bluuebunny/crossref_metadata_2025 huggingface dataset:
Autophagy‐related gene BbATG11 is indispensable for pexophagy and mitophagy, and contributes to stress response, conidiation and virulence in the insect mycopathogen Beauveria bassiana
Authors: Ding Jin‐Li , Peng Yue‐Jin , Chu Xin‐Ling , Feng Ming‐Guang , Ying Sheng‐Hua
Published: July 2018

Autophagy is a conserved degradation system in eukaryotic cells that includes non‐selective and selective processes. Selective autophagy functions as a selective degradation mechanism for specific substrates in which autophagy‐related protein 11 (ATG11) acts as an essential scaffold protein. In B. bassiana, there is a unique ATG11 family protein, which is designated as BbATG11. Disruption of BbATG11 resulted in significantly reduced conidial germination under starvation stress. The mutant ΔBbATG11 displayed enhanced sensitivity to oxidative stress and impaired asexual reproduction. The conidial yield was reduced by approximately 75%, and this defective phenotype could be repressed by increasing exogenous nutrients. The virulence of the ΔBbATG11 mutant strain was significantly impaired as indicated in topical and intra‐hemocoel injection bioassays, with a greater reduction in topical infection. Notably, BbATG11 was involved in pexophagy and mitophagy, but these two autophagic processes appeared in different fungal physiological aspects. Both pexophagy and mitophagy were associated with nutrient shift, starvation stress and growth in the host hemocoel, but only pexophagy appeared in both oxidation‐stressed cells and aerial mycelia. This study highlights that BbATG11 mediates pexophagy and mitophagy in B. bassiana and links selective autophagy to the fungal stress response, conidiation and virulence.
2,3‐Butanediol catabolism in Pseudomonas aeruginosa PAO1
Authors: Liu Qiuyuan , Liu Yidong , Kang Zhaoqi , Xiao Dan , Gao Chao , Xu Ping , Ma Cuiqing
Published: July 2018

2,3‐Butanediol (2,3‐BD) is a primary microbial metabolite that enhances the virulence of Pseudomonas aeruginosa and alters the lung microbiome. 2,3‐BD exists in three stereoisomeric forms: (2R,3R)‐2,3‐BD, meso‐2,3‐BD and (2S,3S)‐2,3‐BD. In this study, we investigated whether and how P. aeruginosa PAO1 utilizes these 2,3‐BD stereoisomers and showed that all three stereoisomers were transformed into acetoin by (2R,3R)‐2,3‐butanediol dehydrogenase (BDH) or (2S,3S)‐2,3‐BDH. Acetoin was cleaved to form acetyl‐CoA and acetaldehyde by acetoin dehydrogenase enzyme system (AoDH ES). Genes encoding (2R,3R)‐2,3‐BDH, (2S,3S)‐2,3‐BDH and the E1 and E2 components of AoDH ES were identified as part of a new 2,3‐BD utilization operon. In addition, the regulatory protein AcoR promoted the expression of this operon using acetaldehyde, a cleavage product of acetoin, as its direct effector. The results of this study elucidate the integrated catabolic role of 2,3‐BD and may provide new insights in P. aeruginosa‐related infections.
Impact of Vitamin D Receptor Gene Polymorphism on Chronic Renal Failure Susceptibility
Authors: Li Li , Wan Qingsong , Yang Shikun , Zhao Saili
Published: July 2018

Our pooled analysis aimed to assess the impact of vitamin D receptor (VDR) gene polymorphism on chronic renal failure (CRF) susceptibility. Relevant studies were searched from multiple databases, then pooled‐analyses were performed using Stata software. Eighteen studies involving 2512 CRF patients and 3630 healthy controls were included. Pooled analysis showed that VDR ApaI and TaqI gene polymorphism were not associated with CRF susceptibility either in Asian or in Caucasians populations, and VDR BsmI and FokI gene polymorphism were not associated with CRF susceptibility in overall populations. The subgroup analysis showed that VDR BsmI gene polymorphism was associated with CRF susceptibility in Chinese under the Allele model (OR = 0.76, 95% CI: 0.59–0.97, P = 0.029). In Spanish individuals, VDR BsmI gene polymorphism was associated with CRF: Recessive model (BB vs. Bb + bb): OR = 1.60, 95% CI: 1.09–2.35, P = 0.016; Additive model (BB + bb vs. Bb): OR = 1.60, 95% CI: 1.21–2.12, P = 0.001). In addition, in the Asian subgroup, VDR FokI gene polymorphism was associated with CRF risk: Allele model (F vs. f): OR = 0.31, 95% CI: 0.16–0.59, P = 0.000; Dominant model (FF + Ff vs. ff): OR = 0.12, 95% CI: 0.03–0.59, P = 0.009 and Recessive model (FF vs. Ff + ff): OR = 0.32, 95% CI: 0.13–0.75, P = 0.009. This pooled analysis showed that VDR BsmI gene polymorphism was associated with CRF risk in the Chinese and Spanish individuals, and, VDR FokI gene polymorphism was associated with CRF risk in Asian subjects. But VDR ApaI and TaqI gene polymorphism were not associated with CRF risk either in Asian or in Caucasian individuals.
Newly designed 16S rRNA metabarcoding primers amplify diverse and novel archaeal taxa from the environment
Authors: Bahram Mohammad , Anslan Sten , Hildebrand Falk , Bork Peer , Tedersoo Leho
Published: July 2018

High‐throughput studies of microbial communities suggest that Archaea are a widespread component of microbial diversity in various ecosystems. However, proper quantification of archaeal diversity and community ecology remains limited, as sequence coverage of Archaea is usually low owing to the inability of available prokaryotic primers to efficiently amplify archaeal compared to bacterial rRNA genes. To improve identification and quantification of Archaea, we designed and validated the utility of several primer pairs to efficiently amplify archaeal 16S rRNA genes based on up‐to‐date reference genes. We demonstrate that several of these primer pairs amplify phylogenetically diverse Archaea with high sequencing coverage, outperforming commonly used primers. Based on comparing the resulting long 16S rRNA gene fragments with public databases from all habitats, we found several novel family‐ to phylum‐level archaeal taxa from topsoil and surface water. Our results suggest that archaeal diversity has been largely overlooked due to the limitations of available primers, and that improved primer pairs enable to estimate archaeal diversity more accurately.
Bayesian inference and simulation approaches improve the assessment of Elo‐ratings in the analysis of social behaviour
Authors: Goffe Adeelia S. , Fischer Julia , Sennhenn‐Reulen Holger
Published: July 2018

The construction of rank hierarchies based on agonistic interactions between two individuals (“dyads”) is an important component in the characterization of the social structure of groups. To this end, winner‐loser matrices are typically created, which collapse the outcome of dyadic interactions over time, resulting in the loss of all information contained in the temporal domain. Methods that track changes in the outcome of dyadic interactions (such as “Elo‐ratings”) are receiving increasing interest. Critically, individual ratings are not just based on the succession of wins and losses, but depend on the values of start ratings and a shift coefficient. Recent studies improved existing methods by introducing a point estimation of these auxiliary parameters on the basis of a maximum likelihood (ML) approach. For a sound assessment of the rank hierarchies generated this way, we argue that measures of uncertainty of the estimates, as well as a quantification of the robustness of the methods, are also needed.

We introduce a Bayesian inference (BI) approach using “partial pooling”, which rests on the assumption that all start ratings are samples from the same distribution. We compare the outcome of the ML approach to that of the BI approach using real‐world data. In addition, we simulate different scenarios to explore in which way the Elo‐rating responds to social events (such as rank changes), and low numbers of observations.

Estimates of the start ratings based on “partial pooling” are more robust than those based on ML, also in scenarios where some individuals have only few observations. Our simulations show that assumed rank differences may fall well within the “uncertain” range, and that low sampling density, unbalanced designs, and coalitionary leaps involving several individuals within the hierarchy may yield unreliable results.

Our results support the view that Elo‐rating can be a powerful tool in the analysis of social behaviour, when the data meet certain criteria. Assessing the uncertainty greatly aids in the interpretation of results. We advocate running simulation approaches to test how well Elo‐ratings reflect the (simulated) true structure and how sensitive the rating is to true changes in the hierarchy.
Lipo‐prostaglandin E1 increases immediate arterial maximal flow velocity of free flap in patients undergoing reconstructive surgery
Authors: Jin Seok‐Joon , Suh Hyunsuk Peter , Lee Joonho , Hwang Jai‐Hyun , Hong Joon Pio (Jp) , Kim Young‐Kug
Published: July 2018

Background

In free flap surgery, the maintenance of proper blood flow after anastomosis of flap pedicle vessels is important. Lipo‐prostaglandin E1 (lipo‐PGE1) has been empirically administered to prevent blood flow insufficiency in a free flap reconstruction. We tested our hypothesis that lipo‐PGE1 administration increases the arterial inflow of free flap. We also evaluated lipo‐PGE1‐related haemodynamic changes and complications.

Methods

Thirty‐seven patients who underwent free flap reconstruction were analysed. Lipo‐PGE1 was administered 10 minutes after the vascular anastomosis of the free flap. The maximal blood flow velocity was measured at the free flap pedicle artery before and 30 minutes after lipo‐PGE1 administration using duplex ultrasonography. The primary outcome was the difference in the maximal blood flow velocity before and 30 minutes after lipo‐PGE1 administration. The arterial blood pressure, heart rate, cardiac output, stroke volume variation, and pulse pressure variation were measured simultaneously. Lipo‐PGE1‐related complications such as hypotension, bradycardia, hypothermia, facial flushing, diarrhoea, apnoea, and seizure were also investigated.

Results

The maximal blood flow velocity was significantly increased at 30 minutes after lipo‐PGE1 administration compared to the level before lipo‐PGE1 administration (mean (standard deviation): 26.3 (8.7) cm/s vs 22.5 (8.0) cm/s, P = 0.002). The haemodynamic variables were not significantly different before and 30 minutes after lipo‐PGE1 administration. No lipo‐PGE1‐related complications occurred.

Conclusions

Lipo‐PGE1 significantly increases the maximal blood flow velocity without complications in patients undergoing free flap reconstruction and may be an effective and safe method of maintaining adequate blood flow in these cases.
Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits
Authors: Ortega‐de San Luis Clara , Sanchez‐Garcia Manuel A. , Nieto‐Gonzalez Jose Luis , García‐Junco‐Clemente Pablo , Montero‐Sanchez Adoracion , Fernandez‐Chacon Rafael , Pascual Alberto
Published: July 2018

The striatum integrates motor behavior using a well‐defined microcircuit whose individual components are independently affected in several neurological diseases. The glial cell line‐derived neurotrophic factor (GDNF), synthesized by striatal interneurons, and Sonic hedgehog (Shh), produced by the dopaminergic neurons of the substantia nigra (DA SNpc), are both involved in the nigrostriatal maintenance but the reciprocal neurotrophic relationships among these neurons are only partially understood. To define the postnatal neurotrophic connections among fast‐spiking GABAergic interneurons (FS), cholinergic interneurons (ACh), and DA SNpc, we used a genetically induced mouse model of postnatal DA SNpc neurodegeneration and separately eliminated Smoothened (Smo), the obligatory transducer of Shh signaling, in striatal interneurons. We show that FS postnatal survival relies on DA SNpc and is independent of Shh signaling. On the contrary, Shh signaling but not dopaminergic striatal innervation is required to maintain ACh in the postnatal striatum. ACh are required for DA SNpc survival in a GDNF‐independent manner. These data demonstrate the existence of three parallel but interdependent neurotrophic relationships between SN and striatal interneurons, partially defined by Shh and GDNF. The definition of these new neurotrophic interactions opens the search for new molecules involved in the striatal modulatory circuit maintenance with potential therapeutic value.
Multiple alleles of ACAN associated with chondrodysplastic dwarfism in Miniature horses
Authors: Eberth J. E. , Graves K. T. , MacLeod J. N. , Bailey E.
Published: July 2018

Chondrodysplastic dwarfism in Miniature horses appeared to be a recessive genetic trait based on the occurrence of affected offspring by normal parents. Dwarf phenotypes vary and range from abnormal abortuses to viable offspring with evidence of skeletal dysplasia. A genome‐wide association study implicated a region of ECA1 with dwarfism in Miniature horses. Aggrecan (ACAN) was a candidate gene in that region, and exons were sequenced to compare DNA sequences for dwarf and non‐dwarf horses. Sequencing led to the discovery of variants in exons 2, 6, 7 and 15 associated with dwarfism. The four variants are identified with reference to Ecab 3.0 (GCF_002863925.1) as g.95291270del (rs1095048841), g.95284530C>T (ERP107353), g.95282140C>G (rs1095048823) and g.95257480_95257500del (rs1095048839) and designated here as D1, D2, D3* and D4 respectively. A previous study at another laboratory reported dwarfism associated with homozygosity for D3*. Homozygotes for those variants and compound heterozygotes for any combination of those variants always expressed a dwarfism phenotype. However, eight additional horses with dwarfism were found, seven of which were heterozygotes for D2, D3* or D4, suggesting the existence of additional ACAN alleles causing dwarfism. Among Miniature horses, the combined frequency of D1, D2, D3* and D4 was 0.163, suggesting a carrier rate of 26.2% for alleles causing chondrodysplastic dwarfism.
Reducing the interval of a growth QTL on chromosome 4 in laying hens
Authors: Lyu S. , Arends D. , Nassar M. K. , Weigend A. , Weigend S. , Preisinger R. , Brockmann G. A.
Published: July 2018

In our previous research, we identified a QTL with an interval of 3.4 Mb for growth on chicken chromosome (GGA) 4 in an advanced intercross population of an initial cross between the New Hampshire inbred line (NHI) and the White Leghorn inbred line (WL77). In the current study, an association analysis was performed in a population of purebred white layers (WLA) with White Leghorn origin. Genotypic data of 130 SNPs within the previously identified 3.4‐Mb region were obtained using a 60K SNP chip. In total, 24 significant SNPs (LOD ≥ 4.44) on GGA4 were detected for daily weigh gain from 8 to 14 weeks and two SNPs (LOD ≥ 4.80) for body weight at 14 weeks. The QTL interval was reduced by 1.9 Mb to an interval of 1.5 Mb (74.6–76.1 Mb) that harbors 15 genes. Furthermore, to identify additional loci for chicken growth, a genome‐wide association study (GWAS) was carried out in a WLA population. The GWAS identified an additional QTL on GGA6 for body weight at six weeks (19.8–21.2 Mb). Our findings showed that by using a WLA population we were able to further reduce the QTL confidence interval previously detected using a NHI × WL77 advanced intercross population.
Gene therapy for C1 esterase inhibitor deficiency in a Murine Model of Hereditary angioedema
Authors: Qiu Ting , Chiuchiolo Maria J. , Whaley Adele S. , Russo Anthony R. , Sondhi Dolan , Kaminsky Stephen M. , Crystal Ronald G. , Pagovich Odelya E.
Published: July 2018

Background

Hereditary angioedema (HAE) is a life‐threatening, autosomal dominant disorder characterized by unpredictable, episodic swelling of the face, upper airway, oropharynx, extremities, genitalia, and gastrointestinal tract. Almost all cases of HAE are caused by mutations in the SERPING1 gene resulting in a deficiency in functional plasma C1 esterase inhibitor (C1EI), a serine protease inhibitor that normally inhibits proteases in the contact, complement, and fibrinolytic systems. Current treatment of HAE includes long‐term prophylaxis with attenuated androgens or human plasma‐derived C1EI and management of acute attacks with human plasma‐derived or recombinant C1EI, bradykinin, and kallikrein inhibitors, each of which requires repeated administration. As an approach to effectively treat HAE with a single treatment, we hypothesized that a one‐time intravenous administration of an adeno‐associated virus (AAV) gene transfer vector expressing the genetic sequence of the normal human C1 esterase inhibitor (AAVrh.10hC1EI) would provide sustained circulating C1EI levels sufficient to prevent angioedema episodes.

Methods

To study the efficacy of AAVrh.10hC1EI, we used CRISPR/Cas9 technology to create a heterozygote C1EI‐deficient mouse model (S63±) that shares characteristics associated with HAE in humans including decreased plasma C1EI and C4 levels. Phenotypically, these mice have increased vascular permeability of skin and internal organs.

Results

Systemic administration of AAVrh.10hC1EI to the S63± mice resulted in sustained human C1EI activity levels above the predicted therapeutic levels and correction of the vascular leak in skin and internal organs.

Conclusion

A single treatment with AAVrh.10hC1EI has the potential to provide long‐term protection from angioedema attacks in affected individuals.
Staphylococcus epidermidis from prosthetic joint infections induces lower IL‐1β release from human neutrophils than isolates from normal flora
Authors: Månsson Emeli , Söderquist Bo , Nilsdotter‐Augustinsson Åsa , Särndahl Eva , Demirel Isak
Published: July 2018

The aim of this study was to test the hypothesis that Staphylococcus epidermidis isolated from prosthetic joint infections (PJIs) differs from S. epidermidis isolated from normal flora in terms of its capacity to induce activation of caspase‐1 and release of IL‐1β in human neutrophils. The amount of active caspase‐1 was determined over 6 h by detecting Ac‐YVAD‐AMC fluorescence in human neutrophils incubated with S. epidermidis isolates from PJIs (ST2) or normal flora. The amount of IL‐1β was detected by ELISA in neutrophil supernatants after 6 h of incubation. Mean IL‐1β release was lower after incubation with S. epidermidis from PJIs compared to isolates from normal flora, but no statistically significant difference was found in active caspase‐1. Substantial inter‐individual differences in both active caspase‐1 and IL‐1β were noted. These results suggest that evasion of innate immune response, measured as reduced capacity to induce release of IL‐1β from human neutrophils, might be involved in the predominance of ST2 in S. epidermidis PJIs, but that other microbe‐related factors are probably also important.
Hepatoprotectivity of Panduratin A against liver damage: In vivo demonstration with a rat model of cirrhosis induced by thioacetamide
Authors: Salama Suzy M. , Ibrahim Ibrahim Abdel Aziz , Shahzad Naiyer , Al‐Ghamdi Saeed , Ayoub Nahla , AlRashdi Ahmed Salim , Abdulla Mahmood Ameen , Salehen Nur'Ain , Bilgen Mehmet
Published: July 2018

This experiment evaluated Panduratin A (PA), a chalcone isolated from Boesenbergia rotunda rhizomes, for its hepatoprotectivity. Rats were subjected to liver damage induced by intra‐peritoneal injection of thioacetamide (TAA). PA was tested first for its acute toxicity and then administered by oral gavage at doses 5, 10, and 50 mg/kg to rats. At the end of the 8th week, livers from all rats were excised and evaluated ex vivo. Measurements included alkaline phosphatase (AP), alanine transaminase (ALT), aspartate transaminase (AST) and gamma‐glutamyl transferase (GGT), serum platelet‐derived growth factor (PDGF) and transforming growth factor (TGF‐β1), and hepatic metalloproteinase enzyme (MMP‐2) and its inhibitor extracellular matrix protein (TIMP‐1). Oxidative stress was measured by liver malondialdehyde (MDA) and nitrotyrosine levels, urinary 8‐hydroxy 2‐ deoxyguanosine (8‐OH‐dG), and hepatic antioxidant enzyme activities. The immunohistochemistry of TGF‐β1 was additionally performed. PA revealed safe dose of 250 mg/kg on experimental rats and positive effect on the liver. The results suggested reduced hepatic stellate cells (HSCs) activity as verified from the attenuation of serum PDGF and TGF‐β1, hepatic MMP‐2 and TIMP‐1, and oxidative stress. The extensive data altogether conclude that PA treatment could protect the liver from the progression of cirrhosis through a possible mechanism inhibiting HSCs activity.
Pregnancy and birth outcomes in a Danish nationwide cohort of women with autoimmune hepatitis and matched population controls
Authors: Grønbæk Lisbet , Vilstrup Hendrik , Jepsen Peter
Published: July 2018

Background

Many patients with autoimmune hepatitis are women of fertile age. Some concerns of these patients are related to pregnancy.

Aim

To conduct a nationwide study on risk of miscarriage, birth rate, and birth outcomes in women with autoimmune hepatitis.

Methods

From Danish healthcare registries, 1994‐2015, we identified 179 births in 103 women with autoimmune hepatitis, 70 of which were first‐time singleton births, and 1623 births in 1051 age‐matched women (population controls), 662 of which were first‐time singleton births. We calculated the risk of miscarriage and the birth rate after autoimmune hepatitis diagnosis in women with autoimmune hepatitis and controls. We used logistic regression to compare the odds of adverse birth outcomes (preterm birth, small for gestational age, congenital malformations and stillbirth) between women with autoimmune hepatitis and controls, adjusting for maternal age and smoking habits.

Results

The risk of miscarriage was similar in women with autoimmune hepatitis and controls: risk ratio 1.17 (95% confidence interval 0.81‐1.68). The first‐time birth rate, including singleton and multiple births, per 1000 person‐years in women with autoimmune hepatitis was 37 (95% confidence interval 29‐46), in controls 32 (95% confidence interval 30‐35). Age at first‐births was similar in women with autoimmune hepatitis and controls. Women with autoimmune hepatitis had an increased risk of preterm birth (adjusted odds ratio 3.19, 95% confidence interval 1.53‐6.64) and small for gestational age babies (adjusted odds ratio = 3.20, 95% confidence interval 0.33‐31.29), but not of congenital malformations (adjusted odds ratio = 1.27, 95% confidence interval 0.48‐3.34) or stillbirth. Birth outcomes did not differ in autoimmune hepatitis patients on or off immunosuppression, and with or without cirrhosis.

Conclusions

In Danish women with autoimmune hepatitis, fertility was unaffected. They had an increased risk of preterm birth and small for gestational age children, but not of congenital malformations or stillbirth.
Games for enhancing basic reading and maths skills: A systematic review of educational game design in supporting learning by people with learning disabilities
Authors: Lämsä Joni , Hämäläinen Raija , Aro Mikko , Koskimaa Raine , Äyrämö Sanna‐Mari
Published: July 2018

The development of games for people with learning disabilities is one way to enhance the quality of learning and respond to the need for inclusive special educational support. Recently, game researchers have highlighted the need for paying more attention to identifying the game design choices that can strengthen learning. This paper reviews recent studies in the field of games that aim at supporting people with difficulties in learning, particularly in basic reading and maths skills. We identify the major characteristics and learning outcomes of the reviewed studies, as well as key design principles that have been used in games for enhancing basic reading and maths skills. The results show that people with specific learning difficulties have positive improvements in the quality of learning. We also found specific gamification elements that have been used to promote the learning of basic reading and maths skills. However, we call for research, which would explicitly examine the effects of game design choices on learning. Currently, the studies that address learning disabilities do not specifically define which kind of games and game design the results refer to, while game design studies do not clarify how these games influence learning. Thus, there is a need to rethink previous empirical studies on game settings for people with learning difficulties via advancing the role of game design in empirical intervention studies.
Explaining early moral hypocrisy: Numerical cognition promotes equal sharing behavior in preschool‐aged children
Authors: Chernyak Nadia , Harris Paul L. , Cordes Sara
Published: July 2018

Recent work has documented that despite preschool‐aged children's understanding of social norms surrounding sharing, they fail to share their resources equally in many contexts. Here we explored two hypotheses for this failure: an insufficient motivation hypothesis and an insufficient cognitive resources hypothesis. With respect to the latter, we specifically explored whether children's numerical cognition—their understanding of the cardinal principle—might underpin their abilities to share equally. In Experiment 1, preschoolers’ numerical cognition fully mediated age‐related changes in children's fair sharing. We found little support for the insufficient motivation hypothesis—children stated that they had shared fairly, and failures in sharing fairly were a reflection of their number knowledge. Numerical cognition did not relate to children's knowledge of the norms of equality (Experiment 2). Results suggest that the knowledge–behavior gap in fairness may be partly explained by the differences in cognitive skills required for conceptual and behavioral equality.
Maternal recurrent pregnancy loss is associated with an increased risk for long‐term neurological morbidity in offspring
Authors: Paz Levy Dorit , Wainstock Tamar , Sheiner Eyal , Sergienko Ruslan , Landau Daniella , Walfisch Asnat
Published: July 2018

Aim

To determine whether maternal history of recurrent pregnancy loss (RPL) impacts on the long‐term neurological health of the offspring.

Method

A population‐based cohort analysis was performed, including all singletons born between 1991 and 2014 at a single regional tertiary centre. Neurological morbidity up to age 18 years (including cognitive, motor, and psychiatric disorders) in children born to mothers with and without a history of RPL was compared. Cumulative neurological morbidity incidence was compared with survival curves and a Weibull multivariable survival model to control for follow‐up time and relevant confounders.

Results

A total of 242 187 deliveries met the inclusion criteria during the study period, 5% (n=12 182) of which were in mothers with RPL. Epilepsy and developmental disorders were significantly more common in the group with RPL (0.95 vs 0.74/1000 person‐years [p=0.009] and 0.22 vs 0.09/1000 person‐years [p<0.001]). The survival curves demonstrated significantly higher cumulative incidences of epilepsy and developmental disorders in the group with RPL. The multivariable model exhibited an independent association between maternal RPL and childhood epilepsy (adjusted hazard ratio 1.23; 95% confidence interval 1.01–1.50) and developmental disorders in the offspring (adjusted hazard ratio 2.41; 95% confidence interval 1.60–3.64).

Interpretation

A history of maternal RPL appears to be independently associated with long‐term neurological morbidity of the offspring.

What this paper adds

Hospitalizations for epilepsy and developmental disorders are significantly more common among children of mothers with a history of recurrent pregnancy loss.
Development and content validation of the Muscular Dystrophy Child Health Index of Life with Disabilities questionnaire for children with Duchenne muscular dystrophy
Authors: Propp Roni , McAdam Laura , Davis Aileen M , Salbach Nancy M , Weir Shannon , Encisa Clarissa , Narayanan Unni G
Published: July 2018

Aim

To develop a patient‐reported outcome measure that comprehensively captures the health‐related priorities of children with Duchenne muscular dystrophy (DMD).

Method

Children withDMDand their parents completed the iteratively revised versions of the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD), followed by a cognitive interview to develop a pilot version of a new measure. Multidisciplinary health care professionals completed an item‐by‐item analysis of the measure and a 14‐item sensibility questionnaire. Minimum content validity ratio for each item of the new measure and the mean score (0–7) for the items of the sensibility questionnaire were calculated.

Results

TheCPCHILDunderwent changes over 19 interviews with children and their parents, resulting in the pilot Muscular Dystrophy Child Health Index of Life with Disabilities (MDCHILD). The content validity ratio of eachMDCHILDitem ranged from 0.85 to 1 based on health care professionals’ ratings. The mean score exceeded the threshold of four for all items of the sensibility questionnaire. Based on child, parent, and health care professional recommendations, 16 items were added, six eliminated, and 15 items modified from the originalCPCHILD. TheMDCHILDconsists of 47 items over seven domains.

Interpretation

TheMDCHILDmet all sensibility criteria by children withDMD, their parents, and health care professionals, and is ready for psychometric evaluation.

What this paper adds

The Muscular Dystrophy Child Health Index of Life with Disabilities (MDCHILD) is a new patient‐reported outcome measure for Duchenne muscular dystrophy (DMD).

The Priority Framework of Outcomes underpins the content for the MDCHILD.

The MDCHILD incorporates the health‐related priorities of males with DMD and their parents.

The MDCHILD was deemed sensible by children, their parents, and health care professionals.
HbA1c values and hospital admissions in children and adolescents receiving continuous subcutaneous insulin infusion therapy
Authors: Evans‐Cheung T. C. , Campbell F. , Yong J. , Parslow R. C. , Feltbower R. G.
Published: July 2018

Aims

To assess HbA1c values and hospitalization rates before, during and after continuous subcutaneous insulin infusion (CSII) therapy.

Methods

Demographic and hospitalization data were extracted from 161 individuals with Type 1 diabetes who received continuous subcutaneous insulin infusion (CSII) therapy between 2002 and 2013 at the Leeds Children and Young People's Diabetes Service for those aged < 20 years. The median (range) age at CSII start was 11.9 (1.1–17.6) years. The median (range) follow‐up time was 2.3 (0–8.1) years. Random intercept models were used to compare HbA1c values before and during CSII initiation (and after CSII for those who discontinued it). Hospitalization rates were calculated for diabetic ketoacidosis and severe hypoglycaemia.

Results

The mean HbA1c concentration decreased by 7 mmol/mol [95% CI 6–8; 0.6% (95% CI 0.5–0.7%)]. For the discontinued group (n=30), mean HbA1c decreased by 5 mmol/mol [95% CI 2–8; 0.4% (95% CI 0.2–0.7%)]. HbA1c returned to pre‐CSII start levels at the end of this therapy. Diabetic ketoacidosis admissions increased threefold during CSII compared with before CSII start [2.2 per 100 person‐years (95% CI 1.3 to 3.6) vs 7.4 per 100 person‐years (95% CI 5.1 to 10.8)] and was highest during the first year of CSII. No difference in severe hypoglycaemia incidence rate was found during CSII compared with the pre‐CSII period.

Conclusions

Despite significant reductions in HbA1c levels for individuals treated with CSII, improvements are needed to reduce diabetic ketoacidosis hospitalizations for those new to the therapy.
Long‐term cost‐effectiveness of a Patient Empowerment Programme for type 2 diabetes mellitus in primary care
Authors: Lian Jinxiao , McGhee Sarah M. , So Ching , Chau June , Wong Carlos K. H. , Wong William C. W. , Lam Cindy L. K.
Published: July 2018

Aim

To evaluate the long‐term cost‐effectiveness of a Patient Empowerment Programme (PEP) for type 2 diabetes mellitus (DM) in primary care.

Materials and Methods

PEP participants were subjects with type 2 DM who enrolled into PEP in addition to enrolment in the Risk Assessment and Management Programme for DM (RAMP‐DM) at primary care level. The comparison group was subjects who only enrolled into RAMP‐DM without participating in PEP (non‐PEP). A cost‐effectiveness analysis was conducted using a patient‐level simulation model (with fixed‐time increments) from a societal perspective. We incorporated the empirical data from a matched cohort of PEP and non‐PEP groups to simulate lifetime costs and outcomes for subjects with DM with or without PEP. Incremental cost‐effectiveness ratios (ICER) in terms of cost per quality adjusted life year (QALY) gained were calculated. Probabilistic sensitivity analysis was conducted with results presented as a cost‐effectiveness acceptability curve.

Results

With an assumption that the PEP effect would last for 5 years as shown by the empirical data, the incremental cost per subject was US $197 and the incremental QALYs gained were 0.06 per subject, which resulted in an ICER of US $3290 per QALY gained compared with no PEP across the lifetime. Probabilistic sensitivity analysis showed 66% likelihood that PEP is cost‐effective compared with non‐PEP when willingness‐to‐pay for a QALY is ≥US $46 153 (based on per capita GDP 2017).

Conclusions

Based on this carefully measured cost of PEP and its potentially large benefits, PEP could be highly cost‐effective from a societal perspective as an adjunct intervention for patients with DM.
Needs for information and reasons for (non)adherence in chronic myeloid leukaemia: Be aware of social activities disturbing daily routines
Authors: Boons Christel C. L. M. , Harbers Lorette , Timmers Lonneke , de Jong Jan , Swart Eleonora L. , Harry Hendrikse N. , Janssen Jeroen J. W. M. , Hugtenburg Jacqueline G.
Published: July 2018

Objectives

To obtain insight into patients’ reasons for medication (non)adherence in chronic myeloid leukaemia (CML) and needs and wishes regarding information and communication.

Methods

A mixed‐method study on the basis of a questionnaire and semi‐structured interviews. The CML patient advocacy group asked patients to participate.

Results

Sixty‐one patients (54 ± 12 years, 43% male) using imatinib, dasatinib or nilotinib participated. Fifteen patients (25%) reported to miss an intake at least once a month. Most were not worried about missing an intake and did not discuss missed intakes with their healthcare provider (HCP). Social activities disturbing daily routines and the wish to avoid side effects resulted in nonadherence. Patients wanted extensive and understandable information provided timely on all aspects of CML treatment, in particular on side effects, and a more supportive HCP attitude.

Conclusions

Nonadherence to CML medication does not cause concern in all patients and is not discussed pro‐actively. HCP have a clear role in supporting medication adherence in CML and must be aware that social activities disturbing daily routines contribute to nonadherence. HCP should discuss (non)adherence in a direct manner, motivate patients to play an active role in managing their medication and timely provide extensive and understandable information on all aspects of CML.
The clinical heterogeneity of Parkinson's disease and its therapeutic implications
Authors: Greenland Julia C. , Williams‐Gray Caroline H. , Barker Roger A.
Published: July 2018

Although Parkinson's disease (PD) is primarily a movement disorder, there are a range of associated nonmotor symptoms, including cognitive impairment, depression and sleep disturbance. These can occur throughout the disease course, even predating the motor syndrome. However, both motor and nonmotor symptoms are variable between individual patients. Rate of disease progression is also heterogenous: although 50% have reached key milestones of either postural instability or dementia within 4 years from diagnosis, almost a quarter have a good prognosis at 10 years. In this review we discuss how a range of different factors including clinical features, pathology and genetics, have been used to describe the heterogeneity of PD. We explore the value of longitudinal studies of incident PD cohorts, based on our own experience in Cambridgeshire, to define differences in rates of disease progression and predictors of outcome, including how such studies have informed the development of prognostic models which can be used at an individual patient level. Finally, we discuss the benefits of better understanding the basis of heterogeneity of PD in terms of implications for the development and trialling of more targeted therapies for different subgroups of patients, including regenerative approaches.
Ophelimus maskelli (Ashmead) et son parasitoïde Closterocerus chamaeleon (Girault) (Hymenoptera: Eulophidae) au Maroc
Authors: Kissayi K. , Benhalima S.
Published: July 2018

Des galles foliaires causant de graves dégâts ont été observées sur Eucalyptus camaldulensis dans la région du Gharb‐Maâmora au cours de l'année 2002. Celles‐ci sont causées par Ophelimus maskelli (Ashmead) (Hymenoptera: Eulophidae) signalé pour la première fois au Maroc. Depuis, cet organisme nuisible s'est propagé à d'autres peuplements d'eucalyptus à l’échelle nationale. Au cours des investigations menées sur le terrain, les auteurs ont observé que les degrés d'infestation d'Eucalyptus camaldulensis diffèrent d'une région à l'autre et ont été classés sur une échelle à 3 niveaux : faible, modéré ou élevé. L’étude du cycle biologique de l'insecte sur le terrain et en laboratoire a révélé la présence de deux générations par an. Ce travail a permis de constater que Closterocerus chamaeleon (Hymenoptera: Eulophidae), parasitoïde utilisé avec succès dans d'autres pays de la region OEPP comme agent de lutte biologique, est présent au Maroc. Le taux de parasitisme observé s'est avéré très élevé ce qui pourrait expliquer le peu de dégâts actuellement causés par l'organisme nuisible gallicole O. maskelli sur l'Eucalyptus camaldulensis au Maroc.
Computational approaches for high‐throughput single‐cell data analysis
Authors: Todorov Helena , Saeys Yvan
Published: July 2018

During the past decade, the number of novel technologies to interrogate biological systems at the single‐cell level has skyrocketed. Numerous approaches for measuring the proteome, genome, transcriptome and epigenome at the single‐cell level have been pioneered, using a variety of technologies. All these methods have one thing in common: they generate large and high‐dimensional datasets that require advanced computational modelling tools to highlight and interpret interesting patterns in these data, potentially leading to novel biological insights and hypotheses. In this work, we provide an overview of the computational approaches used to interpret various types of single‐cell data in an automated and unbiased way.
Communicating nutrition information at the point of purchase: An eye‐tracking study of shoppers at two grocery stores in the United States
Authors: Bartels Mike , Tillack Katherin , Jordan Lin Chung‐Tung
Published: July 2018

Providing nutrition information at the point of purchase is one approach that can be used to help consumers adopt and maintain a healthy diet. Previous research has examined consumer self‐reported notice and use of the information as well as how the design of the information affects its attention and use in a laboratory environment using eye‐tracking methodology. This study advances the literature by applying eye‐tracking methodology to explore consumer visual and choice behavior in a real shopping environment, and by recognizing that nutrition information competes with other visual stimuli in the store and consumers are vulnerable to a “limited attention span” for nutrition information in a shopping setting. Data came from a cross‐sectional survey conducted in two grocery stores in the United States in July 2014 with a convenience sample of 60 grocery shoppers while they were selecting and buying items from one of three product categories (ready‐to‐eat cereal, snacks, and soup). The study finds that point‐of‐purchase nutrition information faced strong competition for participants’ attention from other visual elements in a real shopping environment and the attention is dominated by nonnutrition elements, particularly brand/product name, product imagery, and product pricing. Nutrition‐related information, on the other hand, received much less attention, with claims and front‐of‐package nutrition symbols seen by more participants than the Nutrition Facts label. The study suggests that to more effectively enable nutrition information to “catch the eyes” of shoppers at the point of purchase, increasing consumer exposure to the information and enhancing shopper education may merit further investigation.
Selecting the best risk measure in multiobjective cash management
Authors: Salas‐Molina Francisco
Published: July 2018

In this paper, we consider cash management from a multidimensional perspective in which cost and risk are desired goals to minimize. Cash managers interested in minimizing risk need to select the most appropriate risk measure according to their particular needs. In order to assess the quality of alternative risk measures, we empirically compare eight different risk measures in terms of the combined cost–risk performance of a cash management model. To this end, we rely on goal programming to derive optimal solutions for cash management models. Our results show that risk measures based on cost deviations better capture risk in comparison to those based on a reference cash balance. The methodology proposed in this paper allows cash managers to propose and evaluate new risk measures.
A process control algorithm for reaction‐diffusion minimum time heating cycles for binder removal from green bodies
Authors: Lombardo Stephen J. , Retzloff David G.
Published: July 2018

Minimum time heating cycles have been simulated for binder removal from ceramic green bodies where the product of binder decomposition exits the green body via diffusion. The model consists of the reaction‐diffusion partial differential equation, ordinary differential equations describing the reaction kinetics and a heating function, and algebraic equations, one of which imposes a constraint on concentration or pressure to avoid failure of the green body. Two solution approaches were compared: an earlier approximate method based on the pseudo‐steady state assumption combined with a variational calculus algorithm and a new approach based on the finite element method combined with a process control algorithm. The agreement between the two solution strategies reinforces the validity of the pseudo‐steady state approximation and the utility of the process control methodology. The latter, which was also applied to problems in which no approximate solution was obtainable, is thus a general method for obtaining minimum time heating cycles.
Innate immune cells in reproduction
Authors: Negishi Yasuyuki , Takahashi Hidemi , Kuwabara Yoshimitsu , Takeshita Toshiyuki
Published: July 2018

Fetomaternal immune tolerance is required to prevent fetal rejection during pregnancy; simultaneously, the maternal immune system must also protect the fetus from harmful endogenous and exogenous antigens, including those associated with viral and bacterial infections. Therefore, a delicate immune balance is critical for the maintenance of a successful pregnancy, while disruption of this balance can induce complications such as implantation failure, miscarriage, preterm birth/labor, preeclampsia and fetal growth restriction. While the adaptive immune system is critical for the development of tolerance, this review summarizes evidence that modulation of the innate immunity is also essential for achieving this delicate balance between tolerance and protection. Canonical cells of the innate immune system, including dendritic cells, macrophages, natural killer cells and invariant natural killer T cells, contribute to the modulation of the immune balance at the fetomaternal interface. The newly identified myeloid‐derived suppressor cells and innate lymphoid cells also appear important for successful reproduction. Moreover, it is possible that sterile inflammation facilitates complications of pregnancy via the innate immune system. In this review, the characteristic features and functions of innate immune cells in fetomaternal immunity and their contributions to pregnancy complications related to sterile inflammation are discussed. These insights on innate immune system function in reproduction may provide new perspectives for understanding the mechanisms of fetomaternal tolerance and the etiology of pregnancy complications.
Hysteroscopic tubal occlusion using iso‐amyl‐2‐cyanoacrylate in patients with hydrosalpinx
Authors: Amer Mohamed I. M. , Ahmed Mortada E. , Hassan Dalal A.
Published: July 2018

Aim

The aim of this work is to assess the effectiveness of hysteroscopic tubal occlusion using iso‐amyl‐2‐cyanoacrylate, among infertile women with hydrosalpinx prior to in vitro fertilization (IVF).

Methods

Hysteroscopic injection of fallopian tubes with hydrosalpinx by 0.5 mL iso‐amyl‐2‐cyanoacrylate was done in 40 infertile women planning for IVF. The patients were then followed‐up after 1 and 3 months, with hysterosalpingography (HSG) to confirm complete tubal occlusion. Reinjection with iso‐amyl‐2‐cyanoacrylate was done in these patients with incomplete tubal occlusion after 1 month of the first injection, followed by HSG 2 months later to confirm complete tubal occlusion. Data were prescribed as range, mean and standard deviation (for parametric variables) and range, number and percentage (for categorical variables).

Results

The total number of tubes injected in this study was 54, 42 (77.8%) of which were completely occluded after one injection while 12 (22.2%) were partially occluded. Reinjection of the partially occluded tubes was done, and (HSG) of all patients after 3 months of the primary injection confirmed 48 (88.9%) of the tubes completely occluded while 6 (11.1%) remained partially occluded. Thirty‐two (80%) patients underwent one cycle of IVF/ET (embryo transfer), while 8 (20%) patients did not appear for follow‐up. Among the patients who underwent IVF/ET, 24 (75%) got pregnant, while 8 (25%) failed to conceive. Among the pregnant patients, 8 (33.3%) delivered at term, 3 (12.5%) had first trimester abortion, while the remaining 13 (54.2%) did not deliver yet.

Conclusion

Iso‐amyl‐2‐cyanoacrylate used for hysteroscopic tubal occlusion in patients with hydrosalpinx prior to IVF is safe and effective.
Revisiting Fromm and Bourdieu: Contributions to habitus and realism
Authors: Grillo Carmen M.
Published: July 2018

Realist scholars are increasingly turning their attention to Pierre Bourdieu's concept of habitus or dispositions as a way of theorizing thought and behaviour. In this article, the author offers a contribution, based on Erich Fromm's social psychology, to the realist theory of habitus. The author argues that while Bourdieu and Fromm both see the quest for meaning as the source of subjectivity in social life, Fromm goes further than Bourdieu in analysing the psychodynamic consequences of the acquisition of habitus. Fromm provides additional tools to understand the properties of habitus that emerge from its interaction with primary psychological needs. Principally, Fromm's work reveals an undertheorized set of emergent properties of habitus.