bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantifying Isotopic Heterogeneity of Candidate Reference Materials at the Picogram Sampling Scale
Authors: Ramsey Michael H. , Wiedenbeck Michael
Published: November 2017

We propose a method for quantifying the in situ heterogeneity of solid materials at the picogram test portion scale, illustrating its use by investigating the oxygen isotope ratio (18O−/16O−) of four quartz samples. Using secondary ion mass spectrometry, we could estimate the intrinsic heterogeneity using a large number (~ 100) of closely spaced duplicated measurements. An analysis of variance was then applied to these large data sets to extract the measurement repeatability (typically 0.10–0.15‰, 1s) from the total variability, thereby revealing a variability ranging from 0.18‰ to 2.3‰, which can be attributed to the genuine isotope ratio heterogeneities. A small proportion of outlying values were either rejected manually after inspection, or were accommodated using robust statistics. We also evaluated two distinct approaches for estimating and correcting instrumental drift; the use of a sub‐area of the test material (if shown to have sufficiently low heterogeneity) is judged to be preferable to using a piece of unrelated silicate glass that we believe to be homogeneous. We also compared three approaches for estimating measurement repeatability, from which we show that the ‘duplicate method’ applied to the reference material is preferable to using other methods based either on the drift monitoring material or on assessing residuals of the drift monitoring material after drift correction. Finally, here we propose a strategy for predicting the number of measurements on individual fragments of a material that would be required to achieve a specified target uncertainty.
Capturing and missing the patient's story through outcome measures: A thematic comparison of patient‐generated items in PSYCHLOPS with CORE‐OM and PHQ‐9
Authors: Sales Célia MD , Neves Inês TD , Alves Paula G. , Ashworth Mark
Published: November 2017

Background

There is increasing interest in individualized patient‐reported outcome measures (I‐PROMS), where patients themselves indicate the specific problems they want to address in therapy and these problems are used as items within the outcome measurement tool.

Objective

This paper examined the extent to which 279 items reported in an I‐PROM (PSYCHLOPS) added qualitative information which was not captured by two well‐established outcome measures (CORE‐OM and PHQ‐9).

Design

Comparison of items was only conducted for patients scoring above the “caseness” threshold on the standardized measures.

Setting and patients

107 patients were participating in therapy within addiction and general psychiatric clinical settings.

Main results

Almost every patient (95%) reported at least one item whose content was not covered by PHQ‐9, and 71% reported at least one item not covered by CORE‐OM.

Discussion

Results demonstrate the relevance of individualized outcome assessment for capturing data describing the issues of greatest concern to patients, as nomothetic measures do not always seem to capture the whole story.
Immune correlates of clinical outcome in melanoma
Authors: Pawelec Graham
Published: November 2017

Melanoma has long been recognized as a potentially immunogenic tumour, but only recently has it become clear that the reason for this resides in its many ultraviolet (UV)‐induced mutations and expression of multiple autoantigens which can be targeted by the immune system. The first successful applications of immune‐based treatments included passive immunotherapy using high‐dose interleukin (IL)‐2 and/or adoptive transfer of natural killer (NK)‐cells, as well as active immunotherapy using whole cell‐derived or peptide vaccines. In the intervening decades, it has become clear that these approaches can lead to durable responses in stage III/IV melanoma, and even to functional cures – but only in a vanishingly small fraction of patients. With the advent of immune checkpoint blockade first with anti‐cytotoxic T‐lymphocyte 4 (CTLA‐4), then with anti‐programmed cell death 1 (PD‐1) antibodies, and combinations thereof, the small percentage of responding patients may be increased to half, a major accomplishment in this refractory disease. Improved techniques for identifying mutation‐derived neoantigens and thus more sophisticated active immunotherapies, probably combined with checkpoint blockade, currently hold great promise for further increasing the fraction of responding patients. As additional immunomodulatory antibodies and therapies become available, it will be increasingly important to develop diagnostic tools to determine which particular therapy is likely to elicit the best response for the individual patient. Practically speaking, therapy selection and efficacy monitoring on the basis of the results of a blood test would be most desirable. The purpose of this review is to consider the feasibility of identifying ‘immune signatures’ for predicting responses and determining mechanisms responsible for success or failure of these immunotherapies.
Melter feed viscosity during conversion to glass: Comparison between low‐activity waste and high‐level waste feeds
Authors: Jin Tongan , Chun Jaehun , Dixon Derek R. , Kim Dongsang , Crum Jarrod V. , Bonham Charles C. , VanderVeer Bradley J. , Rodriguez Carmen P. , Weese Brigitte L. , Schweiger Michael J. , Kruger Albert A. , Hrma Pavel
Published: November 2017

During nuclear waste vitrification, a melter feed (a slurry mixture of a nuclear waste and various glass forming and modifying additives) is charged into the melter where undissolved refractory constituents are suspended together with evolved gas bubbles from complex reactions. Knowledge of flow properties of various reacting melter feeds is necessary to understand their unique feed‐to‐glass conversion processes occurring within a floating layer of melter feed called a cold cap. The viscosity of two low‐activity waste (LAW) melter feeds were studied during heating and correlated with volume fractions of undissolved solid phase and gas phase. In contrast to the high‐level waste (HLW) melter feed, the effects of undissolved solid and gas phases play comparable roles and are required to represent the viscosity of LAW melter feeds. This study can help bring physical insights to feed viscosity of reacting melter feeds with different compositions and foaming behavior in nuclear waste vitrification.
Effects of breed proportion and components of heterosis for semen traits in a composite cattle breed
Authors: Khayatzadeh N. , Mészáros G. , Utsunomiya Y. T. , Schmitz‐Hsu F. , Seefried F. , Schnyder U. , Ferenčaković M. , Garcia J. F. , Curik I. , Sölkner J.
Published: November 2017

The aim of this study was to estimate the non‐additive genetic effects of the dominance component of heterosis as well as epistatic loss on semen traits in admixed Swiss Fleckvieh, a composite of Simmental (SI) and Red Holstein Friesian (RHF) cattle. Heterosis is the additional gain in productivity or fitness of cross‐bred progeny over the mid‐purebred parental populations. Intralocus gene interaction usually has a positive effect, while epistatic loss generally reduces productivity or fitness due to lack of evolutionarily established interactions of genes from different breeds. Genotypic data on 38,205 SNP of 818 admixed, as well as 148 RHF and 213 SI bulls as the parental breeds were used to predict breed origin of alleles. The genomewide locus‐specific breed ancestries of individuals were used to calculate effects of breed difference as well as the dominance component of heterosis, while proxies for two definitions of epistatic loss were derived from 100,000 random pairs of loci. The average Holstein Friesian ancestry in admixed bulls was estimated 0.82. Results of fitting different linear mixed models showed including the dominance component of heterosis considerably improved the model adequacy for three of the four traits. Inclusion of epistatic loss increased the accuracy of the models only for our new definition of the epistatic effect for two traits, while the other definition was so highly correlated with the dominance component that statistical separation was impossible.
BIBI: Bayesian inference of breed composition
Authors: Martínez C. A. , Khare K. , Elzo M. A.
Published: November 2017

The aim of this paper was to develop statistical models to estimate individual breed composition based on the previously proposed idea of regressing discrete random variables corresponding to counts of reference alleles of biallelic molecular markers located across the genome on the allele frequencies of each marker in the pure (base) breeds. Some of the existing regression‐based methods do not guarantee that estimators of breed composition will lie in the appropriate parameter space, and none of them account for uncertainty about allele frequencies in the pure breeds, that is, uncertainty about the design matrix. To overcome these limitations, we proposed two Bayesian generalized linear models. For each individual, both models assume that the counts of the reference allele at each marker locus follow independent Binomial distributions, use the logit link and pose a Dirichlet prior over the vector of regression coefficients (which corresponds to breed composition). This prior guarantees that point estimators of breed composition such as the posterior mean pertain to the appropriate space. The difference between these models is that model termed BIBI does not account for uncertainty about the design matrix, while model termed BIBI2 accounts for such an uncertainty by assigning independent Beta priors to the entries of this matrix. We implemented these models in a data set from the University of Florida's multibreed Angus‐Brahman population. Posterior means were used as point estimators of breed composition. In addition, the ordinary least squares estimator proposed by Kuehn et al. () (OLSK) was also computed. BIBI and BIBI2 estimated breed composition more accurately than OLSK, and BIBI2 had a 7.69% improvement in accuracy as compared to BIBI.
TMEM207 hinders the tumour suppressor function of WWOX in oral squamous cell carcinoma
Authors: Bunai Katsuaki , Okubo Hiroshi , Hano Kimika , Inoue Keisuke , Kito Yusuke , Saigo Chiemi , Shibata Toshiyuki , Takeuchi Tamotsu
Published: November 2017

The WW domain‐containing oxidoreductase (WWOX) functions as a tumour suppressor in oral carcinogenesis. As aberrant TMEM207 expression may lead to tumour progression by hampering the tumour suppressor function of WWOX in various cancers, we explored the expression and pathobiological properties of TMEM207, focusing on the WWOX‐mediated regulation of the HIF‐1α pathway in oral squamous cell carcinoma (OSCC). TMEM207 immunoreactivity was detected in 40 of 90 OSCC samples but not in neighbouring non‐tumorous epithelial tissues. Moreover, TMEM207 expression was significantly correlated with lymph node metastasis and poor prognosis. An in situ proximal ligation assay demonstrated the colocalization of TMEM207 and WWOX in invasive OSCC cells, especially glycogen‐rich ones. Enforced expression of TMEM207 abrogated the binding of WWOX to HIF‐1α, increased HIF‐1α and GLUT‐1 expression, even under normoxic conditions, and promoted tumour growth in a xenoplant assay using SAS tongue squamous cancer cells. In contrast, TMEM207 knockdown decreased GLUT‐1 expression in two OSCC cell lines. As a whole, our findings indicate that the aberrant expression of TMEM207 contributes to tumour progression in OSCC, possibly via promoting aerobic glycolysis.
Significance of day‐1 viral response of hepatitis C virus in patients with chronic hepatitis C receiving direct‐acting antiviral therapy
Authors: Toyoda Hidenori , Kumada Takashi , Tada Toshifumi , Yama Tsuyoki , Mizuno Kazuyuki
Published: November 2017

Background and Aim

On‐treatment response of serum hepatitis C virus (HCV) is reportedly less useful to predict the outcome of anti‐HCV therapy with interferon (IFN)‐free regimen with direct‐acting antivirals than with IFN‐based regimens in clinical trials. We evaluated the significance of very early viral response after the start of therapy, which indicates direct HCV response to the drugs, on therapeutic outcome.

Methods

Reductions in serum HCV‐RNA levels were measured at 1 day after the start of therapy in 544 patients who underwent IFN‐free direct‐acting antiviral regimens. The association between these reductions and the achievement or failure of sustained virologic response (SVR) was evaluated.

Results

Patient characteristics did not influence 1‐day reduction in serum HCV‐RNA except for liver fibrosis. There was no difference in 1‐day HCV reduction between SVR and non‐SVR patients treated with a 24‐week regimen. In contrast, in patients treated with a 12‐week regimen, 1‐day reduction was significantly greater in SVR than in non‐SVR patients (P = 0.0013) and was predictive of SVR versus non‐SVR (area under the receiver‐operating characteristics curve: 0.80).

Conclusions

Whereas the reduction in serum HCV‐RNA levels at 1 day after the start of therapy was not associated with treatment outcomes in patients who underwent a 24‐week regimen of IFN‐free therapy, there was an association in patients receiving a 12‐week regimen, and this reduction was predictive of SVR, thus potentially serving as a factor to identify patients at risk of treatment failure.
Protection against β‐amyloid neurotoxicity by a non‐toxic endogenous N‐terminal β‐amyloid fragment and its active hexapeptide core sequence
Authors: Forest Kelly H. , Alfulaij Naghum , Arora Komal , Taketa Ruth , Sherrin Tessi , Todorovic Cedomir , Lawrence James L. M. , Yoshikawa Gene T. , Ng Ho‐Leung , Hruby Victor J. , Nichols Robert A.
Published: November 2017

High levels (μM) of beta amyloid (Aβ) oligomers are known to trigger neurotoxic effects, leading to synaptic impairment, behavioral deficits, and apoptotic cell death. The hydrophobic C‐terminal domain of Aβ, together with sequences critical for oligomer formation, is essential for this neurotoxicity. However, Aβ at low levels (pM‐nM) has been shown to function as a positive neuromodulator and this activity resides in the hydrophilic N‐terminal domain of Aβ. An N‐terminal Aβ fragment (1–15/16), found in cerebrospinal fluid, was also shown to be a highly active neuromodulator and to reverse Aβ‐induced impairments of long‐term potentiation. Here, we show the impact of this N‐terminal Aβ fragment and a shorter hexapeptide core sequence in the Aβ fragment (Aβcore: 10–15) to protect or reverse Aβ‐induced neuronal toxicity, fear memory deficits and apoptotic death. The neuroprotective effects of the N‐terminal Aβ fragment and Aβcore on Aβ‐induced changes in mitochondrial function, oxidative stress, and apoptotic neuronal death were demonstrated via mitochondrial membrane potential, live reactive oxygen species, DNA fragmentation and cell survival assays using a model neuroblastoma cell line (differentiated NG108‐15) and mouse hippocampal neuron cultures. The protective action of the N‐terminal Aβ fragment and Aβcore against spatial memory processing deficits in amyloid precursor protein/PSEN1 (5XFAD) mice was demonstrated in contextual fear conditioning. Stabilized derivatives of the N‐terminal Aβcore were also shown to be fully protective against Aβ‐triggered oxidative stress. Together, these findings indicate an endogenous neuroprotective role for the N‐terminal Aβ fragment, while active stabilized N‐terminal Aβcore derivatives offer the potential for therapeutic application.

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Vitamin C modulates glutamate transport and NMDA receptor function in the retina
Authors: Domith Ivan , Socodato Renato , Portugal Camila C. , Munis Andressa F. , Duarte‐Silva Aline T. , Paes‐de‐Carvalho Roberto
Published: November 2017

Vitamin C (in the reduced form ascorbate or in the oxidized form dehydroascorbate) is implicated in signaling events throughout the central nervous system (CNS). In the retina, a high‐affinity transport system for ascorbate has been described and glutamatergic signaling has been reported to control ascorbate release. Here, we investigated the modulatory role played by vitamin C upon glutamate uptake and N‐methyl‐d‐aspartate (NMDA) receptor activation in cultured retinal cells or in intact retinal tissue using biochemical and imaging techniques. We show that both forms of vitamin C, ascorbate or dehydroascorbate, promote an accumulation of extracellular glutamate by a mechanism involving the inhibition of glutamate uptake. This inhibition correlates with the finding that ascorbate promotes a decrease in cell surface levels of the neuronal glutamate transporter excitatory amino acid transporter 3 in retinal neuronal cultures. Interestingly, vitamin C is prone to increase the activity of NMDA receptors but also promotes a decrease in glutamate‐stimulated [3H] MK801 binding and decreases cell membrane content of NMDA receptor glutamate ionotropic receptor subunit 1 (GluN1) subunits. Both compounds were also able to increase cAMP response element‐binding protein phosphorylation in neuronal nuclei in a glutamate receptor and calcium/calmodulin kinase‐dependent manner. Moreover, the effect of ascorbate is not blocked by sulfinpyrazone and then does not depend on its uptake by retinal cells. Overall, these data indicate a novel molecular and functional target for vitamin C impacting on glutamate signaling in retinal neurons.

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Nerve injury associated with high‐intensity focused ultrasound: A case report
Authors: Sathaworawong Angkana , Wanitphakdeedecha Rungsima
Published: November 2017

Skin laxity is a common cosmetic concern in middle‐aged women. High‐intensity focused ultrasound (HIFU) is one of noninvasive modalities that provides safe and effective improvement in skin laxity and tightening with minimal adverse effects. Concerning an extensive use of HIFU for facial rejuvenation, dermatologists should be aware of potential adverse effects of HIFU treatment. We herein present a case of 33‐year‐old Thai female with facial nerve injury after HIFU treatment for skin laxity.
The relevance of sleep and circadian misalignment for procrastination among shift workers
Authors: Kühnel Jana , Sonnentag Sabine , Bledow Ronald , Melchers Klaus G.
Published: November 2017

This daily diary study contributes to current research uncovering the role of sleep for employees’ effective self‐regulation at work. We focus on shift workers’ effective self‐regulation in terms of their general and day‐specific inclination to procrastinate, that is, their tendency to delay the initiation or completion of work activities. We hypothesized that transitory sleep characteristics (day‐specific sleep quality and sleep duration) and chronic sleep characteristics in terms of circadian misalignment are relevant for procrastination. Sixty‐six shift workers completed two daily questionnaires over the course of one work week, resulting in 332 days of analysis. Results of multilevel regression analyses showed that on days when shift workers slept better and longer—compared to days when they slept worse and shorter—they had more energy and willpower available after sleep and subsequently were less prone to procrastination. Moreover, the more work times (permanent shift) were misaligned with employees’ sleep–wake preferences (chronotype) the more pronounced was shift workers’ inclination to procrastinate at work. The present findings provide important implications for shift workers’ effective functioning at work.

Practitioner Points

To promote shift workers’ effective functioning at work, when scheduling shift work, circadian principles should be taken into account, and work times should be aligned with workers’ chronotypes.

Day‐specific sleep quality and duration co‐vary with procrastination at work. Thus, on days on which procrastination would be especially harmful, sleep of good quality and of sufficient duration should be obtained.
Should short‐term use of alcohol‐containing mouthrinse be avoided for fear of worsening xerostomia?
Authors: Nair R. , Chiu S. E. , Chua Y. K. , Dhillon I. K. , Li J. , Yee Ting Fai R.
Published: November 2017

This study aimed to assess the short‐term effect of alcohol‐containing mouthrinse versus mouthrinse without alcohol on xerostomia scores reported by Xerostomia Inventory (XI) scores and short version of the Xerostomia Inventory (SXI). This study was a two‐group parallel‐arm randomised controlled trial where participants were randomly allocated to twice a day for 7 days use of either alcohol‐containing or alcohol‐free mouthrinse. Allocation was concealed. The participants, the outcome assessors and the statistician were blinded to the allocation status. A total of 163 participants completed the pre‐and post‐intervention data collection. There were no statistically significant differences between the study groups with respect to demographics or other measured independent variables. After adjusting for age and gender, regression coefficient (95% CI) for XI was 0.02 (−1.72‐2.29) and that for SXI was 0.03 (−0.54‐0.83). Both adjusted and unadjusted models showed no significant differences in change in XI or SXI. The mean difference in scores between the groups for XI was −0.45 (−2.45‐1.55) and for SXI was 0.05 (−0.65‐0.75). There was no significant difference in the change in xerostomia levels as a result of short‐term exposure to alcohol‐containing mouthrinse, when compared to those exposed to alcohol‐free mouthrinse. Short‐term use of alcohol‐containing mouthrinse does not result in worsening xerostomia.
An Ancient Virtue and Its Heirs: The Reception of Greatness of Soul in the Arabic Tradition
Authors: Vasalou Sophia
Published: November 2017

This essay examines the reception of the ancient virtue of greatness of soul (or magnanimity) in the Arabic tradition, touching on a range of figures but focusing especially on Miskawayh and even more concertedly on al‐Ghazālī. Influenced by a number of Greek ethical texts available in Arabic translation, both of these thinkers incorporate greatness of soul into their classifications of the virtues and the vices. Yet a closer scrutiny raises questions about this amicable inclusion, and suggests that this virtue stands in an uneasy relationship to the larger ethical schemes of both thinkers. This is substantiated by a careful probing of these thinkers’ considered views on the value of honor and the ethics of self‐evaluation. Yet if the values embedded in the virtue of greatness of soul conflict with these thinkers’ ethical standpoints, there is then an interesting question to ask as to why this conflict should be obscured from view.
Classifying Functioning of Children and Adolescents with Intellectual Disability: The Utility of the International Classification of Functioning, Disability and Health for Children and Youth
Authors: Vale Maria do Carmo , Pereira‐da‐Silva Luís , Pimentel Maria João , Marques Teresa Nunes , Rodrigues Helena , Cunha Gilda , Machado Maria do Céu , Sanches‐Ferreira Manuela , Simeonsson Rune J.
Published: November 2017

Observational cross‐sectional study carried out in a pediatric neurodevelopment unit of a tertiary‐care hospital. A sample of 355 children with median ((min.–max.) 1.0–17.3) years with intellectual disability (30.4% borderline, 43.1% mild, 19.7% moderate, 5.1% severe, and 1.7% profound disability) was seen over a period of 3 years. Based on clinical observation and psychological evaluation, a neurodevelopmental pediatrician selected ICF‐CY body functions codes, and respective qualifiers, to effectively describe functioning of children. Based on evaluation reports, a psychologist and a special educator assigned the previously chosen ICF‐CY body functions codes to 139 and 67 children, respectively. Inter‐rater agreement was estimated using simple and weighted Cohen's kappa coefficients and Gwet's AC1 statistic and Gwet's weighted kappa coefficient statistic. A set of eight ICF‐CY codes was identified as efficiently describing impairments of body functions of children with intellectual disability: global mental functions b117 and b122; specific mental functions b147, b163, b164, and b167; and voice and speech functions b320 and b330. Results indicate a correspondence between the level of severity of qualifiers assigned to ICF‐CY codes and the level of intellectual disability. Inter‐rater agreement was variable among raters, with the best agreements found for qualifying intellectual functions (b117) and psychomotor functions (b122). A profile of eight ICF‐CY codes effectively describes functioning of children with intellectual disability, providing an alternative to medically based classification, based on diagnoses with functionally based classification of children's characteristics. The findings contribute to define a comprehensive set of codes to reliably record individual differences of functioning in this population.
Intrahepatic congenital portosystemic shunts in dogs: short‐ and long‐term outcome of suture attenuation
Authors: Tivers M. S. , Lipscomb V. J. , Bristow P. , Brockman D. J.
Published: November 2017

Objectives

To report the short‐ and long‐term outcomes of one‐ or two‐staged suture attenuation for complete closure of intrahepatic congenital portosystemic shunts in dogs.

Materials and Methods

Retrospective cohort study of dogs surgically treated for intrahepatic congenital portosystemic shunts between February 2000 and March 2015. Long‐term follow‐up was conducted by telephone conversations with the referring veterinary surgeon, owner, or both.

Results

In total, 55 dogs had suture attenuation of their intrahepatic congenital portosystemic shunt; 10 dogs (18·2%) tolerated complete attenuation, whilst 45 dogs (81·8%) tolerated partial attenuation. Postoperative complications occurred in 24 dogs (43·6%), and six dogs (10·9%) died. Repeat surgery was performed in 33 of 39 dogs (84·6%) that had previously undergone partial attenuation, and 27 of these (84·9%) ultimately achieved complete shunt attenuation. One dog (3·0%) died following second surgery, resulting in an overall postoperative mortality of seven of 55 (12·7%). Detailed follow‐up was available for 22 dogs that were still alive at a median of 29 months after surgery (7·4 to 103·1) with a subjectively good quality of life. Of 17 dogs (82·4%), 14 with complete attenuation in one or two surgeries had an excellent outcome compared with one of five dogs (20%) with persistent shunting.

Clinical Significance

Staged suture ligation resulted in a high proportion of complete attenuation and reduced persistent shunting compared with a single surgery. Repeat surgery was associated with fewer complications than the first surgery. The proportion of dogs with an excellent outcome was greater for those that had complete attenuation in one or two surgeries compared with those with persistent shunting.
Sleep and its relation to cognition and behaviour in preschool‐aged children of the general population: a systematic review
Authors: Reynaud Eve , Vecchierini Marie‐Françoise , Heude Barbara , Charles Marie‐Aline , Plancoulaine Sabine
Published: November 2017

This is the first systematic review of the literature on sleep and its relation to cognition and behaviour in preschool‐aged children. In comparison with the literature focused on school‐aged children, knowledge involving preschoolers is rather sparse. A total of 26 studies was included in this review, which revealed a high degree of heterogeneity regarding the type and means of measuring sleep variables and behavioural and cognitive variables, as well as the statistical methods employed. Amongst the 13 articles with the largest sample sizes (top 50% of the included studies, 12 different populations), 12 found that a higher quantity or quality of sleep was associated with better behavioural and/or cognitive outcomes. Results point to an association between sleep, behaviour and cognition as early as preschool years, but the strengths of associations reported in the articles were relatively small. Studies with a smaller sample size were less concordant. It is consistent with our findings that the strengths of association are small, and thus require large sample sizes to ensure statistical detection power. Different aspects of sleep were not associated with all cognitive or behavioural features in the same way, which underscores the need for specific measures rather than general ones such as ‘sleep problems’ or ‘behaviour problems’ to be able to decipher the relationships. There is also a need for large longitudinal studies using objective measures and accounting for confounding factors. The child's genotype has recently been shown to have a moderating role in the association between sleep and behaviour, and should be further explored.
The effect of daylight versus darkness on driver sleepiness: a driving simulator study
Authors: Ahlström Christer , Anund Anna , Fors Carina , Åkerstedt Torbjörn
Published: November 2017

Driver sleepiness studies are often carried out with alert drivers during daytime and sleep‐deprived drivers during night‐time. This design results in a mixture of different factors (e.g. circadian effects, homeostatic effects, light conditions) that may confound the results. The aim of this study was to investigate the effect of light conditions on driver sleepiness. Thirty young male drivers (23.6 ± 1.7 years old) participated in a driving simulator experiment where they drove on a rural road. A 2 × 2 design was used with the conditions daylight versus darkness, and daytime (full sleep) versus night‐time (sleep deprived). The results show that light condition had an independent effect on the sleepiness variables. The subjective sleepiness measured by Karolinska Sleepiness Scale was higher, lateral position more left‐oriented, speed lower, electroencephalogram alpha and theta higher, and blink durations were longer during darkness. The number of line crossings did not change significantly with light condition. The day/night condition had profound effects on most sleepiness indicators while controlling for light condition. The number of line crossings was higher during night driving, Karolinska Sleepiness Scale was higher, blink durations were longer and speed was lower. There were no significant interactions, indicating that light conditions have an additive effect on sleepiness. In conclusion, Karolinska Sleepiness Scale and blink durations increase primarily with sleep deprivation, but also as an effect of darkness. Line crossings are mainly driven by the need for sleep and the reduced alertness at the circadian nadir. Lane position is, however, more determined by light conditions than by sleepiness.
The notion of character friendship and the cultivation of virtue
Authors: Hoyos‐Valdés Diana
Published: November 2017

Most theories about virtue cultivation fall under the general umbrella of the role model approach, according to which virtue is acquired by emulating role models, and where those role models are usually conceived of as superior in some relevant respect to the learners. I argue that although we need role models to cultivate virtue, we also need good and close relationships with people who are not our superiors. The overemphasis on role models is misguided and misleading, and a good antidote draws on the Aristotelian concept of character friendship. Character friendship (a) constitutes a unique form of experience in which we share a substantial way of seeing with a close other; (b) facilitates a unique form of knowledge, the knowledge of a particular person (my‐self and the other's self); (c) develops other emotions important for virtue cultivation besides admiration, such as love, shame, trust, and hope; and (d) is a praxis in which cooperative interactions and discussions function as a bridge between habituation of virtue at home and the public life. Character friendship provides necessary elements for human cultivation of virtue that the sole experience of having a role model does not.
The association between steatosis and diabetes with hepatocellular carcinoma in non‐genotype 3 chronic hepatitis C patients
Authors: Yen Yi‐Hao , Lin Ming‐Tsung , Kuo Fang‐Ying , Chang Kuo‐Chin , Tsai Ming‐Chao , Tseng Po‐Lin , Wu Cheng‐Kun , Lin Jung‐Ting , Hu Tsung‐Hui , Lu Sheng‐Nan , Wang Jing‐Houng , Hung Chao‐Hung , Chen Chien‐Hung
Published: November 2017

Background & Aims

Diabetes mellitus (DM) has been found to be strongly associated with an increased risk of hepatocellular carcinoma (HCC) among chronic hepatitis C (CHC) patients. Several studies have also found an association between metabolic steatosis and the risk of HCC in CHC patients, whether this latter association has been accounted for by the known relationship between DM and HCC is still unknown.

Methods

A cohort consisting of 976 non‐genotype 3 patients histologically proven to have CHC and treated with interferon and ribavirin was studied. Cumulative incidence and HCC risk were analysed using the Kaplan‐Meier method and Cox proportional hazard analysis.

Results

Hepatocellular carcinoma developed in 140 subjects over a median follow‐up period of 97.3 months, while 699 patients achieved sustained virological response (SVR). According to multivariate analyses, age ≥ 60 years, advanced fibrosis and genotype 1 were identified as independent factors significantly associated with HCC development in SVR patients. Furthermore, using the absence of steatosis and absence of DM as references, the presence of steatosis without DM (HR = 2.09, 95% CI = 1.12‐3.9, P = .021), the presence of DM without steatosis (HR = 2.78, 95% CI = 1.3‐5.92, P = .008) and the combined presence of steatosis and DM (HR = 3.25, 95% CI = 1.44‐7.33, P = .004) were identified as independent factors significantly associated with HCC development in the SVR patients. In contrast, steatosis alone, DM alone and the combined presence of steatosis and DM were not associated with HCC development in non‐SVR patients.

Conclusions

Steatosis and DM may be associated with HCC development in non‐genotype 3 CHC patients with SVR.
Oral microbiomes from hunter‐gatherers and traditional farmers reveal shifts in commensal balance and pathogen load linked to diet
Authors: Lassalle Florent , Spagnoletti Matteo , Fumagalli Matteo , Shaw Liam , Dyble Mark , Walker Catherine , Thomas Mark G. , Bamberg Migliano Andrea , Balloux Francois
Published: November 2017

Maladaptation to modern diets has been implicated in several chronic disorders. Given the higher prevalence of disease such as dental caries and chronic gum diseases in industrialized societies, we sought to investigate the impact of different subsistence strategies on oral health and physiology, as documented by the oral microbiome. To control for confounding variables such as environment and host genetics, we sampled saliva from three pairs of populations of hunter‐gatherers and traditional farmers living in close proximity in the Philippines. Deep shotgun sequencing of salivary DNA generated high‐coverage microbiomes along with human genomes. Comparing these microbiomes with publicly available data from individuals living on a Western diet revealed that abundance ratios of core species were significantly correlated with subsistence strategy, with hunter‐gatherers and Westerners occupying either end of a gradient of Neisseria against Haemophilus, and traditional farmers falling in between. Species found preferentially in hunter‐gatherers included microbes often considered as oral pathogens, despite their hosts' apparent good oral health. Discriminant analysis of gene functions revealed vitamin B5 autotrophy and urease‐mediated pH regulation as candidate adaptations of the microbiome to the hunter‐gatherer and Western diets, respectively. These results suggest that major transitions in diet selected for different communities of commensals and likely played a role in the emergence of modern oral pathogens.
Ecological disturbance influences adaptive divergence despite high gene flow in golden perch (Macquaria ambigua): Implications for management and resilience to climate change
Authors: Attard Catherine R. M. , Brauer Chris J. , Sandoval‐Castillo Jonathan , Faulks Leanne K. , Unmack Peter J. , Gilligan Dean M. , Beheregaray Luciano B.
Published: November 2017

Populations that are adaptively divergent but maintain high gene flow may have greater resilience to environmental change as gene flow allows the spread of alleles that have already been tested elsewhere. In addition, populations naturally subjected to ecological disturbance may already hold resilience to future environmental change. Confirming this necessitates ecological genomic studies of high dispersal, generalist species. Here we perform one such study on golden perch (Macquaria ambigua) in the Murray‐Darling Basin (MDB), Australia, using a genome‐wide SNP data set. The MDB spans across arid to wet and temperate to subtropical environments, with low to high ecological disturbance in the form of low to high hydrological variability. We found high gene flow across the basin and three populations with low neutral differentiation. Genotype–environment association analyses detected adaptive divergence predominantly linked to an arid region with highly variable riverine flow, and candidate loci included functions related to fat storage, stress and molecular or tissue repair. The high connectivity of golden perch in the MDB will likely allow locally adaptive traits in its most arid and hydrologically variable environment to spread and be selected in localities that are predicted to become arid and hydrologically variable in future climates. High connectivity in golden perch is likely due to their generalist life history and efforts of fisheries management. Our study adds to growing evidence of adaptation in the face of gene flow and highlights the importance of considering ecological disturbance and adaptive divergence in biodiversity management.
Arabidopsis thaliana plants challenged with uranium reveal new insights into iron and phosphate homeostasis
Authors: Berthet Serge , Villiers Florent , Alban Claude , Serre Nelson B. C. , Martin‐Laffon Jacqueline , Figuet Sylvie , Boisson Anne‐Marie , Bligny Richard , Kuntz Marcel , Finazzi Giovanni , Ravanel Stéphane , Bourguignon Jacques
Published: November 2017

Uranium (U) is a naturally occurring radionuclide that is toxic to plants. It is known to interfere with phosphate nutrition and to modify the expression of iron (Fe)‐responsive genes. The transporters involved in the uptake of U from the environment are unknown. Here, we addressed whether IRT1, a high‐affinity Fe2+ transporter, could contribute to U uptake in Arabidopsis thaliana.

An irt1 null mutant was grown hydroponically in different conditions of Fe bioavailability and phosphate supply, and challenged with uranyl. Several physiological parameters (fitness, photosynthesis) were measured to evaluate the response to U treatment.

We found that IRT1 is not a major route for U uptake in our experimental conditions. However, the analysis of irt1 indicated that uranyl interferes with Fe and phosphate homeostasis at different levels. In phosphate‐sufficient conditions, the absence of the cation chelator EDTA in the medium has drastic consequences on the physiology of irt1, with important symptoms of Fe deficiency in chloroplasts. These effects are counterbalanced by U, probably because the radionuclide competes with Fe for complexation with phosphate and thus releases active Fe for metabolic and biogenic processes.

Our study reveals that challenging plants with U is useful to decipher the complex interplay between Fe and phosphate.
MdWRKY9 overexpression confers intensive dwarfing in the M26 rootstock of apple by directly inhibiting brassinosteroid synthetase MdDWF4 expression
Authors: Zheng Xiaodong , Zhao Yu , Shan Dongqian , Shi Kun , Wang Lin , Li Qingtian , Wang Na , Zhou Jingzhe , Yao Junzhu , Xue Yuan , Fang Shuang , Chu Jinfang , Guo Yan , Kong Jin
Published: November 2017

Dwarfing rootstocks enable high‐density planting and are therefore highly desirable in modern apple (Malus domestica) production. M26 is a semi‐dwarfing rootstock that is used worldwide, but identifying intensive dwarfing rootstock is a major goal of apple breeding programs.

Herein, we show that MdWRKY9 mediates dwarfing by directly inhibiting the transcription of the brassinosteroid (BR) rate‐limiting synthetase MdDWF4 and reducing BR production.

We found that the transcriptional factor MdWRKY9 is highly expressed in all tested dwarfing rootstocks. Transgenic lines of M26 rootstock overexpressing MdWRKY9 exhibit further dwarfing, which resulted from the reduced BR levels and was reversed via exogenous brassinolide treatment. Both an in vivo chromatin immunoprecipitation (ChIP) analysis and an in vitro electrophoretic mobility shift assay (EMSA) indicated that MdWRKY9 binds to the promoter of MdDWF4. Furthermore, MdWRKY9 repressed MdDWF4 expression in stable transgenic apple plants as determined by quantitative PCR. In addition, RNA‐interfered expression of MdWRKY9 in transiently transformed apple calli led to a significant increase of MdDWF4, suggesting MdWRKY9 plays a critical role in regulating the expression of MdDWF4.

We report a novel dwarfing mechanism in perennial woody plants that involves WRKY‐controlled BR production, and present a new dwarfing M26 rootstock for potential applications in apple production.
Nutrient limitation of terrestrial free‐living nitrogen fixation
Authors: Dynarski Katherine A. , Houlton Benjamin Z.
Published: November 2017

Nitrogen (N) fixation by free‐living bacteria is a primary N input pathway in many ecosystems and sustains global plant productivity. Uncertainty exists over the importance of N, phosphorus (P) and molybdenum (Mo) availability in controlling free‐living N fixation rates. Here, we investigate the geographic occurrence and variability of nutrient constraints to free‐living N fixation in the terrestrial biosphere.

We compiled data from studies measuring free‐living N fixation in response to N, P and Mo fertilizers. We used meta‐analysis to quantitatively determine the extent to which N, P and Mo stimulate or suppress N fixation, and if environmental variables influence the degree of nutrient limitation of N fixation.

Across our compiled dataset, free‐living N fixation is suppressed by N fertilization and stimulated by Mo fertilization. Additionally, free‐living N fixation is stimulated by P additions in tropical forests.

These findings suggest that nutrient limitation is an intrinsic property of the biochemical demands of N fixation, constraining free‐living N fixation in the terrestrial biosphere. These findings have implications for understanding the causes and consequences of N limitation in coupled nutrient cycles, as well as modeling and forecasting nutrient controls over carbon–climate feedbacks.
Discordance of pediatric morphea treatment by pediatric dermatologists
Authors: Tollefson Megha M. , Chiu Yvonne E. , Brandling‐Bennett Heather A. , Pope Elena
Published: November 2017

Background/Objectives

Studies describing treatment efficacy in pediatric morphea are lacking. Subspecialists have reached no consensus on how to optimally treat pediatric morphea. The objective of the current study was to describe the most common treatment practices of pediatric dermatologists worldwide who care for children with morphea.

Methods

A survey regarding topical treatment practices of pediatric morphea, with representative case‐based scenarios, was distributed to pediatric dermatologists and results were tallied.

Results

The survey response rate was 13.4%, with 110 respondents in the final analysis. The majority of respondents agreed on red violaceous rim (99%), increased local warmth (75%), raised borders (69%), and dermal thickening (64%) as signs of disease activity. Respondents had less agreement on sclerotic lesions (41%), scaling (43%), dyspigmentation (19%), and atrophy (13%) as signs of disease activity. Ninety‐two percent of respondents used primary therapy or monotherapy with topical medications, including 45% in linear morphea of the limbs and 37% in linear morphea of the head or neck. High‐potency topical corticosteroids were most commonly used (80%), although respondents did not agree on specific regimens. Sixteen different treatment regimens were selected as first‐line therapy for one case scenario of active disease.

Conclusion

The survey found large variation in how pediatric dermatologists treat pediatric morphea. Consensus treatment guidelines developed by pediatric dermatologists and pediatric rheumatologists are urgently needed regarding the efficacy of therapies for pediatric morphea. Prospective studies of treatment efficacy in pediatric morphea are urgently needed as well.
Erythromelanosis follicularis faciei et colli: A clinicoepidemiologic study
Authors: Arif Tasleem , Adil Mohammad , Amin Syed Suhail , Tahseen Mohammad , Dorjay Konchok , Mohtashim Mohd , Singh Manu , Bansal Roopal , Raj Dinesh
Published: November 2017

We describe 25 cases of erythromelanosis follicularis faciei et colli from India. The male:female ratio was 5.25:1 and the average age of onset was 12.3 years. The cheeks, preauricular area, and submandibular region were the sites most commonly affected. Keratosis pilaris was seen in 22 (88%) of the patients.
Exploring intergenerational patterns of infidelity
Authors: WEISER DANA A. , WEIGEL DANIEL J.
Published: November 2017

Three studies explored how parental infidelity is related to offspring's infidelity behavior and used social learning theory to test potential mechanisms. In Study 1, parental infidelity was positively associated with offspring infidelity; trust and relationship self‐efficacy did not mediate the association. In Study 2, infidelity was associated with parental infidelity and more positive infidelity beliefs. In Study 3, parental infidelity was positively associated with offspring infidelity. Study 3 revealed that parental infidelity is associated with offspring reports of receiving negative messages about fidelity and positive messages about infidelity from their family of origin. These communications are linked to more positive and accepting infidelity beliefs. The results of these studies support the conclusion that parent infidelity is associated with an individual's own infidelity.
A scoping review of environmental health nursing research
Authors: Polivka Barbara J. , Chaudry Rosemary V.
Published: November 2017

Objective

The purpose of this scoping review was to determine the extent and focus of published environmental health nursing research.

Design and Sample

The search was limited to peer reviewed, English‐language environmental health nursing research with at least one nursing author, published between 1995 and 2015 in a nursing journal, and catalogued in CINAHL.

Results

Publication of the 548 identified articles occurred in 118 different nursing journals. Annual number of publications increased from nine articles in 1995 to 50 in 2013 and 2014. Most (63%) of the studies occurred in the Unnited States; the remaining studies took place in 33 other countries. Three primary focus areas were identified: disasters/disaster preparedness, occupational health, and the home environment. Other focus areas included environmental exposures, environmental risk perception, secondhand smoke, and environmental health education. The primary populations studied were nurses/nursing students (40%) and adults (26%). Most common research designs employed were cross‐sectional (42%) and qualitative methods (20%).

Conclusions

Findings from this scoping review support a global expansion of published environmental health nursing research addressing a variety of environmental health topics. Additional studies are needed that use more complex research methods and address timely topics such as climate change and sustainability.