bluuebunny/crossref_metadata_2025 huggingface dataset:
The early intervention message: perspectives of parents of children with autism spectrum disorder
Authors: Edwards A. , Brebner C. , McCormack P. , MacDougall C.
Published: November 2016

Background

There is strong evidence that early intervention (EI) can improve outcomes for children with autism spectrum disorder (ASD), and consequently, the importance of EI has been widely promoted to families of children with ASD. However, the perspectives of parents of children with ASD regarding the EI message have not been widely examined.

Methods

This study used qualitative methods to explore parental perspectives on the EI message. Semi‐structured interviews were undertaken with 14 participants from 12 family units to explore the perspectives of parents of children with ASD on the EI message. Thematic analysis was undertaken on the data.

Results

Three central themes were constructed following data analysis: (i) parents' initial perceptions of EI following their child's diagnosis with ASD; (ii) the consequences (both positive and negative) of the EI message; and (iii) parents' perspectives on life after EI. The results of this study indicated that parents were acutely aware of the importance of EI, and although this provided parents with hope immediately post‐diagnosis, it also placed pressure on parental decision‐making regarding which intervention approaches to access for their children with ASD.

Conclusions

The results of this study highlight the importance of carefully considering how health messages, specifically the importance of EI, are communicated to families of children with ASD. Furthermore, the findings of this study also highlight the need for allied health professionals to communicate openly with parents about the anticipated outcomes of EI programmes.
Causes and Consequences of Children's Forgiveness
Authors: van der Wal Reine C. , Karremans Johan C. , Cillessen Antonius H. N.
Published: November 2016

Although the topic of forgiveness has received much attention in research with adults, little is known about the precursors of forgiveness in children. This is unfortunate because research suggests that the capacity to forgive is associated with numerous beneficial outcomes, such as improved social relationships and psychological well‐being. In this article, we examine the determinants and consequences associated with children's propensity to forgive. In the first part, we focus on four determinants: the role of children's characteristics, the relationship between victim and offender, the peer group, and family background. We propose that these determinants—together and on their own—predict children's forgiveness. In the second part, we provide an overview of the consequences of children's forgiveness, both at intrapersonal and interpersonal levels. We close with suggestions for research.
Multimodal analysis based on high‐field magnetic resonance and motor evoked potentials: A case report of multiple sclerosis
Authors: Nakane Shunya , Furutani Kaori , Harada Masafumi , Urushihara Ryo , Matsui Naoko , Izumi Yuishin , Kaji Ryuji
Published: November 2016

Background

Magnetic resonance imaging is widely used in the evaluation of multiple sclerosis (MS). Diffusion tensor imaging can provide information about structural changes in MS that is inaccessible with other magnetic resonance imaging techniques.

Case presentation

We describe the case of a 13‐year‐old girl presenting with muscle weakness in the right lower limb related to a relapse of MS. The patient underwent full tensor imaging with a high‐field magnetic resonance imaging unit and motor evoked potential recording at the phases of relapse and remission. In the diffusion tensor tractography, tracing the left pyramidal tract fiber bundles was improved at relapse compared with at remission. Central motor conduction times and latency were normal at both relapse and remission, but amplitude levels for cortical motor stimulation were higher during remission than relapse. The findings of diffusion tensor imaging reflected the motor evoked potentials results and clinical course.

Conclusions

We tested a new technique that provides visualization of the pyramidal tracts in a patient with MS. Tractography was shown to be a clinically feasible technique that correlates well with clinical symptoms and motor evoked potentials.
Ten‐year all‐cause mortality and its association with vision among Indigenous Australians within Central Australia: the Central Australian Ocular Health Study
Authors: Liu Ebony , Ng Soo K , Kahawita Shyalle , Andrew Nicholas H , Henderson Tim , Craig Jamie E , Landers John
Published: November 2016

Background

No studies to date have explored the association of vision with mortality in Indigenous Australians. We aimed to determine the 10‐year all‐cause mortality and its associations among Indigenous Australians living in Central Australia.

Design

Prospective observational cohort study.

Participants

A total of 1257 (93.0%) of 1347 patients from The Central Australian Ocular Health Study, over the age of 40 years, were available for follow‐up during a 10‐year period.

Methods

All‐cause mortality and its associations with visual acuity, age and gender were analysed.

Main Outcome Measures

All‐cause mortality.

Results

All‐cause mortality was 29.3% at the end of 10 years. Mortality increased as age of recruitment increased: 14.2% (40–49 years), 22.6% (50–59 years), 50.3% (60 years or older) (χ = 59.15; P < 0.00001). Gender was not associated with mortality as an unadjusted variable, but after adjustment with age and visual acuity, women were 17.0% less likely to die (t = 2.09; P = 0.037). Reduced visual acuity was associated with increased mortality rate (5% increased mortality per one line of reduced visual acuity; t = 4.74; P < 0.0001) after adjustment for age, sex, diabetes and hypertension.

Conclusions

The 10‐year all‐cause mortality rate of Indigenous Australians over the age of 40 years and living in remote communities of Central Australia was 29.3%. This is more than double that of the Australian population as a whole. Mortality was significantly associated with visual acuity at recruitment. Further work designed to better understand this association is warranted and may help to reduce this disparity in the future.
Climate and season: the effects on ophthalmic diseases
Authors: Qassim Ayub , Viki Mthulisi , Ng Soo Khai , Jersmann Hubertus , Casson Robert J
Published: November 2016

Seasonal changes and climate have a significant impact on human health. Diseases influenced by temperature and climate conditions are likely to undergo dynamic pattern shifts with consequent impact on human health. A number of infectious and non‐infectious ophthalmic diseases are influenced by temperature and seasonality. Awareness of this is important from public and global health perspective in addition to resource allocation strategies. We examine the evidence for a seasonal pattern to ophthalmic diseases and assess the possible impact of climate change.
Reexamining CEO duality: The surprisingly problematic issues of conceptualization and measurement
Authors: Gove Steve , Junkunc Marc , Bruyaka Olga , Kabbach de Castro Luiz Ricardo , Larraza‐Kintana Martin , Mingo Santiago , Song Yue , Thakur Wernz Pooja
Published: November 2016

Manuscript Type

Empirical

Research Question/Issue

While corporate governance research is the beneficiary of advances in research methodologies and statistical techniques, less attention has been placed on variable measurement. This paper draws into question the conceptualization and measurement of CEO duality by highlighting its largely unrecognized instability and the challenges instability imposes on measuring dichotomous variables. CEO duality is widely used in corporate governance research and frequently operationalized dichotomously as a dummy variable. We present examples of the frequent changes in duality within organizations which challenge our current view of CEO duality.

Research Findings/Insights

We find that the instability of CEO duality in practice varies considerably at both the national and within‐firm levels. We find that a mismatch exists between the current conceptualization of CEO duality, actual patterns of data, and the measures used by governance researchers. The paper draws attention to the limits of conceptualizing and measuring what is seemingly dichotomous data, reviews these in research and in practice, and provides examples, recommendations and assessments of alternate ways existing data can be used.

Theoretical/Academic Implications

Our results draw into question the reliance on a simple dichotomous conceptualization and operationalization of CEO duality in governance research. Data limitations of corporate governance research may be alleviated by directly assessing stability of duality within firms and reimagining concepts in ways that can be measured using existing data.

Practitioner/Policy Implications

CEO duality, a legal but discouraged governance structure, may be changed intentionally or result from a variety of temporary firm‐level factors. Assessing the longitudinal patterns in duality and underlying causes for temporary changes in duality should be incorporated into evaluations of firm governance structures.
The use of nutshell firstly as a natural dye for cotton and wool and then as a natural adsorbent for colour removal of basic dye effluent
Authors: Güneş Elçin , Atav Rıza
Published: November 2016

The aim of this study is to utilise nutshell, which is normally a waste. To this end, in the first part of our study we investigated the usability of nutshell extract solution as a natural dye for the coloration of cotton and wool fabrics. In order to optimise the fastness properties of dyed samples, mordant type was chosen as a variable in experiments and dyeings were carried out at 100 g l−1 extract concentration. After extracting its dye, nutshell was used as adsorbent for colour removal of basic dye effluent. The effect of adsorbent dose, initial dye concentration, and contact time on the adsorption of malachite green (MG) onto nutshell was investigated. Adsorption isotherms and kinetics of MG adsorption onto nutshell were also studied.
Barriers to the use of a federal travel grant by living kidney donors
Authors: Hays Rebecca E. , Thomas Amy Elaine , Mathias Erin , Mezrich Joshua , Mandelbrot Didier A.
Published: November 2016

Living organ donation involves significant out‐of‐pocket costs, which burden donor candidates and may be an obstacle to donation. There is a single US grant (the National Living Donor Assistance Center—NLDAC) to cover live donor travel costs. Although there may be center‐specific variability in grant utilization, prospective donors—and their intended recipients—must also meet eligibility criteria. In fact, the NLDAC grant is used by <10% of US live donors annually. We studied 154 consecutive kidney donor clinic evaluations (November 1, 2014‐August 30, 2015) to determine eligibility and usage patterns during the evaluation process. Of these, 63 (41%) were local, had travel benefits, or declined. Of the remaining 91 prospective donors who might have benefited from grant support, only 29 (32%) obtained the grant. The other 62 (68%) did not meet eligibility screening. The major reason prospective donors were ineligible was that the recipient's household income was outside the required means test (ie, >300% of the federal poverty level) (n=51; 82%). The remaining exclusions (n=11; 18%) included being a nondirected donor, not meeting residency requirements, and “other.” Expanding NLDAC eligibility criteria—by broadening the recipient means test or by taking steps to eliminate it from the NLDAC charter—would reduce financial burdens associated with live donation.
Higher dose of CD34+ peripheral blood stem cells is associated with better survival after haploidentical stem cell transplantation in pediatric patients
Authors: Chen Yao , Xu Lan‐Ping , Liu Kai‐Yan , Chen Huan , Chen Yu‐Hong , Zhang Xiao‐Hui , Wang Yu , Wang Feng‐Rong , Han Wei , Wang Jing‐Zhi , Yan Chen‐Hua , Huang Xiao‐Jun
Published: November 2016

Haploidentical stem cell transplantation (SCT) is increasingly used to treat pediatric patients with malignant or nonmalignant hematological disorders. The CD34+ dose of bone marrow or peripheral blood stem cells (PBSCs) has been shown to be an important determinant of the transplant outcome in adults under various preparative regimens. However, knowledge of the effect of the CD34+ dose in pediatric haploidentical SCT is limited. We analyzed the data of 348 pediatric patients (aged 2‐18 years) with acute or chronic leukemia, myelodysplastic syndrome (MDS), and other hematological disorders that received a transplant between 2002 and 2012. The results of multivariate analysis showed that PBSC CD34+ counts greater than 1.01 × 106 kg−1 improved platelet engraftment, improved overall survival, and reduced nonrelapse mortality. In contrast, a higher PBSC CD34+ dose did not affect the incidence of acute or chronic graft‐versus‐host disease, including engraftment syndrome. These data suggest that a PBSC CD34+ dose greater than 1.01 × 106 kg−1 is optimal for pediatric haploidentical SCT.
Understanding leisure preferences of young people with cerebral palsy
Authors: Copley Jodie
Published: November 2016

This commentary is on the original article by Imms et al. on pages 380–387 of this issue.
Novel hepato‐preferential basal insulin peglispro (BIL) does not differentially affect insulin sensitivity compared with insulin glargine in patients with type 1 and type 2 diabetes
Authors: Porksen Niels , Linnebjerg Helle , Garhyan Parag , Lam Eric C. Q. , Knadler Mary P. , Jacober Scott J. , Hoevelmann Ulrike , Plum‐Moerschel Leona , Watkins Elaine , Gastaldelli Amalia , Heise Tim
Published: November 2016

Aims

Basal insulin peglispro (BIL) is a novel PEGylated basal insulin with a flat pharmacokinetic and glucodynamic profile and reduced peripheral effects, which results in a hepato‐preferential action. In Phase 3 trials, patients with T1DM treated with BIL had lower prandial insulin requirements, yet improved prandial glucose control, relative to insulin glargine (GL). We hypothesized that this may be because of an enhanced sensitivity to prandial insulin with BIL resulting from lower chronic peripheral insulin action.

Materials and methods

Two open‐label, randomized, 2‐period crossover clinical studies were conducted in 28 patients with T1DM and 24 patients with T2DM. In each study period, patients received once‐daily, individualized, stable, subcutaneous doses of BIL or GL for 5 weeks before a euglycaemic 2‐step hyperinsulinemic clamp procedure (with [6,6‐
2H2
]‐glucose in 12 of the patients with T1DM). M‐values were derived from the clamp procedure for all patients, with rate of glucose appearance (Ra) and disappearance (Rd) and insulin sensitivity index (SI) determined from the clamps with [6,6‐
2H2
]‐glucose.

Results

There were no statistically significant differences between BIL and GL in key measures of hepatic (% Ra suppression during the low‐dose insulin infusion; 78.7% with BIL, 81.8% with GL) or peripheral (M‐value and M/I during the high‐dose insulin infusion, Rd and SI) insulin sensitivity in patients with T1DM or T2DM.

Conclusions

The need to reduce prandial insulin observed with BIL during phase 3 trials cannot be explained by the differential effects of BIL and GL on sensitivity to prandial insulin in either T1DM or T2DM.
Randomized, double‐blind, phase III study to evaluate the efficacy and safety of once‐daily treatment with alogliptin and metformin hydrochloride in Japanese patients with type 2 diabetes
Authors: Kaku Kohei , Sumino Shuuji , Katou Masafumi , Nishiyama Yuya , Kinugawa Yoshinobu
Published: November 2016

This randomized, double‐blind, phase III study evaluated the efficacy and safety of once‐daily treatment with alogliptin (25 mg once daily), alone or with metformin hydrochloride (500 mg once daily or 250 mg twice daily), in Japanese patients with type 2 diabetes. The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline to the end of treatment (week 24). The least squares (LS) mean (standard error) change in HbA1c from baseline to the end of treatment (week 24) was 0.16 (0.072)% in alogliptin alone, −0.49 (0.049)% in alogliptin/metformin once daily, and −0.60 (0.049)% in alogliptin/metformin twice daily. The LS mean difference in HbA1c change from baseline between alogliptin/metformin once daily and alogliptin alone (alogliptin/metformin once daily minus alogliptin alone) was −0.65% (95% confidence interval [CI] −0.821, −0.480) and between alogliptin/metformin once daily and twice daily (once daily minus twice daily) was 0.11% (95% CI −0.026, 0.247). The overall frequency of adverse events was similar among the groups. This study showed that the efficacy of alogliptin/metformin once daily was superior to alogliptin alone and non‐inferior to alogliptin/metformin twice daily, and that alogliptin/metformin once daily was safe and well tolerated in Japanese patients with type 2 diabetes.
Quarantine host range testing of Pseudophilothrips ichini, a potential biological control agent of Brazilian peppertree, Schinus terebinthifolia, in North America and Hawaii
Authors: Wheeler Gregory S. , Manrique Veronica , Overholt William A. , McKay Fernando , Dyer Kirsten
Published: November 2016

Brazilian peppertree, Schinus terebinthifolia Raddi (Anacardiaceae), is an invasive weed of natural and agricultural areas of Florida, Hawaii, and Texas (USA). Biological control presents an environmentally safe and cost‐effective control method for invasive populations of this weed. Though many potential agents have been tested for specificity, nearly all have been rejected due to a broad host range. However, one species, a thrips Pseudophilothrips ichini (Hood) (Thysanoptera: Phlaeothripidae), shows promise from field observations and quarantine host range tests. A series of no‐choice, choice, and multiple‐generation tests was conducted on 127 plant taxa (including five mango and four pistachio varieties) from 45 families and 33 orders. In no‐choice starvation tests, the thrips fed and produced offspring on the target weed (124 F1 adults per plant), whereas no or few (<4 F1 adults per plant) were obtained on non‐target species. The primary exception was another exotic invasive tree Schinus molle L., on which an average 20 F1 thrips adults were produced. No‐choice tests indicated that small numbers of F1 offspring were produced on nine other non‐target plant species. The numbers of F1 offspring produced on these plants were <3% of those produced on the target weed. In choice tests, on average two or fewer F1 adults were produced on four non‐target species tested, compared with 64 F1 adults on the target weed. Multiple‐generation tests indicated that three generations of thrips were maintained only on the target weed and S. molle with no differences between these two plant species or across generations. Thus, this thrips species has a narrow host range that includes the two invasive Schinus spp. tested here. If released, the thrips P. ichini will constitute safe and potentially effective biological control of Brazilian peppertree in North America and Hawaii.
A false‐positive food chain error associated with a generic predator gut content ELISA
Authors: Hagler James R.
Published: November 2016

Conventional prey‐specific gut content ELISA (enzyme‐linked immunosorbent assay) and PCR (polymerase chain reaction) assays are useful for identifying predators of insect pests in nature. However, these assays are prone to yielding certain types of food chain errors. For instance, it is possible that prey remains can pass through the food chain as the result of a secondary predator (hyperpredator) consuming a primary predator that had previously consumed the pest. If so, the pest‐specific assay will falsely identify the secondary predator as the organism providing the biological control services to the ecosystem. Recently, a generic gut content ELISA was designed to detect protein‐marked prey remains. That assay proved to be less costly, more versatile, and more reliable at detecting primary predation events than a prey‐specific PCR assay. This study examines the chances of obtaining a ‘false positive’ food chain error with the generic ELISA. Data revealed that the ELISA was 100% accurate at detecting protein‐marked Lygus hesperus Knight (Hemiptera: Miridae) remains in the guts of two (true) primary predators, Hippodamia convergens Guérin‐Méneville (Coleoptera: Coccinellidae) and Collops vittatus (Say) (Coleoptera: Melyridae). However, there was also a high frequency (70%) false positives associated with hyperpredators, Zelus renardii Kolenati (Hemiptera: Reduviidae), that consumed a primary predator that possessed protein‐marked L. hesperus in its gut. These findings serve to alert researchers that the generic ELISA, like the PCR assay, is susceptible to food chain errors.
Isotopic fractionation with morphological change and sexual specificity in the lappet moth Euthrix potatoria
Authors: Sato Nozomu , Azuma Nobuyuki
Published: November 2016

The δ15N values of adult holometabolous insects exceed those of larvae, but otherwise little information on terrestrial invertebrates has been obtained in food‐web analyses using stable isotope ratios (δ15N, δ13C). Changes in δ13C during metamorphosis and differences between males and females have not been examined. We collected the larvae and cocoons of Euthrix potatoria (L.) (Lepidoptera: Lasiocampidae) in the field and used them to assess the species’ isotopic fractionation. Each emerged moth was divided into five body parts. We conducted stable N and C isotope analyses for each body part, as well as for cocoons and exuviae, and also compared stable isotope ratios between sexes. We confirmed δ15N enrichment through metamorphosis and estimated that δ15N enrichment is accomplished by the relative concentration of 15N due to the excretion of copious meconium, which contains abundant 14N. We also observed changes in δ13C values through metamorphosis. Both isotope values tended to change more in males than in females. The proportion of the whole‐adult weight represented by meconium was higher in males than in females, suggesting that high meconium secretion in males contributes to the sexual difference in δ15N. These phenomena may be common in Holometabola, which require a pupal stage. For more accurate food‐web assessments, it is important to consider stable isotope changes during different life cycles, as well as sexual differences.
Changes in visibility as a function of spatial frequency and microsaccade occurrence
Authors: Costela Francisco M. , McCamy Michael B. , Coffelt Mary , Otero‐Millan Jorge , Macknik Stephen L. , Martinez‐Conde Susana
Published: November 2016

Fixational eye movements (FEMs), including microsaccades, drift, and tremor, shift our eye position during ocular fixation, producing retinal motion that is thought to help visibility by counteracting neural adaptation to unchanging stimulation. Yet, how each FEM type influences this process is still debated. Recent studies found little to no relationship between microsaccades and visual perception of spatial frequencies (SF). However, these conclusions were based on coarse analyses that make it hard to appreciate the actual effects of microsaccades on target visibility as a function of SF. Thus, how microsaccades contribute to the visibility of stimuli of different SFs remains unclear. Here, we asked how the visibility of targets of various SFs changed over time, in relationship with concurrent microsaccade production. Participants continuously reported on changes in target visibility, allowing us to time‐lock ongoing changes in microsaccade parameters to perceptual transitions in visibility. Microsaccades restored/increased the visibility of low SF targets more efficiently than that of high SF targets. Yet, microsaccade rates rose before periods of increased visibility, and dropped before periods of diminished visibility, for all the SFs tested, suggesting that microsaccades boosted target visibility across a wide range of SFs. Our data also indicate that visual stimuli fade/become harder to see less often in the presence of microsaccades. In addition, larger microsaccades restored/increased target visibility more effectively than smaller microsaccades. These combined results support the proposal that microsaccades enhance visibility across a broad variety of SFs.
Phenomenological vs. biophysical models of thermal stress in aquatic eggs
Authors: Martin Benjamin T. , Pike Andrew , John Sara N. , Hamda Natnael , Roberts Jason , Lindley Steven T. , Danner Eric M.
Published: November 2016

Predicting species responses to climate change is a central challenge in ecology. These predictions are often based on lab‐derived phenomenological relationships between temperature and fitness metrics. We tested one of these relationships using the embryonic stage of a Chinook salmon population. We parameterised the model with laboratory data, applied it to predict survival in the field, and found that it significantly underestimated field‐derived estimates of thermal mortality. We used a biophysical model based on mass transfer theory to show that the discrepancy was due to the differences in water flow velocities between the lab and the field. This mechanistic approach provides testable predictions for how the thermal tolerance of embryos depends on egg size and flow velocity of the surrounding water. We found support for these predictions across more than 180 fish species, suggesting that flow and temperature mediated oxygen limitation is a general mechanism underlying the thermal tolerance of embryos.
Normal ‘heart’ in Parkinson's disease: is this a distinct clinical phenotype?
Authors: Kim J.‐S. , Park H.‐E. , Park I.‐S. , Oh Y.‐S. , Ryu D.‐W. , Song I.‐U. , Jung Y.‐A. , Yoo I. R. , Choi H.‐S. , Lee P. H. , Lee K.‐S.
Published: November 2016

Background and purpose

Reduction of metaiodobenzylguanidine (MIBG) uptake has been observed in almost all patients with Parkinson's disease (PD), associated with hyposmia, orthostatic hypotension and rapid eye movement sleep behavioral disorder (RBD). In contrast, a subgroup of patients with PD with normal MIBG uptake have been reported to have milder disease and preserved cognition compared with those with lower MIBG. The aim of this study was to investigate whether non‐motor manifestations of PD differ between patients with normal and abnormal myocardial MIBG uptake.

Methods

Among 160 de‐novo cases of PD, 44 had normal MIBG uptake. Twelve candidate non‐motor features were evaluated using questionnaires and laboratory tests.

Results

Patients with decreased MIBG uptake had more constipation, RBD, cognitive impairment, hyposmia and orthostatic hypotension than did those with normal MIBG uptake. On linear regression analysis, orthostatic hypotension, olfactory function and probable RBD were significantly associated with MIBG uptake in PD. The principal component analysis showed that the group with normal MIBG was not associated with non‐motor impairments.

Conclusions

These results suggest that patients with PD with normal MIBG scans have a relatively low disease burden compared with those with abnormal MIBG. Fewer synuclein pathologies in the myocardia and sympathetic ganglia in PD with preserved MIBG uptake might be associated with lower threshold patterns of Braak synuclein pathology for non‐motor manifestations compared with PD with decreased MIBG.
Identifying the epileptogenic zone in interictal resting‐stateMEGsource‐space networks
Authors: Nissen Ida A. , Stam Cornelis J. , Reijneveld Jaap C. , van Straaten Ilse E. C. W. , Hendriks Eef J. , Baayen Johannes C. , De Witt Hamer Philip C. , Idema Sander , Hillebrand Arjan
Published: November 2016

Objective

In one third of patients, seizures remain after epilepsy surgery, meaning that improved preoperative evaluation methods are needed to identify the epileptogenic zone. A potential framework for such a method is network theory, as it can be applied to noninvasive recordings, even in the absence of epileptiform activity. Our aim was to identify the epileptogenic zone on the basis of hub status of local brain areas in interictal magnetoencephalography (MEG) networks.

Methods

Preoperative eyes‐closed resting‐stateMEGrecordings were retrospectively analyzed in 22 patients with refractory epilepsy, of whom 14 were seizure‐free 1 year after surgery. Beamformer‐based time series were reconstructed for 90 cortical and subcortical automated anatomic labeling (AAL) regions of interest (ROIs). Broadband functional connectivity was estimated using the phase lag index in artifact‐free epochs without interictal epileptiform abnormalities. A minimum spanning tree was generated to represent the network, and the hub status of eachROIwas calculated using betweenness centrality, which indicates the centrality of a node in a network. The correspondence of resection cavity to hub values was evaluated on four levels: resection cavity, lobar, hemisphere, and temporal versus extratemporal areas.

Results

Hubs were localized within the resection cavity in 8 of 14 seizure‐free patients and in zero of 8 patients who were not seizure‐free (57% sensitivity, 100% specificity, 73% accuracy). Hubs were localized in the lobe of resection in 9 of 14 seizure‐free patients and in zero of 8 patients who were not seizure‐free (64% sensitivity, 100% specificity, 77% accuracy). For the other two levels, the true negatives are unknown; hence, only sensitivity could be determined: hubs coincided with both the resection hemisphere and the resection location (temporal versus extratemporal) in 11 of 14 seizure‐free patients (79% sensitivity).

Significance

Identifying hubs noninvasively before surgery is a valuable approach with the potential of indicating the epileptogenic zone in patients without interictal abnormalities.
A novel c132‐134del mutation in Unverricht‐Lundborg disease and the review of literature of heterozygous compound patients
Authors: Assenza Giovanni , Benvenga Antonella , Gennaro Elena , Tombini Mario , Campana Chiara , Assenza Federica , Di Pino Giovanni , Di Lazzaro Vincenzo
Published: November 2016

Unverricht‐Lundborg disease or progressive myoclonic epilepsy type 1 (EPM1) is an autosomal recessive disease caused by mutation of the cystatin B gene (CSTB), located on chromosome 21q22.3. The most common mutation is an expansion of unstable dodecamer repetition (CCCCGCCCCGCG), whereas other types of mutations are rare. Among these, heterozygous compound mutations are described to induce a more severe phenotype than that of homozygous dodecameric repetition. We report two siblings affected by heterozygous compound mutations carrying a novel mutation of the deletion of three nucleotides in exon 2 of the gene in position 132–134 of the coding sequence (c.132‐134del) in the allele not including the dodecamer repetition. This mutation results in the loss of two amino acid residues and insertion of an asparagine in position 44 (p.Lys44_Ser45delinsAsn). Our patients presented a very different clinical picture. The male patient had a severe myoclonus, drug‐resistant epilepsy and psychiatric comorbidity, while his affected sister had only very rare seizures and sporadic myoclonic jerks at awakening. The revision of literature about heterozygous compound EPM1 patients confirms this gender phenotypic expressivity, with female patients carrying less severe symptoms than male patients. These data lead to the hypothesis of complex gender‐specific factors interacting with CSTB expressivity in EPM1 patients.
EMILIN3, an extracellular matrix molecule with restricted distribution in skin
Authors: Corallo Diana , Schiavinato Alvise , Bizzotto Dario , Milanetto Martina , Guljelmovic Marija , Keene Douglas R. , Sengle Gerhard , Braghetta Paola , Bonaldo Paolo
Published: November 2016

EMILIN3 is an extracellular matrix glycoprotein that displays a dynamic and restricted expression pattern in connective tissues during post‐natal life. In this study, we report the characterization of EMILIN3 deposition in the skin. In addition, to unravel the functions of this protein in skin homeostasis, we generated Emilin3 null mice and provide evidence that EMILIN3 is dispensable for hair follicle growth and maintenance throughout adult life.
SVEP1 plays a crucial role in epidermal differentiation
Authors: Samuelov Liat , Li Qiaoli , Bochner Ron , Najor Nicole A. , Albrecht Lauren , Malchin Natalia , Goldsmith Tomer , Grafi‐Cohen Meital , Vodo Dan , Fainberg Gilad , Meilik Benjamin , Goldberg Ilan , Warshauer Emily , Rogers Tova , Edie Sarah , Ishida‐Yamamoto Akemi , Burzenski Lisa , Erez Noam , Murray Steve A. , Irvine Alan D. , Shultz Lenny , Green Kathleen J. , Uitto Jouni , Sprecher Eli , Sarig Ofer
Published: November 2016

SVEP1 is a recently identified multidomain cell adhesion protein, homologous to the mouse polydom protein, which has been shown to mediate cell‐cell adhesion in an integrin‐dependent manner in osteogenic cells. In this study, we characterized SVEP1 function in the epidermis. SVEP1 was found by qRT‐PCR to be ubiquitously expressed in human tissues, including the skin. Confocal microscopy revealed that SVEP1 is normally mostly expressed in the cytoplasm of basal and suprabasal epidermal cells. Downregulation of SVEP1 expression in primary keratinocytes resulted in decreased expression of major epidermal differentiation markers. Similarly, SVEP1 downregulation was associated with disturbed differentiation and marked epidermal acanthosis in three‐dimensional skin equivalents. In contrast, the dispase assay failed to demonstrate significant differences in adhesion between keratinocytes expressing normal vs low levels of SVEP1. Homozygous Svep1 knockout mice were embryonic lethal. Thus, to assess the importance of SVEP1 for normal skin homoeostasis in vivo, we downregulated SVEP1 in zebrafish embryos with a Svep1‐specific splice morpholino. Scanning electron microscopy revealed a rugged epidermis with perturbed microridge formation in the centre of the keratinocytes of morphant larvae. Transmission electron microscopy analysis demonstrated abnormal epidermal cell‐cell adhesion with disadhesion between cells in Svep1‐deficient morphant larvae compared to controls. In summary, our results indicate that SVEP1 plays a critical role during epidermal differentiation.
Towards a bacterial treatment for armpit malodour
Authors: Callewaert Chris , Lambert Jo , Van de Wiele Tom
Published: November 2016

Axillary malodour is a frustrating condition for many people. It can lead to significant discomforts and various psychological effects. The underarm microbiome plays a major role in axillary malodour formation. Not only the bacteria on the epidermis, but also and especially those living in the sweat glands, sweat pores and hair follicles play a pivotal role in malodour development. To treat underarm malodour, this viewpoint article envisions a bacterial treatment. Replacing the autochthonous malodour‐causing microbiome with a non‐odour‐causing microbiome, through an armpit bacterial transplantation or direct application of probiotics/non‐odour‐causing bacteria, could resolve the condition. Selective steering of the microbiome with prebiotics, biochemicals or plant extracts can likewise greatly help in improving the underarm odour. Elimination/inhibition of the “bad bugs” and application/stimulation of the “good bugs” will be part of the future treatment for axillary body odour.
Do invasive alien plants benefit more from global environmental change than native plants?
Authors: Liu Yanjie , Oduor Ayub M. O. , Zhang Zhen , Manea Anthony , Tooth Ifeanna M. , Leishman Michelle R. , Xu Xingliang , van Kleunen Mark
Published: November 2016

Invasive alien plant species threaten native biodiversity, disrupt ecosystem functions and can cause large economic damage. Plant invasions have been predicted to further increase under ongoing global environmental change. Numerous case studies have compared the performance of invasive and native plant species in response to global environmental change components (i.e. changes in mean levels of precipitation, temperature, atmosphericCO2concentration or nitrogen deposition). Individually, these studies usually involve low numbers of species and therefore the results cannot be generalized. Therefore, we performed a phylogenetically controlled meta‐analysis to assess whether there is a general pattern of differences in invasive and native plant performance under each component of global environmental change. We compiled a database of studies that reported performance measures for 74 invasive alien plant species and 117 native plant species in response to one of the above‐mentioned global environmental change components. We found that elevated temperature andCO2enrichment increased the performance of invasive alien plants more strongly than was the case for native plants. Invasive alien plants tended to also have a slightly stronger positive response to increased N deposition and increased precipitation than native plants, but these differences were not significant (N deposition:P = 0.051; increased precipitation:P = 0.679). Invasive alien plants tended to have a slightly stronger negative response to decreased precipitation than native plants, although this difference was also not significant (P = 0.060). So while drought could potentially reduce plant invasion, increases in the four other components of global environmental change considered, particularly global warming and atmosphericCO2enrichment, may further increase the spread of invasive plants in the future.
Effects of seasonality, transport pathway, and spatial structure on greenhouse gas fluxes in a restored wetland
Authors: McNicol Gavin , Sturtevant Cove S. , Knox Sara H. , Dronova Iryna , Baldocchi Dennis D. , Silver Whendee L.
Published: November 2016

Wetlands can influence global climate via greenhouse gas (GHG) exchange of carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O). Few studies have quantified the full GHG budget of wetlands due to the high spatial and temporal variability of fluxes. We report annual open‐water diffusion and ebullition fluxes of CO2, CH4, and N2O from a restored emergent marsh ecosystem. We combined these data with concurrent eddy‐covariance measurements of whole‐ecosystem CO2 and CH4 exchange to estimate GHG fluxes and associated radiative forcing effects for the whole wetland, and separately for open‐water and vegetated cover types. Annual open‐water CO2, CH4, and N2O emissions were 915 ± 95 g C‐CO2 m−2 yr−1, 2.9 ± 0.5 g C‐CH4 m−2 yr−1, and 62 ± 17 mg N‐N2O m−2 yr−1, respectively. Diffusion dominated open‐water GHG transport, accounting for >99% of CO2 and N2O emissions, and ~71% of CH4 emissions. Seasonality was minor for CO2 emissions, whereas CH4 and N2O fluxes displayed strong and asynchronous seasonal dynamics. Notably, the overall radiative forcing of open‐water fluxes (3.5 ± 0.3 kg CO2‐eq m−2 yr−1) exceeded that of vegetated zones (1.4 ± 0.4 kg CO2‐eq m−2 yr−1) due to high ecosystem respiration. After scaling results to the entire wetland using object‐based cover classification of remote sensing imagery, net uptake of CO2 (−1.4 ± 0.6 kt CO2‐eq yr−1) did not offset CH4 emission (3.7 ± 0.03 kt CO2‐eq yr−1), producing an overall positive radiative forcing effect of 2.4 ± 0.3 kt CO2‐eq yr−1. These results demonstrate clear effects of seasonality, spatial structure, and transport pathway on the magnitude and composition of wetland GHG emissions, and the efficacy of multiscale flux measurement to overcome challenges of wetland heterogeneity.
Extended half‐life pegylated, full‐length recombinant factor VIII for prophylaxis in children with severe haemophilia A
Authors: Mullins E. S. , Stasyshyn O. , Alvarez‐Román M. T. , Osman D. , Liesner R. , Engl W. , Sharkhawy M. , Abbuehl B. E.
Published: November 2016

Introduction

Primary factor VIII (FVIII) prophylaxis is the optimal treatment in children with severe haemophilia A. They are expected to benefit from extended half‐life (T1/2) FVIII coverage by reduced infusion frequency while maintaining haemostatic efficacy.

Aims

To determine immunogenicity, pharmacokinetics (PK), efficacy, safety and quality of life of prophylaxis with a polyethylene glycol (peg)‐ylated FVIII (BAX 855) based on full‐length recombinant FVIII (ADVATE) in paediatric previously treated patients (PTPs) with severe haemophilia A.

Methods

PTPs <12 years without history of FVIII inhibitors received twice‐weekly infusions of 50 ± 10 IU kg−1 BAX 855 for ≥50 exposure days. Prophylactic dose increases to ≤80 IU kg−1 were allowed under predefined conditions. PK was evaluated after single infusions of 60 ± 5 IU kg−1.

Results

T1/2 and mean residence time were extended 1.3‐ to 1.5‐fold compared to ADVATE (n = 31), depending on the analysis used. The point estimate for the mean annualized bleeding rate in 66 subjects receiving a median of 1.9 weekly infusions of 51.3 IU kg−1 of BAX 855 each was 3.04 (median 2.0); 1.10 (median 0) for joint and 1.16 (median 0) for spontaneous bleeds. Overall, 38% of subjects had zero bleeds. No bleeds were severe. Haemostatic efficacy was rated excellent or good for 90% of bleeds; 91% were treated with one or two infusions. In 8/14 subjects all target joints resolved. No subject developed FVIII inhibitors or persistent binding antibodies that affected safety or efficacy. No adverse reactions occurred.

Conclusion

Twice‐weekly prophylaxis with BAX 855 was safe and efficacious in paediatric PTPs with severe haemophilia A.
Pathological Findings of NASH and NAFLD
Authors:   Working Group*,   Association of Pathologists** for Guidebook of NASH and NAFLD, 2015: The Japan Society of Hepatology
Published: November 2016

Nonalcoholic fatty liver disease (NAFLD) is an increasingly common chronic liver disease worldwide. NAFLD comprises a variety of clinical and histopathological changes that can be broadly divided into nonalcoholic fatty liver (NAFL, simple steatosis) and nonalcoholic steatohepatitis (NASH). The differential diagnosis between NAFL and NASH is important because NASH is a more advanced form. This diagnosis therefore determines the prognosis and therapeutic management. At present the interpretation of NASH is made based on the histopathological features of steatohepatitis, i.e. ‘steatosis’, ‘lobular inflammation’, hepatocyte ‘ballooning, ‘Mallory‐Denk bodies’ and ‘fibrosis’.

Here, we summarize the pathological findings guidelines for NASH as it was already published in 2015 in Japanese in the clinical guidebook organized by the Japan Society of Hepatology.
IgG4‐related disease—experience of 100 consecutive cases from a specialist centre
Authors: Bateman Adrian C , Culver Emma L
Published: November 2016

Aims

To describe the features of 100 consecutive cases referred to a single UK institution in which a diagnosis of IgG4‐related disease (IgG4‐RD) was under consideration.

Methods and results

The histological features were reviewed by a single histopathologist, and cases were categorized according to the 2012 Boston criteria: Category 1—histologically highly suggestive of IgG4‐RD; Category 2—probable histopathological features of IgG4‐RD; and Category 3—insufficient histopathological evidence of IgG4‐RD. A ‘global assessment’ was performed with the available clinical information: Assessment group 1—’definite/very likely IgG4‐RD’; Assessment group 2—’possible IgG4‐RD’; Assessment group 3—’not IgG4‐RD’; and Assessment group 4—insufficient information. The mean IgG4+ plasma cell count and IgG4+/IgG+ ratio were highest in Category 1 [134/high‐power field (HPF); 57%] and Assessment group 1 (113/HPF; 52%), and lowest in Category 3 (11/HPF; 18%) and Assessment group 3 (43/HPF; 31%) (Category comparison of IgG4+ count and ratio, both P < 0.001; Assessment group comparison of IgG4+ count, P < 0.0002; and Assessment group comparison of ratio, P = 0.04). A non‐IgG4‐RD diagnosis was rare in Category 1 (7%) but common in Category 2 (60%) and Category 3 (47%). Stromal reactions to neoplasia and chronic oral ulceration were simulants of IgG4‐RD.

Conclusions

The Boston criteria are linked to the likelihood of IgG4‐RD. Other conditions may show some histological features of IgG4‐RD. The likelihood of IgG4‐RD is much greater when the histological features reach the threshold for Category 1 than when they reach the thresholds for Categories 2 and 3. Despite the utility of the Boston criteria, this study highlights the crucial importance of careful clinicopathological correlation when a diagnosis of IgG4‐RD is under consideration.
Load profiles and flexibility in operation of washing machines and dishwashers in Europe
Authors: Stamminger Rainer , Schmitz Angelika
Published: November 2016

While the energy generation system is changing towards the use of more renewable energies, the problem of how to deal with fluctuating energy supply is increasing. Smart appliances in households are often referenced as one possible solution, as their operation may be shifted in time and, thus, used to balance an unstable energy supply. The potential of such appliances has been studied to date mainly in pilot installations with a very limited number of participants or by making assumptions on what might be possible. With this work, a semi‐representative approach for 12 European countries was used to assess actual consumer habits for the use of washing machines and dishwashers which then could be used to calculate average load profiles for those appliances depending on the time of the day. Using these profiles, it is strait forward to calculate how much load may be shifted by those appliances in a demand response application. This allows aggregators or energy utilities to assign clear financial benefits to the shifting potential of those appliances. Consumers use the shifting of appliance operation already today for various reasons. Investigating these reasons allows to learn already a lot about the flexibility of consumers.
Nitric oxide and pH modulation in gynaecological cancer
Authors: Sanhueza Carlos , Araos Joaquín , Naranjo Luciano , Barros Eric , Subiabre Mario , Toledo Fernando , Gutiérrez Jaime , Chiarello Delia I. , Pardo Fabián , Leiva Andrea , Sobrevia Luis
Published: November 2016

Nitric oxide plays several roles in cellular physiology, including control of the vascular tone and defence against pathogen infection. Neuronal, inducible and endothelial nitric oxide synthase (NOS) isoforms synthesize nitric oxide. Cells generate acid and base equivalents, whose physiological intracellular concentrations are kept due to membrane transport systems, including Na+/H+ exchangers and Na+/HCO3− transporters, thus maintaining a physiological pH at the intracellular (~7.0) and extracellular (~7.4) medium. In several pathologies, including cancer, cells are exposed to an extracellular acidic microenvironment, and the role for these membrane transport mechanisms in this phenomenon is likely. As altered NOS expression and activity is seen in cancer cells and because this gas promotes a glycolytic phenotype leading to extracellular acidosis in gynaecological cancer cells, a pro‐inflammatory microenvironment increasing inducible NOS expression in this cell type is feasible. However, whether abnormal control of intracellular and extracellular pH by cancer cells regards with their ability to synthesize or respond to nitric oxide is unknown. We, here, discuss a potential link between pH alterations, pH controlling membrane transport systems and NOS function. We propose a potential association between inducible NOS induction and Na+/H+ exchanger expression and activity in human ovary cancer. A potentiation between nitric oxide generation and the maintenance of a low extracellular pH (i.e. acidic) is proposed to establish a sequence of events in ovarian cancer cells, thus preserving a pro‐proliferative acidic tumour extracellular microenvironment. We suggest that pharmacological therapeutic targeting of Na+/H+ exchangers and inducible NOS may have benefits in human epithelial ovarian cancer.