophilia A, prophylaxis with factorVIII(FVIII) is typically directed towards trough activity >1 IU/dL; however, some patients still experience spontaneous bleeding events (sBEs).

Aim

Aims were to evaluate relationships of endogenous thrombin potential (ETP) andFVIII:C with occurrence of clinical bleeding.

Methods

GENA‐21 was a prospective, open‐label, phaseIIIb study investigating the safety and efficacy of Nuwiq®(human‐cl rhFVIII) in previously treated adults with severe haemophilia A. The study included a 72‐hour pharmacokinetic (PK) evaluation phase and a 6‐month personalized prophylaxis phase in which treatment was guided byPKparameters. This subanalysis assessedFVIII:C by one‐stage assay andETPby thrombin generation assay in blood samples.

Results

Baseline meanETPwas lower in the 7 patients who experiencedsBEs during personalized prophylaxis versus 25 who did not (n = 32 with data fromPKphase and prophylaxis phase;P = .0002). During personalized prophylaxis (n = 49), only patients with lower median troughETPexperiencedsBEs (8/49 patients;ROC AUC = 0.9421;P < .0001); there was no significant relationship forFVIII:C in predictingsBEs (ROCAUC = 0.5838;P = .4750). Directly following infusion of human‐cl rhFVIII,ETPwas lower in patients who experiencedsBEs versus those who did not (P = .0002), whereasFVIII:C did not differ significantly between these groups.

Conclusions

In adults with severe haemophilia A and reduced thrombin generation, increased frequency of spontaneous bleeding was observed irrespective of troughFVIIIlevels. Thus, personalized prophylaxis should take into account variables other thanFVIII:C. Large prospective trials are needed to verifyETPas a marker for spontaneous bleeding.
Treatment of bleeding episodes in haemophilia A complicated by a factor VIII inhibitor in patients receiving Emicizumab. Interim guidance from UKHCDO Inhibitor Working Party and Executive Committee
Authors: Collins P. W. , Liesner R. , Makris M. , Talks K. , Chowdary P. , Chalmers E. , Hall G. , Riddell A. , Percy C. L. , Hay C. R. , Hart D. P.
Published: June 2018

Emicizumab is a bispecific antibody that activates FX to FXa in the absence of FVIII. It has been shown to reduce bleeding episodes in people with haemophilia A complicated by a FVIII inhibitor. Despite the protection against bleeds, some breakthrough bleeds are inevitable and these may require additional haemostatic treatment. Emicizumab has been associated with severe adverse events when co‐administered with activated prothrombin complex concentrate. To minimize the risk of adverse events, the UK Haemophilia Centre Doctors’ Organisation issues the following updated interim guidance to its Inhibitor Guidelines for managing patients receiving Emicizumab based on the limit published information available in February 2018.
The Jamaican Haemophilia Registry: Describing the burden of disease
Authors: Wharfe G. , Buchner‐Daley L. , Gibson T. , Hilliard P. , Usuba K. , Abad A. , Boma‐Fischer L. , Bouskill V. , Floros G. , Lillicrap D. , Lowe Y. , Lowe D. , Palmer‐Mitchell N. , Rand M. L. , Teitel J. , Tuttle A. , Watson A. , White R. , Young N. L. , Blanchette V. S.
Published: June 2018

Introduction

Jamaica has an estimated 200 persons with haemophilia (PWH), who face significant constraints in access to specialized haemophilia care, including access to clotting factor concentrates.

Aim

The aim of this paper is to establish the current burden of disease in PWH in Jamaica.

Methods

PWH were enrolled through the University Hospital of the West Indies, Jamaica. The impact of haemophilia was assessed using a comprehensive battery of heath outcome measures that included the following: laboratory, clinical information and validated outcome measures of joint structure and function, activity, and health‐related quality of life (HRQoL) to provide a health profile of the Jamaican haemophilia population.

Results

In all, 45 PWH were registered (mean age: 29, range: 0.17‐69 years), including 13 children (<18 years of age) and 32 adults. In this sample, 41 had haemophilia A (30 severe) and 4 had haemophilia B (3 severe); 10 patients with haemophilia A were inhibitor positive. The results indicate that adults with haemophilia in Jamaica have significant joint damage: mean Haemophilia Joint Health Score (HJHS) = 42.1 (SD = 17.3); moderate activity levels − mean Haemophilia Activities List (HAL) score = 64.8 (SD = 17.8); and low HRQoL scores − mean Haemo‐QoL‐A score = 62.3 (SD = 19.4). Results for children are also reported but should be interpreted with caution due to the small sample size.

Conclusions

There is a very high burden of disease in PWH in Jamaica. The health profiles reported in this paper are an essential first step in advocating for a multidisciplinary Comprehensive Care Program for assessment and care of PWH in Jamaica.
Resveratrol regulates the silent information regulator 1–nuclear factor‐κB signaling pathway in intrahepatic cholestasis of pregnancy
Authors: Liao E. , Li Zhizun , Shao Yong
Published: June 2018

Aim

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy‐specific liver disease characterized by raised serum bile acids and adverse fetal outcomes. In this study, we aimed to explore the molecular and biochemical mechanism of resveratrol in regulating the silent information regulator 1–nuclear factor‐κB (SIRT1–NF‐κB) signaling pathway and bile acid biosynthesis in ICP.

Methods

We analyzed serum and placenta samples from 30 normal and ICP pregnancy women. Then we treated HTR‐8/SVneo cells with taurocholic acid (TCA) to mimic ICP conditions before treating these cells with resveratrol, as an activator of SIRT1, and EX‐57, as an inhibitor of SIRT1. We established an ICP rat model to analyze the therapeutic effect of resveratrol.

Results

The expression of SIRT1 protein was higher in normal placenta tissues than in ICP, and the expression of NF‐κB was lower in the normal group than in the ICP group. We found that SIRT1 was downregulated, whereas NF‐κB and tuor necrosis factor‐α (TNF‐α) were upregulated, in syncytiotrophoblast HTR‐8 cells treated with TCA. This phenomenon could be reversed by resveratrol, and these effects could be blocked by Ex‐527.

Conclusion

These data indicate that resveratrol might protect syncytiotrophoblast against TCA‐induced inflammatory injury by upregulation of SIRT1 and downregulation of NF‐κB and TNF‐α. Resveratrol could be a potential therapeutic target for ICP.
Sebaceous adenocarcinomas of the major salivary glands: a clinicopathological analysis of 10 cases
Authors: Soares Ciro D , Morais Thayná M L , Carlos Roman , Jorge Jacks , de Almeida Oslei Paes , de Carvalho Maria G F , Altemani Albina M M
Published: June 2018

Aims

Sebaceous carcinomas are uncommon malignant cutaneous tumours originating from the pilosebaceous unit. Although its occurrence is mostly common in peri‐ocular glands, other anatomical regions of the head and neck may be affected, including major and minor salivary glands.

Methods and results

We describe a series of sebaceous adenocarcinomas of the parotid and submandibular glands. The mean age was 62.1 (range = 31–90) years. Two patients (20%) presented regional or distant metastasis to mandible and lungs. All cases were positive for cytokeratins (AE1AE3 and CK‐5), epithelial membrane antigen and adipophilin and negative for androgen receptor, Factor XIIIa, S‐100, vimentin and perforin. MLH1 and MSH2 were expressed in the nuclei of most tumour cells, and one case showed loss of MSH2 expression. Proliferative index (assessed by Ki‐67 expression) and microvessel density (CD34‐positive vessels) were higher in metastasis‐associated cases. P63 expression was noted in the periphery of the tumour nests, in the basaloid cells, with a mean of 69.2% nuclear positivity.

Conclusions

The sebaceous adenocarcinoma of salivary glands is rare and may show an unfavourable outcome; therefore, its correct diagnosis may be challenging. For this reason, immunohistochemical studies, including adipophilin in particular, constitute an important diagnostic tool.
Analytical estimation of fracture toughness for circumferential cracks in thin hard films on ductile substrates
Authors: Azizpour Ahmad , Soleymani Asma , Poursaeidi Esmaeil
Published: June 2018

In this study, the fracture toughness of circumferential crack caused by indentation effect of a rigid indenter on a thin and elastic coating deposited on the elastic substrate was calculated. In the coating and substrate, the analytical solution of displacement and stress field was used. The complete adhesion was considered for the coating on the substrate. The location of maximum circumferential stress was investigated using the analytical calculation of the stress and it was found that this place was located at a distance away from the center of the indenter. Then, the stress intensity factor and energy release rate for plane strain state was determined, and consequently, the energy release rate for a channel crack was calculated. Finally, the fracture toughness was calculated with energy release rate curves for plane strain crack and crack channeling. This method was used to calculate the fracture toughness of TiN/TiCrN ceramic multilayer coating which was deposited on the GTD450 substrate using the Cathodic Arc PVD method. To validate the results, the analytically calculated crack radius was compared with the experimental crack radius in the fracture load and the difference between the radiuses was in the acceptable range.
Market Power Europe and the Externalization of Higher Education
Authors: Damro Chad , Friedman Yoav
Published: June 2018

Higher education policy has long had important domestic, intergovernmental and values‐based features. However, through the Bologna Process, the European Union (EU) has influenced these traditional features and helped to develop an external dimension to higher education policy in and beyond Europe. Despite these significant changes, scholarship on the EU has not yet interrogated directly the external dimensions of Bologna and the influence the EU wields through this process. This article employs Market Power Europe (MPE) as a conceptual framework to examine the Bologna Process and the EU's role in these important changes. Focusing on the notion of externalization, the article reveals the importance of market factors, multiple means (externalization tools) and actors (beyond intergovernmental) through which the EU influences other actors in higher education policy. The findings contribute to the MPE conceptual framework and encourage further research into the causal mechanisms at play in the under‐studied external dimensions of this policy area.
Controlling Bias in Both Constructed Response and Multiple‐Choice Items When Analyzed With the Dichotomous Rasch Model
Authors: Andrich David , Marais Ida
Published: June 2018

Even though guessing biases difficulty estimates as a function of item difficulty in the dichotomous Rasch model, assessment programs with tests which include multiple‐choice items often construct scales using this model. Research has shown that when all items are multiple‐choice, this bias can largely be eliminated. However, many assessments have a combination of multiple‐choice and constructed response items. Using vertically scaled numeracy assessments from a large‐scale assessment program, this article shows that eliminating the bias on estimates of the multiple‐choice items also impacts on the difficulty estimates of the constructed response items. This implies that the original estimates of the constructed response items were biased by the guessing on the multiple‐choice items. This bias has implications for both defining difficulties in item banks for use in adaptive testing composed of both multiple‐choice and constructed response items, and for the construction of proficiency scales.
Gault's Promise Revisited: The Search For Due Process
Authors: Blitzman Jay D.
Published: June 2018

Fifty years ago, due process was introduced into the juvenile courts, but today children still do not have the guiding hand of counsel at every stage of the proceedings. In assessing the pre‐Gault world, Chief Justice Fortas observed that “[a] child receives the worst of both worlds:…he gets neither the protections accorded to adults nor the solicitous care and regenerative treatment postulated for children.” Fortas opined that “Then as now good will and compassion were admirably prevalent. But recent studies have entered with surprising unanimity, sharp dissent to the vitality of this gentle conception. They suggest that the appearance as well as the actuality of fairness‐ impartiality and orderliness‐ in short the essentials of due process may be a more therapeutic attitude so far as the juvenile is concerned.” The prescience of his observation has found resonance and reinforcement with the 2013 publication of Reforming Juvenile Justice: A Developmental Approach which was commissioned by the Office of Juvenile Justice Delinquency and Prevention (OJJDP).

Reforming Juvenile Justice's emphasis on encouraging not only the perception but the actuality of fairness in all domains connects directly to the essence of Gault's message. “Treating youth fairly and ensuring that they perceive that have been treated fairly and with dignity contribute to positive outcomes in the normal processes of social learning, moral development, and legal socialization adolescence.” The research also demonstrates that public health oriented alternatives to traditional court processing promote social connection and positive youth development. The OJJDP report provides a road map for promoting positive youth development and social engagement by demonstrating that supporting such policies improves public safety outcomes by reducing recidivism. In exploring whether Gault's promise of due process has been realized or is still aspirational, this article suggests that our inquiry requires us to think contextually by considering how children and families are treated in and out of the courtroom. This entails consideration of educational, child welfare and mental health services, as well as the scope of legal entitlements. Equity and fundamental fairness, euphemisms for due process, are what will truly effectuate Gault's promise and should be the benchmark for all courts and systems that engage with children.
Effect of deriving periosteal and endosteal contours from microCTscans on computation of cross‐sectional properties in non‐adults: the femur
Authors: Sládek Vladimír , Sabolová Veronika , Šebesta Ondřej , Zikmund Tomáš , Kaiser Jozef , Čerevková Simona
Published: June 2018

Derivation of periosteal and endosteal contours taken from transversal long bone cross‐sections limits the accuracy of calculated biomechanical properties. Although several techniques are available for deriving both contours, the effect of these techniques on accuracy of calculated cross‐sectional properties in non‐adults is unknown. We examine a sample of 86 non‐adult femora from birth to 12 years of age to estimate the effect of error in deriving periosteal and endosteal contours on cross‐sectional properties. Midshaft cross‐sections were taken from microCTscans and contours were derived using manual, fully automatic, spline, and ellipse techniques. Agreement between techniques was assessed against manually traced periosteal and endosteal contours using percent prediction error (%PE), reduced major axis analysis, and limits of agreement. The %PEs were highest in the medullary area and lowest in the total area. Mean %PEs were sufficiently below the 5% level of acceptable error, except for medullary areas, but individual values can greatly exceed this 5% boundary given the high standard deviation of %PEmeans and wide minimum–maximum range of %PEs. Automatic processing produces greater errors than does combination with manual, spline, and ellipse processing. Although periosteal contour is estimated with stronger agreement compared with endosteal contour, error in deriving periosteal contour has a substantially greater effect on calculated section moduli than does error in deriving endosteal contours. We observed no size effect on the resulting bias. Nevertheless, cross‐sectional properties in a younger age category may be estimated with greater error compared with in an older age category. We conclude that non‐adult midshaft cross‐sectional properties can be derived from microCTscans of femoral diaphyses with mean error of < 5% and that derivation of endosteal contour can be simplified by the ellipse technique because fully automatic derivation of endosteal contour may increase the resulting error, especially in small samples.
Dimorphism throughout the European eel's life cycle: are ontogenetic changes in head shape related to dietary differences?
Authors: De Meyer J. , Goethals T. , Van Wassenbergh S. , Augustijns T. , Habraken J. , Hellemans J. , Vandewiele V. , Dhaene J. , Bouillart M. , Adriaens D.
Published: June 2018

A well‐known link exists between an organism's ecology and morphology. In the European eel, a dimorphic head has been linked to differences in feeding ecology, with broad‐headed eels consuming harder prey items than narrow‐headed ones. Consequently, we hypothesized that broad‐heads should exhibit a cranial musculoskeletal system that increases bite force and facilitates the consumption of harder prey. Using 3D‐reconstructions and a bite model, we tested this hypothesis in two life stages: the sub‐adult yellow eel stage and its predecessor, the elver eel stage. This allowed us to test whether broad‐ and narrow‐headed phenotypes show similar trait differences in both life stages and whether the dimorphism becomes more pronounced during ontogeny. We show that broad‐headed eels in both stages have larger jaw muscles and a taller coronoid, which are associated with higher bite forces. This increased bite force together with the elongated upper and lower jaws in broad‐headed eels can also improve grip during spinning behavior, which is used to manipulate hard prey. Head shape variation in European eel is therefore associated with musculoskeletal variation that can be linked to feeding ecology. However, although differences in muscle volume become more pronounced during ontogeny, this was not the case for skeletal features.
Assessing the Validity of Consumer Ratings for Higher Education: Evidence from a New Survey
Authors: Rothwell Jonathan
Published: June 2018

This analysis assesses the validity of using consumer surveys to measure the quality of colleges using new survey data from the Strada‐Gallup Education Consumer Survey. I develop an individual consumer rating based on responses to 14 items related to the quality of education and implement two validity tests: Do higher ratings predict higher welfare, and do they correspond to objective quality measures? I conclude that they do. Indeed, the mean ratings of at least 20 other alumni provide a better prediction of individual satisfaction than popular college rankings from media sources. Consumers rate their experiences higher after attending not‐for‐profit colleges that generate better economic opportunities, enroll students with higher test scores, employ well‐paid faculty, and graduate a higher percentage of students who eventually earn doctorates. I conclude that survey‐based consumer ratings of postsecondary institutions can provide valid and reliable quality comparisons.
Cutaneous acceptability of a moisturizing cream in subjects with sensitive skin
Authors: Snatchfold Jane
Published: June 2018

Background

Topical cosmetic products can cause adverse reactions in some individuals, particularly those with sensitive skin who may develop irritations or allergic contact dermatitis. Evidence suggests that the frequency of self‐reported sensitive skin is increasing in the general population, placing greater importance on clinical testing of topical cosmetics for potential skin reactivity.

Objectives

To confirm the cutaneous acceptability under normal conditions of use of a moisturizing cream in individuals with sensitive skin.

Methods

This was a prospective, single‐center, open‐label, noncomparative clinical trial conducted in female subjects aged 18‐60 years with Fitzpatrick skin phototype I‐IV and confirmed sensitive skin. Subjects applied the moisturizer twice daily to the body and/or face for 21 ± 2 days. Product acceptability was based on the occurrence of adverse events, investigator assessment of skin adverse reactions, and subjects’ self‐reported feelings of skin discomfort.

Results

Thirty‐five female subjects initiated and completed the study; mean age was 43.2 years and most (89%) had Fitzpatrick skin phototype I‐III. No adverse events or skin adverse reactions of erythema, edema, or skin desquamation were observed. There were no participant reports of skin dryness, prickling, or stinging on any occasion. One subject reported a single event of mild itching, which was considered by the investigator as probably not related to study product.

Conclusions

These findings suggest that the moisturizing cream was well tolerated under normal conditions of use and appropriate for topical use on sensitive skin.
Biofilm formation – what we can learn from recent developments
Authors: Bjarnsholt T. , Buhlin K. , Dufrêne Y. F. , Gomelsky M. , Moroni A. , Ramstedt M. , Rumbaugh K. P. , Schulte T. , Sun L. , Åkerlund B. , Römling U.
Published: June 2018

Although biofilms have been observed early in the history of microbial research, their impact has only recently been fully recognized. Biofilm infections, which contribute to up to 80% of human microbial infections, are associated with common human disorders, such as diabetes mellitus and poor dental hygiene, but also with medical implants. The associated chronic infections such as wound infections, dental caries and periodontitis significantly enhance morbidity, affect quality of life and can aid development of follow‐up diseases such as cancer. Biofilm infections remain challenging to treat and antibiotic monotherapy is often insufficient, although some rediscovered traditional compounds have shown surprising efficiency. Innovative anti‐biofilm strategies include application of anti‐biofilm small molecules, intrinsic or external stimulation of production of reactive molecules, utilization of materials with antimicrobial properties and dispersion of biofilms by digestion of the extracellular matrix, also in combination with physical biofilm breakdown. Although basic principles of biofilm formation have been deciphered, the molecular understanding of the formation and structural organization of various types of biofilms has just begun to emerge. Basic studies of biofilm physiology have also resulted in an unexpected discovery of cyclic dinucleotide second messengers that are involved in interkingdom crosstalk via specific mammalian receptors. These findings even open up new venues for exploring novel anti‐biofilm strategies.
Effect of Light‐Cured Resin Cement Application on Translucency of Ceramic Veneers and Light Transmission of LED Polymerization Units
Authors: Zhang Lei , Luo Xiao Ping , Tan Ren Xiang
Published: June 2018

Purpose

To evaluate the effect of light‐cured resin cement application based on etching and silanization on the translucent property of ceramic veneers in different thicknesses, testing the hypothesis that the surface treatment and subsequent resin cement application could influence the translucency of ceramic veneers. The relationship between translucency of ceramic veneers and light transmission irradiated by LED polymerization units was also determined.

Materials and Methods

40 specimens (10 mm diameter) were fabricated from IPS e.max Press HT A2 ceramic ingots, and polished to 0.3 ± 0.01 mm, 0.5 ± 0.01 mm, 0.7 ± 0.01 mm, 1.0 ± 0.01 mm, and 1.5 ± 0.01 mm thick (n = 8/group). One surface of each disc was etched with HF acid, silanized with Monobond‐S, and applied with a light‐cured resin cement (Variolink N Transparent Base). Before and after the above procedure, the total luminous transmittance (τ) of all specimens was assessed by a spectrophotometer in a wavelength range of 380‐780 nm. A handheld radiometer was used to measure the light intensity irradiated by three LED polymerization units. Light transmission (LT) through ceramic specimens after resin cement application was calculated. Data were statistically analyzed using two‐way ANOVA (p = 0.05) and Tukey's test. The correlation between translucency (τ) of ceramic veneers after resin cement application and light transmission (LT) of curing units was statistically evaluated using Spearman correlation test (p = 0.05).

Results

With the increase of ceramic thickness, the transmittance decreased significantly (p < 0.05). For the 0.3‐mm, 0.5‐mm, and 0.7‐mm‐thick groups, the transmittance of ceramic specimens was statistically significantly lower after resin cement application (p < 0.05). The r value of Bluephase C8 was 0.988, 0.977 for Bluphase, and 0.883 for Bluephase 20i, indicating that the light transmission (LT%) was positively correlated to the translucency of ceramic veneers, regardless of the type of curing units.

Conclusion

After the light‐cured resin cement application based on etching and silanization, the ceramic veneers (less than 0.7‐mm thick) were less translucent, and the translucency decreased when the thickness increased. Because of the lower translucency of ceramic veneers, the light intensity of LED units transmitted to resin layer would decrease when curing.