bluuebunny/crossref_metadata_2025 huggingface dataset:
Multimodal skin lesion classification using deep learning
Authors: Yap Jordan , Yolland William , Tschandl Philipp
Published: September 2018

While convolutional neural networks (CNNs) have successfully been applied for skin lesion classification, previous studies have generally considered only a single clinical/macroscopic image and output a binary decision. In this work, we have presented a method which combines multiple imaging modalities together with patient metadata to improve the performance of automated skin lesion diagnosis. We evaluated our method on a binary classification task for comparison with previous studies as well as a five class classification task representative of a real‐world clinical scenario. We showed that our multimodal classifier outperforms a baseline classifier that only uses a single macroscopic image in both binary melanoma detection (AUC 0.866 vs 0.784) and in multiclass classification (mAP 0.729 vs 0.598). In addition, we have quantitatively showed the automated diagnosis of skin lesions using dermatoscopic images obtains a higher performance when compared to using macroscopic images. We performed experiments on a new data set of 2917 cases where each case contains a dermatoscopic image, macroscopic image and patient metadata.
Remote sensing restores predictability of ectotherm body temperature in the world’s forests
Authors: Algar Adam C. , Morley Kate , Boyd Doreen S.
Published: September 2018

Aim

Rising global temperatures are predicted to increase ectotherms’ body temperatures, benefitting some species but threatening others. Biophysical models predict a key role for shade in buffering these effects, but the difficulty of measuring shade across broad spatial extents limits predictions of ectotherms’ thermal futures at the global scale. Here, we extend biophysical models of ectotherm body temperature to include effects of forest canopy shade, via leaf area index, and test whether considering remotely‐sensed canopy density improves predictions of body temperature variation in heavily shaded habitats.

Location

Worldwide.

Time period

1990–2010.

Major taxa studied

Lizards.

Methods

We test predictions from biophysical ecological theory for how body temperature should vary with microclimate for 269 lizard populations across open, semi‐open and closed habitats worldwide. We extend existing biophysical models to incorporate canopy shade effects via leaf area index, test whether body temperature varies with canopy density as predicted by theory, and evaluate the extent to which incorporating canopy density improves model performance in heavily shaded areas.

Results

We find that body temperatures in open habitats, like deserts, vary with air temperature and incident solar radiation as predicted by biophysical equations, but these relationships break down in forests, where body temperatures become unpredictable. Incorporating leaf area index into our models revealed lower body temperatures in more heavily shaded environments, restoring the predictability of body temperature in forests.

Conclusions

Although biophysical ecological theory can predict ectotherm body temperature in open habitats, like deserts, these relationships decay in closed forests. Models incorporating remotely‐sensed data on canopy density improved predictability of body temperatures in these habitats, providing an avenue to incorporate canopy shade effects into predictions of animals’ vulnerability to climate change. These results highlight the thermal threat of changes in canopy structure and loss of forest cover for the world's ectotherms.
Consumer acceptance of delivery drones in urban areas
Authors: Khan Rabeel , Tausif Sadaf , Javed Malik Ahmed
Published: September 2018

The concept of drone usage for commercial purposes by retailers worldwide is still in its early stages, and unheard of in Pakistan. Moreover, research on consumer perceptions regarding commercial drones in Pakistan and around the world is very sparse. The purpose of this paper is to gauge the level of acceptability and concerns Pakistani consumers may have in accepting the drone delivery technology. This study offers new insights that retailers and delivery companies can use to penetrate target markets in early stages. The authors have executed a quantitative analysis through the means of a survey. A sample of middle‐ and upper class residents of two cities in Pakistan was selected on which purposive sampling technique was applied. A total of 307 responses were collected and these responses were analysed in SPSS. Various analysis techniques were applied including Cronbach’s alpha, the Pearson correlation analysis, regression analysis and cluster analysis. The results show that consumers in Pakistan perceive privacy issues as a primary concern in relation to drone delivery. The results also throw light on the profile of consumer segments that can be targeted by retailers who may desire to use the drone delivery technology in the near future. Using these findings, retailers using the drone delivery mechanism can address consumer’s fears and ambiguities. Retailers can resolve consumer concerns by designing pro‐privacy parameters in the initial service design stage and the infrastructure deployment of drones.
Teaching and Learning Tips 12: Peer observation of teaching
Authors: Shi Connie R. , Nguyen Michael O. , Rana Jasmine , Burgin Susan
Published: September 2018

Challenge: How can clinical teachers continually improve their teaching skills? In addition to student feedback, peer and expert opinion can also provide valuable formative and evaluative feedback to guide self‐improvement efforts. Here, we discuss ways to structure peer observation of teaching in dermatological settings and offer tips on how to optimize the learning experience for both the educator and peer observer.
Temperature and humidity affect the incidence of hand, foot, and mouth disease: a systematic review of the literature – a report from the International Society of Dermatology Climate Change Committee
Authors: Coates Sarah J. , Davis Mark D. P. , Andersen Louise K.
Published: September 2018

Hand, foot, and mouth disease (HFMD) is an enterovirus‐mediated condition that predominantly affects children under 5 years of age. The tendency for outbreaks to peak in warmer summer months suggests a relationship between HFMD and weather patterns. We reviewed the English‐language literature for articles describing a relationship between meteorological variables and HFMD. Seventy‐two studies meeting criteria were identified. A positive, statistically significant relationship was identified between HFMD cases and both temperature (61 of 67 studies, or 91.0%, reported a positive relationship) [CI 81.8–95.8%, P = 0.0001] and relative humidity (41 of 54 studies, or 75.9%) [CI 63.1–85.4%, P = 0.0001]. No significant relationship was identified between HFMD and precipitation, wind speed, and/or sunshine. Most countries reported a single peak of disease each year (most commonly early Summer), but subtropical and tropical climate zones were significantly more likely to experience a bimodal distribution of cases throughout the year (two peaks a year; most commonly late spring/early summer, with a smaller peak in autumn). The rising global incidence of HFMD, particularly in Pacific Asia, may be related to climate change. Weather forecasting might be used effectively in the future to indicate the risk of HFMD outbreaks and the need for targeted public health interventions.
Lipophilic compounds and thermal behaviour of African mango (Irvingia gabonensis (Aubry‐Lecomte ex. O'Rorke) Baill.) kernel fat
Authors: Lieb Veronika M. , Schuster Laura K. , Schmarr Hans‐Georg , Carle Reinhold , Steingass Christof B.
Published: September 2018

Irvingia gabonensis kernels are a promising oleiferous source. Their total lipid content was 72.3%. C14:0 and C12:0 represented the most abundant fatty acids. Triacylglycerols with ECN 32 and 46–48 were identified for the first time by HPLC‐DAD‐ESI‐MSn. Comprehensive GC‐FID and GC‐MS analyses revealed novel insights into minor lipids like phytosterols and tocochromanols. Among the latter, γ‐tocopherol was found to be the major vitamer. β‐Sitosterol and stigmasterol were the prevailing phytosterols in the kernel fat. The high saturation level of the fat resulted in a sharp differential scanning calorimetry melting curve with a high melting temperature of 42.1 °C. The fat remained solid over a wide temperature range and still contained 66.6% solid fats at 35 °C. Consequently, kernels of the African mango provide a viable source for the recovery of solid fats applicable in the food industry as sustainable alternatives to replace palm‐based fats or hardened vegetable oils.
Childhood obesity, weight loss and developmental trajectories predict the persistence and remission of childhood sleep‐disordered breathing
Authors: Frye S. S. , Fernandez‐Mendoza J. , Calhoun S. L. , Gaines J. , Vgontzas A. N. , Liao D. , Bixler E. O.
Published: September 2018

Background

Obesity has been recognized as a risk factor for childhood sleep‐disordered breathing (SDB), yet it remains unclear how obesity and weight change predict the course of childhood SDB.

Objective

The objective of the study is to investigate the role of body weight, upper airway abnormalities and developmental trajectories on the persistence and remission of childhood SDB in the transition to adolescence.

Methods

The Penn State Child Cohort is a representative population sample of 700 children (5–12 years), of whom 421 were followed up as adolescents (12–23 years). Participants underwent a clinical history, physical examination and polysomnography at both time points.

Results

Obesity and enlarged tonsils were cross‐sectionally associated with childhood SDB. Longitudinally, baseline obesity predicted the persistence of childhood SDB (OR = 3.75, 95% CI = 2.00–7.05), while weight loss predicted its remission (OR = 1.67, 95% CI = 1.11–2.50). Children with enlarged tonsils who remitted from SDB had not experienced significant weight loss and only 4.4% had undergone adeno/tonsillectomy. Body fat distribution/composition at follow‐up was similar in those who had remitted from childhood SDB as compared with those who had never experienced SDB, while those who persisted with childhood SDB showed significant android distribution and visceral adiposity at follow‐up.

Conclusions

Our data support a causal role for obesity and weight loss in the chronicity and remission, respectively, of childhood SDB in the transition to adolescence and suggest that remission of SDB is related to developmental trajectories of the upper airway in a significant proportion of children. Thus, targeting childhood obesity and weight gain should be a priority in the prevention and treatment of SDB during this critical developmental period.
Genomic targeting by recombinase‐mediated cassette exchange in the spotted wing drosophila, Drosophila suzukii
Authors: Schetelig M. F. , Yan Y. , Zhao Y. , Handler A. M.
Published: September 2018

Drosophila suzukii is a significant pest of stone and small fruits. The genome of this species has been sequenced and manipulated by transposon‐mediated transformation and CRISPR/Cas9 gene editing. These technologies open a variety of possibilities for functional genomics and genetic modifications that might improve biologically based population control strategies. Both of these approaches, however, would benefit from genome targeting that would avoid position effects and insertional mutations associated with random transposon vector insertions, and the limited DNA fragment insertion size allowed by gene editing. Here, we describe an efficient recombinase‐mediated cassette exchange (RMCE) system for D. suzukii in which heterospecific lox recombination sites were integrated into the genome by transposon‐mediated transformation and subsequently targeted for double recombination by a donor vector in the presence of Cre recombinase. Three loxN/lox2272 landing site lines have previously been created in D. suzukii, and quantitative PCR determined that polyubiquitin‐regulated enhanced green fluorescent protein expression is least susceptible to position effect suppression in the 443_M26m1 line. We presume that RMCE target sites may also be inserted more specifically into the genome by homology‐directed repair gene editing, thereby avoiding position effects and mutations, while eliminating restrictions on the size of donor constructs for subsequent insertion.
Identifying trade‐offs in equity and efficiency for simultaneously optimizing location and multipriority dispatch of ambulances
Authors: Enayati Shakiba , Mayorga Maria E. , Toro‐Díaz Hector , Albert Laura A.
Published: September 2018

The role of emergency medical service (EMS) systems is to provide acute care and possibly transportation to health care facilities to patients experiencing medical emergencies. Since EMS is a public service, it is natural for the community to expect equitable service from these systems; however, there is not a unique agreement on how to measure equity. Most EMS planning literature focuses solely on measures of efficiency, such as minimizing average response time. Solutions based on optimizing efficiency measures alone can be unacceptable when they are achieved at the expense of some players. Such trade‐offs can be more crucial when it comes to high‐priority emergencies. We provide a multicriteria optimization approach aimed at identifying good solutions for several equity and efficiency measures together, based on a joint modeling approach for location and dispatching policy decisions, while considering multiple levels of call priority. We apply our approach to a real‐world data set. We show that the joint approach provides better solutions than using the common assignment of the closest available ambulance, in particular for the equity criteria. We quantify the trade‐offs between different performance measures, and provide Pareto‐efficient solutions. The proposed joint optimization approach can be used to gain insight about the implicit balance between common efficiency measures and discussed equity criteria, hence providing better information to policy makers and EMS system administrators.
Coordinating the retail supply chain with item‐level RFID and excess inventory under a revenue‐cost‐sharing contract
Authors: Li Yanhui , Deng Shuai , Zhang Ying , Liu Bailing
Published: September 2018

This paper considers a supply chain consisting of one supplier and one retailer who jointly invest in item‐level radio frequency identification (RFID) by considering their demands and inventories. Since the supplier can be negative to adopt RFID, the main objective of this study is to design an effective mechanism that maximizes the profits of both players and the whole supply chain by implementing item‐level RFID. For this objective, we propose a novel revenue‐cost‐sharing (RCS) contract based on the bargaining game as the incentive to encourage the implementation, and numerical results show that the RCS contract is considerably more effective than the wholesale‐price contract for supply chain coordination. Moreover, we show that the retail supply chain can be coordinated perfectly under the RCS contract when the thresholds of the revenue/cost sharing rates are set appropriately. This study provides significant managerial insight into the incentive and coordination strategy to implement item‐level RFID in the retail supply chain.
Effectiveness of recruitment and retention strategies in a pregnant adolescent nutrition intervention study
Authors: Wise Nancy J. , Cantrell Mary Ann
Published: September 2018

Aim

To report the methodological strategies used to recruit and retain pregnant adolescents into a nutrition‐focused intervention study.

Background

An important step to meeting the developmental and healthcare needs of pregnant adolescents is to conduct high‐quality research studies that generate reliable and accurate data. However, recruitment and retention of pregnant adolescents into research are challenging and time intensive.

Design

A quasi‐experimental, one‐group, pre, post, 6‐week postintervention repeated measures study was conducted among inner‐city pregnant adolescents.

Method

Study participants’ nutrition knowledge, eating habits, and personal self‐efficacy were measured prior to pregnant adolescents’ participation in the workshop, immediately after the intervention and 6‐weeks following the intervention. A total of four workshops were conducted over 14 months from 2014‐2015.

Results

Gatekeepers were influential in recruitment efforts due to trusting relationship they had with study participants. The use of texting reminders and pregnant adolescent‐related incentives that included gift bags and baby items were also effective recruitment and retention strategies. Despite designing the recruitment strategies and using a developmentally tailored workshop, based on empirical evidence gleaned from pregnant adolescents that was modified to meet study participant's schedules, an adequate sample was unable to be recruited and retained for this study.

Conclusion

High‐quality research studies that generate reliable and accurate data are essential in meeting the developmental and healthcare needs of pregnant adolescents. A major barrier in developing evidence‐based care practices to promote the health of these young mothers and their children involves recruiting and retaining them in research studies.
Patients’ experiences 1–6 months after atrial fibrillation ablation: An holistic perspective
Authors: Bergtun Sønneva , Oterhals Kjersti , Fridlund Bengt
Published: September 2018

Aim

To describe patients’ experiences from a holistic perspective 1–6 months after atrial fibrillation (AF) ablation.

Background

Catheter ablation (CA) is an invasive treatment for AF. While CA has Class 1A indication, the latest guidelines for AF management state there is an urgent need to better understand complications in clinical practice to improve the quality of AF ablation procedures.

Design

A qualitative analytic approach based on a deductive and descriptive design was used.

Methods

Interviews of 19 patients, carried out from September 2016 to February 2017, were analysed using qualitative content analysis.

Findings

Five themes were identified; one in each life dimension due to the deductive design based on a holistic model: (a) having unexpected complications with a slower recovery; (b) discovering one's own self‐management strategies when lacking information and insufficient follow‐up; (c) managing resentment through different coping strategies while emotional reactions depended on feeling better or worse; (d) failing to receive full understanding and support from close ones, with social consequences when the biophysical level did not return to normal; (e) gradually adopting new life perspectives with a hope for a better future, despite having unmet expectations and uncertainty, leading to discovering existential matters.

Conclusion

Patients’ post CA experiences could be understood in terms of a holistic model. Their feelings of uncertainty caused by a lack of medical follow‐up led to emotional reactions, the magnitude of which depended on feeling‐well or worse. Patients’ need more information about possible complications, suggesting follow‐up and patient education needs improvement.
Family carers’ experiences of participating in a weight management programme for overweight children and adolescents with intellectual disabilities: An exploratory study
Authors: Lee Regina L.T. , Brown Michael , Leung Cynthia , Chen Hong , Louie Lobo , Chen Jyu‐Lin , Lee Paul H.
Published: September 2018

Aim

To gain insight into the experiences of family carers participating in a weight management programme via mHealth tools for overweight children and adolescents with intellectual disabilities.

Background

Many weight reduction programs fail to show positive and sustainable impacts due to not involving parents, who are usually unavailable to attend school‐based health programs. The mHealth interactive interventions were carried out in September 2015–August 2016, engaging carers to monitor and sustain their children's healthy lifestyle behaviours at home being one way to achieve this.

Design

Qualitative research design to conduct focus group discussion with family carers involved in a school‐based weight management programme via the mHealth interventions.

Methods

An exploratory study was used to examine family carers’ views of participating in a weight management programme. Focus group interviews examined the in‐depth experiences of 20 family carers in providing social support and monitoring lifestyle behaviours via the mHealth interactive interventions.

Results

Twenty family carers were recruited and four themes emerged: (a) improving family carer–child interactions and communications; (b) gaining useful and practical health information from experts; (c) supporting each other via an mHealth platform; and (d) appreciating the collaborative effort between school personnel and family carers. Family carers stressed the usefulness of the mHealth interactive interventions in monitoring and sustaining the children's healthy lifestyle behaviours at home.

Conclusion

The mHealth interactive interventions for increasing family carers’ involvement and monitoring were well received. The findings provide new insights into using mHealth interventions in future weight management programmes involving parental participation in the home environment.
The relative importance of space compared to topography increases from rare to common tree species across latitude
Authors: Hu Yue‐Hua , Johnson Daniel J. , Mi Xiang‐Cheng , Wang Xu‐Gao , Ye Wan‐Hui , Li Yi‐De , Lian Ju‐Yu , Cao Min
Published: September 2018

Aim

Understanding how spatial distributions of rare and common species are associated with environmental and spatial processes is essential to understanding community assembly. We addressed the following questions: (a) does the relative importance of space and topography vary from rare to common tree species? (b) Are the contributions of topography and space equal? (c) Are the variances explained by topography or space correlated with elevational ranges (ER) at the local scale? (d) Does cell‐size influence those postulated associations?

Location

China and the Americas.

Major taxa studied

Tree species.

Methods

We partitioned the variation in species richness and composition of rare and common tree species by topography and space across a range of extents and grain sizes in eight communities. We calculated contribution ratio (CR) between space and topography to quantify their relative importance. We employed Kendall's rank correlation to determine the relation between CR and commonness. Mixed effect models were used to identify the influence of cell‐size on the results.

Results

The majority of CR values were positively related to increasing commonness, especially for composition. The explained variances by space were always higher than that by topography regardless of commonness. At local scale, variances explained by space or topography were not correlated with ER.

Main conclusions

Our results indicate that the relative importance of space compared to topography increases from rare to common species across forests. We suggest that future studies of community assembly need to account for both space and topography to adequately describe differences in rare and common species assembly mechanisms at range of spatial extents and grain sizes.
Can educational robotics introduce young children to robotics and how can we measure it?
Authors: Castro Emanuela , Cecchi Francesca , Valente Massimiliano , Buselli Elisa , Salvini Pericle , Dario Paolo
Published: September 2018

Studies have shown that educational robotics (ER) may impact student learning, especially in relation to STEM (science, technology, engineering, and mathematics) areas. In the STEM framework, particularly for younger children, the “E” and the “T” are considered to be missing letters, because few studies have concentrated on teaching and evaluating technology and engineering through ER activities. This study aimed to develop and test the efficacy of an ER protocol to teach robotics in a sample of 389 students, hypothesizing that girls would be as successful as boys. A Robotics Questionnaire assessing the basics of robotics was developed for this study. A Wilcoxon nonparametric test was performed in order to evaluate improvements (p < 0.05). A Mann–Whitney nonparametric test was performed in order to test the presence of gender differences (p < 0.05). Data indicated significant improvements for all the age ranges considered. No gender differences were found. In order to evaluate the efficacy of a didactic intervention utilizing ER, it is important to assess the impact on children's technological and engineering (robotics, in particular) knowledge.
No measurable fitness cost to experimentally evolved host defence in the Caenorhabditis elegans–Serratia marcescens host–parasite system
Authors: Penley McKenna J. , Greenberg Arielle B. , Khalid Arooj , Namburar Sathvik R. , Morran Levi T.
Published: September 2018

Host susceptibility to parasites can vary over space and time. Costs associated with the maintenance of host defence are thought to account for a portion of this variation. Specifically, trade‐offs wherein elevated defence is maintained at the cost of fitness in the absence of the parasite may cause levels of host defence to change over time and differ between populations. In previous studies, we found that populations of the host nematode, Caenorhabditis elegans, evolved greater levels of parasite avoidance and resistance against the bacterial parasite, Serratia marcescens. Here, we passaged these host populations either in the presence or absence of the parasite to test for a cost of elevated host defences. After 16 generations, we found that elevated levels of host defence were maintained during evolution in both the presence and absence of the parasite. Further, this maintenance of defence was not the result of limited standing genetic variation, but rather the absence of a measurable cost associated with defence. Therefore, costs associated with host defence may not broadly account for differences in host susceptibility across space and time.
Indirect activation of rhesus macaque (Macaca mulatta) NK cells in oral and mucosal draining lymph nodes
Authors: Ram Daniel R. , Kroll Kyle , Reeves R. Keith
Published: September 2018

The oral mucosae and draining lymph nodes are primary entry points for invading pathogens, particularly during immunosuppressive HIV/SIV infections. Innate immunity against oral stimuli, including natural killer (NK) cells, is understudied. Herein, we demonstrate functional NK cell responses to pathogen‐associated molecular patterns (PAMPs) of potential oral pathogens in rhesus macaques.
Cultural equivalence, reliability and utility of the Portuguese version of the Oral Behaviours Checklist
Authors: Barbosa Cláudia , Manso Maria Conceição , Reis Tiago , Soares Tânia , Gavinha Sandra , Ohrbach Richard
Published: September 2018

Background

Oral behaviors (OBs) must be assessed as part of a biobehavioural evaluation for patients with temporomandibular disorders (TMD).

Objectives

The aims of this study were: to translate and culturally adapt the Oral Behaviors Checklist (OBC) into Portuguese; to evaluate its basic psychometric properties; and to assess the utility of the Portuguese OBC.

Methods

The Portuguese translation, cross‐cultural equivalence, and two studies (Pre‐field test, N = 8, and field test, N = 45) of the OBC adhered to official guidelines of the International RDC/TMD Research Consortium (now, INfORM). In the formal test (N = 120) the Portuguese RDC/TMD was used for TMD diagnosis.

Results

Translation and cultural equivalence of the OBC into Portuguese was reviewed and approved by an expert panel. In the field test, item agreement between English and Portuguese OBC versions was very good (weighted Kappa ≥ 0.934). Test‐retest reliability of the OBCSumScore was excellent intra‐class correlation coefficient ((ICC) = 0.998, P < 0.001). As an initial probe into validity using parallel forms, comparison of the sleep bruxism and awake clenching questions included in the RDC/TMD with the corresponding OBC questions yielded excellent (Kappa = 0.932) and very good (k = 0.850), respectively, convergent validity as well as excellent (that is, poor agreement, kappa = 0.013) discriminant validity for these specific OBs. The mean OBCSumScore was significantly lower for the healthy group, compared to the painful TMD group (ANOVA, P = 0.037).

Conclusions

The Portuguese translation of the OBC exhibits cross‐cultural equivalence for use in Portugal, and the instrument performs with acceptable psychometric properties. The validity of the parafunction construct requires additional research in both Portuguese and other languages.
A systematic review on models of care effectiveness and barriers to Hepatitis C treatment in prison settings in the EU/EEA
Authors: Vroling Hilde , Oordt‐Speets Anouk M. , Madeddu Giordano , Babudieri Sergio , Monarca Roberto , O'Moore Eamonn , Vonk Noordegraaf‐Schouten Marije , Wolff Hans , Montanari Marialinda , Hedrich Dagmar , Tavoschi Lara
Published: September 2018

Hepatitis C prevalence in prison populations is much higher than in the community. Effective hepatitis C treatment within this population does not only have a direct individual health benefit, but may lead to substantial community dividend. We reviewed available evidence on hepatitis C treatment in prison settings, with a focus on the European Union/European Economic Area. A systematic review of the literature (PubMed, EMBASE, Cochrane library) was performed and complemented with searches for conference abstracts and grey literature. Thirty‐four publications were included reporting on the effectiveness, acceptability and economic aspects of hepatitis C virus treatment models of care to achieve treatment completion and sustained viral response in prison settings. Available evidence shows that hepatitis C treatment in prison settings is feasible and the introduction of direct‐acting antivirals will most likely result in increased treatment completion and better clinical outcomes for the prison population, given the caveats of affordability and the need for increased funding for prison health, with the resulting benefits accruing mostly in the community.
Add‐on peginterferon alfa‐2a to nucleos(t)ide analogue therapy for Caucasian patients with hepatitis B ‘e’ antigen‐negative chronic hepatitis B genotype D
Authors: Lampertico Pietro , Brunetto Maurizia R. , Craxì Antonio , Gaeta Giovanni B. , Rizzetto Mario , Rozzi Antonella , Colombo Massimo ,   on behalf of The HERMES Study Group
Published: September 2018

Nucleos(t)ide analogues (NAs) and peginterferon have complementary effects in chronic hepatitis B, but it is unclear whether combination therapy improves responses in genotype D‐infected patients. We conducted an open‐label study of peginterferon alfa‐2a 180 μg/wk added to ongoing NA therapy in hepatitis B e antigen (HBeAg)‐negative, genotype D‐infected patients with hepatitis B virus DNA <20 IU/mL. The primary endpoint was proportion of patients with ≥50% decline in serum HBsAg by the end of the 48‐week add‐on phase. Seventy patients received treatment, 11 were withdrawn at week 24 for no decrease in HBsAg, and 14 withdrew for other reasons. Response rate (per‐protocol population) was 67.4% (29/43) at week 48 (95% confidence interval [CI]: 51, 81) and 50.9% (28/55) at week 96 (95% CI: 38, 66). Median serum HBsAg decreased throughout peginterferon alfa‐2a treatment and was significantly lower than baseline at weeks 48, 72 and 96 (P < 0.001). Decreases in HBsAg of ≥0.5‐log10 and ≥1‐log10 were documented in 19 (44.2%) and 6 (14.0%) patients at week 48 and 6 (10.9%) and 17 (30.9%) patients at week 96. The proportion of patients with HBsAg <1000, <500, <100 and <10 IU/mL at ≥1 timepoint during treatment was 78.6% (n = 44), 57.1% (n = 32), 21.4% (n = 12) and 7.1% (n = 4). Interferon gamma‐induced protein 10 increased from baseline up to week 48, with week 12 levels significantly associated with response at week 48. Addition of peginterferon alfa‐2a to ongoing NA therapy significantly decreased HBsAg levels in HBeAg‐negative patients with genotype D infection (ClinicalTrials.gov NCT01706575).
Switching to peginterferon for chronic hepatitis B patients with hepatitis B e antigen seroconversion on entecavir – A prospective study
Authors: Chan Henry L. Y. , Chan Fiona W. S. , Hui Aric J. , Li Michael K. K. , Chan Kam H. , Wong Grace L. H. , Loo Ching K. , Chim Angel M. L. , Tse Chi H. , Wong Vincent W. S.
Published: September 2018

Nucleos(t)ide analogues (NA) are effective in suppressing hepatitis B virus (HBV) replication, but most patients require long‐term treatment. This study aimed to investigate switching to peginterferon as a strategy to stop NA. Hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B patients who developed HBeAg seroconversion during NA treatment were studied. All patients received open‐label peginterferon alfa‐2a 180 μg/wk for 48 weeks, and NA was stopped at week 4 of peginterferon treatment. The primary endpoint was sustained response, which was defined as negative HBeAg, positive anti‐HBe and HBV DNA <2000 IU/mL at week 72. Other secondary endpoints including HBsAg loss at week 72 were also studied. Forty‐one patients treated with entecavir for 56 ± 23 months were recruited. Sustained response was achieved in 30 patients (73%, 95% confidence interval 58%‐84%). At week 72, 31 (76%) patients had HBeAg seroconversion, 56 (23%) patients had undetectable HBV DNA, 31 (76%) patients had normal ALT, and 6 patients (15%) had HBsAg loss. Baseline HBsAg level was the best predictor for both sustained response and HBsAg loss; the best HBsAg cut‐off for sustained response was <1500 IU/mL and that for HBsAg loss was <500 IU/mL by receiver operating characteristic curve analysis. Twenty‐two of 25 (88%) patients with baseline HBsAg <1500 IU/mL had sustained response. Five of 10 (50%) patients with baseline HBsAg <500 IU/mL developed HBsAg loss. Switching to peginterferon can be considered as a treatment option in NA‐treated patients with HBeAg seroconversion, particularly among those with lower HBsAg levels.
Financial Structure, Industrial Structure, and Economic Development: A New Structural Economics Perspective
Authors: Gong Qiang , Lin Justin Yifu , Zhang Yilin
Published: September 2018

We investigate the evolving relative importance of banks and equity markets during different stages of economic development. Unlike previous studies, we propose a demand‐side theory on the appropriate financial structure for an economy. We show that a bank‐based financial structure is more appropriate than a market‐based structure for developing countries, and that for developed countries, a market‐based financial structure is more appropriate than a bank‐based structure. This is due to the industrial structures of countries and the different advantages of banks and equity markets for serving the real economy. Our findings are consistent with recent empirical facts and provide new perspectives to understand the structural change of a country’s financial system.
A comparison of genomic islands of differentiation across three young avian species pairs
Authors: Irwin Darren E. , Milá Borja , Toews David P. L. , Brelsford Alan , Kenyon Haley L. , Porter Alison N. , Grossen Christine , Delmore Kira E. , Alcaide Miguel , Irwin Jessica H.
Published: September 2018

Detailed evaluations of genomic variation between sister species often reveal distinct chromosomal regions of high relative differentiation (i.e., “islands of differentiation” in FST), but there is much debate regarding the causes of this pattern. We briefly review the prominent models of genomic islands of differentiation and compare patterns of genomic differentiation in three closely related pairs of New World warblers with the goal of evaluating support for the four models. Each pair (MacGillivray's/mourning warblers; Townsend's/black‐throated green warblers; and Audubon's/myrtle warblers) consists of forms that were likely separated in western and eastern North American refugia during cycles of Pleistocene glaciations and have now come into contact in western Canada, where each forms a narrow hybrid zone. We show strong differences between pairs in their patterns of genomic heterogeneity in FST, suggesting differing selective forces and/or differing genomic responses to similar selective forces among the three pairs. Across most of the genome, levels of within‐group nucleotide diversity (πWithin) are almost as large as levels of between‐group nucleotide distance (πBetween) within each pair, suggesting recent common ancestry and/or gene flow. In two pairs, a pattern of the FST peaks having low πBetween suggests that selective sweeps spread between geographically differentiated groups, followed by local differentiation. This “sweep‐before‐differentiation” model is consistent with signatures of gene flow within the yellow‐rumped warbler species complex. These findings add to our growing understanding of speciation as a complex process that can involve phases of adaptive introgression among partially differentiated populations.
Host‐derived population genomics data provides insights into bacterial and diatom composition of the killer whale skin
Authors: Hooper Rebecca , Brealey Jaelle C. , van der Valk Tom , Alberdi Antton , Durban John W. , Fearnbach Holly , Robertson Kelly M. , Baird Robin W. , Bradley Hanson M. , Wade Paul , Gilbert M. Thomas P. , Morin Phillip A. , Wolf Jochen B. W. , Foote Andrew D. , Guschanski Katerina
Published: September 2018

Recent exploration into the interactions and relationship between hosts and their microbiota has revealed a connection between many aspects of the host's biology, health and associated micro‐organisms. Whereas amplicon sequencing has traditionally been used to characterize the microbiome, the increasing number of published population genomics data sets offers an underexploited opportunity to study microbial profiles from the host shotgun sequencing data. Here, we use sequence data originally generated from killer whale Orcinus orca skin biopsies for population genomics, to characterize the skin microbiome and investigate how host social and geographical factors influence the microbial community composition. Having identified 845 microbial taxa from 2.4 million reads that did not map to the killer whale reference genome, we found that both ecotypic and geographical factors influence community composition of killer whale skin microbiomes. Furthermore, we uncovered key taxa that drive the microbiome community composition and showed that they are embedded in unique networks, one of which is tentatively linked to diatom presence and poor skin condition. Community composition differed between Antarctic killer whales with and without diatom coverage, suggesting that the previously reported episodic migrations of Antarctic killer whales to warmer waters associated with skin turnover may control the effects of potentially pathogenic bacteria such as Tenacibaculum dicentrarchi. Our work demonstrates the feasibility of microbiome studies from host shotgun sequencing data and highlights the importance of metagenomics in understanding the relationship between host and microbial ecology.
Wheat blast: from its origins in South America to its emergence as a global threat
Authors: Ceresini Paulo Cezar , Castroagudín Vanina Lilián , Rodrigues Fabrício Ávila , Rios Jonas Alberto , Aucique‐Pérez Carlos Eduardo , Moreira Silvino Intra , Croll Daniel , Alves Eduardo , de Carvalho Giselle , Maciel João Leodato Nunes , McDonald Bruce Alan
Published: September 2018

Wheat blast was first reported in Brazil in 1985. It spread rapidly across the wheat cropping areas of Brazil to become the most important biotic constraint on wheat production in the region. The alarming appearance of wheat blast in Bangladesh in 2016 greatly increased the urgency to understand this disease, including its causes and consequences. Here, we summarize the current state of knowledge of wheat blast and aim to identify the most important gaps in our understanding of the disease. We also propose a research agenda that aims to improve the management of wheat blast and limit its threat to global wheat production.
Novel‐graded traumatic brain injury model in rats induced by closed head impacts
Authors: Wang Hao , Zhu Xiyan , Liao Zhikang , Xiang Hongyi , Ren Mingliang , Xu Minhui , Zhao Hui
Published: September 2018

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Due to the heterogeneity of human TBI, none of the available animal models can reproduce the entire spectrum of TBI. This study was designed to develop a novel‐graded TBI rat model which is induced by closed head impacts (CHI) with reproducible brain damage and neurological dysfunction. A total of 75 male Sprague–Dawley rats (200 ± 20 g) were randomly equally divided into five groups: the Sham, 0.5, 0.6, 0.7 and 0.8 MPa groups. A custom‐made, air‐driven injury apparatus was used to induce CHIs (from 0.5 to 0.8 MPa). The kinematic parameters during the procedure were recorded by a force sensor and a high‐speed camera. Mortality rate, duration of unconsciousness (latency period of righting reflex), modified neurological severity score (mNSS) and whole brain water content (BWC) were examined. Pathological changes were evaluated by hematoxylin‐eosin (HE) stain and immunohistochemical stain for amyloid precursor protein (APP). The impact force and speed were 785.3 ± 14.12 N and 5.71 m/s in the 0.5 MPa group, 837.72 ± 10.41 N and 6.06 m/s in the 0.6 MPa group, 857.65 ± 11.11 N and 6.25 m/s in the 0.7 MPa group, and 955.6 ± 16.35 N and 6.67 m/s in the 0.8 MPa group. The periods of loss of righting reflex in 0.6–0.8 MPa groups were significantly higher than that in the Sham group. The mNSS score and BWC of the 0.8 MPa group remained higher 24 h after injury than other groups. Brain damage was indicated by increased APP expression in TBI rats. In conclusion, the newly developed CHI rat model was a highly controlled and reproducible graded TBI model, and provided a useful tool to investigate the underlying mechanism and therapeutic effects of TBI with various injury severities.
Expanding the spectrum of pediatric NTRK‐rearranged fibroblastic tumors to the central nervous system: A case report with RBPMS‐NTRK3 fusion
Authors: Torre Matthew , Jessop Nicholas , Hornick Jason L. , Alexandrescu Sanda
Published: September 2018

We report a case of a 20‐month‐old male presenting with seizures who was found to have a hyperintense lesion on T2‐weighted images of magnetic resonance imaging in the left medial temporal lobe that was initially clinically and radiologically thought to be either low‐grade glioma or focal cortical dysplasia. Histologic, immunohistochemical and molecular evaluation (array comparative genomic hybridization, Archer fusion panel) of the resection specimen demonstrated a highly infiltrative fibroblastic spindle cell neoplasm with mild nuclear atypia and an RBPMS‐NTRK3 fusion. NTRK‐fused mesenchymal tumors are known to involve extracranial sites but, to our knowledge, have not been described within the central nervous system. Accurate and timely diagnosis of this entity has important prognostic and therapeutic implications, as NTRK‐fused tumors may recur locally and may respond to selective kinase inhibitor therapies.
Obesity in the global haemophilia population: prevalence, implications and expert opinions for weight management
Authors: Wilding J. , Zourikian N. , Di Minno M. , Khair K. , Marquardt N. , Benson G. , Ozelo M. , Hermans C.
Published: September 2018

Overweight and obesity may carry a significant disease burden for patients with haemophilia (PWH), who experience reduced mobility due to joint inflammation, muscle dysfunction and haemophilic arthropathy. This review aimed to define the prevalence and clinical impact of overweight/obesity in the global population of PWH. A detailed literature search pertaining to overweight/obesity in haemophilia in the last 15 years (2003–2018) was conducted, followed by a meta‐analysis of epidemiological data. The estimated pooled prevalence of overweight/obesity in European and North American PWH was 31%. Excess weight in PWH is associated with a decreased range in motion of joints, accelerated loss of joint mobility and increase in chronic pain. Additionally, the cumulative disease burden of obesity and haemophilia may impact the requirement for joint surgery, occurrence of perioperative complications and the prevalence of anxiety and depression that associates with chronic illness. Best practice guidelines for obesity prevention and weight management, based on multidisciplinary expert perspectives, are considered for adult and paediatric PWH. Recommendations in the haemophilia context emphasize the importance of patient education and tailoring engagement in physical activity to avoid the risk of traumatic bleeding.
Motifs in bipartite ecological networks: uncovering indirect interactions
Authors: Simmons Benno I. , Cirtwill Alyssa R. , Baker Nick J. , Wauchope Hannah S. , Dicks Lynn V. , Stouffer Daniel B. , Sutherland William J.
Published: September 2018

Indirect interactions play an essential role in governing population, community and coevolutionary dynamics across a diverse range of ecological communities. Such communities are widely represented as bipartite networks: graphs depicting interactions between two groups of species, such as plants and pollinators or hosts and parasites. For over thirty years, studies have used indices, such as connectance and species degree, to characterise the structure of these networks and the roles of their constituent species. However, compressing a complex network into a single metric necessarily discards large amounts of information about indirect interactions. Given the large literature demonstrating the importance and ubiquity of indirect effects, many studies of network structure are likely missing a substantial piece of the ecological puzzle. Here we use the emerging concept of bipartite motifs to outline a new framework for bipartite networks that incorporates indirect interactions. While this framework is a significant departure from the current way of thinking about bipartite ecological networks, we show that this shift is supported by analyses of simulated and empirical data. We use simulations to show how consideration of indirect interactions can highlight differences missed by the current index paradigm that may be ecologically important. We extend this finding to empirical plant–pollinator communities, showing how two bee species, with similar direct interactions, differ in how specialised their competitors are. These examples underscore the need to not rely solely on network‐ and species‐level indices for characterising the structure of bipartite ecological networks.
Three new approaches to genomic selection
Authors: Wang Lizhi , Zhu Guodong , Johnson Will , Kher Mriga
Published: September 2018

Conventional genomic selection approaches use breeding values to evaluate individual plants or animals and to make selection decisions. Multiple variants of breeding values and selection approaches have been proposed, but they suffer two major limitations. First, selection decisions are not responsive to changes in time and resource availability. Second, selection decisions are not coordinated with related decisions such as mating and resource allocation. We present three new genomic selection approaches that attempt to address these two limitations, which were designed by engineering students in a class project at Iowa State University. Compared with previous approaches using the same data set from the literature, two of these engineering approaches were found to be comparable to the state of the art, and the third one significantly dominated all the previous approaches.